AI transcript
0:00:04 Hello boys and girls, ladies and germs. This is Tim Ferriss. Welcome to another episode of
0:00:09 The Tim Ferriss Show. This episode is deeply personal because as someone who is now in his
0:00:15 late 40s, my eyes have started to go for the first time. I’ve always had 2010 vision and this is
0:00:23 unacceptable for me. So I spoke to everyone I knew and good old Andrew Huberman saw a post that I put
0:00:29 up, texted me, said the person you need to talk to is Dr. Jeffrey Goldberg. So guess who my guest
0:00:35 is today? Dr. Jeffrey Goldberg, professor and chair of ophthalmology and director of the Byers Eye
0:00:41 Institute at Stanford University. He has a wide breadth of expertise. He is a leading scientist
0:00:46 in the development and degeneration of the visual system from eye to brain and their interventions
0:00:51 depending on where you want to go at many points along that chain, although it’s more of a network,
0:00:56 I guess, and a practicing ophthalmologist and surgeon. We dive into all sorts of stuff in this episode,
0:01:02 ranging from super performance or super normal performance. Let’s just say for professional
0:01:10 athletes, if you want to take your vision from normal or pretty good to unbelievably good for,
0:01:16 say, competitive purposes, we talk about that. And we also talk about repair and slowing the
0:01:23 degeneration of the eye, which naturally comes with age. Dr. Goldberg’s research is directed at vision
0:01:27 restoration, including neuroprotection and regeneration of the retina and optic nerve,
0:01:32 a major unmet need in glaucoma and other eye diseases. And we’ll define all of these terms in
0:01:37 the conversation. So don’t worry. His laboratory is developing novel molecular stem cell and
0:01:42 nanotherapeutics approaches for eye repair. And he is widely recognized for translating advances in the lab
0:01:50 into clinical trials for patients. So from bench to bedside in some respect. And I really enjoyed this
0:01:55 conversation. I took a lot of notes. There’s a lot of actionable detail. So we’ll dive right into the
0:01:59 conversation. But first, just a few words from the people who make this podcast possible.
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0:03:42 If I were to update the four-hour work week, which I get asked to do a lot, I would really only add one
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0:05:10 T-I-M, at gamma.app. Optimal minimal. At this altitude, I can run flat out for a half mile before
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0:05:24 The Tim Ferriss Show.
0:05:33 Dr. Jeffrey Goldberg, so nice to meet you. Thanks for making the time.
0:05:36 Absolutely. Thanks for having me on. I’m really looking forward to it.
0:05:43 I have so many questions for you. And as usual, I am scratching my own itch. This is going to be a
0:05:51 selfish conversation for yours truly in some respects because the way this whole thing came about is I put
0:05:58 up a post on social media asking for cutting edge technologies or treatments related to presbyopia,
0:06:05 which for those who don’t recognize the term is a very fancy way of saying age-related visual decline.
0:06:12 If you’re a word nerd like I am, Presbyterian, similar etymology, leadership of the elders.
0:06:20 And I have noticed in the last year that my near work, my near vision has started to falter,
0:06:28 looking at books, looking at my iPhone, looking at supplement bottles. And this has led to somewhat
0:06:36 of a crisis of meaning for me because I have had my identity based on, in some respects, very,
0:06:42 very good eyesight and visual acuity for my entire life. And Andrew Huberman, mutual friend of ours,
0:06:50 texted me and said, I know the guy and listened to our interview, which I did. And for that reason,
0:06:55 we’re going to go all over the place. But I thought we would start where I had to start,
0:07:01 which is super normal visual performance. And these are the notes I scribbled down from your
0:07:04 conversation with Andrew. I recommend everyone listen to it.
0:07:10 Goggles that reduce frame rate for basketball. And that was sort of left hanging a little bit.
0:07:14 You guys didn’t do a deep dive on it. So I want to start right there. Because of course,
0:07:19 there’s preventing decline, there’s maybe a restoring function, and then there’s going further
0:07:27 and taking things as far as you can. And nowhere are the stakes higher and the rewards greater perhaps
0:07:31 than in professional sports. So could you take that and run with it in any way that makes sense?
0:07:37 Yeah, presbyopia, vision of the old. So I’ll tell you just a funny side note. You know, we all get that.
0:07:44 I, like you, have gone my whole life without needing glasses until I hit around age 40. And when everyone
0:07:53 hits around age 40, our lens inside the eye won’t compress and reshape to focus up close. So your distance
0:07:59 vision might still be great, but you just can’t bring that focus in as tight. And I discovered it
0:08:05 accidentally in myself because I was actually like in my house and someone, I found a pair of glasses in
0:08:11 a closet. Like somebody must’ve just left them there. And they’re not the readers. And we couldn’t figure
0:08:16 out who they were. We’re calling around, friends and family, fine. Nobody’s claiming them. And then
0:08:21 one day I just put them on like, let’s see how I look in glasses. And I looked down at my phone and
0:08:29 I’m like, oh my God, wait a second. I can see a lot better with these readers on. And then once you do
0:08:32 it, you’re addicted because good vision is pretty addicting, right?
0:08:33 Yeah, for sure.
0:08:39 Yeah. So now I’m in them too. And, uh, you know, I’m pretending to look so young with you,
0:08:42 not wearing them right now, but here they are just in case.
0:08:45 Yeah. Very common.
0:08:50 It raises a really cool question that you’re raising, which is, you know, like as an eye doctor,
0:08:54 I spent a lot of time and as a researcher spent a lot of time, we could come back to talking about
0:08:58 like, how do we prevent the sick from losing vision on all these big eye diseases? We could come
0:09:04 back to that, but like, there’s a much bigger world of people who have pretty good vision.
0:09:08 Maybe they need glasses, but they’ve got good vision. And how do we think about the difference,
0:09:14 not from sick to normal, but how do we think about the difference from normal to supra normal? And we
0:09:19 know there’s super normal because when, for example, as you bring up professional athletes get
0:09:25 studied, they have better vision. They have better reflex time. They have sharper vision. You know,
0:09:31 we talk about like 20-20 vision. That means like I can see at 20 feet what a quote normal person can
0:09:38 see at 20 feet. So I have normal vision, but you can have 20-12 vision, which means like you can see
0:09:43 at 20 feet what normal people can see at 12 feet, right? You’ve got better than normal. And it turns
0:09:49 out like a lot of pro athletes have that. And then the next question becomes, and you just kind of hinted
0:09:58 at it right there. Can we train to super normal vision? Can we like induce? And almost no one studies
0:10:04 that, but there are some really cool tools and toys that actually might have that effect. And so you brought
0:10:12 up one of them. So we see like our cones inside of our eyes, you know, we’ve got rods and cones. The cones,
0:10:19 they’ve got a refresh rate, you know, around 30 to 60 frames per second, you know, kind of like our
0:10:26 computer screens do, right? And so if you actually subtract out a couple of frames, so if you put on
0:10:37 some glasses that dim one out of every 30th of a second or they dim two out of every 30th or push it
0:10:45 three, and now you’re giving up visual data and I throw a basketball at you, if you’ve got your regular
0:10:53 vision, you’ll catch it. But if I’m only giving you 90% of your vision or 80% or 70% or 60% of that
0:11:02 vision, you might miss the ball, right? But if we practiced and trained in those goggles where you’ve
0:11:07 got to play basketball, throw and catch, shoot, whatever, you know, throw a baseball back and
0:11:14 forth at 70% vision. And then we put you in the game back with a hundred percent vision, right? You’re
0:11:21 going to be like better, faster reflex time, all of that, like hand-eye coordination. So it’s actually
0:11:28 like some of these super normal visual tactics are actually trainable and there’s tools that
0:11:30 athletes are using, but they’re accessible to all of us. Yeah.
0:11:32 You can grab one of those, Tim.
0:11:37 Let’s dig into this a little bit. I have a number of friends who have engineering shops and have played
0:11:43 with sensory substitution experiments and all sorts of wild stuff. In fact, I think there’s some folks at
0:11:49 Stanford who, David Eagleman comes to mind, who’ve developed tools along these lines. We won’t go down
0:11:55 that route. Let me stick with vision for a second and just note that there are, for instance, indigenous
0:12:02 groups in various parts of the Amazon. I’ve seen them in Brazil and in Peru as well, which use eye drops
0:12:11 of various types. Could be from a plant, could be from a toad for improving not near work, but distance work.
0:12:19 So let’s just say using, most of them use shotguns these days, but some still use blowguns and bow and
0:12:24 arrows for hunting, save monkeys, right? So there seems to be something to it. Now you could say, ah,
0:12:31 that’s a bunch of voodoo, voodoo nonsense. But then you have eye drops for, as I understand it,
0:12:37 temporarily inducing more, this isn’t going to be the right term, but flexibility in the lens.
0:12:38 I think, is it pelocarpine?
0:12:43 It’s actually the iris. Yeah. Yeah. So I don’t know what they’re using in the plants,
0:12:52 but we now have FDA approved eye drops. And what they actually do is they bring your pupil size down
0:13:00 by having your iris constrict to a smaller circle. And it turns out that if you have refractive error,
0:13:04 so you need glasses, you know, the shape of the front of your eye, the shape of your lens isn’t
0:13:09 perfect. You have a little bit of glasses or contacts or whatever to correct that, including if it’s not
0:13:16 focusing up to close, you can have reading glasses that change that refractive, you know, that light
0:13:23 light coming into your eyes so that you’re focusing up at close. If you come down to a pinhole, you
0:13:29 actually kind of normalize the light so that it’s as if it’s all coming from infinity and you actually
0:13:35 kind of correct refractive error. One of the ways we can tell if someone needs glasses is we have you
0:13:39 read the eye chart and then we have you read the eye chart through a little pinhole, you know, a little
0:13:43 device you stick in front of that eye and read through a pinhole. And if you can read better through
0:13:50 the pinhole, you actually have better vision and could correct it with glasses. So now we could just
0:13:57 give an eye drop that kind of makes your pupil closer to a pinhole. And then it allows you to see
0:14:02 without glasses near or far. And in fact, people are kind of using it now for near vision for that
0:14:07 presbyopia you were talking about in the beginning. So for people listening, and also for me, frankly,
0:14:16 could you just give a vision 101? And in this case, let’s focus on the eye just so people understand the
0:14:24 basic components of the eye. And part of the reason I want to explore this is there are different levers
0:14:31 you might be able to pull on to improve vision, some of which might be structurally related, but not all at
0:14:36 least to the eye. But could you just lay out the basic anatomy of the eye, the architecture?
0:14:42 Yeah, absolutely. So light comes in the front, goes through the clear window in the front of our eye
0:14:50 called the cornea. You can have corneal diseases, obviously, that block that light from coming through
0:14:55 clearly. But if it’s healthy, that light comes through clearly. The cornea is curved on the front,
0:15:02 and that curvature is actually responsible for curving most of the light into the back of the eye.
0:15:08 Then the light goes through your pupil. So that’s the iris, which is brown and me, but brown, blue,
0:15:13 hazel. So that’s our iris. And the iris can open and close like we were talking about a minute ago.
0:15:17 Comes through the middle of that, the open middle part of that. Goes through the lens.
0:15:24 The lens is like, does fine focusing, you know, a little focusing from far to near, that kind of thing.
0:15:29 That’s what we were saying stiffens as we age. So we can’t go far to near as well as we get older,
0:15:36 kind of passing 40 years old, typically. And then it goes through the gelatinous middle part of the eye.
0:15:41 We call it the vitreous. After the lens is called the vitreous. That’s where floaters are. People who
0:15:46 get floaters, they’re floating. It’s like little concretions of proteins and stuff floating in the
0:15:52 vitreous. It’s a gel. As we get older, that gel turns to water, kind of shrinks up. Our eye doesn’t
0:15:57 shrink because it fills in with, you know, salt water, but the gel shrinks up. And then the light
0:16:03 hits the retina. And our retinas are what we call inverted. So the light actually passes through
0:16:10 almost all of the retina. And then it hits the rods and the cones. And those are the photoreceptors.
0:16:17 They absorb the light, like the photons of light. The rods are really only good for nighttime vision.
0:16:22 They’re only good at like very low light. If you go into normal daytime vision, sitting here in the
0:16:26 room, whatever, those are getting bleached out. You’re not really using your rods too much.
0:16:34 Next to them, the cones. Cones are great for color vision. They’re great for bright lights. They’re
0:16:39 what we use most of the day. That’s what you and I are using mainly right now. The rods and the cones
0:16:48 collect all that light. They process it and transmogrify it into electrical signals. And
0:16:53 those electrical signals are then propagated back forward through the retina. There’s some internal
0:16:57 processing layers in the retina. So it’s not just a layer of film. You’re actually doing some
0:17:02 computation right there in the retina. And then they hit what are called retinal ganglion cells.
0:17:08 And those are the cells that then send a process across the surface of the retina. It’s an axon,
0:17:14 but it’s like a telephone wire. And that then goes back out the back of the eye into what we call the
0:17:19 optic nerve. And that optic nerve connects the eye to the brain. So those retinal ganglion cells are
0:17:24 collecting all the data and sending it all back through the optic nerve to the brain. And then,
0:17:26 of course, the rest of that processing is happening in the brain.
0:17:32 There we go. That was a great summary. Thank you very much. And I’ll tell folks, if you thought that
0:17:39 is a lot to remember, it is a lot to remember. But the point of it is, as I, as my own NF1,
0:17:47 am trying to consider different paths forward with presbyopia, whether it’s glasses, yes,
0:17:52 my readers do fix the problem, right? They do fix the problem, but I am a little concerned of
0:17:57 increased dependency and then increased magnification over time. I know there are arguments for and maybe
0:18:03 some arguments against, but when I put up my social post, and I think people can identify with this,
0:18:10 there was a lot of noise. There were some of the most harebrained, insane, certainly potentially
0:18:18 dangerous suggestions you can imagine. And then there were a few things that came up when I reached
0:18:25 out to, let me get this right, is it vitro retinal surgeon and researcher who I happen to know. And he
0:18:30 sent me a number of white papers, or I shouldn’t say white papers, more so studies and meta-analyses and
0:18:36 so on, that I read up on. And I thought to myself, look at that. Surprise of surprises. A few of the things
0:18:41 that came up repeatedly in the hundreds of responses to my post actually show up in the literature and there
0:18:47 might be something to them. And we’ll definitely come to a number of those. But it can be very overwhelming
0:18:53 for people to try to figure out what to do next. And the reason I wanted you to do that recap, and then I’ll stop
0:19:00 giving my second TED Talk of our conversation, is that much like if someone complains of, say, brain fog
0:19:07 and fatigue, a rose is a rose is a rose is not a rose in the sense that there can be many different
0:19:14 factors and independent variables that contribute to that. So one person might have insulin insensitivity
0:19:19 and trouble with glucose disposal. Somebody else might have Lyme disease or some infectious disease that is
0:19:24 contributing to metabolic dysfunction. I mean, there’s so many different contributing factors
0:19:29 that it helps to, I think, get a little thinly sliced. So in my case, I have the stiffening of
0:19:35 the lens. Please correct my terminology. I also have a really pretty sizable, I’d never seen it before,
0:19:43 I did some really impressive imaging on the eye, but a huge nevus on the back of my right eye that I need
0:19:48 to keep an eye on. So I’ll be following up on that in three or four months. But I wanted to,
0:19:55 I suppose, start with what are other ways to improve vision? Now, there are certain things I’m always
0:20:05 looking for, limited downside potential upside. So for instance, I’m taking the AREDS2 supplement with
0:20:12 lutein and various other ingredients in it. I would say it’s probably not going to help, but within my
0:20:18 patient cohort of the medical practices I work with, there are a few folks who claimed after six weeks that
0:20:22 their vision really improved and they didn’t need their readers, even though technically, mechanistically,
0:20:28 the AREDS2 shouldn’t have helped them. So whether it’s placebo effect or not, interesting outcome. I know the
0:20:34 plural of anecdote is not data, but I was like, ah, okay, sure, I’ll take the supplement. What are some other
0:20:41 sort of cutting-edge treatments or augmentations for improving vision? And I’ll shut up in a second, but I’ve been
0:20:46 very excited to talk to you. So I’m like a chomping at the bit here. Because as you mentioned, I mean,
0:20:53 there’s this sort of eye architecture brain interface. And among professional athletes, just because I’ve
0:21:00 funded a lot of science in this area, low-dose psychedelics also seem to improve visual acuity.
0:21:06 So everyone from Aaron Rodgers to very, very high-level athletes that I will not dox here
0:21:13 report measurable performance improvements that they attribute to increased visual acuity. It’s
0:21:18 probably not changing the anatomy of the eye. So what’s going on, right? So I would just love you
0:21:25 speak to any other means of supercharging visual perception.
0:21:29 There are some things that we have a pretty decent sense on.
0:21:35 Carrots 2 and some of these supplements, you know, first of all, like eating a lot of carrots is
0:21:39 probably not going to actually do it, you know? So great childhood, get the kids to eat their
0:21:46 vegetables. We definitely exercised that ourselves as parents. But Carrots 2, clinically proven,
0:21:53 if you have moderate age-related macular degeneration to slow down your vision loss.
0:21:59 Does that mean it doesn’t work at all if you have mild age-related macular degeneration or if you have
0:22:05 no age-related macular degeneration? It might just be like, we haven’t done a study big enough to detect
0:22:12 those effects. And as you say, like, that’s probably not going to hurt. So, you know, feel free if you
0:22:16 want. We can’t prove it’s helping, but feel free. There are other supplements,
0:22:21 supplements that have, you know, received some study that maybe suggests there isn’t much going
0:22:27 on there that, again, probably not going to hurt. Some patients take CoQ10. Some patients take Ginkgo.
0:22:34 There’s actually maybe the hottest topic in supplement vitamin space right now internationally is actually
0:22:43 vitamin B3, nicotinamide, which has, you know, really been linked to a number of good potential, you know,
0:22:48 kind of medical uses and is receiving a lot of studies. There’s actually international clinical
0:22:54 trials, including one here in the U.S., actually testing whether it could restore vision in certain eye
0:23:00 diseases like glaucoma, which is my specialty. So, definitely some hints in that direction. We already
0:23:08 talked about some device elements. And I think between vision training, like we talked about earlier,
0:23:15 and also visual augmentation, we’re moving into augmented reality. And so, training vision and visual
0:23:22 reflex time almost certainly makes a difference in the activities you’re training in. If you’re training
0:23:29 in basketball, will it also help you doing some weekend surfing? I don’t know, but definitely can
0:23:36 help move you from normal to super normal or help enhance, improve what you’re doing. And then there’s
0:23:43 all sorts of stuff that, I’m going to be honest, Sam, we don’t know because A, it’s kind of really new,
0:23:50 really hot right now, like microdosing certain psychedelics, things like that, that we know act on the
0:23:57 nervous system, including the brain. But the retina in the back of the eye and the optic nerve that
0:24:02 connects the retina to the brain, those are developmentally an outgrowth from the brain.
0:24:09 They are part of the brain. They’re part of the central nervous system. And we barely know about
0:24:17 how to influence the wiring, the plasticity. Are there drugs that we can give? A lot of people have
0:24:23 talked about gabapentin, drugs in that space. Obviously, microdosing and LSD is a really hot
0:24:32 area right now for inducing plasticity. There’s actually great science showing in animal models
0:24:41 and a little bit now in humans that you can actually reopen brain plasticity by dosing some of these
0:24:45 drugs at appropriate doses. Obviously, we’ve got to be careful. We don’t know what the right dose is
0:24:52 yet. But it’s really worth looking at because there’s clear evidence that these are relevant
0:24:57 and likely to have some effects. We just got to figure out a little bit more like how, what’s the
0:25:02 right dose. By the way, when you’re doing it, should you be doing some behavioral training,
0:25:08 like visual training? But these things act on the brain. And about a third of our brain inside our skull
0:25:11 is dedicated to processing vision.
0:25:17 Yeah, there’s a lot there. All right. I’ve been so excited. I’m not just over-caffeinated
0:25:21 because I’m actually not really caffeinated. I might be over-ketoned. I have quite a bit of
0:25:27 ketone mana, Esther, in me at the moment. But putting that aside, I am right now, and this could
0:25:33 make me seem like I’m in the tinfoil hat-wearing crowd, but I had a number of companies reach out to me,
0:25:38 not surprising, after I put up my social posts. Most of them didn’t make any sense. A few of them
0:25:43 seemed to make sense. And the people involved seem to have technical chops and also some pretty
0:25:48 credible research backgrounds. And I’m not going to name the company yet because I’m not done with
0:25:53 my personal testing. But I have been testing at about eight minutes a day. I don’t know the right
0:26:01 descriptor to use. I would say maybe visual perception training to distinguish it from,
0:26:06 and we can talk about this, what I suppose some ophthalmologists or optometrists might call visual
0:26:12 education, right? So trying to improve the ciliary muscle strength and so on around the eyes,
0:26:18 much like if people want to visual sort of the springs around a trampoline. But in this case,
0:26:25 it’s very quick flashes of blurry or not blurry circles, and you need to identify what is more
0:26:32 blurred. And there are many permutations. It adapts to your successes and failures over time.
0:26:43 And it could absolutely be placebo. But after about a month now of using it, I feel like my near vision
0:26:49 vision has improved. Even the woman I’m dating has commented on this. And I’m still waiting. The jury
0:26:57 is out. But this is just to say that I’d love to know what you think of visual improvement that is
0:27:07 not dependent on surgery or drops. Is there something to the various types of visual education? Is there
0:27:14 something there or not? And then when we go maybe upstream a bit, if that’s the right phrasing to
0:27:20 use to the brain, are there interesting approaches like limiting the frame rate or removing a number of
0:27:25 frames that you think are at least plausibly interesting for enhancing performance?
0:27:33 First of all, absolutely. And it does get back to that idea of visual training, reducing frame rate,
0:27:39 training on visual perception. There’s actually a fair amount of data. Actually, there’s enough data
0:27:45 to even say like there’s elements that make it better. For example, if you do visual training where
0:27:52 you’re just showing yourself, you know, like being shown these different objects, maybe they’re getting
0:28:01 smaller, dimmer, blurrier, etc. Your ability to train off of that is significantly better if it demands
0:28:09 a behavioral outcome, a motor action. So for example, you’ve got a point at the right one or choose
0:28:16 something. And it’s not just that you’re mentally thinking that was the sharper image. It’s actually
0:28:21 the motor output of pushing a button or pointing at something or doing an activity that actually
0:28:30 reinforces the visual perception training. So that’s one great example. Another great example is after
0:28:37 concussion. So concussion, traumatic brain injury, of course, very common in athletes because they’re more
0:28:42 likely to get into the, you know, head bumps and things like that, but happens all the times in kids.
0:28:50 Military, very big issue. And the line in between mild concussion, severe concussion, traumatic brain
0:28:59 injury, injury. That’s all on a spectrum, a continuum. And there’s actually decent data from that group of
0:29:07 people that if you get a concussion, actually visual symptoms are some of the more significant symptoms.
0:29:12 You know, ability to focus, ability to sleep and vision are three of the big symptoms that people get
0:29:19 in that concussion through TBI spectrum. And those can be debilitating, right? And kids are out of school,
0:29:24 they’re missing high school, you know, for weeks or longer. It can be really debilitating. Obviously,
0:29:30 if you’re an older adult and you’re in your job situation, really tough. And it turns out,
0:29:38 though, that there are visual perception exercises that you can put patients through in those situations
0:29:45 that in the limited clinical studies that have been done point to a positive effect of basically
0:29:51 rehabbing, like neuro rehabbing you back. Now that, of course, is back from injured to normal. But the
0:29:57 idea that that can also induce the same kind of plastic remodeling in our eye and brain, and particularly
0:30:04 the eye-brain connection in patients who are starting from normal and trying to get themselves up to
0:30:11 supranormal, try to improve performance, visual performance. We’ve set up here a whole human
0:30:18 performance laboratory really just to study these questions. And the data rolling in, you know,
0:30:21 make it look like, hey, there’s something here. This is definitely worth chasing.
0:30:27 What can someone search if they want to find something to read up on related to the concussion
0:30:34 rehabilitation protocol because this type of visual training because there’s a lot of nonsense floating
0:30:40 around and charlatans out there? Any particular search terms or principal investigators or anything that
0:30:40 people can search?
0:30:47 I would say like, you know, if you want to sort of like at least hit some of the science or science-adjacent
0:30:52 web resources, you’re going to want to use a few technical terms in there like concussion,
0:30:59 neuro-rehab, neuro-rehabilitation, plasticity, and then some of the terms you’ve already been
0:31:05 using, you know, visual perception exercises. And then look, in these situations, you’ve got to look
0:31:11 not just at the content, but of the source, right? And so is this like a dude on his blog or is this
0:31:18 coming from a foundation or an institute or one of the academic centers or some of the choices like
0:31:19 that?
0:31:25 Just a quick thanks to one of our sponsors and we’ll be right back to the show.
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0:32:40 slash Tim. All right, Jeff, I would love to hop to another set of interventions. And this is in the
0:32:46 device category. Red light in the morning for mitochondrial health? Question mark. Violet light
0:32:55 to reduce progression of nearsightedness in children. Is there an application of red light or violet light?
0:33:01 To what extent do we have supporting data for using either of these? Do we have an idea of what best
0:33:07 practices look like? Is it only for people with a disease state or can they be potentially used to
0:33:16 preserve vision before vision loss? The disease state data is pretty good. And also the myopia control
0:33:20 is pretty good data too. Just for a definition for folks, what’s myopia?
0:33:28 Myopia is nearsightedness. And you know, it’s an epidemic, more common in Asians or people of Asian
0:33:34 heritage, but common in everyone. And kids can get nearsighted. If you’re a little nearsighted,
0:33:40 it might be annoying to wear glasses. If you get more severely nearsighted, it actually can lead to all
0:33:48 sorts of problems inside the eye. You know, real severe vision loss, even early in life. So it’s a
0:33:56 big one. And then what was really shocking was it turns out that a small dose of daily red light
0:34:04 can slow down progression of myopia in young people. You know, we’re talking about teens and younger even.
0:34:15 So what’s even more shocking to me is that it also works with violet light. So how does it work with light
0:34:22 at the two ends of the visible spectrum? And definitely mitochondria are implicated. Mitochondria are the
0:34:29 little like kind of powerhouses, energy sources inside the cell. They are big player in converting the sugar a cell
0:34:36 takes in into energy that the cell can use for all of the cellular processes. So our bodies clearly need
0:34:43 functioning mitochondria. In fact, one of the big features common across many neurodegenerative
0:34:50 diseases of the eye and the brain is dysfunction of mitochondria. There’s an FDA-approved red light
0:34:57 therapy for patients with macular degeneration, but there’s good data that it may also be supportive
0:35:04 or protective in other eye diseases. And we’re talking to small doses like this is not overwhelmingly
0:35:08 bright lights. And we’re talking about minutes a day. You don’t have to sit in front of it for two
0:35:16 hours a day. So minutes a day. So it’s exciting. The data suggests that the mechanism of action is kind
0:35:21 of giving a little protective booster shot to our mitochondria so that they don’t get dysfunctional,
0:35:26 whether that’s dysfunctional just from normal use throughout the day or dysfunctional because you
0:35:31 happen to have a disease that’s getting in the way of those mitochondria. Now, we don’t know what
0:35:37 the right dose is. We don’t know what the right brightness is. All we know is that in these initial
0:35:41 things that have been tested, initial brightness of how and how many minutes, three minutes a day,
0:35:47 for example, there’s a signal there. There’s something working there. Should we have everybody
0:35:52 buying one on the internet right now, hopping on Amazon, spending 25 bucks, spending three minutes
0:35:58 a day? We don’t have the data to support that. Is it going to hurt? Probably not. Tim, it’s a problem
0:36:03 because we’ve got so many things that are like, oh, that looks promising. And we just need a little
0:36:08 more science. We need a little more study. Yeah. Well, you know, a friend of mine wanted me to write
0:36:15 a blog post about, look, I’m not a doctor. I don’t play one on the internet, but the difference
0:36:21 between sort of getting into science versus getting out of suffering in the sense that you know, and I
0:36:26 know just having been involved with the funding side, like randomized controlled trials are expensive
0:36:32 and they take a long time. But at the same time, if you take the advice of every wackadoodle
0:36:36 running around on the internet, you’re going to have 600 different interventions, some of which
0:36:41 could do a lot of damage or you’re going to get the wrong device. I’ve seen this also because I’ve
0:36:47 talked about accelerated TMS and different types of brain stimulation for potentially addressing
0:36:52 treatment resistant depression. And Nolan Williams at Stanford has done a lot of great research related
0:36:59 to that. And you see these people on YouTube with DIY TMS and they’ve got the polarities reversed.
0:37:06 And I’m just like, oh my God, what are you doing to your poor brain? But I also want to preserve my
0:37:12 vision as long as humanly possible. And maybe you can dispel a concern that I have. And this is based
0:37:17 on the fact that I have a lot of Alzheimer’s and Parkinson’s in my family. And I’m able to be three,
0:37:24 four, some 2.5 times or so more likely to develop Alzheimer’s based on what we currently think we know
0:37:30 than someone who is, I guess, three, three. And it scares the hell out of me. And I’ve had
0:37:37 conversations with audiologists who point out the correlation. I don’t know how strong the signal is
0:37:43 between hearing loss and onset or progression of dementia. Is there something similar for visual loss?
0:37:50 Absolutely. Actually, one of our faculty here has done some of the really foundational research showing that
0:37:58 correlation between vision loss and cognitive decline. And the loss of input, again, vision is our
0:38:05 biggest input sense. It’s driving, you know, a third of our brain is dedicated, as I said, to processing and using
0:38:12 that vision. It interfaces with every other thing that we do. It also is a really critical piece around
0:38:17 depression and mental health. Anxiety is vision. You know, the work that Andy Huberman had done on visual
0:38:24 fear and how that plays into the fear and anxiety pathways, as well as the depression pathways. And not
0:38:32 only does visual decline accelerate cognitive decline, possibly because, in part, because of how depression then
0:38:38 plays in with cognitive. I mean, these things are all clearly related to each other. But also, remarkably,
0:38:45 if you have low vision, let’s say from something as simple and correctable as cataracts, a blurring of
0:38:50 the lens that happens with age. If we all live to 100, we’re all going to need cataract surgery. Some people
0:38:59 younger, some people older. But if you do cataract surgery and restore vision in an older person who
0:39:06 appears to be suffering is suffering with cognitive decline and or depression, you can reverse
0:39:14 a significant amount of that decline in either of those domains. And so it just, again, it speaks to
0:39:21 the interplay of vision with our mental health or cognitive health. This is long-term important stuff.
0:39:26 Tell me if I’m interpreting this the wrong way, but it seems like this would lead to a strong
0:39:33 pro-argument for wearing glasses instead of suffering in silence. I don’t know, but that’s what I hear
0:39:39 when I’m sort of trying to read between the lines. There’s an important myth to dispel, especially when
0:39:47 it comes to presbyopia and wearing reading glasses. Between age 40 and around 60 or so, that lens stiffens and
0:39:54 stiffens and stiffens. And the first year, you only need plus 1.25 glasses. And then three years later, you’re
0:40:02 like, ah, I need plus 1.5, plus 150s. A few years after that, you’re moving up to the 2.0s. Eventually, you’ll peak
0:40:08 out at around 2.5 or 3.0s because that’s the difference, basically. That’s the refractive, the glasses
0:40:14 difference between viewing something at infinity, which from an optics perspective is actually just kind of like
0:40:20 three feet away or further. And viewing something at 14 inches, like comfortable reading distance right in front of us.
0:40:28 So, 2.5 to 3 power of those readers is all you’re going to need. But you’re going to progress through those
0:40:33 numbers, whether you wear the readers or not. So, wear the readers.
0:40:41 I got it. Is it a mistaking causality then where people believe? Because an optometrist said this to me a couple weeks ago,
0:40:44 and I was like, well, I assume you know what the hell you’re talking about, which is always a stupid
0:40:49 assumption, but that you develop increased dependence. But it’s actually just tracking along
0:40:52 with the natural stiffening of the lens in the case of presbyopia.
0:40:58 And it’s psychological dependence. It’s just like what I went through. As soon as I started wearing those
0:41:02 readers by accident, I didn’t think I needed them. I was still reading off my phone. It was fine.
0:41:08 But as soon as I experienced that extra crisp vision, I was like, well, I like that.
0:41:08 Yeah.
0:41:12 Or I got psychologically dependent because like, who doesn’t want their best vision?
0:41:14 Yeah, for sure.
0:41:19 And I’m going to keep saying this. It’s going to get annoying because I’m like a sweaty palm
0:41:24 fanboy, like jumping all over you. But I was very excited to chat with you also because I mean,
0:41:32 the nose, the eyes, these are sort of direct paths into the brain in a sense. And for instance,
0:41:36 I don’t know, I don’t expect you to track all things in all fields. That’d be impossible. But
0:41:44 cognitive therapeutics, it’s a headset that is used and they have a lot of good data. I think
0:41:51 they’re either phase two or phase three. They’ve raised a ton of money and it’s a headset and they
0:41:59 have these visors covering the eyes and then earpieces. And it produces, I want to say, gamma waves in the
0:42:06 brain. There’s more to it, but using flashing lights. And this appears to, I’m going to,
0:42:09 I’m getting into the sort of deep end of my ignorance pool here because I’m pulling from
0:42:16 memory, but it appears to assist in the breakdown of beta amyloid plaque, maybe tau as well. I’m not
0:42:22 really sure. So using flashing light to help people with conditions like Alzheimer’s. I mean,
0:42:28 it’s kind of mind boggling, I guess, literally and metaphorically. And that does come from credible
0:42:33 researchers. I wish I could cite them offhand, but it’s going to take me too much time to find the
0:42:40 scientists involved. But that is one that appears to be Ed Boyden and Lee Huizai out of MIT.
0:42:45 Yep. I know them both. Ed was a graduate student here at Stanford when I was at Stanford.
0:42:50 Oh, amazing. All right. Yeah. So there you go. Are we going to see more of these devices and how
0:42:56 far away are they? Because I’m seeing decline in my near relatives. I’m currently taking care of two
0:43:02 relatives with severe cognitive decline. It scares the hell out of me. And some of them are 3-3, by the
0:43:07 way, and I’m 3-4. So I’m like, good God. Okay. If there’s anything I can do, and I’m already doing
0:43:15 quite a few things, but are there other devices that are sort of on the cusp of being available that you
0:43:21 find interesting? Yeah, I think so. And input through the visual system and output through the visual
0:43:27 system are both looking really interesting these days. So you’re talking about input. Like what can
0:43:34 we stick in through the visual system to influence the rest of our brain? Brainwave activity, plasticity,
0:43:40 like we were talking about before, help preventing cognitive decline. There is very strong data,
0:43:48 for example, that if you give the right amount of electrical activity of our neurons in the eye and
0:43:52 the brain. So the neurons in the brain talk to each other through electrical activity, like little wires.
0:44:00 And too much activity is bad. I mean, really too much activity is epilepsy, for example. Too little is clearly
0:44:05 bad, too. If you have a stroke, then you’ve got no electrical activity in that area of your brain, and it’s just
0:44:12 not working anymore. But providing like kind of that sweet spot in the middle of electrical activity, in addition to
0:44:17 it participating in the processing of whatever that area of the brain does, like in the retin, it’s your
0:44:25 vision, obviously. It also stimulates pathways like plasticity and responsiveness to the survival and
0:44:33 growth factors. And we and others have shown that very clearly in animal research over the years, that you
0:44:40 need not just like the right growth factors circulating around in the brain, but you also need the right levels
0:44:45 of electrical activity so that the neurons are maximally responsive.
0:44:48 Yeah, it’s like weightlifting. You can have all the protein in the world.
0:44:49 Right.
0:44:50 You need the stimulus.
0:44:55 You’ve got to have the right amount, right? You’ve got to match that up. So it’s really cool. Like we actually
0:45:00 know in the eye, the visual stimuli, you were talking about flashes of light, but it turns out like
0:45:08 different cells in our eye respond differentially to different stimuli. We have some cells that fire when the
0:45:14 lights go on. We call those very creatively on cells. We have some cells that fire when the lights go off,
0:45:19 called off cells. We have some cells that are firing like between blue and yellow, others that are
0:45:24 differentiating between red and green. We have some cells that are in charge of motion detection in the
0:45:30 eye. And all that data has got to get back to the brain. But if we stimulate, for example, the motion
0:45:39 direction-sensitive retinal ganglion cells in our retinas in headsets, where we devise cues, you know,
0:45:44 basically imagine you’re flying through like kind of that Star Trek field of stars, you know, like you’re
0:45:50 going into hyperspace, right? And engage, and you’re going into hyperspace, and all those stars speed up by you.
0:45:58 Those are great stimuli for some of our direction-sensitive cells in the eye. And could those
0:46:05 actually stimulate those cells to then like perform better or not degenerate in disease? And so we’ve been
0:46:10 studying those kinds of questions. Cognito’s engaged in that kind of work. And then how does that affect
0:46:17 what’s going on in the brain? Very reasonable that that’s going to actually lead to specific patterns
0:46:22 of activity, flexibility, plasticity that are going to change our brains. And the idea that
0:46:29 some of that work can not happen only in the academic world, but that people are excited about
0:46:36 it and are funding the startup companies and taking that science into that kind of either health domain,
0:46:42 healthspan domain, or consumer domain. Like how do we get the normals protected against the future?
0:46:45 There’s a lot going on there. That’s on the input side.
0:46:52 Yeah. I am going to just bookmark that for a second. And I’m going to highlight a few things that I thought
0:46:58 were of interest, and I’d like you to expand on from your conversation with Andy. So glaucoma,
0:47:05 could you have a normal reading during the day, but higher at night? And then the potential place of,
0:47:10 you know, cannabis edibles. And my question there was, do we know what compounds are responsible?
0:47:12 Well, people are listening to me and they’re like, what the hell are you talking about? So
0:47:18 if that’s enough of a cue, would you mind just discussing that? Because, you know, a big challenge
0:47:24 with people who are trying to do the right thing, they’re trying to get checkups, they’re trying to
0:47:30 get assessed, they’re getting their blood work done, but maybe it’s once a year. And they had their
0:47:35 blood draws, you know, the last one was at 8am and the next one was at 11am. And lo and behold,
0:47:38 their testosterone is really different. They freak out and this, that, and the other thing.
0:47:43 So like timing matters among other things. Could you just speak to glaucoma in that respect?
0:47:49 Absolutely. So let me just back up one step. Glaucoma, after Alzheimer’s disease,
0:47:57 glaucoma is the most common neurodegenerative disease. It’s the number one cause of irreversible
0:48:05 vision loss in the world. It’s a degeneration of that optic nerve connection from the eye to the
0:48:11 brain. So those retinal ganglion cells that are collecting the data in the retina and their axon
0:48:15 fibers, those telephone wires running down the optic nerve carrying that all the vision from the eye to the
0:48:23 brain, they degenerate in glaucoma. If you take all comers, it’s around 2% of people in an aging
0:48:30 population that will have developed glaucoma. If you have a primary family member, a parent,
0:48:37 a sibling, a child with glaucoma, your risk probably goes up to about 20%. So it runs in families. But
0:48:42 just because your parent has it doesn’t mean 100% you’ll have it. There are two main risk factors
0:48:50 for glaucoma. One is increasing age. And we’re all working desperately on correcting that one, but we don’t
0:48:55 have a slam dunk treatment for that yet. The other main risk factor for glaucoma is actually
0:49:01 increasing eye pressure. If you have real high pressure, you’re going to get glaucoma. But a lot
0:49:06 of people with normal looking eye pressure can also develop glaucoma. It’s just like they were more
0:49:12 susceptible. And the eye pressure isn’t just the same number. We’ve got short-term variability and
0:49:16 long-term variability. So long-term is like, you know, this month it might be whatever number.
0:49:20 Next year it might be a little higher, a little lower. You know, you can vary through your life.
0:49:25 But there’s also this short-term variability. It actually varies in our diurnal cycle.
0:49:32 So everybody has a diurnal cycle where you, you know, your circadian rhythm, you know, and some of
0:49:36 us like myself are night people and we love to be up at night and getting up in the morning isn’t our
0:49:41 favorite thing. And other people are the opposite. And all this stuff relates to our diurnal cycle,
0:49:46 our circadian rhythm. You know, you can try to take melatonin and affect that. But your eye pressure
0:49:52 also varies by that. And as you say, like, if I take your eye pressure in the morning and then the
0:49:56 next week I take it in the afternoon and I say, oh my God, your pressure’s gone up. I got to take you to
0:50:02 surgery. Well, wait a second. It might just be because I’m measuring it different times. Now you brought up
0:50:07 like the most common question that I get asked. I’ll tell you the most common question that I get
0:50:14 asked by patients with glaucoma is, hey, can I take cannabis? And, you know, by the way, it’s like,
0:50:21 you know, legal for medical use in many states and frankly, recreational use also in many states and
0:50:28 certainly accessible in every state. Can I take cannabis? Cannabis, whether you smoke it or eat it
0:50:35 in the brownie or take the chewy, it lowers your eye pressure. If you’re using the version,
0:50:40 which are available that where, you know, you feel a little high from it, you know, you get that good
0:50:48 feeling. The problem is that it only really lowers the eye pressure kind of during that time that you’re
0:50:58 getting high. So I tell patients like it works, but you’d have to be high 24-7. So maybe you should
0:51:07 just use this eyedrop instead, right? Do we know which compounds within cannabis are responsible for
0:51:13 the lowering of the eye pressure? Yeah, there’s actually data that both the THCs that do get you
0:51:18 high and the others also that don’t can have that effect. And there’s some cool startup companies
0:51:24 that have been working on trying to isolate and now test in human patients the you-don’t-get-high
0:51:30 versions of those compounds or chemically modifying them. And by the way, turning them into an eye drop
0:51:35 so that it’s really just treating the eye and make that really accessible. You know, you don’t want
0:51:41 to be on your glaucoma treatment and not able to drive. So, you know, it’s got to be compatible
0:51:47 with daily life for most patients, right? So that does work. That does work. Yeah. The second most
0:51:53 common question I get asked is, well, can’t you just like fix my eye or give me stem cells or that
0:51:58 kind of thing? But number one is cannabis. Well, what’s your answer to the stem cells? The magic
0:52:01 stem cells. We’re down there on stem cells. Like, so if you’ve lost your retinal ganglion cell
0:52:07 connection to the brain through the optic nerve, we’re actually getting pretty good at growing retinal
0:52:11 ganglion cells out of human stem cells, like in the laboratory cell culture dish. And we’re
0:52:16 actually starting to make real progress, you know, in animal models to start showing that you can
0:52:21 transplant them in. But I still tell patients, like, don’t go to some clinic that’s telling you
0:52:26 they’ll give you stem cells and pay $18,000 of your hard-earned money. It is not ready for that yet.
0:52:28 Go to Tijuana and get a new pair of eyes.
0:52:29 Exactly. Don’t waste your money.
0:52:34 Well, yeah, that’ll be the least of your problems. It won’t be the money part.
0:52:39 So let me circle back to the cannabis for a second. So I don’t consume much cannabis, but
0:52:46 I have experimented with cannabis for chronic pain and specifically a number of back issues that I have.
0:52:50 And some of it’s congenital. I have a transitional segment and a bunch of arthropathy and blah, blah,
0:52:55 blah, blah, blah. And interestingly, a lot of folks, including people who are sort of credible and
0:53:02 familiar with the literature, recommended CBD. But I did not find it to have a pain-relieving effect
0:53:07 that was sufficient for sleep until adding a little bit of THC, which I thought was actually
0:53:14 pretty interesting. And I’m wondering if, and this actually cycles back to our very short discussion
0:53:21 of psychedelic compounds also, because why might psychedelics, say, improve visual acuity?
0:53:27 You can come up with a dozen sort of plausible explanations. But when you look at, say, the
0:53:36 depression outcomes with psychedelics, people in many different parties in terms of arguing why or
0:53:41 how they exert their effect, one that I think is under-emphasized is the anti-inflammatory effects,
0:53:47 which can be potent in some psychedelics. And you can find studies where they look at anti-inflammatory,
0:53:52 or just standard off-the-shelf anti-inflammatory effects on depression, which can be substantial.
0:54:00 Do we have any data to suggest that anti-inflammatories have any effect on vision or can in any subpopulation
0:54:01 improve vision?
0:54:09 Decades ago, there was a pretty hot focus on to what degree the immune system might be playing
0:54:15 a role, particularly in eye diseases, including the common ones, macular degeneration, glaucoma.
0:54:21 Then it was hard to pull that together, in part, I think, because we didn’t know as much about the
0:54:27 immune system 20, 30 years ago as we do today. And now we know a lot about what we call the innate
0:54:33 immune system, which is not the part that learns about the flu virus and makes you immune the next
0:54:38 time you get the flu virus, but just how our immune system interacts with our body normally,
0:54:46 and how it also might interact with, you know, our gut bacteria, and then cross-react with
0:54:53 our own body, things like that, right? And so it turns out now that we’ve got this much deeper
0:54:58 appreciation from the whole immunology crowd about how the immune system, and in particular,
0:55:05 the innate immune system works, we’re now revisiting in neurodegenerative diseases, including glaucoma,
0:55:12 macular degeneration. And it turns out it is just packed with evidence that the immune system and
0:55:20 innate immunity really play a role. Let me give you one example that is shocking. If you raise the eye
0:55:28 pressure in a mouse, the retinal ganglion cells and the optic nerve will degenerate just like in human
0:55:34 glaucoma. But in a really beautiful set of experiments that came from a woman, a professor
0:55:41 at Harvard, Dong Feng Chen, she showed that if you raise the eye pressure in a mouse that was raised
0:55:47 itself, grew up in a germ-free environment, and doesn’t have kind of all the normal mouse dirty gut
0:55:54 bacteria, and therefore its immune system is at some level fundamentally different, you can raise the
0:55:59 eye pressure in that mouse, but the optic nerve won’t degenerate. They won’t get glaucoma damage.
0:56:05 And then if you take the immune cells out of the first mouse and just put them back into the bloodstream
0:56:12 of the second mouse, then the optic nerve will regenerate. So the immune system is playing a huge
0:56:20 role that was previously totally underappreciated, and there are amazing drug therapy candidates that are
0:56:26 now moving up through the pipeline in towards human testing to test, hey, if we could suppress the immune
0:56:32 system, not totally suppress it, because by the way, we still want to be attacking bacteria and
0:56:39 viruses, but just suppress the little leg of that immune system that’s attacking our body and leading to
0:56:42 neurodegenerative disease, that’s going to be off the charts.
0:56:50 Yeah. You know, I was, as you were talking about the microbiome and so on, I was doing a bunch of
0:56:56 reading for another interview I’ll be doing shortly with the scientist, and one of the stories, and this
0:57:01 is in animal models, of course, but looked at how, and some people have heard through the grapevine,
0:57:09 one way or another, how you could take the microbiome, just for simplicity’s sake, of, say, obese mice and
0:57:15 transplant that to lean mice, and they get fat, or vice versa. I might be getting some of the details
0:57:23 wrong, but roughly you see some very interesting effects. However, if you sever the vagus nerve in
0:57:32 those recipient mice, they do not exhibit those changes. Then some of the questions that are kind
0:57:37 of outstanding is, well, if that indicates that you could, instead of using like ablation or severing
0:57:43 something, stimulation to achieve a similar effect, then what can you start to do? Then you have like
0:57:50 hockey puck size things that you put next to the liver that can, you know, via some technological
0:57:56 wizardry affect these things. But I suppose the more I look at a lot of these things, also with
0:58:02 family with Alzheimer’s, and they might take something like Theracurman, which has, on some
0:58:07 level, anti-inflammatory effects. I’m like, okay, and I don’t want to be a one-trick pony with like
0:58:11 the one thing I keep beating over the head, but it’s like, okay, well, if we know that chronically
0:58:16 inflamed, like microglia, have all of these hosts, or at least they’re associated with a host of
0:58:22 different neurodegenerative diseases and inflammations associated with depression, to what extent can we
0:58:27 mitigate these things? And we’re sort of hitting a bunch of birds with one stone, which is why I’m so
0:58:36 interested in the possibility of using devices. I’m so interested in nutritional ketosis, but also
0:58:42 exogenous ketones. Brain loves this stuff. Also, beta-hydroxybutyrate, very potent anti-inflammatory.
0:58:48 I’m just wondering, do you think that I am just too clever by half and I’m like missing the plot
0:58:54 here? I feel like chronic inflammation, which is kind of like saying business or the arts, right? I mean,
0:58:58 there are like a million different facets to inflammation. You need inflammation for a lot of
0:59:06 reasons. But when it is pathological and chronic, it turns into a big issue. With rapid decline in
0:59:13 eyesight, let’s just say in glaucoma, how often is that comorbid with metabolic syndrome or something
0:59:22 like that when the decline is faster than say average? The earliest data looking at, let’s say
0:59:27 diabetes as a marker of, you know, a lot of patients with type 2 diabetes, it’s associated with what we
0:59:33 call metabolic syndrome, which is this cluster of high lipids, high blood pressure, insulin resistance,
0:59:39 right? And so there was initial data suggesting that a little bit of diabetes might actually be like a
0:59:45 little protective in glaucoma. And then some of the follow-up, like next set of studies suggested like,
0:59:50 no, no, no, maybe it’s a little bit bad for your glaucoma. And so the net-net is it’s probably not
0:59:55 metabolic syndrome as a whole is probably not a huge difference, but I’ll tell you the place where
1:00:03 those two are converging is one of the hottest topics in medical science today, which is these
1:00:12 GLP-1 receptor agonists, which are going to have a huge effect on human health by reducing metabolic
1:00:21 syndrome, overweight, obesity, etc. But also are looking very promising for neuroprotective. And I think it
1:00:25 actually gets to that point, you know, you’re trying to tease yourself, like, are you just like kind of
1:00:31 getting ahead of it? But actually, you’re touching on, I think, where we’re actually coming to as an
1:00:36 understanding as, you know, where the science is going in the field, which is this axis between
1:00:42 the brain, which you think of like, well, isn’t that mostly inside my head, but also the peripheral
1:00:47 nerves that are going out to the whole rest of our body and the immune system. And those two are talking
1:00:53 to each other all the time. And now we’ve got the microbiome and that gut axis is like a third leg of
1:01:01 that stool because that’s clearly also interacting with both the nervous system and the immune system
1:01:07 in very specific ways. So we’re going to see a lot more of that really, I think, come together and
1:01:13 understand more mechanisms. You know, is it going to be one day that we’re all just kind of taking that
1:01:19 like purified poop pill that we just swallow down and it changes our microbiome for the day and it protects
1:01:24 us from Alzheimer’s or glaucova in the future? We’re all hoping that’s going to happen. We’d love
1:01:30 that protection one day. You know, should you buy the poop pill off the internet just yet? I’m not sure.
1:01:38 Yeah, Sri Lankan poop pills from rural children. I’m in. Yeah, you’d be careful with what’s out there on
1:01:42 the internet, guys. And, you know, I’m supporting a company, I might have to bleep this out, but called
1:01:49 Holobiome. And they’re actually creating the most comprehensive library currently of gut microbiome.
1:01:53 because it’s like what you can buy currently off the shelf. First of all, most of it’s dead,
1:01:58 but it’s like inert by the time you consume it. A lot of it doesn’t actually get through
1:02:04 your metabolism to where you want it to be. And it only represents maybe in some, a few dozen,
1:02:10 I don’t know if the right term is strains of bacteria, whereas there’s like thousands upon
1:02:14 thousands. So there’s so much to explore, which is also very exciting.
1:02:18 Let me give you one more idea of what might be that ideal world on the way to that.
1:02:26 We share microbiomes between us. Actually, we had our, like at Stanford Med School years ago when I was
1:02:35 there, we had a microbiology professor and he used to kind of tease, the world is covered with a thin
1:02:42 layer of poop. Because no matter how well you wash your hands after going to the bathroom, like there’s
1:02:47 a couple bacteria that got on your hands or your belt buckle and you’re, you know, and then you shake hands
1:02:52 or pack someone on the back. I don’t want to increase anyone’s anxiety, but the world is covered.
1:02:54 This episode is brought to you by Purell.
1:03:02 There’s a thin layer of poop. What we call clean and dirty, he used to say, is really just how thick
1:03:11 that layer is. Okay. So that joking aside, if you just shack up with someone who’s got great longevity
1:03:18 and probably a great microbiome, a good chance you’re going to absorb their microbiome. Maybe
1:03:25 that’ll be good for you. I got to put that on the dating websites, you know, get your microbiome on
1:03:32 that profile. Craigslist, microbiome casual encounters. So this is going to be a bit of a
1:03:40 hard left, but preservative free strips of tears for dry eye. Why? That was one of my notes from
1:03:44 the conversation that you had with Andrew, because I’m also looking for just low hanging fruit for
1:03:50 people who are contending as we all do with aging eyes. Maybe you could speak to that. And then I do
1:03:55 have to ask about the blood serum for eye drops. Maybe you can hit that too.
1:04:05 Sure. Sure. So look, actually the most common eye disease as we get older is actually dry eye. As we
1:04:11 get older, we make fewer tears. We also make lower quality tears. Our tears at high quality have a
1:04:17 liquid phase, like a water, saltwater phase. There’s also like an oily component to good high quality tears.
1:04:23 And that oily component also kind of dissipates a little bit as we get older, gets less as we get older.
1:04:31 So we make fewer tears and lower quality tears. And a real simple over-the-counter solution for so many
1:04:38 people is just put in some artificial teardrops. The thing is, is that those little bottles come with
1:04:42 preservatives so that, you know, when you use it all month, by the end of the month, it’s not growing
1:04:50 bacteria. And if you’re just using a drop or two a day, fine. That’s getting you by, fine. Just buy
1:04:55 those bottles. They’re the cheapest. But if you’re getting to the point where it’s three, four, five,
1:05:00 six times a day, you like, you know, maybe you work on the computer a lot. So you blink less and your eyes
1:05:06 get drier. You want to use more of those. Then we usually recommend at that stage, switch over to
1:05:12 preservative-free artificial tears. Because it turns out that preservative in those bottles of
1:05:18 drops, at a drop or two a day, fine. But if you’re getting up to a lot of drops a day, the preservative
1:05:24 is actually irritating and kind of inflammatory to the ocular surface. It actually kind of breaks down
1:05:30 some of the cells on the surface of our eyes. So at that point, we like to switch people to
1:05:35 recommending the preservative-free. They’re the ones that come like, usually they come in like a little
1:05:40 strip of tiny little plastic. You break one off. It’s got its own little cap on it. It’s got this
1:05:46 tiny little bubble of fluid that you can squeeze. It really tests, you know, if you’ve got bad fingers
1:05:50 or bad, you know, by the way, if you’ve got bad vision, you’re poking yourself in the eye with it.
1:05:56 So anyway, that’s what we recommend. Switch the preservative-free. And then people who need more than that,
1:06:03 we actually have drugs that, for example, reduce inflammation on the ocular surface to help
1:06:09 the tear quality and quantity bounce back a little bit. And then we also have drugs that
1:06:16 contain growth factors, things like nerve growth factor that are almost certainly also good for
1:06:22 the surface. And when our eyes get dry, the surface, the reason it feels irritating is not just because
1:06:26 it feels dry. It’s actually because the surface starts to break down a little bit. And when you go
1:06:31 to sleep every night and your eyelids are closed and nothing can evaporate, you know, it bounces back
1:06:36 a little bit by morning. So it kind of regenerates or rejuvenates. The ocular surface can regenerate
1:06:43 pretty well every day. But at some point, your eyes are getting dry enough that you’re having much more
1:06:50 chronic problems. And that’s where sometimes we can use what are called serum tears. So our blood serum,
1:06:55 if you take out a blood, like a tube of blood, you’re getting your blood drawn, that tube of blood
1:07:01 has your red blood cells carrying all your oxygen, your white blood cells, which is like your immune
1:07:06 system, and then all just the liquid with the proteins in it. That’s what we call the serum.
1:07:09 That’s the serum. So you could take that tube, you spin the cells out.
1:07:13 Let me ask a dumb question. Is that different from plasma? Are we talking…
1:07:17 Serum and plasma, yeah. Depending how you treat some of those proteins, that’s serum and plasma.
1:07:20 Let’s just say you’re spinning out the cells.
1:07:20 Yep.
1:07:26 And then you can take that serum. Maybe you dilute it a little bit in some of that preservative-free,
1:07:30 you know, artificial tears. Maybe you just use it straight. Usually we dilute it a little bit.
1:07:38 And we can give patients their own serum as artificial teardrops. And that serum is filled
1:07:46 with really good, juicy growth factors that help the surface rejuvenate. And that’s the principle of,
1:07:48 in some patients, using serum tears.
1:07:56 Maybe this is just a difference in terminology, but it makes me think of platelet-rich plasma or
1:08:02 platelet-poor plasma. Are there experiments with different, I’m not sure, concentrations or
1:08:04 cocktails?
1:08:09 Different cocktails. That’s a great way to put it. Yeah. And platelet-rich plasma, again,
1:08:14 one of the reasons that that looks so rejuvenating for our bodies is, again, it’s just like
1:08:21 chock-a-block full of growth factors. And so I don’t know, I’m sure somebody’s testing this
1:08:27 as another way to treat really severe dry eye. Or if your dry eye is so bad, you’re actually
1:08:33 getting like kind of ulcers on the surface of your eyes. Some of the most severe cases might really
1:08:40 benefit from, like serum tears, maybe platelet-rich plasma would work too. So that’s a hot area right
1:08:42 now. And again, filled with growth factors.
1:08:49 We talked about the importance of timing with, say, glaucoma exams, things of that type.
1:08:56 What are some other recommendations for perhaps avoiding common mistakes or filling gaps that are
1:08:59 commonly unfilled? Any recommendations to folks?
1:09:04 There’s a bunch of things. First of all, get an exam. And if you have a family member or blood
1:09:10 relative with eye disease, maybe get that exam even sooner. Take glaucoma as an example. If you
1:09:14 got an exam and you’re 40 and you don’t have a family history and your exam was normal, you don’t
1:09:19 have to come do that full exam every year. You can come back in five or 10 years, try it again.
1:09:23 But especially as we get older. Now, half the people in the world need glasses. Half the people
1:09:29 in the U.S. need glasses. So you might be going into your local eye care provider, optometrist,
1:09:33 getting your glasses checked each year or two anyway, just to see if you’re still in the right
1:09:39 prescription. And they can do the full exam, check for everything else, make sure nothing else looks
1:09:46 suspicious, leave you in great shape. So getting that periodic eye exam, especially as we get older
1:09:52 and more of those age-related diseases like macular degeneration, glaucoma, etc. Obviously,
1:09:57 if you have diabetes, you’re supposed to get an eye exam every year just to make sure because if you’ve
1:10:01 got diabetes and it’s starting to affect the retina inside your eye, we could get ahead of that.
1:10:06 We’ve got good treatments that can prevent you from losing vision. So we want to stay ahead on these
1:10:11 diseases. That’s the main thing. Other things, everyone’s going to get cataracts eventually,
1:10:19 but what can we do to slow down the development of cataracts? Well, one real easy one is reducing
1:10:26 UV light exposure. So you’re out in the sun a lot, wear sunglasses. All sunglasses made today
1:10:32 have UV protection. By the way, all regular glasses that don’t have darkened, tinted shades,
1:10:38 they also block the UV light from going through. So even if you’re wearing your regular glasses outside
1:10:45 because you need glasses, that works too. So wear sunglasses or some sort of eyewear protection.
1:10:50 And then eyewear protection is another big one, depending what industry you’re in. You’re gardening,
1:10:57 you’re in steelworks, you’ve got anything where you’ve got eye injury risk, wear protective eyewear.
1:11:03 It costs like $1.50 at Home Depot to get those really attractive plastic glasses that are wrapped
1:11:10 around. But wear them when you’re in those work situations, that’s a big one too. You see a lot
1:11:14 of athletes now wear eyewear, and sometimes it’s for sun protection, but you’ll see a lot of them when
1:11:19 it’s not that sunny day or they’re even playing inside. And they might be wearing it for prescription,
1:11:20 but also just for eye protection.
1:11:26 Eye protection. Is there anyone out there, and I don’t have a dog in the fight, it’s just that this
1:11:34 conversation around sunlight and exposure is like a religious war online. Is there anyone you would
1:11:42 consider scientifically credible who has any counter argument with respect to UV light? Why it is
1:11:51 important to also get natural exposure or could be important to get exposure to UV light? Or does that
1:11:55 just not exist? Is there a strongman argument for that, or does it just not exist?
1:12:00 I don’t ever want to say something doesn’t exist because there’s someone on the internet.
1:12:03 Well, right, which is why I say scientifically credible.
1:12:10 But no, full spectrum light, white light that goes from violet through red, full spectrum light,
1:12:16 there’s a lot of decent evidence that that’s good and important. By the way, let’s come back to the
1:12:21 development of nearsightedness. You know, we used to say like, oh, maybe people are getting nearsighted
1:12:25 as kids because they’re spending too much in times indoor reading. And so it’s just like too much near
1:12:30 work is leading to nearsightedness. There’s now pretty good data, actually, that it’s not the near work,
1:12:36 it’s the being inside part of reading inside. And if you just send your kid outside and let them read
1:12:41 outside in full spectrum lighting, they could still be doing their near work, doing their homework,
1:12:46 whatever it is. But it’s the full spectrum lighting that will actually slow down their development of
1:12:57 nearsightedness. So you can get full spectrum white light, but skip the UV by either having full spectrum
1:13:02 lighting indoors or through the window and you’ve got a nice sunny window. The sun that comes through
1:13:08 the window, the glass actually filters UV light. So that’s fine. Your car window filters UV light. So
1:13:12 even if you’re not wearing sunglasses inside the car, you’re getting that full spectrum sunlight.
1:13:19 Go outside in the morning, fine. You know, get that first sunlight if you want. But there’s no data
1:13:24 that suggests that part of that full spectrum light has to include UV light.
1:13:32 Okay. Got it. What do you think, and I know that this might be asking a lot, but what do you think we
1:13:40 might be getting wrong currently in any paradigm of how we think about vision or eye health? I mean,
1:13:46 I have a lot of doctor friends, a lot of researcher friends, and I guess it’s especially common among
1:13:49 MDs, but they’ll say, yeah, 50% of what do we know is wrong. We just don’t know which 50%,
1:13:55 which doesn’t mean science is an important guys, by the way, it is incredibly critical for not fooling
1:14:01 ourselves. And I don’t think I need to preach that to you, but what would you not be surprised to see
1:14:08 be overturned in the next five years? If you were like, you know what, we’ve always thought X. And it turns
1:14:19 out, nope. I’m going to pull one out of my personal favorites list for this. And it comes back to these
1:14:27 big ticket eye diseases like glaucoma, macular degeneration, even diabetic retinopathy, and other less
1:14:34 common versions of these degenerations, let’s say, of the retina, the optic nerve. And we have
1:14:41 always said, I mean, I even said earlier in the podcast with you, Tim, that glaucoma is the number
1:14:48 one cause of irreversible blindness in the world. And that I think is going to be the piece that we
1:14:53 overturn. We have always said like, hey, we got to prevent you from losing vision. We got to slow down
1:15:00 the disease because once you’ve lost whatever vision you’ve lost, I can’t get that back for you.
1:15:11 And I think that is about to topple. We are about to get into vision restoration at a level that has
1:15:22 been totally unexpected and totally unprecedented. And the science supporting these directions in these
1:15:31 diseases is getting really, really juicy. We have discovered so many molecular pathways,
1:15:36 approaches to cell therapy. Some of the things we even talked about earlier, like inducing plasticity
1:15:42 in the brain. If I stick a stem cell into the adult retina and I say, hey, I need you to turn into a
1:15:50 retinal cell, hook up with your partners and start doing vision. Well, during development, the retina,
1:15:58 those cells are all developing. They learned to wire up together, do it right. How do we get a cell that
1:16:04 we’re going to put into an adult person to say like, hey, I know all you other retina cells are already
1:16:10 neighbors with each other, but I’m moving into the neighborhood and I want you to accept me. But we’re
1:16:16 figuring out how to induce that plasticity, like open up the neighborhood, let that cell get into the
1:16:24 network, start to participate in the network and restore vision. So it is moving really quickly
1:16:29 right now. And it is starting to translate. This laboratory science is starting to really move
1:16:39 quickly into appropriate, safe human clinical trials. And so I think that is going to be the biggest topple,
1:16:45 is going to be that we can restore vision. And I will not be surprised if our colleagues in the brain
1:16:51 follow suit quickly. You know, we like to tease who’s going to come first, the eye or the brain.
1:16:57 I will not be surprised if our colleagues in the brain follow quickly. And maybe we could restore
1:17:03 cognition in people with severe cognitive disease, Alzheimer’s and these others. So
1:17:11 I think this kind of restoring the central nervous system, including the retina and optic nerve,
1:17:18 spinal cord injury, I think this is all, we’re going to topple that in these next few years.
1:17:21 Well, it’s very exciting. And I also, when I talk to folks, I’m like, look,
1:17:25 I know it seems like one day they’re like, bananas will kill you. And the next day,
1:17:28 like bananas will help you live forever. And it’s like, first of all, a lot of that is
1:17:35 funhouse mirror warping by media coverage. And secondly, there are so many breakthroughs or
1:17:42 breakthroughs that are on the cusp of making their way into clinical practice. I can’t help but be
1:17:48 super optimistic about so many, at least the fields that I have decent amount of exposure to.
1:17:52 And I’m going to ask you a few follow-up questions. But first, I’ll just say for people
1:17:58 interested, if you are interested in looking at how, for instance, and there are multiple ways to
1:18:04 induce greater plasticity in various ways. But if you’re interested in the reopening of critical
1:18:11 periods, which we alluded to earlier, Gould Dolan, who was at Hopkins and is now at UC Berkeley,
1:18:18 has done some wild work and has really rocked the boat in, I think, a very productive way looking at
1:18:26 how MDMA, but also potentially other compounds can potentially do that. And she’s got wild experiments
1:18:34 with octopuses and all this stuff that people should check out. But I believe that at some point,
1:18:40 if she’s not already doing it, she’s going to look at, for instance, using these compounds to help
1:18:47 stroke patients recover motor function. And there are also devices like DARPA and the Defense Language
1:18:54 Institute in Monterey have used for improving language acquisition. I mean, I really feel like there’s a lot of
1:19:02 stuff that is not only happening, but converging in interesting ways. What leads you to believe that
1:19:07 we’re so close? I mean, the next five years is close, right? So is it just the publications you’re
1:19:15 seeing, the types of science that is being done? Is it new and novel ways to induce plasticity? Is it
1:19:19 because the eye people are playing nice with the other brain people? What is actually happening?
1:19:24 You know, I was teasing before, but the truth is like, we eye people love to work closely with our
1:19:30 colleagues in brain because there’s so much shared science. I do think that there’s an increasing
1:19:37 attention to, hey, let’s answer these questions properly. Let’s do proper trials. Let’s really
1:19:42 study these things properly. And let’s also move things out of the laboratory and into human testing,
1:19:46 right? And have it not just be like kind of the fantasy and the mice, but never move it to the
1:19:52 person, right? And so I think that transition, that willingness to grow in that direction,
1:20:03 we’ve had actually, to be honest, like a remarkable two to three decades now of increasing support for
1:20:08 science, you know, at the federal level, but also startups. Biotech has had an amazing age.
1:20:13 And that biotech, you know, when you’ve got an amazing age cooking on the pharma side,
1:20:17 like big pharma, you know, that then trickles down. So that means startups can say like, hey,
1:20:24 let’s roll the dice and test this anti-aging formula because if it hits, there’s a market for it at the
1:20:30 end of the day. Like this is important. These are big impact areas. So I think the investment that we
1:20:36 make in science, and we’re sort of like coming to a head, a culmination. And I think that happens to be
1:20:42 matching in time, the advances we’ve been making in neuroscience. You know, I think we made like
1:20:49 huge advances in immunology and cancer biology a couple decades ago, like even just understanding
1:20:54 what all the cells are. And I think that the analogy is the advances we’ve made even just in the last
1:21:00 decade of being able to like map the brain, not just even down to the cell level, but the cell-cell
1:21:08 connections called synapses. We’re now mapping entire brains at that level and understanding
1:21:13 how they talk to each other and recording and creating. We’ve got a colleague here who just had
1:21:20 an amazing suite of papers, Andreas Tolias and his colleagues, creating a digital twin of the entire
1:21:27 brain. And then you can do experiments on the digital twin of the brain. You don’t have to actually do them
1:21:33 on an animal or a person to start. You could start there. So the advances in neuroscience and
1:21:40 understanding of plasticity and all of these elements, I think are converging with the advances
1:21:46 that we’ve just been willing to make over the last couple of decades in healthcare, health-related
1:21:54 research, discovery research, translational research, clinical trial research. And I think we’re just kind of
1:21:57 seeing those two converge right now in an amazing way.
1:22:03 If you don’t mind, let’s talk about mitochondria again for a second. So mitochondria, often referred
1:22:09 to as the powerhouses of the cell. I won’t bore people with more ketone talk, but also read a piece
1:22:15 recently from a very credible scientist, beautifully written also, about how they’re not just the powerhouses,
1:22:20 but maybe the motherboards of the cell. And there’s actually a lot of what you could view as social
1:22:29 interaction between mitochondria and among mitochondria. Really, just the deeper you go,
1:22:32 the more interesting it becomes. And I’m wondering outside of the red light,
1:22:41 if there are other interventions or technologies, biologics, anything that you think are interesting
1:22:46 for improving mitochondrial health within the visual system, however you want to take that.
1:22:52 Mitochondria, not only are they social with each other and they actually talk to each other,
1:22:59 they actually fuse and then separate. They get trafficked up. Neurons, we talked about the ones
1:23:03 that stretch from the eye to the brain. There are neurons, of course, that stretch from the top of our
1:23:07 brain all the way down to the bottom of our spinal cord. There are neurons that stretch from our spinal
1:23:12 cord all the way down to our toe tip. These are some long cells, right? And they’re trafficking
1:23:19 mitochondria all up and down. So they are social creatures for sure. But it turns out they’re yet a
1:23:25 third thing. So they’re powerhouses, they’re social creatures, but they’re also scaffolds. And they’re
1:23:34 actually like kind of the foundation upon which a lot of other cellular signaling that’s regulating what a
1:23:42 cell is supposed to do is happening on the surface of the mitochondria. So you got metabolism, energy,
1:23:51 scaffolding of signaling. And so no wonder half of our neurodegenerative diseases are associated with
1:23:57 one or another defect that we can trace back to mitochondria. So that kind of adds up at the end
1:24:01 of the day when you look at it that way. And some of the things we’ve already talked about, I mean,
1:24:08 you brought up red light therapy, that would be one for sure. But vitamin B3, nicotinamide,
1:24:14 it’s directly affecting some of that metabolic signaling that is interfacing with the mitochondria
1:24:24 metabolism biology. And so actually a lot of these supplements that are about metabolism end up having
1:24:28 some link back to mitochondria. Yeah, I was going to say, it’s kind of hard to dodge the mitochondria.
1:24:34 Yeah, yeah, yeah. And look, it’s cool. Look, I mean, I just read that they’re now doing successful
1:24:42 mitochondrial transplants, like for example, into an embryo. So you can have inherited diseases where the
1:24:49 disease is inherited because your mitochondria are bad. Mitochondria get most of their proteins and lipids
1:24:53 and all of that that make up a mitochondria. They got most of that built from the nucleus,
1:24:58 the regular DNA of the cell. But they have a little bit of DNA themselves that makes some of
1:25:05 the proteins inside the mitochondria. And so you can inherit that mitochondrial DNA that has mutations and
1:25:12 have real serious diseases. It’s now been shown you can transplant mitochondria so that baby will not
1:25:19 have an inherited mitochondrial disease. Is it that far off to think that we could like transplant
1:25:27 mitochondria into the retina of your eye and stave off another decade of glaucoma? These things are on
1:25:33 the table. So definitely on the table. Wow. Okay. So I saw some news about, I think, you can’t trust the
1:25:38 headlines, but basically babies with three parents, so to speak, out of the UK. Now, so you mentioned
1:25:44 embryo. So this is a case where you’d be taking third-party mitochondria. You’re hitting it. That’s
1:25:51 exactly what I was talking about. So you got DNA from the mom in the egg cell. You got DNA from the dad
1:26:00 in the sperm. But you could take a third party’s mitochondria outside of their cell, inject it into
1:26:06 that egg, just like the sperm went into the egg. And now that egg with mom and dad’s DNA and a third
1:26:13 person’s mitochondria, including their mitochondrial DNA, will propagate and form the whole embryo. And
1:26:16 it’s an amazing headline. Like, does that mean there’s three parents involved?
1:26:22 I mean, it’s equally fascinating when you just understand what you’re describing.
1:26:29 And part of the reason I’ve been reading and really trying to do a deep dive, always dangerous when you
1:26:35 are only half scientifically literate, but on my mom’s side of the family, a lot of Alzheimer’s.
1:26:41 And my mom’s had some deterioration as well, but she’s APO33. And also just word to the wise,
1:26:45 again, not a doctor. Talk to your medical professional. But if you’re trying to evaluate
1:26:52 your metabolic health, don’t just get fasting glucose taken because you can get lucky with
1:26:58 fasting glucose. And you might even do hemoglobin A1c, which is like a running three-month average of
1:27:01 your fasting glucose. This may be a simple way to think about it, something like that.
1:27:08 But also get your insulin measured because that was missed by my mom’s local doc for many,
1:27:14 many years. And her fasting glucose, even her hemoglobin A1c was kind of within tolerable levels.
1:27:20 And then her insulin was, it was so out of range as to just jump off the page.
1:27:24 And so then I was looking at it and there, of course, could be a million different contributing
1:27:32 factors. But I was like, I wonder if there’s some type of issue in her mitochondria, in which
1:27:37 case my understanding is you do inherit the mitochondria from your mom’s side is my understanding.
1:27:42 And I was like, okay, well, if that’s the case, I’d like to, I don’t know if there’s anything to be
1:27:50 done about it at this point, frankly. But if there is even a small possibility that you could do
1:27:55 something about it, I’m like, well, I’d like to kind of know what I’m dealing with. So that’s the
1:27:59 genesis of me asking about also the mitochondrial health side of things.
1:28:05 Yeah. We don’t have like a great blood test for your mitochondria yet, but obviously you could get
1:28:13 it sequenced. We don’t know how much, you know, like your fidelity to mom’s mitochondria might play
1:28:18 a role in your future cognitive health. I would add to your list though, two other standard screening
1:28:25 tests that certainly are likely to impact your cognitive health as you age. And with that, again,
1:28:30 the eyes part of the brain, your visual health too. And that’s going to be your lipids,
1:28:38 your fasting lipids, and your blood pressure. And, you know, like every bit of science points to,
1:28:45 yes, you can inherit it, your APOE genes that can change your risk, but a very big contributor is going
1:28:50 to be your lipids and your blood pressure, because those are going to contribute to what we call
1:28:59 microvascular disease and ultimately brain atrophy as we get older and ultimately cognitive function.
1:29:05 And if you could be really ahead of the curve and be really clean with your lipids, whether that’s
1:29:11 with diet and exercise or upgrading to some of the medicines that help with that and really clean with
1:29:17 your blood pressure, again, diet and exercise, or there are medicines we can give to help with that.
1:29:25 But staying ahead of the curve on those is almost certainly a huge contributor to your later cognitive
1:29:25 health.
1:29:32 I’ve got those suspects under control and very well dialed. I’m just like, are the mitochondria the
1:29:36 boogeyman in the closet that I’m not contending with? But yeah, I’m trying to do all the stuff you
1:29:42 would expect to also help support mitochondrial health. And I don’t think this is immediately
1:29:50 obvious. People think of exercise as body exercise, but if you want to increase the brain-derived neurotrophic
1:29:56 factor release and clotho release, which hopefully someday soon we’ll have as an injectable therapy
1:30:04 for humans, exercise, you got to do it. Do some weight training, do some zone two, do a VO2 maximum once in a
1:30:07 while. It’s incredibly valuable.
1:30:11 And I think the important thing for listeners is that, and when I say listeners, I include myself
1:30:17 because I intellectually know I need to do more exercise and, you know, I still got to figure out
1:30:21 how to get around to actually doing that more exercise. So, so I’m in the listener crowd here of
1:30:28 what I need to say, but the important thing to remember is that the biggest gain comes from going
1:30:36 from none to some. Yes. If you go from some to twice as much, yeah, there’s an improvement there
1:30:45 too, but not as big as the value proposition of going from none to some. Yeah. Yeah. Just scale it
1:30:50 down guys if you have to, but don’t do nothing. Don’t do nothing because you feel like I’m not, I can’t do,
1:30:56 I can’t do a million hours. So I’m throwing in the towel and I can’t, I won’t do any, you know,
1:31:02 half an hour, four or five days a week, brisk walk at that heart rate up, have it count, you know,
1:31:09 easy, you know, like make it easy on yourself. If you want to then go nuts and do like hardcore
1:31:14 weight training, hit your Peloton, have your trainer, you know, train for a marathon. Okay, fine.
1:31:19 But that biggest difference in your life was going from none to some.
1:31:24 Can I give you the greatest non sequitur in the history of my podcast? It’s just because you
1:31:31 mentioned that your number one, most common question was, can I have cannabis? So I’m lucky
1:31:37 to know a bunch of very amazing docs and blah, blah, blah. You know, I interview people, so I get to meet a
1:31:43 lot of fascinating folks. And one of these super high end, really sophisticated docs, he was telling me
1:31:49 the most, can you guess, I’ll give you a shot. I’ll give you a shot on the three pointer. What
1:31:53 do you think has, I’ll be astonished if you guess this, because even if you believed it, you probably
1:31:58 wouldn’t say it, but what do you, what do you think is most, one of his most common questions is that he
1:32:02 gets that, that he still refuses to answer publicly. I’ve wanted him to do it.
1:32:06 Oh my God, this is a guess what you’re thinking. You’d better, you know, as when we’re in training for
1:32:11 medicine, we get asked questions like this all the time. And some of them are like, okay, I want you to
1:32:16 guess what I’m thinking. Go ahead. Three trial. No, no. All right. Let me say, lay it on, lay it on.
1:32:22 What did he say? This is the question he gets all the time, which is from male patients. How can I
1:32:30 shave my balls safely? This is the question he gets more than any others. Like, really? I’ve done all
1:32:35 this training. I’ve done all this. And that’s the question that I get more often than not. Anyway,
1:32:39 I don’t know why I feel compelled to share that. Sorry. I’m going to trust that he’s not an eye
1:32:46 doctor. Cause I never get that. Yeah. He’s like, what are you talking about?
1:32:50 You interview a lot of people. What did Matt McConaughey say to that question?
1:32:56 Maybe this should be one of my rapid fire questions that I finished with.
1:32:59 I’ll take a pass on that one. I don’t have enough experience to talk.
1:33:04 Yeah. Yeah. No, we can, we can both pass on that one, but is there anything else that we
1:33:10 haven’t covered that you would like to mention any treatment or research or researchers that you think
1:33:15 people should take a look at? I mean, we talked a bit about mitochondria, certainly talked to the
1:33:21 lens. We talked about glaucoma and hopefully within the next five years, as you said, being able to
1:33:27 potentially restore function or stave it off to a much greater extent. We didn’t really get into
1:33:30 treating nerves. I have a note about treating nerves, but I’m not sure we need to cover that.
1:33:35 Is there anything else that you’d like to mention that we didn’t have a chance to discuss?
1:33:41 I want people to understand that first of all, these are all amazing questions. You’ve hit a wide range
1:33:49 and we can’t answer them without doing the science behind it. So first of all, you know,
1:33:56 as they might be dry and said, science is real. So first of all, science is real. And second of all,
1:34:01 like, you know, I would just encourage people, you know, like ask your, in this case, eye care provider,
1:34:07 like, you know, what’s going on with me? Are there clinical trials? Like volunteering to be in clinical
1:34:14 trials. I’ll tell you, I know like patients are so grateful when they get into our clinics here
1:34:21 and they get into a clinical trial because they are accessing a treatment before it is publicly
1:34:25 available to see if it’s going to work. We don’t know if it’s going to work, but they’re taking a swing at
1:34:31 that. And they are so grateful to get into these trials. But I always say like, we are so grateful,
1:34:38 like we can’t do the trials and therefore decide whether you should take the supplement or use this
1:34:46 virtual reality device or go in front of red lights every day or microdose LSD or change your microbiome.
1:34:51 We can’t figure that out if we don’t have the patients come be in the clinical trials and volunteer
1:34:58 their time and energy, the extra trips to the office to get their eyes measured or special pictures taken or
1:35:03 all that kind of stuff. So I say like, I know you’re grateful to be in this trial, but I’m grateful to
1:35:09 you too. We are grateful to the patient. So I think like, we’ve all got to participate in science as a
1:35:14 community so we can do these trials and figure out like how we’re going to fix ourselves and go from
1:35:20 disease to normal. And by the way, go from normal to supranormal, right? We got to prove that, right?
1:35:26 Yeah. Where would you suggest people search for or find clinical trials around them? And I’ll just
1:35:33 reiterate what you said. I’ve seen so many studies that I’ve been involved with hit a wall with subject
1:35:40 or patient recruitment. They just hit a wall. They really, really benefit from people who are
1:35:44 proactive. But if someone’s listening, they’re like, that sounds amazing. I’d love to actually see what
1:35:51 this looks like in practice and maybe figure or help people figure out something in the process for
1:35:56 almost for myself. Where do they even look? Where would they begin? One really good place in the U.S.
1:36:05 to look is a website called clinicaltrials.gov. So it’s got it right there in the name. And you go on the
1:36:12 front page for clinicaltrials.gov and you type in your disease. So you could type in glaucoma, diabetes,
1:36:21 whatever it is. And it’ll give you a list of here’s trials that are recruiting right now actively. And then you
1:36:27 can click on any of those and say like, oh, that one’s in my city or it’s not my city, but I’m going
1:36:32 to call or send the email to them anyway and say like, hey, could I be eligible for that? So that’s
1:36:38 probably one great resource. And then the other would be, again, for diseases would be in the case of
1:36:48 research for specific diseases. Almost every disease has one or more foundations or patient support
1:36:54 sites that bring people together. You know, I think of one in our backyard here in San Francisco
1:36:59 called the Glaucoma Research Foundation. There’s another one in New York City called the Glaucoma
1:37:07 Foundation. Dozens more, of course, but like they also maintain websites that have a lot of patient
1:37:14 directed information, patient facing, what to learn about your disease. You know, you were asking before,
1:37:19 like where’s a reliable source to learn about stuff. That’s one. But they’ll also sometimes talk through like
1:37:25 what’s happening in clinical trial space or where is that happening or where are some hot spots for clinical
1:37:32 trials. So I think that’s another. Those are a couple of good resources. Of course, nowadays, Google, you know,
1:37:37 just any web search engine, you know, it’ll get you started in the right direction.
1:37:43 Yeah, perfect. And if people are wondering, well, Tim, have you done any of this yourself? Yeah,
1:37:51 I’ve actually, I’ve been a subject in all sorts of different studies from undergrad all the way up to
1:37:56 a few years ago for various things, including at Stanford way back in the day when I was just a few
1:38:03 years after college. So it’s fascinating also just to see what it looks like in real life. What does
1:38:08 scientific study look like when it’s implemented? Well, thank you so much, Jeff. This has been
1:38:14 fantastic, wide ranging romp. It’s still and will continue to be intensely personal. So I will keep
1:38:24 people listening posted. I promise not to sell you any Kratom eye masks through some, you know, MLM scheme.
1:38:28 And I will be continuing to investigate all of this. This has been super helpful. I took a ton of notes.
1:38:35 Is there anywhere you would point people to find you online or learn more about you?
1:38:40 Yeah, absolutely, Tim. You know, you joked in the beginning that this podcast is yours and certainly allowed to be
1:38:47 self-serving, but I’ll throw one plug in here at the end, the Stanford ophthalmology website. We actually maintain
1:38:54 a list of clinical trials. And again, if we want to tap this whole team here on the back, our faculty, our clinical
1:39:01 research staff, everyone involved in it. Stem to Stern is fantastic. And I’d like to point out like,
1:39:07 you know, a lot of the clinical trials of trying to pull things out of the lab and test them in
1:39:12 patients for the first time, a lot of work on vision restoration, vision protection and restoration clinical
1:39:17 trials going on right here. My work and some of the work of our amazing faculty and staff here. So you can
1:39:22 actually go to the Stanford, Google Stanford ophthalmology clinical trials. We have a web page
1:39:29 on our Stanford ophthalmology site that goes disease by disease and has contact info and how you plug right
1:39:33 into the trials here. And we have people in our community participating, but we have people who fly
1:39:38 in from everywhere to participate in these clinical trials. So we’re happy to see if we can fit you into.
1:39:45 Beautiful. And for people listening, I will link to that in the show notes at Tim dot blog slash podcast.
1:39:51 So that’ll be easy to find. If you just search Jeffrey Goldberg, Goldberg, I think you might be the only
1:39:56 Goldberg. There might be one other search Jeffrey Goldberg and it’ll pop right up and you’ll be able to find the
1:40:02 links. Jeffrey, thanks so much. I really appreciate the time. And to everybody listening, as mentioned, show notes,
1:40:07 Tim dot blog slash podcast, you’ll be able to find links to everything we discussed and more until next time.
1:40:15 Be just a bit kinder than is necessary to others, but also to yourself. And thanks for tuning in.
1:40:22 Hey, guys, this is Tim again. Just one more thing before you take off. And that is five bullet Friday.
1:40:27 Would you enjoy getting a short email from me every Friday that provides a little fun before the weekend?
1:40:33 Between one and a half and two million people subscribe to my free newsletter, my super short newsletter called
1:40:40 Five Bullet Friday. Easy to sign up, easy to cancel. It is basically a half page that I send out every
1:40:45 Friday to share the coolest things I’ve found or discovered or have started exploring over that week.
1:40:50 It’s kind of like my diary of cool things. It often includes articles I’m reading, books I’m reading,
1:40:57 albums, perhaps gadgets, gizmos, all sorts of tech tricks and so on that get sent to me by my friends,
1:41:04 including a lot of podcast guests and these strange esoteric things end up in my field and then I test
1:41:10 them and then I share them with you. So if that sounds fun, again, it’s very short, a little tiny
1:41:15 bite of goodness before you head off for the weekend, something to think about. If you’d like to try it out,
1:41:22 just go to Tim dot blog slash Friday, type that into your browser, Tim dot blog slash Friday, drop in
1:41:27 your email and you’ll get the very next one. Thanks for listening. If I were to update the four hour work
1:41:35 week, which I get asked to do a lot, I would really only add one thing and that is a section on AI tools
1:41:40 because for everything I described with virtual assistants and with so much more you can do with
1:41:47 technology immediately. And that can be automated, delegated. There’s so much that you can do. And
1:41:53 this is also why I recommend this episode sponsor gamma for creating incredible professional slide
1:41:58 decks, better, cheaper, and faster than you ever thought possible. It’s pretty head spinning. I polled
1:42:04 all of you on social 10 million plus people about gamma and some of you called it a game changer,
1:42:09 mind blowing and far and away the best product in the category. Those are all your quotes with gamma.
1:42:14 You can just drop in an idea and outline a document, a PowerPoint and gamma will turn it into a stunning
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1:42:51 Listeners get one month free of gamma pro by using promo code Tim at checkout. So use promo code Tim,
1:42:59 T-I-M at gamma.app. As many of you know, for the last few years, I’ve been sleeping on a midnight luxe
1:43:04 mattress from today’s sponsor. He looks sleep. I also have one in the guest bedroom downstairs and feedback from
1:43:09 friends has always been fantastic. Kind of over the top, to be honest. I mean, they frequently say
1:43:13 it’s the best night of sleep they’ve had in ages. What kind of mattresses and what do you do? What’s
1:43:18 the magic juju? It’s something they comment on without any prompting from me whatsoever. I also
1:43:25 recently had a chance to test the Helix Sunset Elite in a new guest bedroom, which I sometimes sleep in,
1:43:30 and I picked it for its very soft but supportive feel to help with some lower back pain that I’ve had.
1:43:35 The Sunset Elite delivers exceptional comfort while putting the right support in the right spots.
1:43:40 It’s made with five tailored foam layers, including a base layer with full perimeter zoned lumbar support,
1:43:45 right where I need it, and middle layers with premium foam and micro coils that create a soft
1:43:49 contouring feel. Which also means if I feel like I want to sleep on my side, I can do that without worrying
1:43:54 about other aches and pains I might create. And with a luxurious pillow top for pressure relief,
1:43:58 I look forward to nestling into that bed every night that I use it.
1:44:04 The best part, of course, is that it helps me wake up feeling fully rested with a back that feels supple
1:44:07 instead of stiff. That is the name of the game for me these days.
1:44:14 Helix offers a 100-night sleep trial, fast, free shipping, and a 15-year warranty. So check it all out.
1:44:23 And now you can get 27% off anything on their websites or site-wide. So just go to helixsleep.com/tim.
1:44:29 One more time, helixsleep.com/tim. With Helix, better sleep starts now.
1:44:30 Helix starts now.
0:00:09 The Tim Ferriss Show. This episode is deeply personal because as someone who is now in his
0:00:15 late 40s, my eyes have started to go for the first time. I’ve always had 2010 vision and this is
0:00:23 unacceptable for me. So I spoke to everyone I knew and good old Andrew Huberman saw a post that I put
0:00:29 up, texted me, said the person you need to talk to is Dr. Jeffrey Goldberg. So guess who my guest
0:00:35 is today? Dr. Jeffrey Goldberg, professor and chair of ophthalmology and director of the Byers Eye
0:00:41 Institute at Stanford University. He has a wide breadth of expertise. He is a leading scientist
0:00:46 in the development and degeneration of the visual system from eye to brain and their interventions
0:00:51 depending on where you want to go at many points along that chain, although it’s more of a network,
0:00:56 I guess, and a practicing ophthalmologist and surgeon. We dive into all sorts of stuff in this episode,
0:01:02 ranging from super performance or super normal performance. Let’s just say for professional
0:01:10 athletes, if you want to take your vision from normal or pretty good to unbelievably good for,
0:01:16 say, competitive purposes, we talk about that. And we also talk about repair and slowing the
0:01:23 degeneration of the eye, which naturally comes with age. Dr. Goldberg’s research is directed at vision
0:01:27 restoration, including neuroprotection and regeneration of the retina and optic nerve,
0:01:32 a major unmet need in glaucoma and other eye diseases. And we’ll define all of these terms in
0:01:37 the conversation. So don’t worry. His laboratory is developing novel molecular stem cell and
0:01:42 nanotherapeutics approaches for eye repair. And he is widely recognized for translating advances in the lab
0:01:50 into clinical trials for patients. So from bench to bedside in some respect. And I really enjoyed this
0:01:55 conversation. I took a lot of notes. There’s a lot of actionable detail. So we’ll dive right into the
0:01:59 conversation. But first, just a few words from the people who make this podcast possible.
0:02:05 As many of you know, for the last few years, I’ve been sleeping on a midnight luxe mattress from
0:02:10 today’s sponsor, Helix Sleep. I also have one in the guest bedroom downstairs and feedback from
0:02:15 friends has always been fantastic. Kind of over the top, to be honest. I mean, they frequently say
0:02:19 it’s the best night of sleep they’ve had in ages. What kind of mattresses? What do you do? What’s the
0:02:25 magic juju? It’s something they comment on without any prompting for me whatsoever. I also recently had a
0:02:31 chance to test the Helix Sunset Elite in a new guest bedroom, which I sometimes sleep in. And I picked it
0:02:36 for its very soft but supportive feel to help with some lower back pain that I’ve had. The Sunset Elite
0:02:41 delivers exceptional comfort while putting the right support in the right spots. It is made with five
0:02:47 tailored foam layers, including a base layer with full perimeter zoned lumbar support right where I need
0:02:53 it. And middle layers with premium foam and micro coils that create a soft contouring feel, which also
0:02:57 means if I feel like I want to sleep on my side, I can do that without worrying about other aches and
0:03:02 pains I might create. And with a luxurious pillow top for pressure relief, I look forward to nestling
0:03:07 into that bed every night that I use it. The best part, of course, is that it helps me wake up feeling
0:03:13 fully rested with a back that feels supple instead of stiff. That is the name of the game for me these
0:03:20 days. Helix offers a 100-night sleep trial, fast, free shipping, and a 15-year warranty. So check it all out.
0:03:28 And now you can get 27% off anything on their website, so site-wide. So just go to helixsleep.com
0:03:35 slash Tim. One more time, helixsleep.com slash Tim. With Helix, better sleep starts now.
0:03:42 If I were to update the four-hour work week, which I get asked to do a lot, I would really only add one
0:03:48 thing. And that is a section on AI tools. Because for everything I described with virtual assistants
0:03:55 and with so much more, you can do with technology immediately. And that can be automated, delegated.
0:04:02 There’s so much that you can do. And this is also why I recommend this episode sponsor Gamma for creating
0:04:07 incredible professional slide decks better, cheaper, and faster than you ever thought possible.
0:04:13 It’s pretty head-spinning. I polled all of you on social, 10 million plus people, about Gamma.
0:04:17 And some of you called it a game-changer, mind-blowing, and far and away the best product
0:04:22 in the category. Those are all your quotes. With Gamma, you can just drop in an idea, an outline,
0:04:27 a document, a PowerPoint, and Gamma will turn it into a stunning, ready-to-share presentation
0:04:32 in seconds. And if you want to turn that into a website or whatever else, again, snap of the
0:04:37 fingers and it’s done. With more than 50 million users, it’s already the most popular AI presentation
0:04:43 platform in the world. So stop wasting time dragging stuff around, fidgeting with bullet points, and let
0:04:49 Gamma turn your content into high-quality presentations so you can spend your time on other things that
0:04:57 matter. Explore Gamma today at gamma.app. That’s G-A-M-M-A dot A-P-P. Gamma.app. Listeners get
0:05:02 one month free of Gamma Pro by using promo code TIM at checkout. So use promo code TIM,
0:05:10 T-I-M, at gamma.app. Optimal minimal. At this altitude, I can run flat out for a half mile before
0:05:15 my hands start shaking. Can I ask you a personal question? Now would it seem an appropriate time.
0:05:20 What if I did the opposite? I’m a cybernetic organism living tissue over metal endoskeleton.
0:05:24 The Tim Ferriss Show.
0:05:33 Dr. Jeffrey Goldberg, so nice to meet you. Thanks for making the time.
0:05:36 Absolutely. Thanks for having me on. I’m really looking forward to it.
0:05:43 I have so many questions for you. And as usual, I am scratching my own itch. This is going to be a
0:05:51 selfish conversation for yours truly in some respects because the way this whole thing came about is I put
0:05:58 up a post on social media asking for cutting edge technologies or treatments related to presbyopia,
0:06:05 which for those who don’t recognize the term is a very fancy way of saying age-related visual decline.
0:06:12 If you’re a word nerd like I am, Presbyterian, similar etymology, leadership of the elders.
0:06:20 And I have noticed in the last year that my near work, my near vision has started to falter,
0:06:28 looking at books, looking at my iPhone, looking at supplement bottles. And this has led to somewhat
0:06:36 of a crisis of meaning for me because I have had my identity based on, in some respects, very,
0:06:42 very good eyesight and visual acuity for my entire life. And Andrew Huberman, mutual friend of ours,
0:06:50 texted me and said, I know the guy and listened to our interview, which I did. And for that reason,
0:06:55 we’re going to go all over the place. But I thought we would start where I had to start,
0:07:01 which is super normal visual performance. And these are the notes I scribbled down from your
0:07:04 conversation with Andrew. I recommend everyone listen to it.
0:07:10 Goggles that reduce frame rate for basketball. And that was sort of left hanging a little bit.
0:07:14 You guys didn’t do a deep dive on it. So I want to start right there. Because of course,
0:07:19 there’s preventing decline, there’s maybe a restoring function, and then there’s going further
0:07:27 and taking things as far as you can. And nowhere are the stakes higher and the rewards greater perhaps
0:07:31 than in professional sports. So could you take that and run with it in any way that makes sense?
0:07:37 Yeah, presbyopia, vision of the old. So I’ll tell you just a funny side note. You know, we all get that.
0:07:44 I, like you, have gone my whole life without needing glasses until I hit around age 40. And when everyone
0:07:53 hits around age 40, our lens inside the eye won’t compress and reshape to focus up close. So your distance
0:07:59 vision might still be great, but you just can’t bring that focus in as tight. And I discovered it
0:08:05 accidentally in myself because I was actually like in my house and someone, I found a pair of glasses in
0:08:11 a closet. Like somebody must’ve just left them there. And they’re not the readers. And we couldn’t figure
0:08:16 out who they were. We’re calling around, friends and family, fine. Nobody’s claiming them. And then
0:08:21 one day I just put them on like, let’s see how I look in glasses. And I looked down at my phone and
0:08:29 I’m like, oh my God, wait a second. I can see a lot better with these readers on. And then once you do
0:08:32 it, you’re addicted because good vision is pretty addicting, right?
0:08:33 Yeah, for sure.
0:08:39 Yeah. So now I’m in them too. And, uh, you know, I’m pretending to look so young with you,
0:08:42 not wearing them right now, but here they are just in case.
0:08:45 Yeah. Very common.
0:08:50 It raises a really cool question that you’re raising, which is, you know, like as an eye doctor,
0:08:54 I spent a lot of time and as a researcher spent a lot of time, we could come back to talking about
0:08:58 like, how do we prevent the sick from losing vision on all these big eye diseases? We could come
0:09:04 back to that, but like, there’s a much bigger world of people who have pretty good vision.
0:09:08 Maybe they need glasses, but they’ve got good vision. And how do we think about the difference,
0:09:14 not from sick to normal, but how do we think about the difference from normal to supra normal? And we
0:09:19 know there’s super normal because when, for example, as you bring up professional athletes get
0:09:25 studied, they have better vision. They have better reflex time. They have sharper vision. You know,
0:09:31 we talk about like 20-20 vision. That means like I can see at 20 feet what a quote normal person can
0:09:38 see at 20 feet. So I have normal vision, but you can have 20-12 vision, which means like you can see
0:09:43 at 20 feet what normal people can see at 12 feet, right? You’ve got better than normal. And it turns
0:09:49 out like a lot of pro athletes have that. And then the next question becomes, and you just kind of hinted
0:09:58 at it right there. Can we train to super normal vision? Can we like induce? And almost no one studies
0:10:04 that, but there are some really cool tools and toys that actually might have that effect. And so you brought
0:10:12 up one of them. So we see like our cones inside of our eyes, you know, we’ve got rods and cones. The cones,
0:10:19 they’ve got a refresh rate, you know, around 30 to 60 frames per second, you know, kind of like our
0:10:26 computer screens do, right? And so if you actually subtract out a couple of frames, so if you put on
0:10:37 some glasses that dim one out of every 30th of a second or they dim two out of every 30th or push it
0:10:45 three, and now you’re giving up visual data and I throw a basketball at you, if you’ve got your regular
0:10:53 vision, you’ll catch it. But if I’m only giving you 90% of your vision or 80% or 70% or 60% of that
0:11:02 vision, you might miss the ball, right? But if we practiced and trained in those goggles where you’ve
0:11:07 got to play basketball, throw and catch, shoot, whatever, you know, throw a baseball back and
0:11:14 forth at 70% vision. And then we put you in the game back with a hundred percent vision, right? You’re
0:11:21 going to be like better, faster reflex time, all of that, like hand-eye coordination. So it’s actually
0:11:28 like some of these super normal visual tactics are actually trainable and there’s tools that
0:11:30 athletes are using, but they’re accessible to all of us. Yeah.
0:11:32 You can grab one of those, Tim.
0:11:37 Let’s dig into this a little bit. I have a number of friends who have engineering shops and have played
0:11:43 with sensory substitution experiments and all sorts of wild stuff. In fact, I think there’s some folks at
0:11:49 Stanford who, David Eagleman comes to mind, who’ve developed tools along these lines. We won’t go down
0:11:55 that route. Let me stick with vision for a second and just note that there are, for instance, indigenous
0:12:02 groups in various parts of the Amazon. I’ve seen them in Brazil and in Peru as well, which use eye drops
0:12:11 of various types. Could be from a plant, could be from a toad for improving not near work, but distance work.
0:12:19 So let’s just say using, most of them use shotguns these days, but some still use blowguns and bow and
0:12:24 arrows for hunting, save monkeys, right? So there seems to be something to it. Now you could say, ah,
0:12:31 that’s a bunch of voodoo, voodoo nonsense. But then you have eye drops for, as I understand it,
0:12:37 temporarily inducing more, this isn’t going to be the right term, but flexibility in the lens.
0:12:38 I think, is it pelocarpine?
0:12:43 It’s actually the iris. Yeah. Yeah. So I don’t know what they’re using in the plants,
0:12:52 but we now have FDA approved eye drops. And what they actually do is they bring your pupil size down
0:13:00 by having your iris constrict to a smaller circle. And it turns out that if you have refractive error,
0:13:04 so you need glasses, you know, the shape of the front of your eye, the shape of your lens isn’t
0:13:09 perfect. You have a little bit of glasses or contacts or whatever to correct that, including if it’s not
0:13:16 focusing up to close, you can have reading glasses that change that refractive, you know, that light
0:13:23 light coming into your eyes so that you’re focusing up at close. If you come down to a pinhole, you
0:13:29 actually kind of normalize the light so that it’s as if it’s all coming from infinity and you actually
0:13:35 kind of correct refractive error. One of the ways we can tell if someone needs glasses is we have you
0:13:39 read the eye chart and then we have you read the eye chart through a little pinhole, you know, a little
0:13:43 device you stick in front of that eye and read through a pinhole. And if you can read better through
0:13:50 the pinhole, you actually have better vision and could correct it with glasses. So now we could just
0:13:57 give an eye drop that kind of makes your pupil closer to a pinhole. And then it allows you to see
0:14:02 without glasses near or far. And in fact, people are kind of using it now for near vision for that
0:14:07 presbyopia you were talking about in the beginning. So for people listening, and also for me, frankly,
0:14:16 could you just give a vision 101? And in this case, let’s focus on the eye just so people understand the
0:14:24 basic components of the eye. And part of the reason I want to explore this is there are different levers
0:14:31 you might be able to pull on to improve vision, some of which might be structurally related, but not all at
0:14:36 least to the eye. But could you just lay out the basic anatomy of the eye, the architecture?
0:14:42 Yeah, absolutely. So light comes in the front, goes through the clear window in the front of our eye
0:14:50 called the cornea. You can have corneal diseases, obviously, that block that light from coming through
0:14:55 clearly. But if it’s healthy, that light comes through clearly. The cornea is curved on the front,
0:15:02 and that curvature is actually responsible for curving most of the light into the back of the eye.
0:15:08 Then the light goes through your pupil. So that’s the iris, which is brown and me, but brown, blue,
0:15:13 hazel. So that’s our iris. And the iris can open and close like we were talking about a minute ago.
0:15:17 Comes through the middle of that, the open middle part of that. Goes through the lens.
0:15:24 The lens is like, does fine focusing, you know, a little focusing from far to near, that kind of thing.
0:15:29 That’s what we were saying stiffens as we age. So we can’t go far to near as well as we get older,
0:15:36 kind of passing 40 years old, typically. And then it goes through the gelatinous middle part of the eye.
0:15:41 We call it the vitreous. After the lens is called the vitreous. That’s where floaters are. People who
0:15:46 get floaters, they’re floating. It’s like little concretions of proteins and stuff floating in the
0:15:52 vitreous. It’s a gel. As we get older, that gel turns to water, kind of shrinks up. Our eye doesn’t
0:15:57 shrink because it fills in with, you know, salt water, but the gel shrinks up. And then the light
0:16:03 hits the retina. And our retinas are what we call inverted. So the light actually passes through
0:16:10 almost all of the retina. And then it hits the rods and the cones. And those are the photoreceptors.
0:16:17 They absorb the light, like the photons of light. The rods are really only good for nighttime vision.
0:16:22 They’re only good at like very low light. If you go into normal daytime vision, sitting here in the
0:16:26 room, whatever, those are getting bleached out. You’re not really using your rods too much.
0:16:34 Next to them, the cones. Cones are great for color vision. They’re great for bright lights. They’re
0:16:39 what we use most of the day. That’s what you and I are using mainly right now. The rods and the cones
0:16:48 collect all that light. They process it and transmogrify it into electrical signals. And
0:16:53 those electrical signals are then propagated back forward through the retina. There’s some internal
0:16:57 processing layers in the retina. So it’s not just a layer of film. You’re actually doing some
0:17:02 computation right there in the retina. And then they hit what are called retinal ganglion cells.
0:17:08 And those are the cells that then send a process across the surface of the retina. It’s an axon,
0:17:14 but it’s like a telephone wire. And that then goes back out the back of the eye into what we call the
0:17:19 optic nerve. And that optic nerve connects the eye to the brain. So those retinal ganglion cells are
0:17:24 collecting all the data and sending it all back through the optic nerve to the brain. And then,
0:17:26 of course, the rest of that processing is happening in the brain.
0:17:32 There we go. That was a great summary. Thank you very much. And I’ll tell folks, if you thought that
0:17:39 is a lot to remember, it is a lot to remember. But the point of it is, as I, as my own NF1,
0:17:47 am trying to consider different paths forward with presbyopia, whether it’s glasses, yes,
0:17:52 my readers do fix the problem, right? They do fix the problem, but I am a little concerned of
0:17:57 increased dependency and then increased magnification over time. I know there are arguments for and maybe
0:18:03 some arguments against, but when I put up my social post, and I think people can identify with this,
0:18:10 there was a lot of noise. There were some of the most harebrained, insane, certainly potentially
0:18:18 dangerous suggestions you can imagine. And then there were a few things that came up when I reached
0:18:25 out to, let me get this right, is it vitro retinal surgeon and researcher who I happen to know. And he
0:18:30 sent me a number of white papers, or I shouldn’t say white papers, more so studies and meta-analyses and
0:18:36 so on, that I read up on. And I thought to myself, look at that. Surprise of surprises. A few of the things
0:18:41 that came up repeatedly in the hundreds of responses to my post actually show up in the literature and there
0:18:47 might be something to them. And we’ll definitely come to a number of those. But it can be very overwhelming
0:18:53 for people to try to figure out what to do next. And the reason I wanted you to do that recap, and then I’ll stop
0:19:00 giving my second TED Talk of our conversation, is that much like if someone complains of, say, brain fog
0:19:07 and fatigue, a rose is a rose is a rose is not a rose in the sense that there can be many different
0:19:14 factors and independent variables that contribute to that. So one person might have insulin insensitivity
0:19:19 and trouble with glucose disposal. Somebody else might have Lyme disease or some infectious disease that is
0:19:24 contributing to metabolic dysfunction. I mean, there’s so many different contributing factors
0:19:29 that it helps to, I think, get a little thinly sliced. So in my case, I have the stiffening of
0:19:35 the lens. Please correct my terminology. I also have a really pretty sizable, I’d never seen it before,
0:19:43 I did some really impressive imaging on the eye, but a huge nevus on the back of my right eye that I need
0:19:48 to keep an eye on. So I’ll be following up on that in three or four months. But I wanted to,
0:19:55 I suppose, start with what are other ways to improve vision? Now, there are certain things I’m always
0:20:05 looking for, limited downside potential upside. So for instance, I’m taking the AREDS2 supplement with
0:20:12 lutein and various other ingredients in it. I would say it’s probably not going to help, but within my
0:20:18 patient cohort of the medical practices I work with, there are a few folks who claimed after six weeks that
0:20:22 their vision really improved and they didn’t need their readers, even though technically, mechanistically,
0:20:28 the AREDS2 shouldn’t have helped them. So whether it’s placebo effect or not, interesting outcome. I know the
0:20:34 plural of anecdote is not data, but I was like, ah, okay, sure, I’ll take the supplement. What are some other
0:20:41 sort of cutting-edge treatments or augmentations for improving vision? And I’ll shut up in a second, but I’ve been
0:20:46 very excited to talk to you. So I’m like a chomping at the bit here. Because as you mentioned, I mean,
0:20:53 there’s this sort of eye architecture brain interface. And among professional athletes, just because I’ve
0:21:00 funded a lot of science in this area, low-dose psychedelics also seem to improve visual acuity.
0:21:06 So everyone from Aaron Rodgers to very, very high-level athletes that I will not dox here
0:21:13 report measurable performance improvements that they attribute to increased visual acuity. It’s
0:21:18 probably not changing the anatomy of the eye. So what’s going on, right? So I would just love you
0:21:25 speak to any other means of supercharging visual perception.
0:21:29 There are some things that we have a pretty decent sense on.
0:21:35 Carrots 2 and some of these supplements, you know, first of all, like eating a lot of carrots is
0:21:39 probably not going to actually do it, you know? So great childhood, get the kids to eat their
0:21:46 vegetables. We definitely exercised that ourselves as parents. But Carrots 2, clinically proven,
0:21:53 if you have moderate age-related macular degeneration to slow down your vision loss.
0:21:59 Does that mean it doesn’t work at all if you have mild age-related macular degeneration or if you have
0:22:05 no age-related macular degeneration? It might just be like, we haven’t done a study big enough to detect
0:22:12 those effects. And as you say, like, that’s probably not going to hurt. So, you know, feel free if you
0:22:16 want. We can’t prove it’s helping, but feel free. There are other supplements,
0:22:21 supplements that have, you know, received some study that maybe suggests there isn’t much going
0:22:27 on there that, again, probably not going to hurt. Some patients take CoQ10. Some patients take Ginkgo.
0:22:34 There’s actually maybe the hottest topic in supplement vitamin space right now internationally is actually
0:22:43 vitamin B3, nicotinamide, which has, you know, really been linked to a number of good potential, you know,
0:22:48 kind of medical uses and is receiving a lot of studies. There’s actually international clinical
0:22:54 trials, including one here in the U.S., actually testing whether it could restore vision in certain eye
0:23:00 diseases like glaucoma, which is my specialty. So, definitely some hints in that direction. We already
0:23:08 talked about some device elements. And I think between vision training, like we talked about earlier,
0:23:15 and also visual augmentation, we’re moving into augmented reality. And so, training vision and visual
0:23:22 reflex time almost certainly makes a difference in the activities you’re training in. If you’re training
0:23:29 in basketball, will it also help you doing some weekend surfing? I don’t know, but definitely can
0:23:36 help move you from normal to super normal or help enhance, improve what you’re doing. And then there’s
0:23:43 all sorts of stuff that, I’m going to be honest, Sam, we don’t know because A, it’s kind of really new,
0:23:50 really hot right now, like microdosing certain psychedelics, things like that, that we know act on the
0:23:57 nervous system, including the brain. But the retina in the back of the eye and the optic nerve that
0:24:02 connects the retina to the brain, those are developmentally an outgrowth from the brain.
0:24:09 They are part of the brain. They’re part of the central nervous system. And we barely know about
0:24:17 how to influence the wiring, the plasticity. Are there drugs that we can give? A lot of people have
0:24:23 talked about gabapentin, drugs in that space. Obviously, microdosing and LSD is a really hot
0:24:32 area right now for inducing plasticity. There’s actually great science showing in animal models
0:24:41 and a little bit now in humans that you can actually reopen brain plasticity by dosing some of these
0:24:45 drugs at appropriate doses. Obviously, we’ve got to be careful. We don’t know what the right dose is
0:24:52 yet. But it’s really worth looking at because there’s clear evidence that these are relevant
0:24:57 and likely to have some effects. We just got to figure out a little bit more like how, what’s the
0:25:02 right dose. By the way, when you’re doing it, should you be doing some behavioral training,
0:25:08 like visual training? But these things act on the brain. And about a third of our brain inside our skull
0:25:11 is dedicated to processing vision.
0:25:17 Yeah, there’s a lot there. All right. I’ve been so excited. I’m not just over-caffeinated
0:25:21 because I’m actually not really caffeinated. I might be over-ketoned. I have quite a bit of
0:25:27 ketone mana, Esther, in me at the moment. But putting that aside, I am right now, and this could
0:25:33 make me seem like I’m in the tinfoil hat-wearing crowd, but I had a number of companies reach out to me,
0:25:38 not surprising, after I put up my social posts. Most of them didn’t make any sense. A few of them
0:25:43 seemed to make sense. And the people involved seem to have technical chops and also some pretty
0:25:48 credible research backgrounds. And I’m not going to name the company yet because I’m not done with
0:25:53 my personal testing. But I have been testing at about eight minutes a day. I don’t know the right
0:26:01 descriptor to use. I would say maybe visual perception training to distinguish it from,
0:26:06 and we can talk about this, what I suppose some ophthalmologists or optometrists might call visual
0:26:12 education, right? So trying to improve the ciliary muscle strength and so on around the eyes,
0:26:18 much like if people want to visual sort of the springs around a trampoline. But in this case,
0:26:25 it’s very quick flashes of blurry or not blurry circles, and you need to identify what is more
0:26:32 blurred. And there are many permutations. It adapts to your successes and failures over time.
0:26:43 And it could absolutely be placebo. But after about a month now of using it, I feel like my near vision
0:26:49 vision has improved. Even the woman I’m dating has commented on this. And I’m still waiting. The jury
0:26:57 is out. But this is just to say that I’d love to know what you think of visual improvement that is
0:27:07 not dependent on surgery or drops. Is there something to the various types of visual education? Is there
0:27:14 something there or not? And then when we go maybe upstream a bit, if that’s the right phrasing to
0:27:20 use to the brain, are there interesting approaches like limiting the frame rate or removing a number of
0:27:25 frames that you think are at least plausibly interesting for enhancing performance?
0:27:33 First of all, absolutely. And it does get back to that idea of visual training, reducing frame rate,
0:27:39 training on visual perception. There’s actually a fair amount of data. Actually, there’s enough data
0:27:45 to even say like there’s elements that make it better. For example, if you do visual training where
0:27:52 you’re just showing yourself, you know, like being shown these different objects, maybe they’re getting
0:28:01 smaller, dimmer, blurrier, etc. Your ability to train off of that is significantly better if it demands
0:28:09 a behavioral outcome, a motor action. So for example, you’ve got a point at the right one or choose
0:28:16 something. And it’s not just that you’re mentally thinking that was the sharper image. It’s actually
0:28:21 the motor output of pushing a button or pointing at something or doing an activity that actually
0:28:30 reinforces the visual perception training. So that’s one great example. Another great example is after
0:28:37 concussion. So concussion, traumatic brain injury, of course, very common in athletes because they’re more
0:28:42 likely to get into the, you know, head bumps and things like that, but happens all the times in kids.
0:28:50 Military, very big issue. And the line in between mild concussion, severe concussion, traumatic brain
0:28:59 injury, injury. That’s all on a spectrum, a continuum. And there’s actually decent data from that group of
0:29:07 people that if you get a concussion, actually visual symptoms are some of the more significant symptoms.
0:29:12 You know, ability to focus, ability to sleep and vision are three of the big symptoms that people get
0:29:19 in that concussion through TBI spectrum. And those can be debilitating, right? And kids are out of school,
0:29:24 they’re missing high school, you know, for weeks or longer. It can be really debilitating. Obviously,
0:29:30 if you’re an older adult and you’re in your job situation, really tough. And it turns out,
0:29:38 though, that there are visual perception exercises that you can put patients through in those situations
0:29:45 that in the limited clinical studies that have been done point to a positive effect of basically
0:29:51 rehabbing, like neuro rehabbing you back. Now that, of course, is back from injured to normal. But the
0:29:57 idea that that can also induce the same kind of plastic remodeling in our eye and brain, and particularly
0:30:04 the eye-brain connection in patients who are starting from normal and trying to get themselves up to
0:30:11 supranormal, try to improve performance, visual performance. We’ve set up here a whole human
0:30:18 performance laboratory really just to study these questions. And the data rolling in, you know,
0:30:21 make it look like, hey, there’s something here. This is definitely worth chasing.
0:30:27 What can someone search if they want to find something to read up on related to the concussion
0:30:34 rehabilitation protocol because this type of visual training because there’s a lot of nonsense floating
0:30:40 around and charlatans out there? Any particular search terms or principal investigators or anything that
0:30:40 people can search?
0:30:47 I would say like, you know, if you want to sort of like at least hit some of the science or science-adjacent
0:30:52 web resources, you’re going to want to use a few technical terms in there like concussion,
0:30:59 neuro-rehab, neuro-rehabilitation, plasticity, and then some of the terms you’ve already been
0:31:05 using, you know, visual perception exercises. And then look, in these situations, you’ve got to look
0:31:11 not just at the content, but of the source, right? And so is this like a dude on his blog or is this
0:31:18 coming from a foundation or an institute or one of the academic centers or some of the choices like
0:31:19 that?
0:31:25 Just a quick thanks to one of our sponsors and we’ll be right back to the show.
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0:32:40 slash Tim. All right, Jeff, I would love to hop to another set of interventions. And this is in the
0:32:46 device category. Red light in the morning for mitochondrial health? Question mark. Violet light
0:32:55 to reduce progression of nearsightedness in children. Is there an application of red light or violet light?
0:33:01 To what extent do we have supporting data for using either of these? Do we have an idea of what best
0:33:07 practices look like? Is it only for people with a disease state or can they be potentially used to
0:33:16 preserve vision before vision loss? The disease state data is pretty good. And also the myopia control
0:33:20 is pretty good data too. Just for a definition for folks, what’s myopia?
0:33:28 Myopia is nearsightedness. And you know, it’s an epidemic, more common in Asians or people of Asian
0:33:34 heritage, but common in everyone. And kids can get nearsighted. If you’re a little nearsighted,
0:33:40 it might be annoying to wear glasses. If you get more severely nearsighted, it actually can lead to all
0:33:48 sorts of problems inside the eye. You know, real severe vision loss, even early in life. So it’s a
0:33:56 big one. And then what was really shocking was it turns out that a small dose of daily red light
0:34:04 can slow down progression of myopia in young people. You know, we’re talking about teens and younger even.
0:34:15 So what’s even more shocking to me is that it also works with violet light. So how does it work with light
0:34:22 at the two ends of the visible spectrum? And definitely mitochondria are implicated. Mitochondria are the
0:34:29 little like kind of powerhouses, energy sources inside the cell. They are big player in converting the sugar a cell
0:34:36 takes in into energy that the cell can use for all of the cellular processes. So our bodies clearly need
0:34:43 functioning mitochondria. In fact, one of the big features common across many neurodegenerative
0:34:50 diseases of the eye and the brain is dysfunction of mitochondria. There’s an FDA-approved red light
0:34:57 therapy for patients with macular degeneration, but there’s good data that it may also be supportive
0:35:04 or protective in other eye diseases. And we’re talking to small doses like this is not overwhelmingly
0:35:08 bright lights. And we’re talking about minutes a day. You don’t have to sit in front of it for two
0:35:16 hours a day. So minutes a day. So it’s exciting. The data suggests that the mechanism of action is kind
0:35:21 of giving a little protective booster shot to our mitochondria so that they don’t get dysfunctional,
0:35:26 whether that’s dysfunctional just from normal use throughout the day or dysfunctional because you
0:35:31 happen to have a disease that’s getting in the way of those mitochondria. Now, we don’t know what
0:35:37 the right dose is. We don’t know what the right brightness is. All we know is that in these initial
0:35:41 things that have been tested, initial brightness of how and how many minutes, three minutes a day,
0:35:47 for example, there’s a signal there. There’s something working there. Should we have everybody
0:35:52 buying one on the internet right now, hopping on Amazon, spending 25 bucks, spending three minutes
0:35:58 a day? We don’t have the data to support that. Is it going to hurt? Probably not. Tim, it’s a problem
0:36:03 because we’ve got so many things that are like, oh, that looks promising. And we just need a little
0:36:08 more science. We need a little more study. Yeah. Well, you know, a friend of mine wanted me to write
0:36:15 a blog post about, look, I’m not a doctor. I don’t play one on the internet, but the difference
0:36:21 between sort of getting into science versus getting out of suffering in the sense that you know, and I
0:36:26 know just having been involved with the funding side, like randomized controlled trials are expensive
0:36:32 and they take a long time. But at the same time, if you take the advice of every wackadoodle
0:36:36 running around on the internet, you’re going to have 600 different interventions, some of which
0:36:41 could do a lot of damage or you’re going to get the wrong device. I’ve seen this also because I’ve
0:36:47 talked about accelerated TMS and different types of brain stimulation for potentially addressing
0:36:52 treatment resistant depression. And Nolan Williams at Stanford has done a lot of great research related
0:36:59 to that. And you see these people on YouTube with DIY TMS and they’ve got the polarities reversed.
0:37:06 And I’m just like, oh my God, what are you doing to your poor brain? But I also want to preserve my
0:37:12 vision as long as humanly possible. And maybe you can dispel a concern that I have. And this is based
0:37:17 on the fact that I have a lot of Alzheimer’s and Parkinson’s in my family. And I’m able to be three,
0:37:24 four, some 2.5 times or so more likely to develop Alzheimer’s based on what we currently think we know
0:37:30 than someone who is, I guess, three, three. And it scares the hell out of me. And I’ve had
0:37:37 conversations with audiologists who point out the correlation. I don’t know how strong the signal is
0:37:43 between hearing loss and onset or progression of dementia. Is there something similar for visual loss?
0:37:50 Absolutely. Actually, one of our faculty here has done some of the really foundational research showing that
0:37:58 correlation between vision loss and cognitive decline. And the loss of input, again, vision is our
0:38:05 biggest input sense. It’s driving, you know, a third of our brain is dedicated, as I said, to processing and using
0:38:12 that vision. It interfaces with every other thing that we do. It also is a really critical piece around
0:38:17 depression and mental health. Anxiety is vision. You know, the work that Andy Huberman had done on visual
0:38:24 fear and how that plays into the fear and anxiety pathways, as well as the depression pathways. And not
0:38:32 only does visual decline accelerate cognitive decline, possibly because, in part, because of how depression then
0:38:38 plays in with cognitive. I mean, these things are all clearly related to each other. But also, remarkably,
0:38:45 if you have low vision, let’s say from something as simple and correctable as cataracts, a blurring of
0:38:50 the lens that happens with age. If we all live to 100, we’re all going to need cataract surgery. Some people
0:38:59 younger, some people older. But if you do cataract surgery and restore vision in an older person who
0:39:06 appears to be suffering is suffering with cognitive decline and or depression, you can reverse
0:39:14 a significant amount of that decline in either of those domains. And so it just, again, it speaks to
0:39:21 the interplay of vision with our mental health or cognitive health. This is long-term important stuff.
0:39:26 Tell me if I’m interpreting this the wrong way, but it seems like this would lead to a strong
0:39:33 pro-argument for wearing glasses instead of suffering in silence. I don’t know, but that’s what I hear
0:39:39 when I’m sort of trying to read between the lines. There’s an important myth to dispel, especially when
0:39:47 it comes to presbyopia and wearing reading glasses. Between age 40 and around 60 or so, that lens stiffens and
0:39:54 stiffens and stiffens. And the first year, you only need plus 1.25 glasses. And then three years later, you’re
0:40:02 like, ah, I need plus 1.5, plus 150s. A few years after that, you’re moving up to the 2.0s. Eventually, you’ll peak
0:40:08 out at around 2.5 or 3.0s because that’s the difference, basically. That’s the refractive, the glasses
0:40:14 difference between viewing something at infinity, which from an optics perspective is actually just kind of like
0:40:20 three feet away or further. And viewing something at 14 inches, like comfortable reading distance right in front of us.
0:40:28 So, 2.5 to 3 power of those readers is all you’re going to need. But you’re going to progress through those
0:40:33 numbers, whether you wear the readers or not. So, wear the readers.
0:40:41 I got it. Is it a mistaking causality then where people believe? Because an optometrist said this to me a couple weeks ago,
0:40:44 and I was like, well, I assume you know what the hell you’re talking about, which is always a stupid
0:40:49 assumption, but that you develop increased dependence. But it’s actually just tracking along
0:40:52 with the natural stiffening of the lens in the case of presbyopia.
0:40:58 And it’s psychological dependence. It’s just like what I went through. As soon as I started wearing those
0:41:02 readers by accident, I didn’t think I needed them. I was still reading off my phone. It was fine.
0:41:08 But as soon as I experienced that extra crisp vision, I was like, well, I like that.
0:41:08 Yeah.
0:41:12 Or I got psychologically dependent because like, who doesn’t want their best vision?
0:41:14 Yeah, for sure.
0:41:19 And I’m going to keep saying this. It’s going to get annoying because I’m like a sweaty palm
0:41:24 fanboy, like jumping all over you. But I was very excited to chat with you also because I mean,
0:41:32 the nose, the eyes, these are sort of direct paths into the brain in a sense. And for instance,
0:41:36 I don’t know, I don’t expect you to track all things in all fields. That’d be impossible. But
0:41:44 cognitive therapeutics, it’s a headset that is used and they have a lot of good data. I think
0:41:51 they’re either phase two or phase three. They’ve raised a ton of money and it’s a headset and they
0:41:59 have these visors covering the eyes and then earpieces. And it produces, I want to say, gamma waves in the
0:42:06 brain. There’s more to it, but using flashing lights. And this appears to, I’m going to,
0:42:09 I’m getting into the sort of deep end of my ignorance pool here because I’m pulling from
0:42:16 memory, but it appears to assist in the breakdown of beta amyloid plaque, maybe tau as well. I’m not
0:42:22 really sure. So using flashing light to help people with conditions like Alzheimer’s. I mean,
0:42:28 it’s kind of mind boggling, I guess, literally and metaphorically. And that does come from credible
0:42:33 researchers. I wish I could cite them offhand, but it’s going to take me too much time to find the
0:42:40 scientists involved. But that is one that appears to be Ed Boyden and Lee Huizai out of MIT.
0:42:45 Yep. I know them both. Ed was a graduate student here at Stanford when I was at Stanford.
0:42:50 Oh, amazing. All right. Yeah. So there you go. Are we going to see more of these devices and how
0:42:56 far away are they? Because I’m seeing decline in my near relatives. I’m currently taking care of two
0:43:02 relatives with severe cognitive decline. It scares the hell out of me. And some of them are 3-3, by the
0:43:07 way, and I’m 3-4. So I’m like, good God. Okay. If there’s anything I can do, and I’m already doing
0:43:15 quite a few things, but are there other devices that are sort of on the cusp of being available that you
0:43:21 find interesting? Yeah, I think so. And input through the visual system and output through the visual
0:43:27 system are both looking really interesting these days. So you’re talking about input. Like what can
0:43:34 we stick in through the visual system to influence the rest of our brain? Brainwave activity, plasticity,
0:43:40 like we were talking about before, help preventing cognitive decline. There is very strong data,
0:43:48 for example, that if you give the right amount of electrical activity of our neurons in the eye and
0:43:52 the brain. So the neurons in the brain talk to each other through electrical activity, like little wires.
0:44:00 And too much activity is bad. I mean, really too much activity is epilepsy, for example. Too little is clearly
0:44:05 bad, too. If you have a stroke, then you’ve got no electrical activity in that area of your brain, and it’s just
0:44:12 not working anymore. But providing like kind of that sweet spot in the middle of electrical activity, in addition to
0:44:17 it participating in the processing of whatever that area of the brain does, like in the retin, it’s your
0:44:25 vision, obviously. It also stimulates pathways like plasticity and responsiveness to the survival and
0:44:33 growth factors. And we and others have shown that very clearly in animal research over the years, that you
0:44:40 need not just like the right growth factors circulating around in the brain, but you also need the right levels
0:44:45 of electrical activity so that the neurons are maximally responsive.
0:44:48 Yeah, it’s like weightlifting. You can have all the protein in the world.
0:44:49 Right.
0:44:50 You need the stimulus.
0:44:55 You’ve got to have the right amount, right? You’ve got to match that up. So it’s really cool. Like we actually
0:45:00 know in the eye, the visual stimuli, you were talking about flashes of light, but it turns out like
0:45:08 different cells in our eye respond differentially to different stimuli. We have some cells that fire when the
0:45:14 lights go on. We call those very creatively on cells. We have some cells that fire when the lights go off,
0:45:19 called off cells. We have some cells that are firing like between blue and yellow, others that are
0:45:24 differentiating between red and green. We have some cells that are in charge of motion detection in the
0:45:30 eye. And all that data has got to get back to the brain. But if we stimulate, for example, the motion
0:45:39 direction-sensitive retinal ganglion cells in our retinas in headsets, where we devise cues, you know,
0:45:44 basically imagine you’re flying through like kind of that Star Trek field of stars, you know, like you’re
0:45:50 going into hyperspace, right? And engage, and you’re going into hyperspace, and all those stars speed up by you.
0:45:58 Those are great stimuli for some of our direction-sensitive cells in the eye. And could those
0:46:05 actually stimulate those cells to then like perform better or not degenerate in disease? And so we’ve been
0:46:10 studying those kinds of questions. Cognito’s engaged in that kind of work. And then how does that affect
0:46:17 what’s going on in the brain? Very reasonable that that’s going to actually lead to specific patterns
0:46:22 of activity, flexibility, plasticity that are going to change our brains. And the idea that
0:46:29 some of that work can not happen only in the academic world, but that people are excited about
0:46:36 it and are funding the startup companies and taking that science into that kind of either health domain,
0:46:42 healthspan domain, or consumer domain. Like how do we get the normals protected against the future?
0:46:45 There’s a lot going on there. That’s on the input side.
0:46:52 Yeah. I am going to just bookmark that for a second. And I’m going to highlight a few things that I thought
0:46:58 were of interest, and I’d like you to expand on from your conversation with Andy. So glaucoma,
0:47:05 could you have a normal reading during the day, but higher at night? And then the potential place of,
0:47:10 you know, cannabis edibles. And my question there was, do we know what compounds are responsible?
0:47:12 Well, people are listening to me and they’re like, what the hell are you talking about? So
0:47:18 if that’s enough of a cue, would you mind just discussing that? Because, you know, a big challenge
0:47:24 with people who are trying to do the right thing, they’re trying to get checkups, they’re trying to
0:47:30 get assessed, they’re getting their blood work done, but maybe it’s once a year. And they had their
0:47:35 blood draws, you know, the last one was at 8am and the next one was at 11am. And lo and behold,
0:47:38 their testosterone is really different. They freak out and this, that, and the other thing.
0:47:43 So like timing matters among other things. Could you just speak to glaucoma in that respect?
0:47:49 Absolutely. So let me just back up one step. Glaucoma, after Alzheimer’s disease,
0:47:57 glaucoma is the most common neurodegenerative disease. It’s the number one cause of irreversible
0:48:05 vision loss in the world. It’s a degeneration of that optic nerve connection from the eye to the
0:48:11 brain. So those retinal ganglion cells that are collecting the data in the retina and their axon
0:48:15 fibers, those telephone wires running down the optic nerve carrying that all the vision from the eye to the
0:48:23 brain, they degenerate in glaucoma. If you take all comers, it’s around 2% of people in an aging
0:48:30 population that will have developed glaucoma. If you have a primary family member, a parent,
0:48:37 a sibling, a child with glaucoma, your risk probably goes up to about 20%. So it runs in families. But
0:48:42 just because your parent has it doesn’t mean 100% you’ll have it. There are two main risk factors
0:48:50 for glaucoma. One is increasing age. And we’re all working desperately on correcting that one, but we don’t
0:48:55 have a slam dunk treatment for that yet. The other main risk factor for glaucoma is actually
0:49:01 increasing eye pressure. If you have real high pressure, you’re going to get glaucoma. But a lot
0:49:06 of people with normal looking eye pressure can also develop glaucoma. It’s just like they were more
0:49:12 susceptible. And the eye pressure isn’t just the same number. We’ve got short-term variability and
0:49:16 long-term variability. So long-term is like, you know, this month it might be whatever number.
0:49:20 Next year it might be a little higher, a little lower. You know, you can vary through your life.
0:49:25 But there’s also this short-term variability. It actually varies in our diurnal cycle.
0:49:32 So everybody has a diurnal cycle where you, you know, your circadian rhythm, you know, and some of
0:49:36 us like myself are night people and we love to be up at night and getting up in the morning isn’t our
0:49:41 favorite thing. And other people are the opposite. And all this stuff relates to our diurnal cycle,
0:49:46 our circadian rhythm. You know, you can try to take melatonin and affect that. But your eye pressure
0:49:52 also varies by that. And as you say, like, if I take your eye pressure in the morning and then the
0:49:56 next week I take it in the afternoon and I say, oh my God, your pressure’s gone up. I got to take you to
0:50:02 surgery. Well, wait a second. It might just be because I’m measuring it different times. Now you brought up
0:50:07 like the most common question that I get asked. I’ll tell you the most common question that I get
0:50:14 asked by patients with glaucoma is, hey, can I take cannabis? And, you know, by the way, it’s like,
0:50:21 you know, legal for medical use in many states and frankly, recreational use also in many states and
0:50:28 certainly accessible in every state. Can I take cannabis? Cannabis, whether you smoke it or eat it
0:50:35 in the brownie or take the chewy, it lowers your eye pressure. If you’re using the version,
0:50:40 which are available that where, you know, you feel a little high from it, you know, you get that good
0:50:48 feeling. The problem is that it only really lowers the eye pressure kind of during that time that you’re
0:50:58 getting high. So I tell patients like it works, but you’d have to be high 24-7. So maybe you should
0:51:07 just use this eyedrop instead, right? Do we know which compounds within cannabis are responsible for
0:51:13 the lowering of the eye pressure? Yeah, there’s actually data that both the THCs that do get you
0:51:18 high and the others also that don’t can have that effect. And there’s some cool startup companies
0:51:24 that have been working on trying to isolate and now test in human patients the you-don’t-get-high
0:51:30 versions of those compounds or chemically modifying them. And by the way, turning them into an eye drop
0:51:35 so that it’s really just treating the eye and make that really accessible. You know, you don’t want
0:51:41 to be on your glaucoma treatment and not able to drive. So, you know, it’s got to be compatible
0:51:47 with daily life for most patients, right? So that does work. That does work. Yeah. The second most
0:51:53 common question I get asked is, well, can’t you just like fix my eye or give me stem cells or that
0:51:58 kind of thing? But number one is cannabis. Well, what’s your answer to the stem cells? The magic
0:52:01 stem cells. We’re down there on stem cells. Like, so if you’ve lost your retinal ganglion cell
0:52:07 connection to the brain through the optic nerve, we’re actually getting pretty good at growing retinal
0:52:11 ganglion cells out of human stem cells, like in the laboratory cell culture dish. And we’re
0:52:16 actually starting to make real progress, you know, in animal models to start showing that you can
0:52:21 transplant them in. But I still tell patients, like, don’t go to some clinic that’s telling you
0:52:26 they’ll give you stem cells and pay $18,000 of your hard-earned money. It is not ready for that yet.
0:52:28 Go to Tijuana and get a new pair of eyes.
0:52:29 Exactly. Don’t waste your money.
0:52:34 Well, yeah, that’ll be the least of your problems. It won’t be the money part.
0:52:39 So let me circle back to the cannabis for a second. So I don’t consume much cannabis, but
0:52:46 I have experimented with cannabis for chronic pain and specifically a number of back issues that I have.
0:52:50 And some of it’s congenital. I have a transitional segment and a bunch of arthropathy and blah, blah,
0:52:55 blah, blah, blah. And interestingly, a lot of folks, including people who are sort of credible and
0:53:02 familiar with the literature, recommended CBD. But I did not find it to have a pain-relieving effect
0:53:07 that was sufficient for sleep until adding a little bit of THC, which I thought was actually
0:53:14 pretty interesting. And I’m wondering if, and this actually cycles back to our very short discussion
0:53:21 of psychedelic compounds also, because why might psychedelics, say, improve visual acuity?
0:53:27 You can come up with a dozen sort of plausible explanations. But when you look at, say, the
0:53:36 depression outcomes with psychedelics, people in many different parties in terms of arguing why or
0:53:41 how they exert their effect, one that I think is under-emphasized is the anti-inflammatory effects,
0:53:47 which can be potent in some psychedelics. And you can find studies where they look at anti-inflammatory,
0:53:52 or just standard off-the-shelf anti-inflammatory effects on depression, which can be substantial.
0:54:00 Do we have any data to suggest that anti-inflammatories have any effect on vision or can in any subpopulation
0:54:01 improve vision?
0:54:09 Decades ago, there was a pretty hot focus on to what degree the immune system might be playing
0:54:15 a role, particularly in eye diseases, including the common ones, macular degeneration, glaucoma.
0:54:21 Then it was hard to pull that together, in part, I think, because we didn’t know as much about the
0:54:27 immune system 20, 30 years ago as we do today. And now we know a lot about what we call the innate
0:54:33 immune system, which is not the part that learns about the flu virus and makes you immune the next
0:54:38 time you get the flu virus, but just how our immune system interacts with our body normally,
0:54:46 and how it also might interact with, you know, our gut bacteria, and then cross-react with
0:54:53 our own body, things like that, right? And so it turns out now that we’ve got this much deeper
0:54:58 appreciation from the whole immunology crowd about how the immune system, and in particular,
0:55:05 the innate immune system works, we’re now revisiting in neurodegenerative diseases, including glaucoma,
0:55:12 macular degeneration. And it turns out it is just packed with evidence that the immune system and
0:55:20 innate immunity really play a role. Let me give you one example that is shocking. If you raise the eye
0:55:28 pressure in a mouse, the retinal ganglion cells and the optic nerve will degenerate just like in human
0:55:34 glaucoma. But in a really beautiful set of experiments that came from a woman, a professor
0:55:41 at Harvard, Dong Feng Chen, she showed that if you raise the eye pressure in a mouse that was raised
0:55:47 itself, grew up in a germ-free environment, and doesn’t have kind of all the normal mouse dirty gut
0:55:54 bacteria, and therefore its immune system is at some level fundamentally different, you can raise the
0:55:59 eye pressure in that mouse, but the optic nerve won’t degenerate. They won’t get glaucoma damage.
0:56:05 And then if you take the immune cells out of the first mouse and just put them back into the bloodstream
0:56:12 of the second mouse, then the optic nerve will regenerate. So the immune system is playing a huge
0:56:20 role that was previously totally underappreciated, and there are amazing drug therapy candidates that are
0:56:26 now moving up through the pipeline in towards human testing to test, hey, if we could suppress the immune
0:56:32 system, not totally suppress it, because by the way, we still want to be attacking bacteria and
0:56:39 viruses, but just suppress the little leg of that immune system that’s attacking our body and leading to
0:56:42 neurodegenerative disease, that’s going to be off the charts.
0:56:50 Yeah. You know, I was, as you were talking about the microbiome and so on, I was doing a bunch of
0:56:56 reading for another interview I’ll be doing shortly with the scientist, and one of the stories, and this
0:57:01 is in animal models, of course, but looked at how, and some people have heard through the grapevine,
0:57:09 one way or another, how you could take the microbiome, just for simplicity’s sake, of, say, obese mice and
0:57:15 transplant that to lean mice, and they get fat, or vice versa. I might be getting some of the details
0:57:23 wrong, but roughly you see some very interesting effects. However, if you sever the vagus nerve in
0:57:32 those recipient mice, they do not exhibit those changes. Then some of the questions that are kind
0:57:37 of outstanding is, well, if that indicates that you could, instead of using like ablation or severing
0:57:43 something, stimulation to achieve a similar effect, then what can you start to do? Then you have like
0:57:50 hockey puck size things that you put next to the liver that can, you know, via some technological
0:57:56 wizardry affect these things. But I suppose the more I look at a lot of these things, also with
0:58:02 family with Alzheimer’s, and they might take something like Theracurman, which has, on some
0:58:07 level, anti-inflammatory effects. I’m like, okay, and I don’t want to be a one-trick pony with like
0:58:11 the one thing I keep beating over the head, but it’s like, okay, well, if we know that chronically
0:58:16 inflamed, like microglia, have all of these hosts, or at least they’re associated with a host of
0:58:22 different neurodegenerative diseases and inflammations associated with depression, to what extent can we
0:58:27 mitigate these things? And we’re sort of hitting a bunch of birds with one stone, which is why I’m so
0:58:36 interested in the possibility of using devices. I’m so interested in nutritional ketosis, but also
0:58:42 exogenous ketones. Brain loves this stuff. Also, beta-hydroxybutyrate, very potent anti-inflammatory.
0:58:48 I’m just wondering, do you think that I am just too clever by half and I’m like missing the plot
0:58:54 here? I feel like chronic inflammation, which is kind of like saying business or the arts, right? I mean,
0:58:58 there are like a million different facets to inflammation. You need inflammation for a lot of
0:59:06 reasons. But when it is pathological and chronic, it turns into a big issue. With rapid decline in
0:59:13 eyesight, let’s just say in glaucoma, how often is that comorbid with metabolic syndrome or something
0:59:22 like that when the decline is faster than say average? The earliest data looking at, let’s say
0:59:27 diabetes as a marker of, you know, a lot of patients with type 2 diabetes, it’s associated with what we
0:59:33 call metabolic syndrome, which is this cluster of high lipids, high blood pressure, insulin resistance,
0:59:39 right? And so there was initial data suggesting that a little bit of diabetes might actually be like a
0:59:45 little protective in glaucoma. And then some of the follow-up, like next set of studies suggested like,
0:59:50 no, no, no, maybe it’s a little bit bad for your glaucoma. And so the net-net is it’s probably not
0:59:55 metabolic syndrome as a whole is probably not a huge difference, but I’ll tell you the place where
1:00:03 those two are converging is one of the hottest topics in medical science today, which is these
1:00:12 GLP-1 receptor agonists, which are going to have a huge effect on human health by reducing metabolic
1:00:21 syndrome, overweight, obesity, etc. But also are looking very promising for neuroprotective. And I think it
1:00:25 actually gets to that point, you know, you’re trying to tease yourself, like, are you just like kind of
1:00:31 getting ahead of it? But actually, you’re touching on, I think, where we’re actually coming to as an
1:00:36 understanding as, you know, where the science is going in the field, which is this axis between
1:00:42 the brain, which you think of like, well, isn’t that mostly inside my head, but also the peripheral
1:00:47 nerves that are going out to the whole rest of our body and the immune system. And those two are talking
1:00:53 to each other all the time. And now we’ve got the microbiome and that gut axis is like a third leg of
1:01:01 that stool because that’s clearly also interacting with both the nervous system and the immune system
1:01:07 in very specific ways. So we’re going to see a lot more of that really, I think, come together and
1:01:13 understand more mechanisms. You know, is it going to be one day that we’re all just kind of taking that
1:01:19 like purified poop pill that we just swallow down and it changes our microbiome for the day and it protects
1:01:24 us from Alzheimer’s or glaucova in the future? We’re all hoping that’s going to happen. We’d love
1:01:30 that protection one day. You know, should you buy the poop pill off the internet just yet? I’m not sure.
1:01:38 Yeah, Sri Lankan poop pills from rural children. I’m in. Yeah, you’d be careful with what’s out there on
1:01:42 the internet, guys. And, you know, I’m supporting a company, I might have to bleep this out, but called
1:01:49 Holobiome. And they’re actually creating the most comprehensive library currently of gut microbiome.
1:01:53 because it’s like what you can buy currently off the shelf. First of all, most of it’s dead,
1:01:58 but it’s like inert by the time you consume it. A lot of it doesn’t actually get through
1:02:04 your metabolism to where you want it to be. And it only represents maybe in some, a few dozen,
1:02:10 I don’t know if the right term is strains of bacteria, whereas there’s like thousands upon
1:02:14 thousands. So there’s so much to explore, which is also very exciting.
1:02:18 Let me give you one more idea of what might be that ideal world on the way to that.
1:02:26 We share microbiomes between us. Actually, we had our, like at Stanford Med School years ago when I was
1:02:35 there, we had a microbiology professor and he used to kind of tease, the world is covered with a thin
1:02:42 layer of poop. Because no matter how well you wash your hands after going to the bathroom, like there’s
1:02:47 a couple bacteria that got on your hands or your belt buckle and you’re, you know, and then you shake hands
1:02:52 or pack someone on the back. I don’t want to increase anyone’s anxiety, but the world is covered.
1:02:54 This episode is brought to you by Purell.
1:03:02 There’s a thin layer of poop. What we call clean and dirty, he used to say, is really just how thick
1:03:11 that layer is. Okay. So that joking aside, if you just shack up with someone who’s got great longevity
1:03:18 and probably a great microbiome, a good chance you’re going to absorb their microbiome. Maybe
1:03:25 that’ll be good for you. I got to put that on the dating websites, you know, get your microbiome on
1:03:32 that profile. Craigslist, microbiome casual encounters. So this is going to be a bit of a
1:03:40 hard left, but preservative free strips of tears for dry eye. Why? That was one of my notes from
1:03:44 the conversation that you had with Andrew, because I’m also looking for just low hanging fruit for
1:03:50 people who are contending as we all do with aging eyes. Maybe you could speak to that. And then I do
1:03:55 have to ask about the blood serum for eye drops. Maybe you can hit that too.
1:04:05 Sure. Sure. So look, actually the most common eye disease as we get older is actually dry eye. As we
1:04:11 get older, we make fewer tears. We also make lower quality tears. Our tears at high quality have a
1:04:17 liquid phase, like a water, saltwater phase. There’s also like an oily component to good high quality tears.
1:04:23 And that oily component also kind of dissipates a little bit as we get older, gets less as we get older.
1:04:31 So we make fewer tears and lower quality tears. And a real simple over-the-counter solution for so many
1:04:38 people is just put in some artificial teardrops. The thing is, is that those little bottles come with
1:04:42 preservatives so that, you know, when you use it all month, by the end of the month, it’s not growing
1:04:50 bacteria. And if you’re just using a drop or two a day, fine. That’s getting you by, fine. Just buy
1:04:55 those bottles. They’re the cheapest. But if you’re getting to the point where it’s three, four, five,
1:05:00 six times a day, you like, you know, maybe you work on the computer a lot. So you blink less and your eyes
1:05:06 get drier. You want to use more of those. Then we usually recommend at that stage, switch over to
1:05:12 preservative-free artificial tears. Because it turns out that preservative in those bottles of
1:05:18 drops, at a drop or two a day, fine. But if you’re getting up to a lot of drops a day, the preservative
1:05:24 is actually irritating and kind of inflammatory to the ocular surface. It actually kind of breaks down
1:05:30 some of the cells on the surface of our eyes. So at that point, we like to switch people to
1:05:35 recommending the preservative-free. They’re the ones that come like, usually they come in like a little
1:05:40 strip of tiny little plastic. You break one off. It’s got its own little cap on it. It’s got this
1:05:46 tiny little bubble of fluid that you can squeeze. It really tests, you know, if you’ve got bad fingers
1:05:50 or bad, you know, by the way, if you’ve got bad vision, you’re poking yourself in the eye with it.
1:05:56 So anyway, that’s what we recommend. Switch the preservative-free. And then people who need more than that,
1:06:03 we actually have drugs that, for example, reduce inflammation on the ocular surface to help
1:06:09 the tear quality and quantity bounce back a little bit. And then we also have drugs that
1:06:16 contain growth factors, things like nerve growth factor that are almost certainly also good for
1:06:22 the surface. And when our eyes get dry, the surface, the reason it feels irritating is not just because
1:06:26 it feels dry. It’s actually because the surface starts to break down a little bit. And when you go
1:06:31 to sleep every night and your eyelids are closed and nothing can evaporate, you know, it bounces back
1:06:36 a little bit by morning. So it kind of regenerates or rejuvenates. The ocular surface can regenerate
1:06:43 pretty well every day. But at some point, your eyes are getting dry enough that you’re having much more
1:06:50 chronic problems. And that’s where sometimes we can use what are called serum tears. So our blood serum,
1:06:55 if you take out a blood, like a tube of blood, you’re getting your blood drawn, that tube of blood
1:07:01 has your red blood cells carrying all your oxygen, your white blood cells, which is like your immune
1:07:06 system, and then all just the liquid with the proteins in it. That’s what we call the serum.
1:07:09 That’s the serum. So you could take that tube, you spin the cells out.
1:07:13 Let me ask a dumb question. Is that different from plasma? Are we talking…
1:07:17 Serum and plasma, yeah. Depending how you treat some of those proteins, that’s serum and plasma.
1:07:20 Let’s just say you’re spinning out the cells.
1:07:20 Yep.
1:07:26 And then you can take that serum. Maybe you dilute it a little bit in some of that preservative-free,
1:07:30 you know, artificial tears. Maybe you just use it straight. Usually we dilute it a little bit.
1:07:38 And we can give patients their own serum as artificial teardrops. And that serum is filled
1:07:46 with really good, juicy growth factors that help the surface rejuvenate. And that’s the principle of,
1:07:48 in some patients, using serum tears.
1:07:56 Maybe this is just a difference in terminology, but it makes me think of platelet-rich plasma or
1:08:02 platelet-poor plasma. Are there experiments with different, I’m not sure, concentrations or
1:08:04 cocktails?
1:08:09 Different cocktails. That’s a great way to put it. Yeah. And platelet-rich plasma, again,
1:08:14 one of the reasons that that looks so rejuvenating for our bodies is, again, it’s just like
1:08:21 chock-a-block full of growth factors. And so I don’t know, I’m sure somebody’s testing this
1:08:27 as another way to treat really severe dry eye. Or if your dry eye is so bad, you’re actually
1:08:33 getting like kind of ulcers on the surface of your eyes. Some of the most severe cases might really
1:08:40 benefit from, like serum tears, maybe platelet-rich plasma would work too. So that’s a hot area right
1:08:42 now. And again, filled with growth factors.
1:08:49 We talked about the importance of timing with, say, glaucoma exams, things of that type.
1:08:56 What are some other recommendations for perhaps avoiding common mistakes or filling gaps that are
1:08:59 commonly unfilled? Any recommendations to folks?
1:09:04 There’s a bunch of things. First of all, get an exam. And if you have a family member or blood
1:09:10 relative with eye disease, maybe get that exam even sooner. Take glaucoma as an example. If you
1:09:14 got an exam and you’re 40 and you don’t have a family history and your exam was normal, you don’t
1:09:19 have to come do that full exam every year. You can come back in five or 10 years, try it again.
1:09:23 But especially as we get older. Now, half the people in the world need glasses. Half the people
1:09:29 in the U.S. need glasses. So you might be going into your local eye care provider, optometrist,
1:09:33 getting your glasses checked each year or two anyway, just to see if you’re still in the right
1:09:39 prescription. And they can do the full exam, check for everything else, make sure nothing else looks
1:09:46 suspicious, leave you in great shape. So getting that periodic eye exam, especially as we get older
1:09:52 and more of those age-related diseases like macular degeneration, glaucoma, etc. Obviously,
1:09:57 if you have diabetes, you’re supposed to get an eye exam every year just to make sure because if you’ve
1:10:01 got diabetes and it’s starting to affect the retina inside your eye, we could get ahead of that.
1:10:06 We’ve got good treatments that can prevent you from losing vision. So we want to stay ahead on these
1:10:11 diseases. That’s the main thing. Other things, everyone’s going to get cataracts eventually,
1:10:19 but what can we do to slow down the development of cataracts? Well, one real easy one is reducing
1:10:26 UV light exposure. So you’re out in the sun a lot, wear sunglasses. All sunglasses made today
1:10:32 have UV protection. By the way, all regular glasses that don’t have darkened, tinted shades,
1:10:38 they also block the UV light from going through. So even if you’re wearing your regular glasses outside
1:10:45 because you need glasses, that works too. So wear sunglasses or some sort of eyewear protection.
1:10:50 And then eyewear protection is another big one, depending what industry you’re in. You’re gardening,
1:10:57 you’re in steelworks, you’ve got anything where you’ve got eye injury risk, wear protective eyewear.
1:11:03 It costs like $1.50 at Home Depot to get those really attractive plastic glasses that are wrapped
1:11:10 around. But wear them when you’re in those work situations, that’s a big one too. You see a lot
1:11:14 of athletes now wear eyewear, and sometimes it’s for sun protection, but you’ll see a lot of them when
1:11:19 it’s not that sunny day or they’re even playing inside. And they might be wearing it for prescription,
1:11:20 but also just for eye protection.
1:11:26 Eye protection. Is there anyone out there, and I don’t have a dog in the fight, it’s just that this
1:11:34 conversation around sunlight and exposure is like a religious war online. Is there anyone you would
1:11:42 consider scientifically credible who has any counter argument with respect to UV light? Why it is
1:11:51 important to also get natural exposure or could be important to get exposure to UV light? Or does that
1:11:55 just not exist? Is there a strongman argument for that, or does it just not exist?
1:12:00 I don’t ever want to say something doesn’t exist because there’s someone on the internet.
1:12:03 Well, right, which is why I say scientifically credible.
1:12:10 But no, full spectrum light, white light that goes from violet through red, full spectrum light,
1:12:16 there’s a lot of decent evidence that that’s good and important. By the way, let’s come back to the
1:12:21 development of nearsightedness. You know, we used to say like, oh, maybe people are getting nearsighted
1:12:25 as kids because they’re spending too much in times indoor reading. And so it’s just like too much near
1:12:30 work is leading to nearsightedness. There’s now pretty good data, actually, that it’s not the near work,
1:12:36 it’s the being inside part of reading inside. And if you just send your kid outside and let them read
1:12:41 outside in full spectrum lighting, they could still be doing their near work, doing their homework,
1:12:46 whatever it is. But it’s the full spectrum lighting that will actually slow down their development of
1:12:57 nearsightedness. So you can get full spectrum white light, but skip the UV by either having full spectrum
1:13:02 lighting indoors or through the window and you’ve got a nice sunny window. The sun that comes through
1:13:08 the window, the glass actually filters UV light. So that’s fine. Your car window filters UV light. So
1:13:12 even if you’re not wearing sunglasses inside the car, you’re getting that full spectrum sunlight.
1:13:19 Go outside in the morning, fine. You know, get that first sunlight if you want. But there’s no data
1:13:24 that suggests that part of that full spectrum light has to include UV light.
1:13:32 Okay. Got it. What do you think, and I know that this might be asking a lot, but what do you think we
1:13:40 might be getting wrong currently in any paradigm of how we think about vision or eye health? I mean,
1:13:46 I have a lot of doctor friends, a lot of researcher friends, and I guess it’s especially common among
1:13:49 MDs, but they’ll say, yeah, 50% of what do we know is wrong. We just don’t know which 50%,
1:13:55 which doesn’t mean science is an important guys, by the way, it is incredibly critical for not fooling
1:14:01 ourselves. And I don’t think I need to preach that to you, but what would you not be surprised to see
1:14:08 be overturned in the next five years? If you were like, you know what, we’ve always thought X. And it turns
1:14:19 out, nope. I’m going to pull one out of my personal favorites list for this. And it comes back to these
1:14:27 big ticket eye diseases like glaucoma, macular degeneration, even diabetic retinopathy, and other less
1:14:34 common versions of these degenerations, let’s say, of the retina, the optic nerve. And we have
1:14:41 always said, I mean, I even said earlier in the podcast with you, Tim, that glaucoma is the number
1:14:48 one cause of irreversible blindness in the world. And that I think is going to be the piece that we
1:14:53 overturn. We have always said like, hey, we got to prevent you from losing vision. We got to slow down
1:15:00 the disease because once you’ve lost whatever vision you’ve lost, I can’t get that back for you.
1:15:11 And I think that is about to topple. We are about to get into vision restoration at a level that has
1:15:22 been totally unexpected and totally unprecedented. And the science supporting these directions in these
1:15:31 diseases is getting really, really juicy. We have discovered so many molecular pathways,
1:15:36 approaches to cell therapy. Some of the things we even talked about earlier, like inducing plasticity
1:15:42 in the brain. If I stick a stem cell into the adult retina and I say, hey, I need you to turn into a
1:15:50 retinal cell, hook up with your partners and start doing vision. Well, during development, the retina,
1:15:58 those cells are all developing. They learned to wire up together, do it right. How do we get a cell that
1:16:04 we’re going to put into an adult person to say like, hey, I know all you other retina cells are already
1:16:10 neighbors with each other, but I’m moving into the neighborhood and I want you to accept me. But we’re
1:16:16 figuring out how to induce that plasticity, like open up the neighborhood, let that cell get into the
1:16:24 network, start to participate in the network and restore vision. So it is moving really quickly
1:16:29 right now. And it is starting to translate. This laboratory science is starting to really move
1:16:39 quickly into appropriate, safe human clinical trials. And so I think that is going to be the biggest topple,
1:16:45 is going to be that we can restore vision. And I will not be surprised if our colleagues in the brain
1:16:51 follow suit quickly. You know, we like to tease who’s going to come first, the eye or the brain.
1:16:57 I will not be surprised if our colleagues in the brain follow quickly. And maybe we could restore
1:17:03 cognition in people with severe cognitive disease, Alzheimer’s and these others. So
1:17:11 I think this kind of restoring the central nervous system, including the retina and optic nerve,
1:17:18 spinal cord injury, I think this is all, we’re going to topple that in these next few years.
1:17:21 Well, it’s very exciting. And I also, when I talk to folks, I’m like, look,
1:17:25 I know it seems like one day they’re like, bananas will kill you. And the next day,
1:17:28 like bananas will help you live forever. And it’s like, first of all, a lot of that is
1:17:35 funhouse mirror warping by media coverage. And secondly, there are so many breakthroughs or
1:17:42 breakthroughs that are on the cusp of making their way into clinical practice. I can’t help but be
1:17:48 super optimistic about so many, at least the fields that I have decent amount of exposure to.
1:17:52 And I’m going to ask you a few follow-up questions. But first, I’ll just say for people
1:17:58 interested, if you are interested in looking at how, for instance, and there are multiple ways to
1:18:04 induce greater plasticity in various ways. But if you’re interested in the reopening of critical
1:18:11 periods, which we alluded to earlier, Gould Dolan, who was at Hopkins and is now at UC Berkeley,
1:18:18 has done some wild work and has really rocked the boat in, I think, a very productive way looking at
1:18:26 how MDMA, but also potentially other compounds can potentially do that. And she’s got wild experiments
1:18:34 with octopuses and all this stuff that people should check out. But I believe that at some point,
1:18:40 if she’s not already doing it, she’s going to look at, for instance, using these compounds to help
1:18:47 stroke patients recover motor function. And there are also devices like DARPA and the Defense Language
1:18:54 Institute in Monterey have used for improving language acquisition. I mean, I really feel like there’s a lot of
1:19:02 stuff that is not only happening, but converging in interesting ways. What leads you to believe that
1:19:07 we’re so close? I mean, the next five years is close, right? So is it just the publications you’re
1:19:15 seeing, the types of science that is being done? Is it new and novel ways to induce plasticity? Is it
1:19:19 because the eye people are playing nice with the other brain people? What is actually happening?
1:19:24 You know, I was teasing before, but the truth is like, we eye people love to work closely with our
1:19:30 colleagues in brain because there’s so much shared science. I do think that there’s an increasing
1:19:37 attention to, hey, let’s answer these questions properly. Let’s do proper trials. Let’s really
1:19:42 study these things properly. And let’s also move things out of the laboratory and into human testing,
1:19:46 right? And have it not just be like kind of the fantasy and the mice, but never move it to the
1:19:52 person, right? And so I think that transition, that willingness to grow in that direction,
1:20:03 we’ve had actually, to be honest, like a remarkable two to three decades now of increasing support for
1:20:08 science, you know, at the federal level, but also startups. Biotech has had an amazing age.
1:20:13 And that biotech, you know, when you’ve got an amazing age cooking on the pharma side,
1:20:17 like big pharma, you know, that then trickles down. So that means startups can say like, hey,
1:20:24 let’s roll the dice and test this anti-aging formula because if it hits, there’s a market for it at the
1:20:30 end of the day. Like this is important. These are big impact areas. So I think the investment that we
1:20:36 make in science, and we’re sort of like coming to a head, a culmination. And I think that happens to be
1:20:42 matching in time, the advances we’ve been making in neuroscience. You know, I think we made like
1:20:49 huge advances in immunology and cancer biology a couple decades ago, like even just understanding
1:20:54 what all the cells are. And I think that the analogy is the advances we’ve made even just in the last
1:21:00 decade of being able to like map the brain, not just even down to the cell level, but the cell-cell
1:21:08 connections called synapses. We’re now mapping entire brains at that level and understanding
1:21:13 how they talk to each other and recording and creating. We’ve got a colleague here who just had
1:21:20 an amazing suite of papers, Andreas Tolias and his colleagues, creating a digital twin of the entire
1:21:27 brain. And then you can do experiments on the digital twin of the brain. You don’t have to actually do them
1:21:33 on an animal or a person to start. You could start there. So the advances in neuroscience and
1:21:40 understanding of plasticity and all of these elements, I think are converging with the advances
1:21:46 that we’ve just been willing to make over the last couple of decades in healthcare, health-related
1:21:54 research, discovery research, translational research, clinical trial research. And I think we’re just kind of
1:21:57 seeing those two converge right now in an amazing way.
1:22:03 If you don’t mind, let’s talk about mitochondria again for a second. So mitochondria, often referred
1:22:09 to as the powerhouses of the cell. I won’t bore people with more ketone talk, but also read a piece
1:22:15 recently from a very credible scientist, beautifully written also, about how they’re not just the powerhouses,
1:22:20 but maybe the motherboards of the cell. And there’s actually a lot of what you could view as social
1:22:29 interaction between mitochondria and among mitochondria. Really, just the deeper you go,
1:22:32 the more interesting it becomes. And I’m wondering outside of the red light,
1:22:41 if there are other interventions or technologies, biologics, anything that you think are interesting
1:22:46 for improving mitochondrial health within the visual system, however you want to take that.
1:22:52 Mitochondria, not only are they social with each other and they actually talk to each other,
1:22:59 they actually fuse and then separate. They get trafficked up. Neurons, we talked about the ones
1:23:03 that stretch from the eye to the brain. There are neurons, of course, that stretch from the top of our
1:23:07 brain all the way down to the bottom of our spinal cord. There are neurons that stretch from our spinal
1:23:12 cord all the way down to our toe tip. These are some long cells, right? And they’re trafficking
1:23:19 mitochondria all up and down. So they are social creatures for sure. But it turns out they’re yet a
1:23:25 third thing. So they’re powerhouses, they’re social creatures, but they’re also scaffolds. And they’re
1:23:34 actually like kind of the foundation upon which a lot of other cellular signaling that’s regulating what a
1:23:42 cell is supposed to do is happening on the surface of the mitochondria. So you got metabolism, energy,
1:23:51 scaffolding of signaling. And so no wonder half of our neurodegenerative diseases are associated with
1:23:57 one or another defect that we can trace back to mitochondria. So that kind of adds up at the end
1:24:01 of the day when you look at it that way. And some of the things we’ve already talked about, I mean,
1:24:08 you brought up red light therapy, that would be one for sure. But vitamin B3, nicotinamide,
1:24:14 it’s directly affecting some of that metabolic signaling that is interfacing with the mitochondria
1:24:24 metabolism biology. And so actually a lot of these supplements that are about metabolism end up having
1:24:28 some link back to mitochondria. Yeah, I was going to say, it’s kind of hard to dodge the mitochondria.
1:24:34 Yeah, yeah, yeah. And look, it’s cool. Look, I mean, I just read that they’re now doing successful
1:24:42 mitochondrial transplants, like for example, into an embryo. So you can have inherited diseases where the
1:24:49 disease is inherited because your mitochondria are bad. Mitochondria get most of their proteins and lipids
1:24:53 and all of that that make up a mitochondria. They got most of that built from the nucleus,
1:24:58 the regular DNA of the cell. But they have a little bit of DNA themselves that makes some of
1:25:05 the proteins inside the mitochondria. And so you can inherit that mitochondrial DNA that has mutations and
1:25:12 have real serious diseases. It’s now been shown you can transplant mitochondria so that baby will not
1:25:19 have an inherited mitochondrial disease. Is it that far off to think that we could like transplant
1:25:27 mitochondria into the retina of your eye and stave off another decade of glaucoma? These things are on
1:25:33 the table. So definitely on the table. Wow. Okay. So I saw some news about, I think, you can’t trust the
1:25:38 headlines, but basically babies with three parents, so to speak, out of the UK. Now, so you mentioned
1:25:44 embryo. So this is a case where you’d be taking third-party mitochondria. You’re hitting it. That’s
1:25:51 exactly what I was talking about. So you got DNA from the mom in the egg cell. You got DNA from the dad
1:26:00 in the sperm. But you could take a third party’s mitochondria outside of their cell, inject it into
1:26:06 that egg, just like the sperm went into the egg. And now that egg with mom and dad’s DNA and a third
1:26:13 person’s mitochondria, including their mitochondrial DNA, will propagate and form the whole embryo. And
1:26:16 it’s an amazing headline. Like, does that mean there’s three parents involved?
1:26:22 I mean, it’s equally fascinating when you just understand what you’re describing.
1:26:29 And part of the reason I’ve been reading and really trying to do a deep dive, always dangerous when you
1:26:35 are only half scientifically literate, but on my mom’s side of the family, a lot of Alzheimer’s.
1:26:41 And my mom’s had some deterioration as well, but she’s APO33. And also just word to the wise,
1:26:45 again, not a doctor. Talk to your medical professional. But if you’re trying to evaluate
1:26:52 your metabolic health, don’t just get fasting glucose taken because you can get lucky with
1:26:58 fasting glucose. And you might even do hemoglobin A1c, which is like a running three-month average of
1:27:01 your fasting glucose. This may be a simple way to think about it, something like that.
1:27:08 But also get your insulin measured because that was missed by my mom’s local doc for many,
1:27:14 many years. And her fasting glucose, even her hemoglobin A1c was kind of within tolerable levels.
1:27:20 And then her insulin was, it was so out of range as to just jump off the page.
1:27:24 And so then I was looking at it and there, of course, could be a million different contributing
1:27:32 factors. But I was like, I wonder if there’s some type of issue in her mitochondria, in which
1:27:37 case my understanding is you do inherit the mitochondria from your mom’s side is my understanding.
1:27:42 And I was like, okay, well, if that’s the case, I’d like to, I don’t know if there’s anything to be
1:27:50 done about it at this point, frankly. But if there is even a small possibility that you could do
1:27:55 something about it, I’m like, well, I’d like to kind of know what I’m dealing with. So that’s the
1:27:59 genesis of me asking about also the mitochondrial health side of things.
1:28:05 Yeah. We don’t have like a great blood test for your mitochondria yet, but obviously you could get
1:28:13 it sequenced. We don’t know how much, you know, like your fidelity to mom’s mitochondria might play
1:28:18 a role in your future cognitive health. I would add to your list though, two other standard screening
1:28:25 tests that certainly are likely to impact your cognitive health as you age. And with that, again,
1:28:30 the eyes part of the brain, your visual health too. And that’s going to be your lipids,
1:28:38 your fasting lipids, and your blood pressure. And, you know, like every bit of science points to,
1:28:45 yes, you can inherit it, your APOE genes that can change your risk, but a very big contributor is going
1:28:50 to be your lipids and your blood pressure, because those are going to contribute to what we call
1:28:59 microvascular disease and ultimately brain atrophy as we get older and ultimately cognitive function.
1:29:05 And if you could be really ahead of the curve and be really clean with your lipids, whether that’s
1:29:11 with diet and exercise or upgrading to some of the medicines that help with that and really clean with
1:29:17 your blood pressure, again, diet and exercise, or there are medicines we can give to help with that.
1:29:25 But staying ahead of the curve on those is almost certainly a huge contributor to your later cognitive
1:29:25 health.
1:29:32 I’ve got those suspects under control and very well dialed. I’m just like, are the mitochondria the
1:29:36 boogeyman in the closet that I’m not contending with? But yeah, I’m trying to do all the stuff you
1:29:42 would expect to also help support mitochondrial health. And I don’t think this is immediately
1:29:50 obvious. People think of exercise as body exercise, but if you want to increase the brain-derived neurotrophic
1:29:56 factor release and clotho release, which hopefully someday soon we’ll have as an injectable therapy
1:30:04 for humans, exercise, you got to do it. Do some weight training, do some zone two, do a VO2 maximum once in a
1:30:07 while. It’s incredibly valuable.
1:30:11 And I think the important thing for listeners is that, and when I say listeners, I include myself
1:30:17 because I intellectually know I need to do more exercise and, you know, I still got to figure out
1:30:21 how to get around to actually doing that more exercise. So, so I’m in the listener crowd here of
1:30:28 what I need to say, but the important thing to remember is that the biggest gain comes from going
1:30:36 from none to some. Yes. If you go from some to twice as much, yeah, there’s an improvement there
1:30:45 too, but not as big as the value proposition of going from none to some. Yeah. Yeah. Just scale it
1:30:50 down guys if you have to, but don’t do nothing. Don’t do nothing because you feel like I’m not, I can’t do,
1:30:56 I can’t do a million hours. So I’m throwing in the towel and I can’t, I won’t do any, you know,
1:31:02 half an hour, four or five days a week, brisk walk at that heart rate up, have it count, you know,
1:31:09 easy, you know, like make it easy on yourself. If you want to then go nuts and do like hardcore
1:31:14 weight training, hit your Peloton, have your trainer, you know, train for a marathon. Okay, fine.
1:31:19 But that biggest difference in your life was going from none to some.
1:31:24 Can I give you the greatest non sequitur in the history of my podcast? It’s just because you
1:31:31 mentioned that your number one, most common question was, can I have cannabis? So I’m lucky
1:31:37 to know a bunch of very amazing docs and blah, blah, blah. You know, I interview people, so I get to meet a
1:31:43 lot of fascinating folks. And one of these super high end, really sophisticated docs, he was telling me
1:31:49 the most, can you guess, I’ll give you a shot. I’ll give you a shot on the three pointer. What
1:31:53 do you think has, I’ll be astonished if you guess this, because even if you believed it, you probably
1:31:58 wouldn’t say it, but what do you, what do you think is most, one of his most common questions is that he
1:32:02 gets that, that he still refuses to answer publicly. I’ve wanted him to do it.
1:32:06 Oh my God, this is a guess what you’re thinking. You’d better, you know, as when we’re in training for
1:32:11 medicine, we get asked questions like this all the time. And some of them are like, okay, I want you to
1:32:16 guess what I’m thinking. Go ahead. Three trial. No, no. All right. Let me say, lay it on, lay it on.
1:32:22 What did he say? This is the question he gets all the time, which is from male patients. How can I
1:32:30 shave my balls safely? This is the question he gets more than any others. Like, really? I’ve done all
1:32:35 this training. I’ve done all this. And that’s the question that I get more often than not. Anyway,
1:32:39 I don’t know why I feel compelled to share that. Sorry. I’m going to trust that he’s not an eye
1:32:46 doctor. Cause I never get that. Yeah. He’s like, what are you talking about?
1:32:50 You interview a lot of people. What did Matt McConaughey say to that question?
1:32:56 Maybe this should be one of my rapid fire questions that I finished with.
1:32:59 I’ll take a pass on that one. I don’t have enough experience to talk.
1:33:04 Yeah. Yeah. No, we can, we can both pass on that one, but is there anything else that we
1:33:10 haven’t covered that you would like to mention any treatment or research or researchers that you think
1:33:15 people should take a look at? I mean, we talked a bit about mitochondria, certainly talked to the
1:33:21 lens. We talked about glaucoma and hopefully within the next five years, as you said, being able to
1:33:27 potentially restore function or stave it off to a much greater extent. We didn’t really get into
1:33:30 treating nerves. I have a note about treating nerves, but I’m not sure we need to cover that.
1:33:35 Is there anything else that you’d like to mention that we didn’t have a chance to discuss?
1:33:41 I want people to understand that first of all, these are all amazing questions. You’ve hit a wide range
1:33:49 and we can’t answer them without doing the science behind it. So first of all, you know,
1:33:56 as they might be dry and said, science is real. So first of all, science is real. And second of all,
1:34:01 like, you know, I would just encourage people, you know, like ask your, in this case, eye care provider,
1:34:07 like, you know, what’s going on with me? Are there clinical trials? Like volunteering to be in clinical
1:34:14 trials. I’ll tell you, I know like patients are so grateful when they get into our clinics here
1:34:21 and they get into a clinical trial because they are accessing a treatment before it is publicly
1:34:25 available to see if it’s going to work. We don’t know if it’s going to work, but they’re taking a swing at
1:34:31 that. And they are so grateful to get into these trials. But I always say like, we are so grateful,
1:34:38 like we can’t do the trials and therefore decide whether you should take the supplement or use this
1:34:46 virtual reality device or go in front of red lights every day or microdose LSD or change your microbiome.
1:34:51 We can’t figure that out if we don’t have the patients come be in the clinical trials and volunteer
1:34:58 their time and energy, the extra trips to the office to get their eyes measured or special pictures taken or
1:35:03 all that kind of stuff. So I say like, I know you’re grateful to be in this trial, but I’m grateful to
1:35:09 you too. We are grateful to the patient. So I think like, we’ve all got to participate in science as a
1:35:14 community so we can do these trials and figure out like how we’re going to fix ourselves and go from
1:35:20 disease to normal. And by the way, go from normal to supranormal, right? We got to prove that, right?
1:35:26 Yeah. Where would you suggest people search for or find clinical trials around them? And I’ll just
1:35:33 reiterate what you said. I’ve seen so many studies that I’ve been involved with hit a wall with subject
1:35:40 or patient recruitment. They just hit a wall. They really, really benefit from people who are
1:35:44 proactive. But if someone’s listening, they’re like, that sounds amazing. I’d love to actually see what
1:35:51 this looks like in practice and maybe figure or help people figure out something in the process for
1:35:56 almost for myself. Where do they even look? Where would they begin? One really good place in the U.S.
1:36:05 to look is a website called clinicaltrials.gov. So it’s got it right there in the name. And you go on the
1:36:12 front page for clinicaltrials.gov and you type in your disease. So you could type in glaucoma, diabetes,
1:36:21 whatever it is. And it’ll give you a list of here’s trials that are recruiting right now actively. And then you
1:36:27 can click on any of those and say like, oh, that one’s in my city or it’s not my city, but I’m going
1:36:32 to call or send the email to them anyway and say like, hey, could I be eligible for that? So that’s
1:36:38 probably one great resource. And then the other would be, again, for diseases would be in the case of
1:36:48 research for specific diseases. Almost every disease has one or more foundations or patient support
1:36:54 sites that bring people together. You know, I think of one in our backyard here in San Francisco
1:36:59 called the Glaucoma Research Foundation. There’s another one in New York City called the Glaucoma
1:37:07 Foundation. Dozens more, of course, but like they also maintain websites that have a lot of patient
1:37:14 directed information, patient facing, what to learn about your disease. You know, you were asking before,
1:37:19 like where’s a reliable source to learn about stuff. That’s one. But they’ll also sometimes talk through like
1:37:25 what’s happening in clinical trial space or where is that happening or where are some hot spots for clinical
1:37:32 trials. So I think that’s another. Those are a couple of good resources. Of course, nowadays, Google, you know,
1:37:37 just any web search engine, you know, it’ll get you started in the right direction.
1:37:43 Yeah, perfect. And if people are wondering, well, Tim, have you done any of this yourself? Yeah,
1:37:51 I’ve actually, I’ve been a subject in all sorts of different studies from undergrad all the way up to
1:37:56 a few years ago for various things, including at Stanford way back in the day when I was just a few
1:38:03 years after college. So it’s fascinating also just to see what it looks like in real life. What does
1:38:08 scientific study look like when it’s implemented? Well, thank you so much, Jeff. This has been
1:38:14 fantastic, wide ranging romp. It’s still and will continue to be intensely personal. So I will keep
1:38:24 people listening posted. I promise not to sell you any Kratom eye masks through some, you know, MLM scheme.
1:38:28 And I will be continuing to investigate all of this. This has been super helpful. I took a ton of notes.
1:38:35 Is there anywhere you would point people to find you online or learn more about you?
1:38:40 Yeah, absolutely, Tim. You know, you joked in the beginning that this podcast is yours and certainly allowed to be
1:38:47 self-serving, but I’ll throw one plug in here at the end, the Stanford ophthalmology website. We actually maintain
1:38:54 a list of clinical trials. And again, if we want to tap this whole team here on the back, our faculty, our clinical
1:39:01 research staff, everyone involved in it. Stem to Stern is fantastic. And I’d like to point out like,
1:39:07 you know, a lot of the clinical trials of trying to pull things out of the lab and test them in
1:39:12 patients for the first time, a lot of work on vision restoration, vision protection and restoration clinical
1:39:17 trials going on right here. My work and some of the work of our amazing faculty and staff here. So you can
1:39:22 actually go to the Stanford, Google Stanford ophthalmology clinical trials. We have a web page
1:39:29 on our Stanford ophthalmology site that goes disease by disease and has contact info and how you plug right
1:39:33 into the trials here. And we have people in our community participating, but we have people who fly
1:39:38 in from everywhere to participate in these clinical trials. So we’re happy to see if we can fit you into.
1:39:45 Beautiful. And for people listening, I will link to that in the show notes at Tim dot blog slash podcast.
1:39:51 So that’ll be easy to find. If you just search Jeffrey Goldberg, Goldberg, I think you might be the only
1:39:56 Goldberg. There might be one other search Jeffrey Goldberg and it’ll pop right up and you’ll be able to find the
1:40:02 links. Jeffrey, thanks so much. I really appreciate the time. And to everybody listening, as mentioned, show notes,
1:40:07 Tim dot blog slash podcast, you’ll be able to find links to everything we discussed and more until next time.
1:40:15 Be just a bit kinder than is necessary to others, but also to yourself. And thanks for tuning in.
1:40:22 Hey, guys, this is Tim again. Just one more thing before you take off. And that is five bullet Friday.
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1:40:50 It’s kind of like my diary of cool things. It often includes articles I’m reading, books I’m reading,
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1:41:22 just go to Tim dot blog slash Friday, type that into your browser, Tim dot blog slash Friday, drop in
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Dr. Jeffrey Goldberg is Professor and Chair of Ophthalmology and Director of the Byers Eye Institute at Stanford University, a leading scientist in the development and degeneration of the visual system from eye to brain, and a practicing ophthalmologist and surgeon.
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Timestamps:
[00:00:00] Start.
[00:05:30] How do you solve a problem like presbyopia?
[00:08:34] The athletic benefits of training supranormal (better than 20/20) vision.
[00:11:49] Indigenous eye drops and FDA-approved pilocarpine for presbyopia.
[00:14:05] Understanding basic eye anatomy.
[00:17:27] Exploring AREDS 2, CoQ10, ginkgo, vitamin B3, and other supplements for vision.
[00:23:00] Visual training devices and psychedelic-prompted brain plasticity.
[00:25:12] Thoughts on visual training effectiveness and motor action requirements.
[00:28:29] Concussion rehabilitation and visual perception exercises.
[00:32:36] Red light and violet light therapy for myopia and mitochondrial health.
[00:36:07] Vision loss correlation with cognitive decline and depression.
[00:39:36] Presbyopia progression and psychological dependence on readers.
[00:41:15] Cognito Therapeutics headset for Alzheimer’s treatment.
[00:46:46] Glaucoma basics: neurodegenerative disease and risk factors.
[00:48:53] Eye pressure variability and diurnal cycles.
[00:50:02] Cannabis effects on eye pressure and compound isolation.
[00:51:47] Stem cell research for vision restoration.
[00:53:09] Anti-inflammatory effects and immune system role in eye diseases.
[00:55:15] Gut microbiome connection to glaucoma in animal models.
[00:58:43] Metabolic syndrome and GLP-1 receptor agonists.
[01:00:50] Microbiome sharing and future therapeutic possibilities.
[01:03:31] Dry eye treatment: preservative-free tears and serum drops.
[01:08:43] Vision screening recommendations and UV protection.
[01:11:22] Full-spectrum light benefits vs. UV exposure.
[01:13:27] Paradigm shifts: irreversible vision loss becoming reversible.
[01:17:18] Convergence of neuroscience advances and biotech investment.
[01:21:58] Miraculous mitochondria: health, transplants, and three-parent babies.
[01:26:24] My family history concerns and metabolic health screening.
[01:29:26] Exercise’s biggest gain: going from none to some.
[01:33:03] Clinical trial participation resources and parting thoughts.
*
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