The Tim Ferriss Show Transcripts: Dr. Jeffrey Goldberg — Creating Supranormal Vision, Cutting-Edge Science for Eye Health, Supplements, Red Light Therapy, and The Future of Eyesight Restoration (#823)

Please enjoy this transcript of my interview with Dr. Jeffrey Goldberg, chair of the Department of Ophthalmology and director of the Byers Eye Institute at Stanford University. He is a leading scientist in the development and degeneration of the visual system from eye to brain and a professor, practicing ophthalmologist, and surgeon.

Dr. Goldberg is a member of the National Academy of Medicine and has won a number of prestigious awards, including Scientist of the Year by the Hope for Vision foundation and the Cogan award from the Association for Research in Vision and Ophthalmology. Dr. Goldberg received his BS magna cum laude from Yale University and his MD and PhD from Stanford University, where he made significant discoveries about the failure of optic nerve regeneration. 

Dr. Goldberg’s research is directed at vision restoration, including neuroprotection and regeneration of the retina and optic nerve, a major unmet need in glaucoma and other eye diseases. His laboratory is developing novel molecular, stem-cell, and nanotherapeutics approaches for eye repair, and he is widely recognized for translating advances in the lab into clinical trials for patients. 

A number of his innovations have spun out into startups and clinical-stage companies, and he serves as medical and scientific advisor to a number of ophthalmic start-up, pharma, and device companies. His goal is to translate scientific discoveries to patient therapies.

Transcripts may contain a few typos. With many episodes lasting 2+ hours, it can be difficult to catch minor errors. Enjoy!

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Tim Ferriss: Dr. Jeffrey Goldberg. So nice to meet you. Thanks for making the time.

Dr. Jeffrey Goldberg: Absolutely. Thanks for having me on. I’m really looking forward to it.

Tim Ferriss: I have so many questions for you. And as usual, I’m scratching my own itch. This is going to be a selfish conversation for yours truly, in some respects, because the way this whole thing came about is I put up a post on social media asking for cutting edge technologies or treatments related to presbyopia. Which for those who don’t recognize the term is a very fancy way of saying age-related visual decline. If you’re a word nerd like I am, presbyterian, similar etymology. Leadership of the elders.

And I have noticed in the last year that my near work, my near vision has started to falter looking at books, looking at my iPhone, looking at supplement bottles. And this has led to somewhat of a crisis of meaning for me because I have had my identity based on, in some respects, very, very good eyesight and visual acuity for my entire life.

And Andrew Huberman, a mutual friend of ours, texted me and said, “I’ve got the guy. I know the guy.” And, “Listen to our interview.” Which I did. And for that reason, we’re going to go all over the place, but I thought we would start where I had to start, which is supranormal visual performance. And these is the notes I scribbled down from your conversation with Andrew, I recommend everyone listen to it, goggles that reduce frame rate for basketball.

And that was sort of left hanging a little bit. You guys didn’t do a deep dive on it. So I want to start right there. Because of course there’s preventing decline, there’s maybe restoring function, and then there’s going further and taking things as far as you can. And nowhere are the stakes higher and the rewards greater perhaps than in professional sports. So could you take that and run with it in any way that makes sense?

Dr. Jeffrey Goldberg: Yeah, sure, sure, sure. And yeah, presbyopia, vision of the old. So I’ll tell you just a funny side note. We all get that. I, like you, have gone my whole life without needing glasses until I hit around age 40. And when everyone hits around age 40, our lens inside the eye won’t compress and reshape to focus up close. So your distance vision might still be great, but you just can’t bring that focus in as tight. And I discovered it accidentally in myself, because I was actually in my house and I found a pair of glasses in a closet, somebody must’ve just left them there.

Tim Ferriss: I see where this is going.

Dr. Jeffrey Goldberg: And it turned out they were readers and we couldn’t figure out whose they were. We’re calling around, friends and family. Fine, nobody’s claiming. And then one day I just put them on. “Let’s see how I look in glasses.” And I look down at my phone and I’m like, “Oh, my God, wait a second. I can see a lot better with these readers on.” And then once you do it, you’re addicted because good vision is pretty addicting, right?

Tim Ferriss: Yeah, for sure.

Dr. Jeffrey Goldberg: So now I’m in them too and I’m pretending to look so young with you not wearing them right now, but here they are, just in case. Yeah.

Tim Ferriss: Yeah, very common. Yeah, very, very common.

Dr. Jeffrey Goldberg: So it raises a really cool question that you’re raising, which is as an eye doctor I spent a lot of time, and as a researcher spend a lot of time — we could come back to talking about how do we prevent the sick from losing vision on all these big eye diseases? We could come back to that. But there’s a much bigger world of people who have pretty good vision. Maybe they need glasses, but they’ve got good vision.

And how do we think about the difference, not from sick to normal, but how do we think about the difference from normal to supranormal? And we know they’re supranormal because when, for example, as you bring up, professional athletes get studied, they have better vision. They have better reflex time, they have sharper vision. We talk about 20/20 vision. That means I can see at 20 feet what a “normal” person can see at 20 feet, so I have normal vision. But you can have 20/12 vision, which means you can see at 20 feet what normal people can see at 12 feet. You’ve got better than normal. And it turns out a lot of pro athletes have that.

And then the next question becomes, and you just kind of hinted at it right there, can we train to supranormal vision? Can we induce supra — ? And almost no one studies that. But there are some really cool tools and toys that actually might have that effect. And so you brought up one of them. So we see, like our cones inside of our eyes, we’ve got rods and cones, the cones, they’ve got a refresh rate around 30 to 60 frames per second, kind of like our computer screens do.

And so if you actually subtract out a couple of frames, so if you put on some glasses that dim one out of every 30th of a second, or they dim two out of every 30th, or push it, three, and now you’re giving up visual data, and I throw a basketball at you, if you’ve got your regular vision, you’ll catch it. But if I’m only giving you 90 percent of your vision, or 80 percent or 70 percent or 60 percent of that vision, you might miss the ball. Right?

Tim Ferriss: Yeah.

Dr. Jeffrey Goldberg: But if we practiced and trained in those goggles, where you’ve got to play basketball, throwing and catch, shoot, whatever, throw a baseball back and forth at 70 percent vision, and then we put you in the game back with 100 percent vision. You’re going to be better, faster reflex time, all of that. Hand-eye coordination. So it’s actually like some of these supranormal visual tactics are actually trainable and there’s tools that athletes are using, but they’re accessible to all of us, yeah.

Tim Ferriss: All right, so I — 

Dr. Jeffrey Goldberg: You can grab one of those, Tim.

Tim Ferriss: Yeah, let’s dig into this a little bit. I have a number of friends who have engineering chops and have played with sensory substitution experiments and all sorts of wild stuff. And in fact, I think there’s some folks at Stanford, David Eagleman comes to mind, who’ve developed tools along these lines. We won’t go down that route. 

Let me stick with vision for a second and just note that there are, for instance, indigenous groups in various parts of the Amazon, I’ve seen them in Brazil and in Peru as well, which use eye drops of various types. Could be from a plant, could be from a toad, for improving not near work but distance work. Most of them use shotguns these days, but some still use blow guns and bow and arrows for hunting, say, monkeys.

So there seems to be something to it. Now you could say, “Ah, that’s a bunch of voodoo hoodoo nonsense.” But then you have eye drops for, as I understand it, temporarily inducing more, this isn’t going to be the right term, but flexibility in the lens. Is it pilocarpine? 

Dr. Jeffrey Goldberg: It’s actually the iris. Yeah, yeah.

Tim Ferriss: The iris. There we go.

Dr. Jeffrey Goldberg: So I don’t know what they’re using in the plants, but we now have FDA approved eye drops, and what they actually do is they bring your pupil size down by having your iris constrict to a smaller circle. And it turns out that if you have refractive error, so you need glasses, the shape of the front of your eye, the shape of your lens isn’t perfect, you have a little bit of glasses or contacts, or whatever to correct that, including if it’s not focusing up to close, you can have reading glasses that change that refractive, that light coming into your eye so that you’re focusing up at close. If you come down to a pinhole, you actually kind of normalize the light so that it’s as if it’s all coming from infinity and you actually kind of correct refractive error.

One of the ways we can tell if someone needs glasses is we have you read the eye chart, and then we have you read the eye chart through a little pinhole, a little device you stick in front of that eye, and read through a pinhole. And if you can read better through the pinhole, you actually have better vision and could correct it with glasses. So now we could just give an eye drop that kind of makes your pupil closer to a pinhole and then it allows you to see without glasses, near or far. In fact, people are using it now for near vision, for that presbyopia you were talking about in the beginning.

Tim Ferriss: So for people listening, and also for me frankly, could you just give a vision 101, and in this case, let’s focus on the eye, just so people understand the basic components of the eye.

Dr. Jeffrey Goldberg: Yeah.

Tim Ferriss: And part of the reason I want to explore this is there are different levers you might be able to pull on to improve vision, some of which might be structurally related, but not all, at least to the eye. But could you just lay out the basic anatomy of the eye, the architecture?

Dr. Jeffrey Goldberg: Yeah, absolutely. So light comes in the front, goes through the clear window in the front of our eye called the cornea. You can have corneal diseases obviously that block that light from coming through clearly, but if it’s healthy, that light comes through clearly. The cornea is curved on the front, and that curvature is actually responsible for curving most of the light into the back of the eye.

Then the light goes through your pupil. So that’s the iris, which it’s brown in me, but brown, blue, hazel. So that’s our iris. And the iris can open and close like we were talking about a minute ago. Comes through the middle of that, the open middle part of that, goes through the lens. The lens does fine focusing, a little focusing from far to near, that kind of thing. And that’s what we were saying, stiffens as we age. So we can’t go far to near as well as we get older, you’re passing 40 years old, typically.

And then it goes through the gelatinous middle part of the eye. We call it the vitreous. After the lens is called the vitreous. That’s where floaters are. People who get floaters, they’re floating, it’s like little concretions of proteins and stuff floating in the vitreous. It’s a gel. As we get older, that gel turns to water, kind of shrinks up. Our eye doesn’t shrink because it fills in with salt water, but the gel shrinks up.

And then the light hits the retina. And our retinas are what we call inverted. So the light actually passes through almost all of the retina and then it hits the rods and the cones. And those are the photoreceptors. They absorb the light, like the photons of light. The rods are really, really only good for nighttime vision. They’re only good at very low light. If you go into normal daytime vision, sitting here in the room, whatever, those are getting bleached out, you’re not really using your rods too much.

And next to them, the cones. The cones are great for color vision, they’re great for bright lights. They’re what we use most of the day. That’s what you and I are using mainly right now. The rods and the cones collect all that light. They process it and transmogrify it into electrical signals. And those electrical signals are then propagated back forward through the retina. There’s some internal processing layers in the retina, so it’s not just a layer of film, you’re actually doing some computation right there in the retina.

And then they hit what are called retinal ganglion cells. And those are the cells that then send a process across the surface of the retina. It’s an axon, but it’s like a telephone wire. And that then goes back out the back of the eye into what we call the optic nerve. And that optic nerve connects the eye to the brain. So those retinal ganglion cells are collecting all the data and sending it all back through the optic nerve to the brain. And then of course all that rest of that processing is happening in the brain.

Tim Ferriss: All right, there we go. That was a great summary. Thank you very much. And I’ll tell folks, if you thought that is a lot to remember, it is a lot to remember. But the point of it is, as I, as my own N of one, am trying to consider different paths forward with presbyopia, whether it’s glasses, yes, my readers do fix the problem, they do fix the problem, but I am a little concerned of increased dependency and then increased magnification over time. I know there are arguments for and maybe some arguments against, but when I put up my social post, and I think people can identify with this, there was a lot of noise. There were some of the most harebrained, insane, certainly potentially dangerous suggestions you can imagine.

And then there were a few things that came up when I reached out to, and let me get this right, is it a vitreoretinal surgeon and researcher — 

Dr. Jeffrey Goldberg: Uh-huh.

Tim Ferriss: — who I happen to know, and he sent me a number of white papers, or I shouldn’t say white papers, more so studies and meta-analyses and so on that I read up on. And I thought to myself, “Look at that. Surprise of surprises.” A few of the things that came up repeatedly in the hundreds of responses to my post actually show up in the literature and there might be something to them. And we’ll definitely come to a number of those.

But it can be very overwhelming 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 giving my second TED talk of our conversation, is that much like if someone complains of, say, brain fog and fatigue, a rose is a rose is a rose is not a rose, in the sense that there can be many different factors and independent variables that contribute to that. So one person might have insulin insensitivity and trouble with glucose disposal. Somebody else might have Lyme disease or some infectious disease that is contributing to metabolic dysfunction. I mean, there’s so many different contributing factors that it helps to, I think, get a little thinly sliced.

So in my case, I have the stiffening of the lens. Please correct my terminology. I also have a really pretty sizable, I’d never seen it before, I did some really impressive imaging on the eye, but a huge nevus on the back of my right eye that I need to keep an eye on. So I’ll be following up on that in three or four months. But I wanted to, I suppose start with, what are other ways to improve vision?

Now there’s certain things I’m always looking for: limited downside, potential upside. So for instance, I’m taking the AREDS 2 supplement with lutein and various other ingredients in it. I would say it’s probably not going to help, but within my patient cohort of the medical practices I work with, there are a few folks who claimed after six weeks that their vision really improved and they didn’t need their readers, even though technically, mechanistically, the AREDS 2 shouldn’t have helped them. So whether it’s placebo effect or not, interesting outcome. I know the plural of anecdote is not data, but I was like, “Ah, okay, sure, I’ll take the supplement.”

What are some other cutting-edge treatments or augmentations for improving vision? And I’ll shut up in a second, but I’ve been very excited to talk to you, so I’m chomping at the bit here. Because as you mentioned, there’s this sort of eye architecture, brain interface. And among professional athletes, just because I’ve funded a lot of science in this area, low dose psychedelics also seem to improve visual acuity. So everyone from Aaron Rodgers, to very, very high level athletes that I will not dox here, report measurable performance improvements that they attribute to increased visual acuity. Well, it’s probably not changing the anatomy of the eye, so what’s going on? So I would just love you to speak to any other means of supercharging visual perception.

Dr. Jeffrey Goldberg: There are some things that we have a pretty decent sense on. AREDS 2 and some of these supplements — first of all, eating a lot of carrots, it’s probably not going to actually do it. So great, childhood, get the kids to eat their vegetables. We definitely exercised that ourselves as parents. But AREDS 2 clinically proven, if you have moderate age-related macular degeneration, to slow down your vision loss. Does that mean it doesn’t work at all if you have mild age-related macular degeneration or if you have no age-related macular degeneration? It might just be like we haven’t done a study big enough to detect those effects. And as you say, that’s probably not going to hurt, so feel free if you want. We can’t prove it’s helping, but feel free.

There are other supplements that have received some study that maybe suggest there isn’t much going on there, that again, they’re probably not going to hurt. Some patients take CoQ10, some patients take ginkgo. There is actually, maybe the hottest topic in supplement vitamin space right now internationally, is actually vitamin B3, nicotinamide, which has really been linked to a number of good potential medical uses and is receiving a lot of study. There’s actually international clinical trials, including one here in the US, actually testing whether it could restore vision in certain eye diseases like glaucoma, which is my specialty. So definitely some hints in that direction.

We already talked about some device elements, and I think between vision training, like we talked about earlier, and also visual augmentation, we’re moving into augmented reality. And so training vision and visual reflex time almost certainly makes a difference in the activities you’re training in. If you’re training in basketball, will it also help you doing some weekend surfing? I don’t know. But definitely can help move you from normal to supranormal or help enhance and improve what you’re doing.

And then there’s all sorts of stuff that, I’m going to be honest, Tim, we don’t know. Because A, it’s really new, really hot right now, like microdosing certain psychedelics, things like that, that we know act on the nervous system, including the brain. But the retina, in the back of the eye, and the optic nerve that connects the retina to the brain, those are developmentally an outgrowth from the brain. They are part of the brain, they’re part of the central nervous system, and we barely know about how to influence the wiring, the plasticity.

Are there drugs that we can give? A lot of people have talked about gabapentin and drugs in that space. Obviously microdosing in LSD is a really hot area right now for inducing plasticity. There’s actually great science showing in animal models, and a little bit now in humans, that you can actually reopen brain plasticity by dosing some of these drugs at appropriate doses. Obviously we’ve got to be careful, we don’t know what the right dose is yet.

But it’s really worth looking at because there’s clear evidence that these are relevant and likely to have some effects. We’ve just got to figure out a little bit more like how, what’s the right dose? By the way, when you’re doing it, should you be doing some behavioral training, like visual training? But these things act on the brain, and about a third of our brain inside our skull is dedicated to processing vision.

Tim Ferriss: Yeah, there’s a lot there. All right. I have been so — I’m not just over-caffeinated because I’m actually not really caffeinated, I might be over-ketoned. I have quite a bit of ketone monoester in me at the moment. But putting that aside, so I am right now, and this could make me seem like I’m in the tinfoil-hat-wearing crowd, but I had a number of companies reach out to me, not surprising after I put up my social posts. Most of them didn’t make any sense. A few of them seemed to make sense, and the people involved seemed to have technical chops and also some pretty credible research backgrounds. And I’m not going to name the company X, I’m not done with my personal testing.

But I have been testing at about eight minutes a day, I don’t know the right descriptor to use, I would say maybe visual perception training. To distinguish it from, and we can talk about this, what I suppose some ophthalmologists or optometrists might call visual education. So trying to improve the ciliary muscle strength and so on around the eyes. Much like, if people want a visual, sort of the springs around a trampoline. But in this case it’s very quick flashes of blurry or not blurry circles, and you need to identify what is more blurred. And there are many permutations. It adapts to your successes and failures over time. And it could absolutely be placebo, but after about a month now of using it, I feel like my near vision has improved. Even the woman I’m dating has commented on this. And I am still waiting. The jury is out. But this is just to say that I’d love to know what you think of visual improvement that is not dependent on surgery or drops. Is there something to the various types of visual education? Is there something there or not? And then when we go maybe upstream a bit, if that’s the right phrasing to use, to the brain, are there interesting approaches like limiting the frame rate, or removing a number of frames, that you think are at least plausibly interesting for enhancing performance?

Dr. Jeffrey Goldberg: Yeah. First of all, absolutely. And it does get back to that idea of visual training, the reducing frame rate, training on visual perception. There’s actually a fair amount of data. Actually, there’s enough data to even say there’s elements that make it better. For example, if you do visual training where you’re just showing yourself, like being shown these different objects, maybe they’re getting smaller, dimmer, blurrier, etc., your ability to train off of that is significantly better if it demands a behavioral outcome, a motor action.

So for example, you’ve got to point at the right one or choose something. And it’s not just that you’re mentally thinking that was the sharper image, it’s actually the motor output of pushing a button, or pointing at something, or doing an activity that actually reinforces the visual perception training. So that’s one great example.

Another great example is after concussion. So concussion, traumatic brain injury, of course, very common in athletes because they’re more likely to get into the head bumps and things like that, but it happens all the time in kids.

Tim Ferriss: Military. Very big problem.

Dr. Jeffrey Goldberg: Military. A very, very big issue. And the line in between mild concussion, severe concussion, traumatic brain injury, that’s all on a spectrum, a continuum. And there’s actually decent data from that group of people, that if you get a concussion, actually visual symptoms are some of the more significant symptoms. Ability to focus, ability to sleep, and vision are three of the big symptoms that people get in that concussion through TBI spectrum. And those can be debilitating, right? And kids are out of school, they’re missing high school for weeks or longer. It can be really debilitating. 

Obviously, if you’re an older adult and you’re in your job situation, really tough. And it turns out though, that there are visual perception exercises that you can put patients through in those situations that, in the limited clinical studies that have been done, point to a positive effect of basically rehabbing, like neurorehabbing you back. Now, that of course is back from injured to normal, but the idea that that can also induce the same kind of plastic remodeling in our eye and brain, and particularly the eye-brain connection in patients who are starting from normal and trying to get themselves up to supranormal, try to improve performance, visual performance. We’ve set up here a whole human performance laboratory, really just to study these questions and the data rolling in make it look like, hey, there’s something here. This is definitely worth chasing. Yeah.

Tim Ferriss: What can someone search if they want to find something to read up on related to the concussion rehabilitation protocol? Because this type of visual training, because there’s a lot of nonsense floating around and charlatans out there. Any particular search terms or principle investigators or anything that people can search?

Dr. Jeffrey Goldberg: I would say, if you want to at least hit some of the science or science-adjacent web resources, you’re going to want to use a few technical terms in there, like concussion, neurorehab, neurorehabilitation, plasticity, and then some of the terms you’ve already been using, visual perception exercises. And then, look, in these situations, you’ve got to look not just at the content but of the source, right? And so, is this a dude on his blog, or is this coming from a foundation, or an institute, or one of the academic centers, or some of the choices like that?

Tim Ferriss: All right, Jeff, I would love to hop to another set of interventions, and this is in the device category. Red light in the morning for mitochondrial health, question mark? Violet light to reduce progression of nearsightedness in children. Is there an application of red light or violet light? To what extent do we have supporting data for using either of these? Do we have an idea of what best practices look like? Is it only for people with a disease state or can they be potentially used to preserve vision before vision loss?

Dr. Jeffrey Goldberg: Yeah, the disease state data is pretty good. And also the myopia control is pretty good data too.

Tim Ferriss: Just for a definition for folks, what’s myopia?

Dr. Jeffrey Goldberg: Myopia is nearsightedness and it’s an epidemic, more common in Asians or people of Asian heritage, but common in everyone. And kids can get nearsighted. If you’re a little nearsighted, it might be annoying to wear glasses. If you get more severely nearsighted, it actually can lead to all sorts of problems inside the eye, real severe vision loss, even early in life. So that’s a big one. And then what was really shocking was it turns out that a small dose of daily red light can slow down progression of myopia in young people. We’re talking about teens and younger even. So what’s even more shocking to me is that it also works with violet light. So how’s it work with light at the two ends of the visible spectrum? And definitely mitochondria are implicated.

Mitochondria are the little power houses, energy sources inside the cell. They are a big player in converting the sugar a cell takes in into energy that the cell can use for all of the cellular processes. So our bodies clearly need functioning mitochondria. In fact, one of the big features common across many neurodegenerative diseases of the eye and the brain is dysfunction of mitochondria. There’s an FDA-approved red light therapy for patients with macular degeneration, but there’s good data that it may also be supportive or protective in other eye diseases. And we’re talking in small doses. This is not overwhelmingly bright lights and we’re talking about minutes a day. You don’t have to sit in front of it for two hours a day, so minutes a day. So it’s exciting.

The data suggests that the mechanism of action is giving a little protective booster shot to our mitochondria so that they don’t get dysfunctional, whether that’s dysfunctional just from normal use throughout the day or dysfunctional because you happen to have a disease that’s getting in the way of those mitochondria. So now, we don’t know what the right dose is. We don’t know what the right brightness is. All we know is that in these initial things that have been tested, the initial brightness of how and how many minutes, three minutes a day, for example, there’s a signal there. There’s something working there. Should we have everybody buying one on the internet right now, hopping on Amazon, spending 25 bucks, spending three minutes a day? We don’t have the data to support that. Is it going to hurt? Probably not. So, Tim, it’s a problem because we’ve got so many things that are like, “Oh, that looks promising,” and we just, we need a little more science. We need a little more study.

Tim Ferriss: Yeah. Well, a friend of mine wanted me to write a blog post about — look, I’m not a doctor. I don’t play one on the internet, but the difference between getting into science versus getting out of suffering in the sense that you know and I know of just having been involved with the funding side, randomized controlled trials are expensive and they take a long time. But at the same time, if you take the advice of every wackadoodle running around on the internet, you’re going to have 600 different interventions, some of which could do a lot of damage. Or you’re going to get the wrong device. 

I’ve seen this all since I’ve talked about accelerated TMS and different types of brain stimulation for potentially addressing treatment-resistant depression. And Nolan Williams at Stanford has done a lot of great research related to that. And you see these people on YouTube with DIY TMS and they’ve got the polarities reversed, and I’m just like, “Oh, my God, what are you doing to your poor brain?” But I also want to preserve my vision as long as humanly possible, and maybe you can dispel a concern that I have, and this is based on the fact that I have a lot of Alzheimer’s and Parkinson’s in my family. And I’m APOE3/4, some 2.5 times or so more likely to develop Alzheimer’s, based on what we currently think we know, than someone who is, I guess, 3/3. And it scares the hell out of me. And I’ve had conversations with audiologists who point out the correlation, I don’t know how strong the signal is, between hearing loss and onset or progression of dementia. Is there something similar for visual loss?

Dr. Jeffrey Goldberg: Absolutely. Actually, one of our faculty here has done some of the really foundational research showing that correlation between vision loss and cognitive decline, and the loss of input. Again, vision is our biggest input sense. It’s driving, a third of our brain is dedicated, as I said, to processing and using that vision, and interfaces with every other thing that we do. It also is a really critical piece around depression and mental health. Anxiety is vision, the work that Andy Huberman had done on visual fear and how that plays into the fear and anxiety pathways as well as the depression pathways. And not only does visual decline accelerate cognitive decline, possibly because, in part, because of how depression then plays in with cognitive. These things are all clearly related to each other, but also remarkably, if you have low vision, let’s say from something as simple and correctable as cataracts, a blurring of the lens that happens with age.

If we all live to a hundred, we’re all going to need cataract surgery, some people younger, some people older. But if you do cataract surgery and restore vision in an older person who appears to be suffering, is suffering with cognitive decline and/or depression, you can reverse a significant amount of that decline in either of those domains. And so it just, again, it speaks to the interplay of vision with our mental health, our cognitive health, and this is long-term, important stuff.

Tim Ferriss: And this, tell me if I’m interpreting this the wrong way, but it seems like this would lead to a strong pro argument for wearing glasses instead of suffering in silence. I don’t know, but that’s what I hear when I’m trying to read between the lines.

Dr. Jeffrey Goldberg: There’s an important myth to dispel, especially when it comes to presbyopia and wearing reading glasses. Between age 40 and around 60 or so, that lens stiffens, and stiffens, and stiffens. And the first year you only need +1.25 glasses, and then three years later you’re like, “Ah, I need +1.5, +1.50s.” A few years after that, you’re moving up to the 2.0s. Eventually you’ll peak out at around 2.5 or 3.0s, because that’s the difference, basically. That’s the refractive, the glasses difference between viewing something at infinity, which from an optics perspective is actually just three feet away or further, and viewing something at 14 inches, comfortable reading distance, right in front of us. So 2.5 to 3 power of those readers is all you’re going to need, but you’re going to progress through those numbers whether you wear the readers or not. So wear the readers!

Tim Ferriss: I got it. Is it a mistake in causality then, where people believe?

Dr. Jeffrey Goldberg: Yeah.

Tim Ferriss: Because an optometrist said this to me a couple of weeks ago, and I was like, “Well, I assume you know what the hell you’re talking about,” which is always a stupid assumption, but that you develop increased dependence, but it’s actually just tracking along with the natural stiffening of the lens, in the case of presbyopia.

Dr. Jeffrey Goldberg: It is and it’s psychological dependence. It’s just like what I went through as soon as I started wearing those readers by accident. I didn’t think I needed them. I was still reading off my phone. It was fine, but as soon as I experienced that extra crisp vision, I was like, “Well, I like that.”

Tim Ferriss: Yeah.

Dr. Jeffrey Goldberg: So I got psychologically dependent because who doesn’t want their best vision?

Tim Ferriss: Yeah, for sure. And I’m going to keep saying this, it’s going to get annoying because I’m like a sweaty-palmed fanboy, jumping all over you, but I was very excited to chat with you also because the nose, the brain, these are direct paths into the brain in a sense. And for instance, I don’t know, I don’t expect you to track all things in all fields. That’d be impossible, but Cognito Therapeutics, it’s a headset that is used and they have a lot of good data. I think they’re either phase two or phase three. They’ve raised a ton of money, and it’s a headset, and they have these visors covering the eyes, and then earpieces. And it produces, I want to say, gamma waves in the brain. There’s more to it, but using flashing lights, and this appears to — I’m getting into the deep end of my ignorance pool here, pulling from memory, but it appears to assist in the breakdown of beta-amyloid plaque, maybe tau as well. I’m not really sure.

So using flashing light to help people with conditions like Alzheimer’s. It’s mind-boggling, I guess, literally and metaphorically. And that does come from credible researchers. I wish I could cite them offhand, but it’s going to take me too much time to find the scientists involved. But that is one that appears to be — Ed Boyden and Li-Huei Tsai out of MIT.

Dr. Jeffrey Goldberg: Yeah. Yep, I know them both. Ed was a graduate student here at Stanford when I was at Stanford.

Tim Ferriss: Oh, amazing.

Dr. Jeffrey Goldberg: Yep, yep.

Tim Ferriss: Yeah, so there you go.

Dr. Jeffrey Goldberg: Yeah.

Tim Ferriss: Are we going to see more of these devices and how far away are they? Because I’m seeing decline in my near relatives. I’m currently taking care of two relatives with severe cognitive decline. It scares the hell out of me. And some of them are 3/3, by the 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 quite a few things, but are there other devices that are on the cusp of being available that you find interesting?

Dr. Jeffrey Goldberg: Yeah, I think so, and input through the visual system and output through the visual system are both looking really interesting these days. So you’re talking about input. What can we stick in through the visual system to influence the rest of our brain, brainwave activity, plasticity, like we were talking about before, help preventing cognitive decline? We actually, there is very strong data, for example, that if you give the right amount of electrical activity of our neurons in the eye and the brain — so the neurons in the brain talk to each other through electrical activity, like little wires and too much activity is bad. Really too much activity is epilepsy, for example, Too little’s clearly bad too. If you have a stroke, then you’ve got no electrical activity in that area of your brain and it’s just not working anymore. But providing that sweet spot in the middle of electrical activity, in addition to it participating in the processing of whatever that area of the brain does. In the retina, it’s your vision, obviously.

It also stimulates pathways like plasticity and responsiveness to the survival and growth factors. And we and others have shown that very clearly in animal research over the years, that you need not just the right growth factors circulating around in the brain, but you also need the right levels of electrical activity so that the neurons are maximally responsive.

Tim Ferriss: Yeah, it’s like weightlifting. You can have all the protein in the world.

Dr. Jeffrey Goldberg: Right.

Tim Ferriss: You need the stimulus.

Dr. Jeffrey Goldberg: You’ve got to have the right amount, right? You’ve got to match that up, and so it’s really cool. We actually know in the eye the visual — you were talking about flashes of light, but it turns out different cells in our eye respond differentially to different stimuli. We have some cells that fire when the lights go on. We call those, very creatively, ON cells. We have some cells that fire when the lights go off, called OFF cells. We have some cells that are firing between blue and yellow, others that are differentiating between red and green. We have some cells that are in charge of motion detection in the eye, and all that data has got to get back to the brain. But if we stimulate, for example, the motion-direction-sensitive retinal ganglion cells in our retinas in headsets where we devise cues — 

Basically imagine you’re flying through that Star Trek field of stars, like you’re going into hyperspace, right? To engage, and you’re going into — and all those stars speed up by you. Those are great stimuli for some of our direction-sensitive cells in the eye. And could those actually stimulate those cells to then perform better or not degenerate in disease? And so we’ve been studying those kinds of questions. Cognito’s engaged in that kind of work. And then how does that affect what’s going on in the brain? Very reasonable that that’s going to actually lead to specific patterns of activity, flexibility, plasticity that are going to change our brains. And the idea that some of that work can not happen only in the academic world, but that people are excited about it, and are funding the startup companies, and taking that science into that either health domain, healthspan domain or consumer domain. How do we get the normals protected against the future? There’s a lot going on there. That’s on the input side.

Tim Ferriss: Yeah. Okay. I am going to just bookmark that for a second, and I’m going to highlight a few things that I thought were of interest and I’d like you to expand on from your conversation with Andy. So glaucoma, could you have a normal reading during the day, but higher at night? And then the potential place of cannabis edibles.

And my question there was do we know what compounds are responsible? People are listening to me and they’re like, “What the hell are you talking about?” So if that’s enough of a cue, would you mind just discussing that? Because a big challenge with people who are trying to do the right thing. They’re trying to get check-ups. They’re trying to get assessed/ they’re getting their blood work done, but maybe it’s once a year and they had their blood draws, the last one was at 8:00 a.m. and the next one was at 11:00 a.m., and lo and behold, their testosterone is really different and they freak out, and this, that and the other thing. So timing matters among other things. Could you just speak to glaucoma in that respect?

Dr. Jeffrey Goldberg: Absolutely. So let me just back up one step. Glaucoma, after Alzheimer’s disease, glaucoma is the most common neurodegenerative disease. It’s the number one cause of irreversible vision loss in the world. It’s a degeneration of that optic nerve connection from the eye to the brain. So those retinal ganglion cells that are collecting the data in the retina and their axon fibers, those telephone wires running down the optic nerve, carrying that, all the vision from the eye to the brain, they degenerate in glaucoma. If you take all comers, it’s around two percent of people in an aging population that will have developed glaucoma. If you have a primary family member, a parent, a sibling, a child with glaucoma, your risk probably goes up to about 20 percent. So it runs in families, but just because your parent has it doesn’t mean a hundred percent you’ll have it.

There are two main risk factors for glaucoma. One is increasing age, and we’re all working desperately on correcting that one, but we don’t have a slam dunk treatment for that yet. 

The other main risk factor for glaucoma is actually increasing eye pressure. If you have real high pressure, you’re going to get glaucoma. But a lot of people with normal looking eye pressure can also develop glaucoma. It’s just like they were more susceptible, and the eye pressure isn’t just the same number. We’ve got short-term variability and long-term variability. So long-term is, this month, it might be whatever number, next year, it might be a little higher, a little lower. You can vary through your life. But there’s also this short-term variability. It actually varies in our diurnal cycle. So everybody has a diurnal cycle where you — your circadian rhythm, and some of us, like myself, are night people, and we love to be up at night, and getting up in the morning isn’t our favorite thing, and other people are the opposite. And all this stuff relates to our diurnal cycle, our circadian rhythm.

You can try to take melatonin and affect that, but your eye pressure also varies by that. And as you say, if I take your eye pressure in the morning and then the next week I take it in the afternoon and I say, “Oh, my God, your pressure’s gone up. I’ve got to take you to surgery.” Well, wait a second. It might just be because I’m measuring at different times. 

Now, you brought up the most common question that I get asked. I’ll tell you the most common question that I get asked by patients with glaucoma is, “Hey, can I take cannabis?” And by the way, it’s like legal for medical use in many states and frankly, recreational use also in many states, and certainly accessible in every state. Can I take cannabis? Cannabis, whether you smoke it, or eat it in the brownie, or take the chewy, it lowers your eye pressure, if you’re using the version which are available where you feel a little high from it, you get that good feeling. The problem is that it only really lowers the eye pressure during that time that you’re getting high. So I tell patients, it works but you’d have to be high 24/7, so maybe you should just use this eye drop instead, right?

Tim Ferriss: Do we know which compounds within cannabis are responsible for the lowering of the eye pressure?

Dr. Jeffrey Goldberg: Yeah. There’s actually data that both the THCs that do get you high and the others also that don’t can have that effect. And there’s some cool startup companies that have been working on trying to isolate and now test in human patients the, you don’t get high versions of those compounds or chemically modifying them, and by the way, turning them into an eye drop so that it’s really just treating the eye and make that really accessible. You don’t want to be on your glaucoma treatment and not able to drive, so — 

Tim Ferriss: Yeah, that’d be a bummer. Trade-offs.

Dr. Jeffrey Goldberg: — it’s got to be compatible with daily life for most patients, right? Yeah, so that does work. That does work.

Tim Ferriss: Mm-hmm, so — 

Dr. Jeffrey Goldberg: The second most common question I get asked is, “Well, can’t you just fix my eye, or give me stem cells?” Or that kind of thing, but number one is cannabis.

Tim Ferriss: Well, what’s your answer to the stem cells, the magic stem cells?

Dr. Jeffrey Goldberg: We’re getting there on stem cells. So if you’ve lost your retinal ganglion cell connection to the brain through the optic nerve, we are actually getting pretty good at growing retinal ganglion cells out of human stem cells, in the laboratory cell culture dish. And we’re actually starting to make real progress, in animal models to start, showing that you can transplant them in. But I still tell patients, don’t go to some clinic that’s telling you they’ll give you stem cells and pay $18,000 of your hard-earned money. It is not ready for that yet.

Tim Ferriss: Go to Tijuana and get a new pair of eyes.

Dr. Jeffrey Goldberg: Exactly. Don’t waste your money.

Tim Ferriss: Well, yeah, that’ll be the least of your problems, will be the money part. So let me circle back to the cannabis for a second. So I don’t consume much cannabis, but I have experimented with cannabis for chronic pain and specifically a number of back issues that I have and some of it’s congenital. I have a transitional segment and a bunch of orthopathy and blah, blah, blah, blah, blah. And interestingly, a lot of folks, including people who are sort of credible and familiar with the literature, recommended CBD, but I did not find it to have a pain-relieving effect that was sufficient for sleep until adding a little bit of THC, which I thought was actually pretty interesting.

And I’m wondering if this actually cycles back to our very short discussion of psychedelic compounds also because why might psychedelics, say, improve visual acuity? You can come up with a dozen sort of plausible explanations, but when you look at, say, the depression outcomes with psychedelics, people on many different parties in terms of arguing why or how they exert their effect, one that I think is under emphasized is the anti-inflammatory effects, which can be potent in some psychedelics. And you can find studies where they look at anti-inflammatory, just standard off the shelf anti-inflammatory effects on depression, which can be substantial. Do we have any data to suggest that anti-inflammatories have any effect on vision or can in any subpopulation improve vision?

Dr. Jeffrey Goldberg: Yeah, absolutely. So decades ago there was a pretty hot focus on to what degree the immune system might be playing a role, particularly in eye diseases including the common ones, macular degeneration, glaucoma, and then it was hard to pull that together in part I think because we didn’t know as much about the immune system 20, 30 years ago as we do today. And now we know a lot about what we call the innate immune system, which is not the part that learns about the flu virus and makes you immune the next time you get the flu virus. But just how our immune system interacts with our body normally and how it also might interact with our gut bacteria and then cross-react with our own body, things like that. And so it turns out now that we’ve got this much deeper appreciation from the whole immunology crowd about how the immune system and in particular the innate immune system works, we’re now revisiting in neurodegenerative diseases, including glaucoma macular degeneration, and it turns out it is just packed with evidence that the immune system and innate immunity really play a role.

Let me give you one example that is shocking. If you raise the eye pressure in a mouse, the retinal ganglion cells and the optic nerve will degenerate just like in human glaucoma, but in a really beautiful set of experiments that came from a woman, a professor at Harvard, Dongfeng Chen, she showed that if you raised the eye pressure in a mouse that was raised itself, grew up in a germ-free environment and doesn’t have all the normal mouse dirty gut bacteria and therefore its immune system is at some level fundamentally different, you can raise the eye pressure in that mouse, but the optic nerve won’t degenerate, they won’t get glaucoma damage. And then if you take the immune cells out of the first mouse and just put them back into the bloodstream of the second mouse, then the optic nerve will regenerate.

Tim Ferriss: Wow.

Dr. Jeffrey Goldberg: So the immune system is playing a huge role that was previously totally underappreciated and they’re amazing drug therapy candidates that are now moving up through the pipeline towards human testing to test, hey, if we could suppress the immune system. Not totally suppress it because by the way, we still want to be attacking bacteria and viruses but just suppress the little leg of that immune system that’s attacking our body and leading to neurodegenerative disease, that’s going to be off the charts.

Tim Ferriss: As you’re talking about the microbiome and so on, I was doing a bunch of reading for another interview I’ll be doing shortly with the scientist and one of the stories, and this is in animal models of course, but looked at how — and some people have heard through the grapevine one way or another how you could take the microbiome just for simplicity’s sake of say obese mice and transplant that to lean mice and they get fat or vice versa. And I might be getting some of the details wrong, but roughly you see some very interesting effects. However, if you sever the vagus nerve in those recipient mice, they do not exhibit those changes.

And so then some of the questions that are kind of outstanding is, well, if that indicates that you could instead of using ablation or severing something stimulation to achieve a similar effect, then what can you start to do? And then you have hockey puck size things that you put next to the liver that can via some technological wizardry affect these things. But God, I suppose that the more I look at a lot of these things also with family with Alzheimer’s and they might take something like Theracurmin, which has, on some level, inflammatory effects. I’m like, okay, well, and I don’t want to be a one trick pony with the one thing I keep beating over the head, but it’s like, okay, well, if we know that inflamed like microglia have all of these hosts, or at least they’re associated with a host of different neurodegenerative diseases and inflammations associated with depression, to what extent can we mitigate these things and we’re sort of hitting a bunch of birds with one stone.

Does that make any sense? Which is why I’m so interested in the possibility of using devices. I’m so interested in the ketogenic nutritional ketosis, but also exogenous ketones. Brain loves this stuff also, the beta hydroxybutyrate, very potent anti-inflammatory. I’m just wondering, do you think that I am just too clever by half and I’m missing the plot here? 

I feel like chronic inflammation, which is kind of like saying business or the arts, right? I mean there are a million different facets to inflammation. You need inflammation for a lot of reasons, but when it is pathological and chronic, it turns into a big issue. With rapid decline in eyesight, let’s just say in glaucoma, how often is that comorbid with metabolic syndrome or something like that when the decline is faster than, say, average?

Dr. Jeffrey Goldberg: The earliest data looking at, let’s say diabetes as a marker of a lot of patients with type two diabetes, it’s associated with what we call metabolic syndrome, which is this cluster of high lipids, high blood pressure, insulin resistance. And so there was initial data suggesting that a little bit of diabetes might actually be a little protective in glaucoma.

And then some of the follow up next set of studies suggested like, no, no, no. Maybe it’s a little bit bad for your glaucoma. And so the net is it’s probably not metabolic syndrome as a whole is probably not a huge difference. But I’ll tell you the place where those two are converging is one of the hottest topics in medical science today, which is these GLP-1 receptor agonists, which are going to have a huge effect on human health by reducing metabolic syndrome, overweight, obesity, et cetera. But also are looking very promising for neuroprotective.

And I think it actually gets to that point. You’re trying to tease yourself, are you just getting ahead of it? But actually you’re touching on, I think where we’re actually coming to as an understanding is where the science is going in the field, which is this axis between the brain, which you think of, well, isn’t that mostly inside my head, but also the peripheral nerves that are going out to the whole rest of our body and the immune system and those two are talking to each other all the time and now we’ve got the microbiome and that gut axis is like a third leg of that stool because that’s clearly also interacting with both the nervous system and the immune system in very specific ways.

So we’re going to see a lot more of that really, I think, come together and understand more mechanisms. Is it going to be one day that we’re all just kind of taking that purified poop pill that we just swallow down and it changes our microbiome for the day and it protects us from Alzheimer’s or glaucoma in the future? We’re all hoping that’s going to happen. We’d love that protection one day. Should you buy the poop pill off the internet just yet? I’m not sure. Yeah, I don’t think so.

Tim Ferriss: Yeah, Sri Lankan poop pills from rural children. I’m in. Yeah, be careful with what’s out there on the internet, guys. And I’m not supporting a company, I might have to bleep this out, but called Holobiome and they’re actually creating the most comprehensive library currently of gut microbiota because it’s like what you can buy currently off the shelf. First of all, most of it’s dead. It’s inert by the time you consume it. A lot of it doesn’t actually get through your metabolism to where you want it to be. And it only represents maybe in a few dozen, I don’t know what the right term is, strains of bacteria. Whereas there’s like thousands upon thousands. So there’s so much to explore, which is also very exciting.

Dr. Jeffrey Goldberg: Let me give you one more idea of what might be that ideal world on the way to that.

Tim Ferriss: Yeah.

Dr. Jeffrey Goldberg: We share microbiomes between us. Actually we had our at Stanford Med School years ago when I was there, we had a microbiology professor and he used to kind of tease the world is covered with a thin layer of poop because no matter how well you wash your hands after going to the bathroom, there’s a couple bacteria that got on your hands or your belt buckle and then you shake hands or pat someone on the back. I don’t want to increase anyone’s anxiety, but the world is covered — 

Tim Ferriss: This episode is brought to you by Purell.

Dr. Jeffrey Goldberg: There’s a thin layer of poop. “What we call clean and dirty,” he used to say, “is really just how thick that layer is.” Okay, so that joking aside, if you just shack up with someone who’s got great longevity and a great microbiome, good chance you’re going to absorb their microbiome, maybe that’ll be good for you.

Tim Ferriss: Look at that.

Dr. Jeffrey Goldberg: They’ve got to put that on the dating websites. Get your microbiome on that profile.

Tim Ferriss: Right? Craigslist, microbiome casual encounters. So this is going to be a bit of a hard left, but preservative-free strips of tears for dry eye. Why? That was one of my notes from the conversation that you had with Andrew because I’m also looking for just low-hanging fruit for people who are contending as we all do with aging eyes. Maybe you could speak to that. And then I do have to ask about the blood serum for eye drops. Maybe you can hit that too.

Dr. Jeffrey Goldberg: Sure, sure. So look, actually the most common eye disease as we get older is actually dry eye. As we get older, we make fewer tears. We also make lower quality tears. Our tears at high quality have a liquid phase, like a water, salt water phase. There’s also like an oily component to good, high-quality tears. And that oily component also kind of dissipates a little bit as we get older, gets less as we get older. So we make fewer tears and lower quality tears. And a real simple over-the-counter solution for so many people is just put in some artificial tear drops.

The thing is that those little bottles come with preservatives so that when you use it all month, by the end of the month, it’s not growing bacteria. And if you’re just using a drop or two a day, fine, that’s getting you by, fine. Just buy those bottles. They’re the cheapest. But if you’re getting to the point where it’s three, four, five, six times a day, maybe you work on the computer a lot so you blink less and your eyes get drier, you want to use more of those, then we usually recommend at that stage switch over to preservative-free artificial tears because it turns out that preservative in those bottles of drops at a drop or two a day, fine. But if you’re getting up to a lot of drops a day, the preservative is actually irritating and kind of inflammatory to the ocular surface. It actually kind of breaks down some of the cells on the surface of our eyes.

So at that point, we like to switch people to recommending the preservative-free. They’re the ones that come — like usually they come in a little strip of tiny little plastic. You break one off, it’s got its own little cap on it. It’s got this tiny little bubble of fluid that you can squeeze. It really tests if you’ve got bad fingers or bad — by the way, if we’ve got bad vision, you’re poking yourself in the eye with it. So anyway, that’s what we recommend. Switch to preservative-free. And then people who need more than that, we actually have drugs that, for example, reduce on the ocular surface to help the tear quality and quantity come bounce back a little bit.

And then we also have drugs that contain growth factors, things like nerve growth factor that are almost certainly also good for the surface. And when our eyes get dry, the surface, the reason it feels irritating is not just because it feels dry, it’s actually because the surface starts to break down a little bit. And when you go to sleep every night and your eyelids are closed and nothing can evaporate, it bounces back a little bit by morning. So it kind of regenerates or rejuvenates. The ocular surface can regenerate pretty well every day, but at some point your eyes are getting dry enough that you’re having much more chronic problems.

And that’s where sometimes we can use what are called serum tears. So our blood serum, if you take out a blood, like a tube of blood, you’re getting your blood drawn. That tube of blood has your red blood cells carrying all your oxygen, your white blood cells, which is like your immune system, and then all just the liquid with the proteins in it. That’s what we call the serum. That’s the serum. So you could take that tube, you spin the cells out — 

Tim Ferriss: Let me ask a dumb question. Is that different from plasma or are we talking — 

Dr. Jeffrey Goldberg: Serum and plasma. Yeah, depending how you treat some of those proteins, that’s serum and plasma. Let’s just say you’re spinning out the cells and then you can take that serum. Maybe you dilute it a little bit in some of that preservative free artificial tears. Maybe you just use it straight. Usually we dilute it a little bit and we can give patients their own serum as artificial tear drops. And that serum is filled with really good juicy growth factors that help the surface rejuvenate. And that’s the principle of, in some patients, using serum tears.

Tim Ferriss: Maybe this is just a difference in terminology, but it makes me think of a platelet-rich plasma or platelet-poor plasma. Are there experiments with different, I’m not sure, concentrations or cocktails?

Dr. Jeffrey Goldberg: Different cocktails. That’s a great way to put it. Yeah. And platelet-rich plasma, again, one of the reasons that that looks so rejuvenating for our bodies is again, it’s just like chock-a-block full of growth factors. And so I don’t know, I’m sure somebody’s testing this as another way to treat really severe dry eye, or if your dry eye is so bad, you’re actually getting kind of ulcers on the surface of your eyes. Some of the most severe cases might really benefit from like serum tears. Maybe platelet-rich plasma would work too. So that’s a hot area right now. And again, filled with growth factors.

Tim Ferriss: So we talked about the importance of timing with, say, glaucoma exams, things of that type. What are some other recommendations for perhaps avoiding common mistakes or filling gaps that are commonly unfilled? Any recommendations to folks?

Dr. Jeffrey Goldberg: Yeah, there’s a bunch of things. First of all, get an exam and if you have a family member, a blood relative with eye disease, maybe get that exam even sooner. Take glaucoma as an example. If you got an exam and you’re 40 and you don’t have a family history and your exam was normal, you don’t have to come do that full exam every year. You could come back in five or 10 years, try it again. But especially as we get older now, half the people in the world need glasses, half the people in the US need glasses. So you might be going in to your local eye care provider, optometrist, getting your glasses checked each year or two anyway, just to see if you’re still in the right prescription and they can do the full exam, check for everything else, make sure nothing else looks suspicious, leave you in great shape.

So getting that periodic eye exam, especially as we get older and more of those age related diseases like macular degeneration, glaucoma, et cetera. Obviously if you have diabetes, you’re supposed to get an eye exam every year just to make sure, because if you’ve got diabetes and it’s starting to affect the retina inside your eye, we could get ahead of that. We’ve got good treatments that can prevent you from losing vision. So we want to stay ahead on these diseases. That’s the main thing. Other things, everyone’s going to get cataracts eventually, but what can we do to slow down the development of cataracts? Well, one real easy one is reducing UV light exposure. So you’re out in the sun a lot, wear sunglasses. All sunglasses made today have UV protection. By the way, all regular glasses that don’t have darkened tinted shades, they also block the UV light from going through.

So even if you’re wearing your regular glasses outside because you need glasses, that works too. So wear sunglasses or some sort of eyewear protection. And then eyewear protection is another big one. Depending on what industry you’re in, you’re gardening, you’re in steelworks, you’ve got anything where you’ve got eye injury risk, wear a protective eyewear. It costs like a buck 50 at Home Depot to get those really attractive plastic glasses that are wraparound, but wear them when you’re in those work situations. That’s a big one too. You see a lot of athletes now wear eyewear and sometimes it’s for sun protection, but you’ll see a lot of them when it’s not that sunny day or they’re even playing inside and they might be wearing it for prescription, but also just for eye protection.

Tim Ferriss: Eye protection. Is there anyone out there, and I don’t have a dog in the fight, it’s just that this conversation around sunlight and exposure, it’s like a religious war online. Is there anyone you would consider scientifically credible who has any counter-argument with respect to UV light, why it is important to also get natural exposure or could be important to get exposure to UV light? Or does that just not exist? Is there a strongman argument for that or does it just not exist?

Dr. Jeffrey Goldberg: I don’t ever want to say something doesn’t exist because someone on the internet — 

Tim Ferriss: Which is why I say scientifically credible.

Dr. Jeffrey Goldberg: But no, full-spectrum light, white light that goes from violet through red, full-spectrum light. There’s a lot of decent evidence that that’s good and important. By the way, let’s come back to the development of nearsightedness. We used to say like, oh, maybe people are getting nearsighted as kids because they’re spending too much [of their time] indoor reading. And so it’s just like too much near work is leading to nearsightedness. There’s now pretty good data actually that it’s not the near work, it’s the being inside part of reading inside. And if you just send your kid outside and let them read outside in full-spectrum lighting, they could still be doing their near work or doing their homework, whatever it is, but it’s the full-spectrum lighting that will actually slow down their development of nearsightedness.

So you can get full-spectrum white light, but skip the UV by either having full-spectrum lighting indoors or through the window and you’ve got a nice sunny window. The sun that comes through the window, the glass actually filters UV light, so that’s fine. Your car window filters UV light. So even if you’re not wearing sunglasses inside the car, you’re getting that full-spectrum sunlight. Go outside in the morning, fine, get that first sunlight if you want. But there’s no data that suggests that part of that full-spectrum light has to include UV light.

Tim Ferriss: Okay, got it.I know that this might be asking a lot, but what do you think we might be getting wrong currently in any paradigm of how we think about vision or eye health? Right? I mean, I have a lot of doctor friends, a lot of researcher friends, and I guess it’s especially common among MDs, but they’ll say, yeah, 50 percent of what we know is wrong. We just don’t know which 50 percent. Which doesn’t mean science isn’t important, guys. By the way, it is incredibly critical for not fooling ourselves. And anyway, I don’t think I need to preach that to you, but what would you not be surprised to see overturned in the next five years if you were like, you know what? We’ve always thought X and it turns out, nope, it’s different.

Dr. Jeffrey Goldberg: I’m going to pull one out of my personal favorites list here.

Tim Ferriss: Yeah, great.

Dr. Jeffrey Goldberg: And it comes back to these big ticket eye diseases like glaucoma, macular degeneration, even diabetic retinopathy and other less common versions of these degenerations, let’s say, of the retina, the optic nerve. And we have always said, I even said earlier in the podcast with you, Tim, that glaucoma is the number one cause of irreversible blindness in the world. That I think is going to be the piece that we overturn. We have always said, “Hey, we’ve got to prevent you from losing vision. We’ve got to slow down the disease because once you’ve lost whatever vision you’ve lost, I can’t get that back for you.” And I think that is about to topple.

We are about to get into vision restoration at a level that has been totally unexpected and totally unprecedented, and the science supporting these directions in these diseases is getting really, really juicy. We have discovered so many molecular pathways, approaches to cell therapy. Some of the things we even talked about earlier, like inducing plasticity in the brain. If I stick a stem cell into the adult retina and I say, “Hey, I need you to turn into a retinal cell, hook up with your partners and start doing vision.” Well, during development, the retina, those cells are all developing. They learn to wire up together, do it right.

How do we get a cell that we’re going to put into an adult person to say like, “Hey, I know all you other retina cells are already neighbors with each other, but I’m moving into the neighborhood and I want you to accept me.” But we’re figuring out how to induce that plasticity, like open up the neighborhood, let that cell get into the network, start to participate in the network and restore vision. So it is moving really quickly right now and it is starting to translate, this laboratory science is starting to really move quickly into appropriate, safe human clinical trials. And so I think that is going to be the biggest topple is going to be that we can restore vision. And I will not be surprised if our colleagues in the brain follow suit quickly. We like to tease who’s going to come first, the eye or the brain. I will not be surprised if our colleagues in the brain follow quickly and maybe we could restore cognition in people with severe cognitive disease, Alzheimer’s and these others. So I think this kind of restoring the central nervous system, including the retina and optic nerve, spinal cord injury, I think this is all, we’re going to topple that in these next few years.

Tim Ferriss: That’s very exciting. When I talk to folks I’m like, look, I know it seems like one day, they’re like bananas will kill you and the next day bananas will help you live forever. And it’s like, first of all, a lot of that is fun house mirror warping by media coverage. And secondly, there are so many breakthroughs or breakthroughs that are on the cusp of making their way into clinical practice. I can’t help but be super optimistic about so many, at least the fields that I have a decent amount of exposure to. And I’m going to ask you a few follow up questions, but first, I’ll just say for people interested, if you are interested in looking at how, for instance, and there are multiple ways to induce greater plasticity in various ways, but if you’re interested in the reopening of critical periods, which we alluded to earlier, Gul Dolen, who was at Hopkins and is now at UC Berkeley, has done some wild work and has really rocked the boat and I think a very productive way looking at how MDMA but also potentially other compounds can potentially do that.

And she’s got wild experiments with octopuses and all this stuff that people should check out. But I believe that at some point, if she’s not already doing it, she’s going to look at, for instance, using these compounds to help stroke patients recover motor function. And there are also devices like DARPA and the defense language in Monterey have used for improving language acquisition. I mean, I really feel like there’s a lot of stuff that is not only happening but converging in interesting ways. What leads you to believe that we’re so close, the next five years is close, right? So is it just the publications you’re seeing, the types of science that is being done? Is it just new and novel ways to induce plasticity? Is it because the plasticity gang is finally playing nice with the eye people who are playing nice with the other brain people? What is actually happening?

Dr. Jeffrey Goldberg: Some of those things, like I was teasing before, but the truth is, we, eye people, love to work closely with our colleagues in brain because there’s so much shared science. I do think that there’s an increasing attention to, hey, let’s answer these questions properly, let’s do proper trials, let’s really study these things properly and let’s also move things out of the laboratory and into human testing and have it not just be the fantasy and the mice, but never move it to the person. And so I think that transition, that willingness to grow in that direction, we’ve had actually, to be honest, a remarkable two to three decades now of increasing support for science at the federal level, but also startups. Biotech has had an amazing age and that biotech, when you’ve got an amazing age cooking on the pharma side like big pharma, that then trickles down. So that means startups can say like, “Hey, let’s roll the dice and test this anti-aging formula because if it hits, there’s a market for it at the end of the day. This is important. These are big impact areas.”

So I think the investment that we make in science plays out and we’re sort of coming to a head a culmination. And I think that happens to be matching in time the advances we’ve been making in neuroscience. I think we made huge advances in immunology and cancer biology a couple decades ago, even just understanding what all the cells are. And I think that the analogy is the advances we’ve made even just in the last decade of being able to map the brain, not just even down to the cell level, but the cell-to-cell connections called synapses. We’re now mapping entire brains at that level and understanding how they talk to each other and recording and creating. We’ve got a colleague here who just had an amazing suite of papers, Andreas Tolias and his colleagues creating a digital twin of the entire brain.

And then you can do experiments on the digital twin of the brain. You don’t have to actually do them on an animal or a person to start. You could start there. So the advances in neuroscience and understanding of plasticity and all of these elements I think are converging with the advances that we’ve just been willing to make over the last couple of decades in healthcare, health-related research, discovery research, translational research, clinical trial research. And I think we’re just kind of seeing those two converge right now in an amazing way.

Tim Ferriss: If you don’t mind, let’s talk about mitochondria again for a second. So mitochondria, often referred to as the powerhouses of the cell, I won’t bore people with more ketone talk, but also read a piece recently from a very credible scientist, beautifully written also, about how they’re not just the powerhouses but maybe the motherboards of the cell. And there’s actually a lot of what you could view as social interaction between mitochondria and among mitochondria. Really just the deeper you go, the more interesting it becomes. And I’m wondering outside of the red light, if there are other interventions or technologies, biologics, anything, that you think are interesting for improving mitochondrial health within the visual system, however you want to take that.

Dr. Jeffrey Goldberg: Yeah, absolutely. And in fact, mitochondria, not only are they social with each other and they actually talk to each other, they actually fuse and then separate. They get trafficked up neurons. We talked about the ones that stretch from the eye to the brain. There are neurons of course that stretch from the top of our brain all the way down to the bottom of our spinal cord. There are neurons that stretch from our spinal cord all the way down to our toe tip. These are some long cells and they’re trafficking mitochondria all up and down. So they are social creatures for sure, but it turns out they’re yet a third thing. So they’re powerhouses, they’re social creatures, but they’re also scaffolds and they’re actually the foundation upon which a lot of other cellular signaling that’s regulating what a cell is supposed to do is happening on the surface of the mitochondria.

And so you’ve got metabolism, energy, scaffolding of signaling. And so no wonder half of our neurodegenerative diseases are associated with one or another defect that we can trace back to mitochondria. So that kind of adds up at the end of the day when you look at it that way. And some of the things we’ve already talked about, I mean you brought up red light therapy, that would be one for sure, but vitamin B3, nicotinamide, it’s directly affecting some of that metabolic signaling that is interfacing with the mitochondria metabolism biology. And so actually a lot of these supplements that are about metabolism end up having some link back to mitochondria.

Tim Ferriss: Yeah, I was going to say it’s kind of hard to dodge the mitochondria.

Dr. Jeffrey Goldberg: Yeah. Yeah. And look, it’s cool. Look, I mean I just read that they’re now doing successful mitochondrial transplants, for example, into an embryo. So you can have inherited diseases where the disease is inherited because your mitochondria are bad. Mitochondria get most of their proteins and lipids and all of that that make up a mitochondria. They got most of that built from the nucleus, the regular DNA of the cell. But they have a little bit of DNA themselves that make some of the proteins inside the mitochondria. And so you can inherit that mitochondrial DNA that has mutations and have real serious diseases. It’s now been shown you can transplant mitochondria so that that baby will not have an inherited mitochondrial disease. Is it that far off to think that we could transplant mitochondria into the retina of your eye and stave off another decade of glaucoma? These things are on the table, so definitely interesting.

Tim Ferriss: Okay, so I saw some news about, I think you can’t trust the headlines, but basically babies with three parents, so to speak, out of the UK now. So you mentioned the embryo. So this is a case where you’d be taking third-party mitochondria — 

Dr. Jeffrey Goldberg: You’re hitting it. That’s exactly what I was talking about. So you’ve got DNA from the mom in the egg cell. You’ve got DNA from the dad in the sperm. But you could take a third party’s mitochondria outside of their cell, inject it into that egg just like the sperm went into the egg, and now that egg with Mom and Dad’s DNA and a third person’s mitochondria, including their mitochondrial DNA, will propagate and form the whole embryo. And it’s kind of, I mean it’s an amazing headline. Does that mean there’s three parents involved?

Tim Ferriss: I mean, it’s equally fascinating when you just understand what you’re describing. And part of the reason I’ve been reading and really trying to do a deep dive, always dangerous when you are only half scientifically literate. But on my mom’s side of the family, a lot of Alzheimer’s and my mom’s had some deterioration as well, but she’s APOE 3/3. And I’m looking at it, I’m like, I wonder if there — and also just word to the wise, again, not a doctor, talk to your medical professional, but if you’re trying to evaluate your metabolic health, don’t just get fasting glucose taken because you can get lucky with fasting glucose and you might even do hemoglobin A1C, which is a running three-month average of your fasting glucose is maybe a simple way to think about it, something like that. But also get your insulin measured because that was missed by my mom’s local doc for many, many years.

And her fasting glucose, even her hemoglobin A1C was kind of within tolerable levels. Then her insulin was, it was so out of range as to just jump off the page. And so then I was looking at it, and there of course could be a million different contributing factors, but I was like, I wonder if there’s some type of issue in her mitochondria, in which case, my understanding is you do inherit the mitochondria from your mom’s side is my understanding. 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 done about it at this point, frankly, but if there is even a small possibility that you could do something about it, I’m like, well, I’d like to kind of know what I’m dealing with. So that’s the genesis of me asking about also the mitochondrial health side of things.

Dr. Jeffrey Goldberg: We don’t have a great blood test for your mitochondria. Obviously, you could get it sequenced. We don’t know how much your fidelity to mom’s mitochondria might play a role in your future cognitive health. I would add to your list though, to other standard screening tests — 

Tim Ferriss: Yeah, please.

Dr. Jeffrey Goldberg: — that certainly are likely to impact your cognitive health as you age. And with that, again, the eye’s part of the brain, your visual health too, and that’s going to be your lipids, your fasting lipids, and your blood pressure. And every bit of science points to, yes, you can inherit it, your ApoE genes that can change your risk. But a very big contributor is going to be your lipids and your blood pressure because those are going to contribute to what we call microvascular disease and ultimately, brain atrophy as we get older and ultimately, cognitive function. And if you could be really ahead of the curve and be really clean with your lipids, whether that’s with diet and exercise or upgrading to some of the medicines that help with that and really clean with your blood pressure, again, diet and exercise or there are medicines we can give to help with that, staying ahead of the curve on those is almost certainly a huge contributor to your later cognitive health.

Tim Ferriss: Yeah, I’ve got those suspects under control and very well-dialed. I’m just like, are the mitochondria the boogeyman in the closet that I’m not contending with? But yeah, I’m trying to do all the stuff you would expect to also help support mitochondrial health and I don’t think this is immediately obvious, people think of exercise as body exercise. But if you want to increase the brain-derived neurotrophic factor release and Klotho release, which hopefully someday soon we will have, it’s an injectable therapy for humans, exercise, you’ve got to do it, do some weight training, do some Zone 2, do VO2 max every once in a while. It’s incredibly valuable.

Dr. Jeffrey Goldberg: And I think the important thing for listeners is that, and when I say listeners, I include myself because I intellectually know I need to do more exercise and I’ve still got to figure out how to get around to actually doing that more exercise. So I’m in the listener crowd here of what I need to say, but the important thing to remember is that the biggest gain comes from going from none to some.

Tim Ferriss: Yes.

Dr. Jeffrey Goldberg: If you go from some to twice as much, yeah, there’s an improvement there too, but not as big as the value proposition of going from none to some.

Tim Ferriss: Yeah, yeah. Just scale it down, guys, if you have to, but don’t do nothing.

Dr. Jeffrey Goldberg: Don’t do nothing because you feel like “I can’t do a million hours, so I’m throwing in the towel and I won’t do any.” Half an hour, four or five days a week, brisk walk, get that heart rate up, have it count, easy. Make it easy on yourself. If you want to then go nuts and do hardcore weight training, hit your Peloton, have your trainer, train for a marathon, okay, fine. But that biggest difference in your life was going from none to some.

Tim Ferriss: Can I give you the greatest non sequitur in the history of my podcast? It’s just because you mentioned that your number one most common question was, “Can I have cannabis?” So I’m lucky to know a bunch of very amazing docs and blah, blah, blah. I interview people, so I get to meet a lot of fascinating folks and one of these super high-end, really sophisticated docs, he was telling me the most, can you guess? I’ll give you a shot. I’ll give you a shot on the three-pointer. What do you think his — I’ll be astonished if you guessed this. Even if you believed it, you probably wouldn’t say it. But what do you think one of his most common questions is that he still refuses to answer publicly? I’ve wanted him to do it.

Dr. Jeffrey Goldberg: Oh, my God, this is a guess what you’re thinking. When we’re in training for medicine, we get asked questions like this all the time, and some of them are like, “Okay, I want you to guess what I’m thinking. Go ahead. Three trials.”

Tim Ferriss: No, no. All right, let me save you the trouble.

Dr. Jeffrey Goldberg: All right, lay it on. Lay it on. What did he say?

Tim Ferriss: This is the question he gets all the time, which is from male patients. “How can I shave my balls safely?” This is the question he gets more than any other. He’s like, “Really? I’ve done all this training, I’ve done all this. And that’s the question that I get more often than not.” Anyway, I don’t know why I felt compelled to share that. Sorry.

Dr. Jeffrey Goldberg: I’m going to trust that he’s not an eye doctor because I never get that question.

Tim Ferriss: Yeah, that’s right. He’s like, “What are you talking about?”

Dr. Jeffrey Goldberg: Tim, you interview a lot of people. What did Matt McConaughey say to that question?

Tim Ferriss: Maybe this should be one of my rapid fire questions that I finish with.

Dr. Jeffrey Goldberg: I’ll pick a path on that one. I don’t have enough experience to talk about that.

Tim Ferriss: Yeah, yeah. No, we can both pass on that one. But is there anything else that we haven’t covered that you would like to mention? Any treatment or research or researchers that you think people should take a look at? I mean, we talked a bit about mitochondria, certainly talked about the lens, we talked about glaucoma and hopefully within the next five years, as you said, being able to potentially restore function or stave it off to a much greater extent. We didn’t really get into treating nerves. I have a note about treating nerves, but I’m not sure we need to cover that. Is there anything else that you’d like to mention that we didn’t have a chance to discuss?

Dr. Jeffrey Goldberg: Look, I want people to understand that first of all, these are all amazing questions. You’ve hit a wide range and we can’t answer them without doing the science behind it. So first of all, as They Might Be Giants said, “Science is real.” So first of all, science is real. And second of all, I would just encourage people, ask your, in this case, eye care provider, “What’s going on with me? Are there clinical trials?” Volunteering to be in clinical trials, I’ll tell you, I know patients are so grateful when they get into our clinics here and they get into a clinical trial because they’re accessing a treatment before it is publicly 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 that and they’re so grateful to get into these trials.

But I always say, “We are so grateful. We can’t do the trials and therefore, decide whether you should take the supplement or use this virtual reality device or go in front of red lights every day or microdose LSD or change your microbiome. We can’t figure that out if we don’t have the patients come be in the clinical trials and volunteer their time and energy, the extra trips to the office to get their eyes measured or special pictures taken or all that kind of stuff.” So I say, “I know you’re grateful to be in this trial, but I’m grateful to you too.” We are grateful to the patients. So I think we’ve all got to participate in science as a community so we can do these trials and figure out how we’re going to fix ourselves and go from disease to normal. And by the way, go from normal to supranormal. Right? We’ve got to prove it, right?

Tim Ferriss: Yeah. Where would you suggest people search for or find clinical trials around them? And I’ll just reiterate what you said. I have seen so many studies that I’ve been involved with hit a wall with subject or patient recruitment. They just hit a wall.

Dr. Jeffrey Goldberg: That’s a tough one, right?

Tim Ferriss: They really, really benefit from people who are proactive. But if someone’s listening, they’re like, “That sounds amazing. I’d love to actually see what this looks like in practice and maybe figure or help people figure out something in the process for others or myself,” where do they even look? Where would they begin?

Dr. Jeffrey Goldberg: One really good place in the US to look is a website called clinicaltrials.gov. So it’s got it right there in the name, and you go on the front page for clinicaltrials.gov and you type in your disease. So you could type in glaucoma, diabetes, whatever it is. It’ll give you a list of, here’s trials that are recruiting right now actively. And then you can click on any of those and say like, “Oh, that one’s in my city,” or “It’s not in my city, but I’m going to call or send an email to them anyway and say like, ‘Hey, could I be eligible for that?'” So that’s probably one great resource. And then the other would be, again, for diseases would be in the case of research for specific diseases, almost every disease has one or more foundations or patient support sites that bring people together.

And I think of one in our backyard, here in San Francisco called The Glaucoma Research Foundation. There’s another one in New York City called The Glaucoma Foundation, dozens more of course, but they also maintain websites that have a lot of patient-directed information, patient-facing, what to learn about your disease. You were asking before, where’s a reliable source to learn about stuff? That’s one. But they’ll also sometimes talk through what’s happening in clinical trial space or where is that happening or where some hot spots for clinical trials. So I think those are a couple good resources. Of course, nowadays, Google, just any web search engine, it’ll get you started in the right direction.

Tim Ferriss: Yeah, perfect. And if people are wondering, “Well, Tim, have you done any of this yourself?” Yeah, actually, I’ve been a subject in all sorts of different studies from undergrad all the way up to a few years ago for various things, including at Stanford, way back in the day, just a few years after college. So it’s fascinating also just to see what it looks like in real life. What does scientific study look like when it’s implemented? Well, thank you so much, Jeff. This has been a fantastic wide-ranging romp. It’s still and will continue to be intensely personal. So I will keep people listening posted. I promise not to sell you any kratom eye masks through some MLM scheme. And I will be continuing to investigate all of this. This has been super helpful. I took a ton of notes. Is there anywhere you would point people to find you online or learn more about you?

Dr. Jeffrey Goldberg: Yeah, absolutely, Tim, and you joked in the beginning that this podcast is yours and certainly allowed to be self-serving. But I’ll throw one plug in here at the end, the Stanford Ophthalmology website. We actually maintain a list of clinical trials. And again, if we want to tap this whole team here on the back, our faculty, our clinical research staff, everyone involved in it, stem to stern is fantastic. And I’d like to point out a lot of the clinical trials of trying to pull things out of the lab and test them in patients for the first time, a lot of work on vision restoration, vision protection and restoration. Clinical trials going on right here. My work and some of the work of our amazing faculty and staff here.

So you can actually go to Google Stanford Ophthalmology Clinical Trials. We have a web page on our Stanford Ophthalmology site that goes disease by disease and has contact info in how you plug right into the trials here. And we have people in our community participating, but we have people who fly in from everywhere to participate in these clinical trials. So we’re happy to see if we can fit you in too.

Tim Ferriss: Beautiful. And for people listening, I will link to that in the show notes at tim.blog/podcast. So that’ll be easy to find. If you just search Jeffrey Goldberg or Goldberg, I think you might be the only Goldberg. There might be one other. Search Jeffrey Goldberg, and it’ll pop right up and you’ll be able to find the links. Jeffrey, thanks so much. I really appreciate the time. And to everybody listening, as mentioned, show notes, tim.blog/podcast, you’ll be able to find links to everything we discussed and more. And until next time, be just a bit kinder than as necessary to others, but also to yourself. And thanks for tuning in.

The post The Tim Ferriss Show Transcripts: Dr. Jeffrey Goldberg — Creating Supranormal Vision, Cutting-Edge Science for Eye Health, Supplements, Red Light Therapy, and The Future of Eyesight Restoration (#823) appeared first on The Blog of Author Tim Ferriss.