Eight out of every 10 Americans take a supplement. That's the highest number ever recorded. But, there's a problem. A

lot of these pills have no evidence to back them up, and they sit behind massive marketing

budgets. So, I set out to investigate the most popular supplements on the planet. Anti-aging, muscle growth, heart

health, brain health, gut health, sleep. From fish oil to creatine, protein powder, vitamin D, and dozens of others.

I put everything I've learned in 30 years of medicine and research science into this investigation.

And what I found often blew me away. Some of the most popular supplements have the worst evidence behind them. And

others that I thought were just hype actually have interesting effects. So, I ranked every single supplement on the

list. Thumbs up when the claim is backed by evidence, and less than half of the supplements I looked at made that

ranking. Or thumbs down, current evidence does not support the claim. By the way, I don't sell any supplements. I

don't sell prescription drugs, either. No one tells me what to say, and there are zero sales pitches in this video.

And along the way, I'll share with you which supplements I personally take and which I give to my own family. Let's

start with the biggest promise of all, anti-aging supplements. These pills are supposed to keep you young and postpone

death. But, can they deliver on that massive promise? One of the most popular drugs marketed as anti-aging is

something called rapamycin. Rapamycin is a drug that inhibits a growth switch we have inside our cells called the mTOR

pathway. And the mTOR pathway does affect lifespan in lab animals. I actually did some of these experiments

back in grad school, and it's super interesting. You can crank the pathway up or down, and it does affect how long

the animals live. It's fascinating. But, we're not mice. We're not lab animals. So, what happens in actual humans? In

humans, rapamycin modulates the immune system. So, it's actually used as a prescription drug. It's often given to

patients with organ transplants to try to tone down the immune system and prevent organ rejection. And

interestingly, those patients have a lower risk of specific types of cancer, usually skin cancers. The exact reasons

and implications are still unclear. It's being investigated. Other than that, the data on rapamycin in humans is pretty

mixed. There's a recent trial that reported improved well-being in participants receiving rapamycin.

Risk of infections depends which trial you look at. In some, we see higher, some we see lower

risk of infections in patients receiving rapamycin. And in some studies, rapamycin appears to raise cholesterol

and triglycerides. There's no evidence right now that rapamycin affects human aging or human lifespan.

So, calling it an anti-aging supplement for people is basically marketing. It's a clear thumbs down for that claim, not

supported by current evidence. Interesting preliminary results, but right now couldn't possibly recommend

rapamycin for human anti-aging. Another prescription drug that's very popular in the anti-aging world is metformin.

Metformin is also prescription drug used in medicine, often prescribed to people with type 2 diabetes. And there's lots

of trials showing that it improves glucose control, blood sugar control in diabetics. And there's a very long

randomized trial, a 10-year trial, showing that metformin helps prevent diabetes complications like heart

attacks and even deaths, total deaths in diabetics compared to diet alone. Okay, what about someone who doesn't have

diabetes? There's some evidence that in pre-diabetics, metformin may affect what's called the epigenetic clocks. So,

these are supposed to be biomarkers of the rate of aging. Although how reliable they are is It's

controversial. What about people who don't have diabetes or pre-diabetes? The data's pretty mixed. One trial found

that Metformin actually counters some of the benefits of exercise in older individuals. Another trial found no

effect of Metformin on epigenetic clocks in participants who were not diabetic or pre-diabetic, although they did have HIV

in that trial. But there's also some studies reporting benefits, for example, improved gait speed was reported in one

trial in elderly participants receiving Metformin. So bottom line, Metformin for diabetes in people with diabetes, thumbs

up, lots of evidence there. For healthy individuals as a general anti-aging supplement, clearly the

thumbs down. Interesting mixed data, but the idea that it's an anti-aging drug for human beings is currently not

supported by the evidence. All right, next on the list we're going to look at another very popular supplement marketed

as an anti-aging compound. It's got mad press over the years, and that's Resveratrol. So

Resveratrol's a natural compound found in the skin of grapes and in some berries. And unlike the other two

drugs we looked at, it's not used in medicine. It's not a prescription drug. But it does have really interesting data

on it. There are trials looking at diabetics again, and Resveratrol seems to help reduce waist circumference,

cholesterol, and blood pressure. And it might also help improve glucose control, glucose metabolism, kidney function,

some aspects of memory, reduce liver fat, and inflammation. So definitely some really promising results. There are

also some red flags when it comes to Resveratrol. One small trial found that Resveratrol blunts the benefits of

exercise in older participants, similar to what we saw with Metformin. Specifically,

improvements in VO2 max and blood work, those were blunted in the participants receiving Resveratrol. There's also some

studies reporting benefits of resveratrol for exercise performance. So again, here the data is mixed. There's

one signal of concern. There's a couple trials in patients with Alzheimer's. They see faster loss of brain size

on patients receiving resveratrol, although the exact clinical implications are still unclear. Bottom line, very

similar to the others, some really interesting preliminary data there, but as a general anti-aging supplement,

thumbs down right now, the evidence is does not support that claim. This needs a lot more work and a lot more

clarification before it's ready for prime time. All right, we're going to look at two last ones in this category

of anti-aging. Then we'll move on to heart health, where I found some of the biggest

surprises. NAD is a molecule that we all have in our bodies. It plays a role in energy metabolism, a number of functions

in the body. And NAD levels drop gradually with age. So the idea was, let's add it back and see if we can

rescue aging or improve uh some functions in elderly people. One issue is that NAD seems to have poor

bioavailability. So if you take NAD directly, the NAD itself, your levels of NAD don't go up

much. So what people do is they take precursors, molecules like NR and NMN, which are then converted in your body to

NAD. And those do work. They raise NAD levels in the body. But does that provide any actual benefit? So a recent

systematic review went over dozens of trials with these molecules, and they found

basically no clinical benefit in human beings. So a clear thumbs down right now for NAD. So far we have no demonstrated

benefit in humans. Remember, thumbs down doesn't mean the supplement causes harm, right? It just means

currently the evidence does not support the claim. All right, last one in this chapter is collagen. Collagen is also

marketed as a anti-aging supplement, but for skin, as an anti-wrinkle supplement. Here I found a ton of uncertainty, a

number of meta-analyses disagreeing basically with each other. I went over a number of trials one by one. Several

report that collagen hydrolyzed peptides can deliver some benefits, improved skin elasticity, improved skin hydration, and

in some trials reduced wrinkles. But, there's also plenty of trials finding negative results, so a lot of what we

call heterogeneity. And the results for wrinkles actually seem to be the least compelling, the

least impressive, and arguably that's the one that people would be interested in the most. So, it's hard to be sure if

collagen really is having these uh skin rejuvenation effects or not. There might be an effect there. I'm not saying there

isn't, but if it's real, it's probably not a huge. So, this one is pretty debatable. You might call it a thumbs

sideways, completely uncertain right now. If I had to decide either way, I might

go thumbs up, but it'll be like a really, really weak thumbs up. By the way, all

of these rankings are completely open to change. If the evidence changes, my opinion changes. So, bottom line, none

of the anti-aging supplements, the most popular ones out there, impressed me evidence-wise. I don't take any of them,

and this has led to my first rule of supplements, which is usually the bigger the promise, the weaker the evidence.

Now, not every supplement out there is just hype. I've made that mistake before of assuming that there's a number of

supplements that actually have strong evidence behind them. Just to give you a quick example, creatine is a very

popular supplement in the fitness world for athletic performance, for muscle building, and there's dozens of

randomized trials looking at creatine. So, creatine monohydrate is the most common form, and that combined with

exercise, combined with resistance training, with lifting weights, not sitting on the couch,

does increase strength and muscle mass. So, it's a clear thumbs up for that specific claim for creatine. Dozens of

randomized trials support that effect. We'll talk about creatine and the brain function, creatine and cognition a

little bit later cuz that's another big question. The typical dose in trials for creatine is somewhere between 3 and 5 g

a day with an optional loading phase of about 20 g a day for about a week. Now, let's go over some common safety

questions for creatine real quick. Does creatine mess up your kidneys? Does it cause cancer? And does it cause your

hair to fall out? So, kidney function, several trials have looked at this. They found no effect of creatine supplements

on kidney function in the general population. What creatine does is it raises your levels of creatinine because

creatinine is a breakdown product of creatine. And in people with kidney failure, creatinine levels go up. So, it

can look like the person has worse kidney function.

But, I think it's an artifact. When you look at other measures of kidney function, they're not worse on creatine

supplements. So, that's for general population, people with healthy kidneys. If you already have

a chronic kidney disease, kidney failure, something like that, there's more uncertainty just because there's

not no studies in that very specific population. Talk to your doctor if that's your case

before you start creatine. And we actually have a whole video talking about that very specific problem, and

I'll link that below. As for cancer, there were some studies in lab animals that suggested a link, but the best

evidence we have in humans up to several years has not found a signal of concern for cancer uh for creatine supplements.

Although, very long-term data, like decades of follow-up, that's a lot more limited. And for hair loss, the bottom

line is the evidence does not support that creatine supplements cause hair loss. And we also have a full video on

that, which I'll link below as well. Okay, another example real quick is protein powder. This is another

ubiquitous supplement in the fitness world. So, protein powder is not magic. It's just a convenient way to add a bit

more protein to the diet. And lots of trials on that together with training again, yes, it helps improve strength

and body composition. Basically, increase muscle. And there's some evidence, not as strong as the muscle,

but some suggestive evidence that protein powder might also help reduce body fat a bit. And this is ultimately

about the total amount of protein. So, the effect seems to level off around 1.6 g of protein per kilo of body weight per

day. And that's protein in the diet, right? So, above that, we see diminishing returns. Whey is the most

studied form of protein powder, but there are many others and that have been studied as well, including some

vegetable forms like soy. Basically, they all work. It's ultimately essentially about the total

amount of protein. There's some questions about the heavy metal content of protein powder. We have a whole video

going over the details. The bottom line is that this is a little overplayed. Most brands have either

non-detectable or levels that are well below thresholds of concern. So, protein powder for strength and for muscle mass,

for hypertrophy, clear thumbs up. Randomized trials back that up. All right, let's talk about heart health.

And here, I found some of the biggest surprises. Some of the supplements that are super popular,

the evidence is surprisingly weak and some even have safety concerns. And then one supplement that is hyped a

lot less, I found some really interesting effects, actually. So, let's start with vitamin

K2. This is one of the most popular supplements out there. I've seen hundreds of people, no exaggeration,

pushing vitamin K2 on social media for heart health. The idea is that K2 keeps calcium out of your arteries and it

protects your heart. It's heart healthy in the long run. And sometimes K2 is suggested, recommended by itself,

sometimes with vitamin D. And there's a couple very recent trials from this year showing that, yeah, vitamin K2

supplementation can slow down calcium deposition in the artery wall. The calcium score still

goes up, but it goes up slower in people receiving vitamin K2 supplements. But is that a good thing for the heart?

Because the relationship between calcification and plaque stability is actually a little complex. There's a

growing body of evidence that at least in some cases calcium can actually improve plaque

stability, especially big chunks of calcium, what we call macrocalcification,

which is mostly what you see with a calcium score. And then small specs of calcium, what we call

microcalcification, that's usually linked to plaque instability.

So, we just can't assume that less calcium in the artery wall means a healthier heart and fewer heart attacks.

It's just not that simple. So, there is endless conjecture out there in these recommendations to take A2 for the

heart. The bottom line is we don't know. Nobody knows what the net effect, what the

total effect of K2 supplements is on heart health, heart attacks, strokes, angina, revascularization procedures.

There are no trials that were designed to properly measure these outcomes in people receiving K2 supplements with or

without vitamin D. So, we don't really know what effect, if any, vitamin K2 has on these outcomes. All these studies out

there look at what we call intermediate biomarkers. So, it's things like calcium score, insulin resistance, measures of

artery wall stiffness. So, those are interesting, those are relevant, but they're preliminary. So, vitamin K2 for

heart health, a clear thumbs down. Not that it's harmful, but that the current evidence does not support

the claim that vitamin K2 with or without vitamin D is cardioprotective, is good for your

heart or good for your arteries in general. Hopefully, it's going to turn out to be amazing in the future. Right

now, nobody knows, and the popularity of K2 is running way ahead of the clinical data. So, for what it's worth, I don't

take K2 for heart health, and I don't give it to my family members, even the ones that have very high calcium and a

lot of plaque. And this has led to my second rule of supplements, which is the evidence has to match the promise. A lot

of marketing for supplements shows you evidence for one thing and then promises another. Calcium rising slower in the

artery wall isn't necessarily better heart health. A change to your microbiome isn't necessarily better gut

health or better digestion. Right? So, you want to pay attention to that switcheroo. Let's contrast the data we

just looked at to another supplement that I see hyped a lot less on social media, and that's red yeast rice. So,

there's a very large trial that gave participants a red yeast rice extract called Xuezhikang. This is a Chinese

product. I'm sure I'm butchering the pronunciation. Our Chinese-speaking viewers will let me know. But, they

basically gave this extract of red yeast rice to thousands of participants who had a history of heart attacks. And so,

half of the participants of the trial got this extract, the other half got a placebo as a control group. And they

followed them for over 4 years, pretty respectable follow-up, and they saw substantial reduction in these heart

endpoints, things like heart attacks and even mortality, total deaths. Now, there's some serious limitations to that

trial as well, which we'll touch on in a second. But, this standard of evidence, this

type of study, this type of trial is something that we don't have currently for vitamin K2 and heart

health or for a number of other supplements that we're going to be looking at.

That's the point I'm trying to make. And this has led to my third rule of supplements, which is that the most

popular supplements are often the least validated. All right. Limitations of this big trial we just talked about.

First of all, it's never been replicated. It's a one-off. Second, it's a specific product and it's

a specific population with a history of heart attacks. So, it doesn't prove what happens to

healthy people. Completely different question. So, for me, this would be a very cautious thumbs up, a very modest

thumbs up for that specific product in that specific population. Okay, what if you don't have access to this

Xuezhikang? What if you grab a random red yeast rice product at your local health store? Then it becomes more of a

guess, but we're going to go over some factors that can help you make more of an educated guess. So, one problem with

red yeast rice, and this has been studied, is you can't trust what's on the label. The active principle in red

yeast rice that is responsible for most of the biological effect is something called monacolin K.

And studies have found a huge variability in the content of monacolin K in different brands. Up to a 100-fold.

Some brands had no detectable monacolin K. So, it's kind of the wild, wild west. And this is a problem for all

supplements really because the legislation, the regulations for supplements are really lax.

One way around this is to rely on third-party certified brands. That way you know what's in the pill. In terms of

dose, what they gave them in that big trial was twice daily 600 mg of Xuezhikang, that extract.

So, that's 1,200 mg a day. And later studies have estimated that this corresponds to about 7 to 10 mg of

monacolin K, in that ballpark. Although, we have to bear in mind, this Xuezhikang, this extract, contains other

molecules as well beyond just monacolin K. So, that big trial actually doesn't prove which specific component delivered

the benefits. But, here's something really interesting about red yeast rice that most people don't realize.

Monacolin K is the exact same molecule as Lovastatin.

So, Lovastatin is an older statin, a weaker statin that is is not prescribed much anymore. They're the same thing

chemically. They're the exact same molecule. So, that means that the mechanism of action of Monacolin K is

known. It's not a mystery. And we would expect similar benefits and similar uh side effects, potential side effects as

for a weak statin. Another rough measure to know what's in your supplement is blood work because Monacolin K

just like Lovastatin, they're the same thing lowers LDL cholesterol. So, measuring your blood work, look at your

LDL cholesterol levels before and after you start taking a red yeast rice. It's one way to know what's in there. It's

not the most precise measurement in the world, but it gives you a sense of whether you have any Monacolin K in

there or not and the approximate amount, the approximate biological effect. All right, next on our list is fish oil.

This is a big one. Fish oil and omega-3s for heart health, we've heard this many times. So, one big trial looked at

25,000 people and gave half of them fish oil. And it contained 460 mg of EPA and 380 mg of

DHA. So, these are long omega-3s present in fish and seafood. And basically, they found no effect of the fish oil on total

cardiovascular outcomes, total cardiovascular events or cancer outcomes that they looked at.

But then in a secondary analysis, they did find a significant reduction in heart attacks specifically 28% fewer

heart attacks in people receiving the fish oil. And interestingly, this effect was seen only in participants that ate

low amounts of fish under 1.5 servings a week and not in participants who ate more fish. So, it's

possible. It's a plausible explanation that what the fish oil is doing, these supplements are doing, is replacing

those omega-3s that are not coming from the diet. Now, I want to be very clear that this is very much a gray area.

There are several trials also that find no benefit of omega-3s of fish oil.

So, this is very much controversial. I'm not trying to present this as very clear. And so, my takeaway from all of

this is if you have a diverse diet with some fish, some seafood with plenty of omega-3s, then adding a supplement on

top, adding some fish oil on top, is unlikely to do anything. We have no evidence that that provides a benefit

for the heart. So, it's thumbs down for that context. If your diet doesn't include fish oil and seafood, then I

think it's more debatable. Not a slam dunk at all, but more of an arguable context. Full disclosure, I take

an omega-3 supplement, an algae oil, because I don't have much fish and seafood in my diet.

But, it's not clear at all whether it's going to provide a benefit in the long run or not. We also want to be careful

with the dose of omega-3s. There's randomized trial data showing that at a very high doses of several grams a day,

the risk of atrial fibrillation, that's a type of arrhythmia, goes up. So, I generally try to stay

under 1.5 grams a day or even under 1 g a day. There's no clear cut-off here, but based on the trial data that I've

seen out there, uh in these ranges, it seems to be less of an issue. Just to clarify, there are

some prescription omega-3 uh formulations out there for specific issues for people, for example, with

very high triglycerides. Your cardiologist may prescribe that. So, they're usually EPA alone at very

high dose, like 4 g a day. So, that's completely different from your regular over-the-counter

omega-3 supplement or fish oil. All right, let's go over a couple more popular supplements for heart health

real quick. Nattokinase, CoQ10, and serrapeptase, and then we'll move on to brain health and other topics. So,

nattokinase is an enzyme isolated from natto, from fermented soybeans, and it has very interesting preliminary data.

It seems to affect blood clotting, but is it good or bad for heart health at the end of the day? And the bottom line

is no one knows. There's no trials designed properly powered for heart health

outcomes like heart attack, strokes, angina, things like that that affect your quality of life and that really

matter at the end of the day. There is one study that's widely shared online that suggested a very impressive drop in

many different metrics of blood work and even a reduction of plaque size. However, this is not a proper trial.

There's no randomization. There's no proper control group. There's a lot of biases in that type of study design. So,

it doesn't show that it's nattokinase causing any of these effects. The largest randomized trial using

nattokinase lasted a couple years. They found no improvement for artery wall metrics or for blood work. One caveat is

they used a lower dose. They used 2,000 units of nattokinase daily, whereas some of these other studies

with the more impressive claims, but that are methodologically much weaker, some use much higher doses, around

10,000 units. So, the trial we have so far, that longest randomized trial, doesn't

address what happens with a higher dose of nattokinase. So, right now, nattokinase for heart health, clear

thumbs down. Very interesting preliminary data, nowhere near enough to support the idea that it's a heart

healthy supplement or to recommend to millions of people. All right, CoQ10 is a compound present naturally in our

cells. It's involved in the energy metabolism. And CoQ10 levels go down in some people

taking statins. So, the idea here, very reasonable, was let's add back CoQ10 and see if it improves anything. But,

randomized trials have been disappointing. No consistent benefit of CoQ10 given to people

on statins. One possible exception are people with heart failure. There is some randomized trial evidence of benefit

there, including a reduction in cardiovascular outcomes and even deaths. So, for that population, I would nudge

it up to a cautious thumbs up. I think it's just one randomized trial so far showing those benefits.

In general, for everybody else, giving people CoQ10 on or off a statin,

thumbs down. Very interesting idea, but the evidence currently does not back it up. And finally, we have serrapeptase.

Serrapeptase is an enzyme. There's trials giving the supplement to people post-surgery. It seems to improve the

swelling and the pain, so it might have an anti-inflammatory effect. And it also seems to play a role for blood clotting.

So, the idea was, well, maybe this helps unclog arteries or helps prevent heart attacks. But, it's never been tested in

humans for any of that. So, clear thumbs down right now for heart health. Very interesting ideas, very interesting

preliminary data, not nearly enough evidence to recommend to human beings. Out of all these supplements popular for

heart health, the only one I take is omega-3s. And the only reason I take it is because I have little to no fish and

seafood in my diet. Otherwise, I wouldn't even take that one. Okay, here's another one, another popular

supplement or supplement-like product where you can pretty much just save your money. And that's specialty salts. So,

all these popular salt alternatives, the Himalayan pink salt, the Celtic sea salt, the Baja sea salt, one of the main

marketing pitches is that they contain trace minerals, things like manganese and boron.

And it's true that they contain more of those than your regular table salt, but the amounts are still minute. These

salts are still overwhelmingly sodium chloride, like 97 or 98%. Studies have tried to estimate this. You would need

to eat a colossal amount of salt to get a meaningful amount of these trace elements from

Himalayan salt. It's just not a good bet for most people. Also, most of these products are not iodized. So, if you

replace your regular table salt, most brands of which are iodized, with one of these popular salts, just

make sure you have some iodine in your diet elsewhere. So, if you like the color or if you like the taste for

culinary purposes, that's totally fine. But, there's no health reason to buy these specialty salts. Clear

thumbs down for the health claims. All right, next let's look at blood sugar and diabetes. And here, I found some

massive contrasts. Let's start with berberine, which is a well-known supplement marketed as the natural

metformin. And there are dozens of randomized trials showing that, yes, it can help control blood sugar, reduce

blood sugar, both fasting blood sugar and postprandial after a meal. And hemoglobin A1C, glycated hemoglobin,

it can also improve that a bit. And these trials are usually in diabetic patients. And there's also some evidence

that berberine may help reduce cholesterol, triglycerides, and even blood pressure.

So, thumbs up for berberine and blood sugar control for that claim specifically

in people who have abnormal blood sugar, right? Like diabetics. Healthy people don't need to take

berberine. I don't take it. And by the way, saying that it's nature's metformin, that's basically hype. That's

not supported either. Because as we saw in the beginning of the video, metformin has a different level of evidence. A big

trial showing reduction of actual diabetes complications like things like heart attacks and even deaths. So,

berberine hasn't shown that. So, it's not accurate to say that they're equivalent.

But, berberine has clearly been shown in dozens of trials to help reduce blood sugar in diabetics, which I think is a

legit benefit. We have plenty of evidence that that provides benefits. Now, possible side effects of berberine,

like any supplement by the way, potential side effects can happen with any pill, prescription or not.

Some people report GI side effects, bloating, gas, discomfort. Also, it can interact with some medications. This is

also a general point for pretty much most supplements. Talk to your doctor before you start berberine or any

supplement really. And be especially cautious if you're pregnant. Again, general point for any supplement. Okay,

I want to contrast berberine to another supplement that's pretty popular and aggressively marketed out there by

influencers, and that's Anti-Spike. So, this is marketed for its blood sugar control properties, but it has never

been scientifically tested in humans or otherwise. What they did was they took some existing products and they mixed

everything together and they just went straight to marketing. But, active principles of different products can

interact and they can lose effects that they have when they're alone or they can gain new effects, including side

effects. So, we have to test these things. So, Anti-Spike for blood sugar control, a clear thumbs down. There's no

compelling rigorous evidence to back it up. And speaking of hype, another one that's hyped to high heaven is AG1 or

Athletic Greens One. This is a supplement that's marketed by every podcaster and his grandma. And the

pitch tends to be really vague, things like it supports your energy, it improves your immune system, your

digestion, just really vague stuff like that. But, the largest trial using AG1 actually found no improvement. They

measured tons of metrics of blood work and nothing got better. Kidney function, liver function, cholesterol, etc., etc.,

nothing improved. Now, AG1 is a powder from greens. So, if you have a poor diet with not a lot of vitamins and you take

this thing, yeah, you're going to get more vitamins. But, you can basically get a multivitamin that costs 10 times

less. AG1 goes for about $100 a pouch. It's incredibly expensive. Just eat a salad, honestly. Another

claim I've seen out there is that it makes changes to your microbiome, but everything we eat changes our

microbiome. In fact, in that same study, the placebo group had some changes to their microbiome. And the actual changes

to digestion reported by the participants, nothing changed significantly. There was no significant

benefit. So, for most of these vague claims around AG1, clear thumbs down. Just a little side note, how do they

sell these supplements that have little to no evidence behind them? AG1 or anti-spike.

They use testimonials. Basically, you go on the website and has all these stories from random people saying they felt

better or they solved some health issue. This has zero scientific value. Don't fall for testimonials. Testimonials are

for chumps. That's the truth. They don't account for placebo effect, for all kinds of biases. I mean, how can you

tell that those are even real people on the website? So, you really want to watch out for that. People lean on

testimonials when they don't have real evidence. All right, let's move on to bone health and then we'll look at brain

health, sleep, etc. And for bone health, again, I was surprised because some of the most popular supplements have

surprisingly weak evidence. And then some that are much less known, much less hyped, I actually found some

interesting effects. So, when you think about bone health, first thing that comes to mind is vitamin D and calcium.

But I was actually surprised to find how thin the evidence is for those. Several large trials with thousands of

participants have found no benefit of vitamin D or calcium supplements or both combined

for risk of fractures or falls in a general population, especially in higher quality trials. I did find some

exceptions, so I want to show you that. There's one study where they looked at very elderly women, average age 84, in

residential care with a relatively low calcium intake before the trial, and they gave them vitamin D and calcium

supplements, and they saw a substantial reduction in risk of fractures. So, I think the takeaway here is similar to

what we saw with the omega-3s. If you are a fairly healthy person with not very high risk of fractures, and you

have a diverse diet with vitamin D with calcium, then adding a supplement on top there's very little evidence behind it.

I would give it a thumbs down for that general claim. But, if you can't get enough vitamin D or calcium or both for

some reason, uh then I think it's more reasonable to supplement. And I think this is a

general rule for supplements that are essential nutrients. Vitamin D and calcium are essential nutrients, and so

there are many others like vitamin B12 or vitamin C or iron. For all of those, my logic is ideally get it from your

diet, but if for some reason you're not getting enough, then it's reasonable to supplement. Great source of vitamin D

include fatty fish, organs like liver, fortified milks, and some other fortified foods. And we also make

vitamin D ourselves in our skin when we're exposed to sunlight. Calcium we get mainly from dairy, from fortified

plant milks, and from green vegetables low in oxalates like collard greens. Here are some special groups of people

that might want to consider a vitamin D supplement. If you have food restrictions, for example, vegans, if

you're not exposed to much sunlight, if you're inside indoors a lot of the time, you need either from fortified foods or

from a supplement you need to get vitamin D. People with some gut conditions that impair absorption,

sometimes they can't get enough, and so a supplement can help get a little bit more. And vitamin D is also often

recommended for children and during pregnancy because they're phases of higher needs. And you want to pay

special attention if you have osteoporosis. You want to make sure that you're getting enough adequate intake of

vitamin D and calcium. Now, I want to point out one last thing on vitamin D. There are some interesting results not

for bone health specifically, but the things like cancer mortality and even total deaths, there are some

signals out there in a a of studies uh linking vitamin D supplementation to lower risk of those. The exact details

are still being worked out. For me, when it comes to vitamin D, if you're not sure, when in doubt, if you don't know

if you're getting enough, I lean towards supplementing with a reasonable amount. And for maintenance, 1,000 2,000

international units a day is plenty if you don't have some special condition or you're not frankly deficient. And at

that modest dose, we see very little downside. For calcium, you ideally want to get it from foods. The supplements

have some drawbacks. The risk of kidney stones can go up in some people, but if you can't get enough calcium from your

diet for some reason, then supplementing is reasonable. Let's move on. Another popular one for bone health is K2. Our

friend K2 is back. Vitamin K2, although here it's a different form. So, there are different forms of vitamin K2. The

studies for heart health that we look at, they usually use MK7. The studies for bone health

use MK4. And this question of vitamin K2 and bone health makes total sense because it's true that vitamin K2 can

help calcium set in bone. So, it's totally reasonable, totally intelligent to ask the question. And

here, unlike the heart situation, we have a number of trials that actually looked at these end outcomes of

fractures. The bottom line is that several Japanese trials from the early 2000s found lower

risk of fractures with very high dose vitamin K2, again, the MK4 form, not the MK7.

Usually around 45 mg a day, which is a very high dose. For the heart studies, it's usually in the microgram range,

like 100 to 1,000 times less. And these studies in bone health are usually looking at postmenopausal women, often

with osteoporosis. Very specific population. Now, this plot thickens because after these smaller studies in

the earlier 2000s in Japan, they ran a bigger trial with thousands of people to try to really nail this

question and it basically flopped. They didn't see any benefit for

fractures. And a number of more recent meta-analysis combining trials have also found no significant benefit of vitamin

K2 for fractures. Sometimes what you see is a small improvement in bone mineral density

that doesn't actually reflect in reduced fracture risk. So again, we have this problem of the

biomarkers versus actual hard endpoints. So the mixed data with K2 and bone health is why in some Asian countries

like Japan K2 is approved as osteoporosis treatment but in the West mostly it's not. Most

European countries and in the US it's not used routinely. So it's really hard to make a call here. I would say for

that specific population postmenopausal osteoporotic women it's really a thumb sideways. But if I

had to say, I would go a weak thumbs up. And that's specific for MK4 type of vitamin K2 and for that high dose,

right? Not a random supplement, not MK7 at a much lower dose. And that's for a very specific population, which is what

they trialed. Right? For a general population vitamin K2 to improve bone health there's no data to back it up. So

it would be a thumbs down for that general claim, right? I don't take K2 for bone health cuz it's never been

shown to help my demographic. If you decide to take vitamin K2, bear in mind it can interact

with some blood thinners. So as always talk to your doctor. Okay, we're going to move on to brain health. I just want

to point out real quick there's a number of supplements that have some randomized trial evidence in osteoarthritis to

improve symptoms like swelling and pain. So collagen, glucosamine, and chondroitin, sometimes combined,

sometimes separate, and turmeric extracts. Those supplements have some trial data showing symptomatic

improvement for osteoarthritis patients specifically. Out of all these supplements marketed for bone health,

the only one I take is vitamin D, and that's because I don't have much in my diet.

But again, I don't have osteoporosis. I'm not a postmenopausal woman. So, I don't think it has to be

cookie-cutter. And this is my fourth rule of supplements. Right for me, maybe not for thee. Supplements can have very

specific indications, and they could be right for one population or one person and not be right for another. All right,

let's look at brain health. And I changed my mind on some of these. I was surprised by the evidence here again.

So, let's start with fish oil. Fish oil makes a comeback. And again, we've heard we've all heard

fish oil omega-3s for the brain. But actually, as I went over, many professional health organizations,

they're not enthusiastic about fish oil for brain health for cognitive function. And this surprised me after I went over

the evidence. So, here's an example. Here's an article on the Harvard website where they say studies have found an

association between fish intake and lower risk of cognitive decline. But supplements from fish oil have not

shown the same effect. And they even cited one of their doctors who says, "I'm not aware of any new evidence about

omega-3 supplements that indicates they're brain boosting." So, this surprised me a lot because I've seen a

number of trials suggesting some benefit. Here's an example. This is a randomized double-blind

placebo-controlled study. They gave patients who had cognitive decline already, had already started on

omega-3 supplement, 900 mg of DHA, and it improved performance in learning and memory tests. Here's a recent systematic

review. Omega-3 supplements showed improvement in attention, perceptual speed, language, memory, visual-spatial

function, and global cognitive ability. Here's a meta-analysis of randomized trials.

Supplementing with omega-3s decreased the rate of cognitive decline. Now, there's plenty of trials also finding

negative results, maybe even most. And even these ones that I found, usually the magnitude of the effect is pretty

modest. So, I'm not trying to say that the evidence is all positive, but the establishment is hiding the truth from

you. This isn't Diary of a CEO. But, I don't really understand saying no fact, no trials showing benefit. Seems to me

that there's probably something there. Now, why do some trials show benefit and some don't? That's the question, right?

And I think there's a plausible explanation, which we already covered, by the way, when we talked about

omega-3s. If you have a diet that's diverse, that contains omega-3s, that contains some fish and seafood, adding a

supplement on top is probably not going to do much. But, if you have a diet without any omega-3s, without fish,

without seafood, then that's a different context. And in fact, there is a systematic review that found that

overall, omega-3 supplements did not improve cognitive performance. But, when they looked specifically at people who

had low omega-3 status, low levels of omega-3s in their body before the trial, there, in that population, the omega-3

supplement improved short-term memory specifically. So, yeah, if you eat a diverse diet with some fatty fish like

salmon or sardines, adding a pill on top, there's no evidence that that's going to improve

your brain health. I would say thumbs down for that claim. But, if you have little or no fish and seafood and have

omega-3s, which is not uncommon in our society, then I think it's possible, not proven

beyond all doubt, but possible that it might help a bit. And this became my rule number five for

supplements. More is not necessarily better. For a lot of these nutrients, you want to get the right amount. You

want to get enough of them. But, just trying to pile on as much as you can, mega-dosing,

doesn't provide any benefit, and in many cases can actually cause harm. Another thing I want to point out real quick,

when we look at studies in people who already have Alzheimer's, there you typically don't see a benefit of omega-3

supplements. It's more common to see it in people who are not so far advanced in the disease process. And as we said, you

want to have some caution regarding the dose of omega-3 supplements because of that risk of atrial fibrillation. We

covered all that. One last frequently asked question is whether fish oil or algae oil make a difference. They both

work. They both raise your blood levels of omega-3s. Just one thing to watch out is the algae oil is sometimes all or

almost all DHA and very low levels of EPA, but that depends on the brand. So, check the label. EPA and DHA have

different functions in your nervous system. I think the best bet, the safest bet, is to get a mix of both. Okay,

another really interesting one for brain health is creatine. There's a growing body of evidence suggesting a benefit of

creatine supplements for cognitive function, specifically memory and attention. And the effect is usually

stronger in specific populations. Older adults or people under stress, people who are sleep-deprived, also in people

who don't consume much creatine in their diet like vegans or vegetarians. So, I would give this one a cautious thumbs-up

for creatine supplements and brain health, especially in these specific populations. But bear in mind, this

thumbs-up is a lot less enthusiastic than the thumbs-up for creatine and strength and muscle, which is a very

clear thumbs-up, a lot of trial data backing that up. And another little note is for the brain effects, you don't need

to load. There's no loading phase needed. Uh the purpose of the loading phase is to saturate the muscle. Now,

here's one where I changed my mind. And this this type of exercise is really good. It's humbling. You you're always

learning, you're always investigating. And that was multivitamins. And multivitamins, we're talking about these

products that have dozens of vitamins and minerals mixed in that you find at your health store, even at the grocery

store. And most of the data out there for these is pretty disappointing, not a lot of

benefits. So, I was pretty cynical about them. But, there is a randomized trial that

found a benefit for global cognition and specific types of memory in older adults taking a multivitamin. The authors even

estimated that this corresponded to slowing down cognitive aging by about 2 years. And there's also a systematic

review putting together a number of trials, and they found multivitamins improved a specific memory test,

immediate free recall memory, but not other cognitive domains. Now, is this because a lot of people, especially

elderly people, don't have a very good diet? They're not getting a lot of vitamins and minerals, and so the

supplement is kind of replacing that. That's possible. It hasn't been shown, so we don't know that for sure. So, I

have changed my mind on multivitamins. I would give this a cautious a weak thumbs-up, especially for these

populations, or elderly population, especially with a poor diet or low appetite,

impaired digestion, because we don't see a lot of downside of multivitamins if we're not mega-dosing, if it's not one

nutrient in isolation in a massive dose. Before we move on to sleep and gut health, just want to point out there's a

number of nutrients that are critical for brain health, for your nervous system, that are essential nutrients,

like B12 and folate. And again, >> [clears throat] >> ideally get it from your diet, but if

you can't for some reason, supplement. All right, let's look at sleep and stress. Here I got one of the

biggest surprises that again humbled me pretty bad. So, let's start with melatonin, probably the most famous

supplement for sleep and insomnia. And this one surprised me negatively. So, melatonin is a hormone produced by a

part of our brain called the pineal gland, and it signals to our body that it's

night time, and it helps lower your blood pressure and your body temperature. It helps you relax and fall

asleep. And it does have an effect on sleep in general and insomnia, but it's pretty modest. It helps you fall asleep

an average of 7 minutes earlier, and it helps you sleep an average of 8 minutes longer, and it might help sleep quality

in general a little bit. So, I was surprised. I thought melatonin was more effective, more demonstrated. Now, these

are the averages for all the participants, so as always, individual results vary. Where melatonin is more

effective is jet lag, try to shift your circadian rhythm. There the effect is more is stronger. So, melatonin in

general for insomnia, I would give it a weaker thumbs up, but try it again. Individual results vary.

And melatonin for jet lag, I would give that a stronger thumbs up. Next, let's look at ashwagandha. This is one of the

ones that surprised me the most. I thought this was all influencer hype, but it turns out it does have some

evidence behind it. So, ashwagandha is a shrub, and extracts of that plant have been used in trials, especially for

stress and anxiety. And there's some evidence that can help with sleep, although the effect there is more

modest. And these trials definitely have some limitations, but we see a signal consistently, so I think it's probably

real. The dose depends a lot on the trial and the product, the specific product they use. It's usually in the

hundreds of milligrams a day. Usually 200 to 600 milligrams a day, that ballpark. Now, one caveat with

ashwagandha is we don't have a lot of long-term safety data. So, I would be cautious if you're pregnant. If you have

a liver disease, there are some rare reports of liver injury. Um also some reports of thyroid

problems, and it can also interact with some medications. Like we said, this is pretty much a general rule. So, talk to

your doctor before you start ashwagandha. I would say that for relief of anxiety and stress, especially

short-term, let's say a couple weeks, not years, I would give that a cautious thumbs up. All right, last couple ones

for sleep and stress, magnesium is a big one, very be Magnesium is a mineral that your body

uses for multiple functions, for your bones, for your muscles, for your brain. And magnesium again is an essential

nutrient, so if you can't get enough from your diet, then supplementing is reasonable. Good sources of magnesium

include spinach and other leafy greens, also beans, nuts, seeds, whole grains, fruits like bananas for example, and

dark chocolate. Now, magnesium is popular for sleep among other things, but I actually found the evidence for

that is pretty thin. There's a suggestive link of possible effect on sleep latency. That's how long it takes

you to fall asleep, but not very strong, not very compelling. So, for the sleep claim specifically, I would actually go

thumbs down at the moment. Magnesium also often marketed for muscle cramps, and there also I found the evidence to

be pretty disappointing. There are a couple of effects of magnesium where I found better evidence. A small drop in

blood pressure, for migraines, and as a laxative for people with constipation. For those, I would go more thumbs up.

All right, last supplement in the sleep and stress chapter, and that's L-theanine, which is a component of tea,

and there's growing evidence that it can help with sleep. Some meta-analyses back that up as well. So, I'd go a cautious

thumbs up for L-theanine and sleep. All right, finally, let's go over gut health and digestion, and let's start with one

of the most popular supplements out there, psyllium husk. So, psyllium husk is an extract of a plant, and it's

basically purified soluble fiber, which is the type of fiber that your microbiome

digests, ferments. And people normally take psyllium husk for constipation, and yes, there are randomized trials backing

that effect, but what fewer people realize is it can also work the other way around. For

loose stool, for diarrhea, psyllium husk can also help normalize stool consistency. Now, some people

report bloating and gas with psyllium husk. It's a fiber at the end of the day, so you want to introduce it slowly,

and then gradually ramp it up. So, it's a thumbs-up for constipation or loose stool, both backed by randomized trial

evidence. Contrast that to probiotics in general, where I think the marketing is completely out of control. So,

probiotics are products that contain some living microorganisms, and they're generally marketed for gut health. The

main problem is that probiotic isn't one thing. It can depend enormously, depending on the product, depending on

the strain, depending on the dose, and they can have completely different effects. There is a famous trial that

found that a specific probiotic composition worsened microbiome recovery after taking antibiotics. We do see

benefits of probiotics in specific contexts, specific probiotics, specific species. So, antibiotic-associated

diarrhea. You start taking an antibiotic, it disrupts your microbiome, and you get diarrhea. There are specific

probiotics, specific species, Lactobacillus rhamnosus GG and Saccharomyces boulardii.

Those species have trial evidence supporting that they can help prevent this type of diarrhea.

So, thumbs-up for that specific probiotic in that specific context. For a random probiotic, grabbing a random

bottle at the health store for gut health in general, I would give that a strong thumbs-down.

Not just because there's not enough evidence to back up that choice, but in some cases, it can even cause

harm. For some conditions of the GI tract, like IBS, there's ongoing investigation. It's possible

that it provides a benefit, but it's less clear, less established. And you want to be especially careful if you're

immunocompromised, taking a probiotic for that population can sometimes cause infections. And I

want to leave you with my golden rule of supplements, which is that you can't out-supplement a terrible diet. There's

no point going to McDonald's every day, and then buying the fancy supplement. It's not going to save you. Supplements,

as the name indicates, are accessories. They're cherries on top. So, you want to get the diet right first. And on that

note, what's a good diet? We covered all of that in this previous video. Check that out. I'll meet you in there.