#387 Supplements Shorten Lifespan, What to Eat to Get 100g of Protein - Q&A

Siim Land (0:00)

All right, first Q&A of 2024 If you want to ask me a question in the future, then make sure you follow me on Instagram at Siim Land. The first question is, are there any supplements that actually shorten your lifespan? That is a very, you know, interesting and thought provoking question. And when we are talking about supplements, then of course, most supplements don't have, you know, they're not really that well studied over the long term. There are, of course, many supplements that have a long track record of safety and effectiveness. You know, some of them are like magnesium, fish oil, glycine, those things there, they've been used for decades without any observation in increased mortality. And those kind of things actually the opposite, you know, with fish oil and not necessarily fish oil, but any omega-3 supplements as well as magnesium, then those actually appear to reduce the risk of heart disease and neurodegeneration and those kind of things. Now, I'll name a few supplements that have some association with increased mortality. And those primarily are like these antioxidant supplements. And there are a few studies indicating that antioxidant supplementation like vitamin A and vitamin E specifically are associated with increased risk of mortality, which is obviously interesting because a lot of them, you know, mechanistic theories about aging have to do with increased oxidative stress and inflammation. It's the free radical theory of aging or the mitochondrial free radical theory of aging that aging is caused by this accumulation of reactive oxygenous species and free radicals that cause inflammation and oxidative stress in the body.

And the theory goes that if you suppress that, then you also increase longevity. But what they actually find in animal studies is that if you completely like suppress oxidative stress or if you like, you know, use antioxidant supplements in these animals, then they don't live longer. And in some cases, they actually live shorter. So there is some benefits to having mild amount of oxidative stress. So it's called the phenomenon of mitohormesis. So small amount of reactive oxygen species, they act as a signaling molecule that turn on the body's antioxidant defense systems endogenously and have some other systemic benefits. So like, the perfect example of this is exercise. Exercise increases oxidative stress and increases reactive oxygen species. But those reactive oxygen species mediate a lot of the benefits that you see from exercise. And what you also see is that blunting that inflammation and blunting that oxidative stress after exercise actually also suppresses the beneficial adaptations you see from exercise. So you don't want to minimize, or you don't want to suppress all of the inflammation and oxidative stress, especially after exercise. And especially with antioxidant supplementation like vitamin C or vitamin A, and even like N-acetylcysteine after exercise, first of all, it has been shown to blunt some of the muscle hypertrophy response, muscle growth response, but it also can mitigate some of the other beneficial adaptations from exercise. So the theory of complete nullification of oxidative stress as beneficial is not really shown to be true.

More accurately, it's the theory of the mitohormesis, that small amount of oxidative stress is actually beneficial for longevity by increasing your body's own antioxidant defense systems and pretty much making the body more resilient.

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The problem here is that people who have some sort of a, you know, adduress health condition, some sort of a comorbidity, they're taking health supplements, they're taking antioxidants, so they're already at a higher risk of mortality because of their comorbidities. And the use of antioxidants is just an association in that scenario. Is there any danger of taking antioxidants in otherwise healthy people with that increased risk of mortality?

The evidence for that is quite limited, but I wouldn't just, even for a healthy person, you wouldn't need to take antioxidant supplements in large doses, especially, because it's going to actually make your body more vulnerable to oxidative stress, and it makes the body less resilient, and it can even potentially blunt some of the positive adaptations of our exercise. So you don't want to take a large amount of antioxidants, like, willy-nilly, you don't want to take large amounts of antioxidants if you don't have a reason for it. Now, there are situations and times where it is beneficial, like if you have an infection, you got a cold, you have some other, let's say, high inflammatory states, then yes, in those cases, antioxidants can be good to lower that excess oxidative stress, but you definitely don't want to do it after exercise, and you definitely don't want to take them regularly all the time if you don't have any sickness. Now, vitamin C is probably an exception because even if you take like super large amounts of vitamin C, you tend to just excrete it, you waste it, you don't really, you know, it doesn't have any like adverse effects directly, whereas with vitamin A and vitamin E or beta-carotene supplementation as well as on the list, that's not apparently, based on the studies, it causes more harm than good. With NAC, NAC doesn't reduce or it doesn't increase the risk of mortality in otherwise normal people, but it does just blunt the positive effects of exercise. And NAC as an antioxidant that raises good and harm, in human studies, in the elderly people, actually reduces the hallmarks of aging and reduces the other functional declines associated with aging. Now, it might work only in the elderly people, but NAC is more of a safer antioxidant, if that makes sense. So at least we don't have any data that NAC would be associated with increased mortality, and in fact, it's probably the opposite. But you still don't want to take large amounts of NAC. First of all, if you're young, and if you don't have any inflammation, it's just that when you're older than 45 years of age, then your glutathione levels naturally decline, and your inflammation and oxygen stress increases as a result of that. And NAC plus glycine, the glycine-glycine-NAC combo, GlyNAC, that raises glutathione backup and then minimizes or lowers the oxidative stress and inflammation. And lastly, the phenomenon of polypharmacy, which describes taking multiple medications itself is associated with increased mortality, but this association is also because of people who take a lot of pills and pharmaceuticals, different blood pressure medication, blood sugar medication, all these other medications, they're already at a high, by the state of comorbidities. So they're already at a high risk of mortality because they have many comorbidities. And that's what increases their mortality risk, more so than just the fact of taking more pills, if that makes sense. But if you don't need to take that many pills, then you shouldn't really take them either, in my opinion. All right, next question. How long does NMN take to work in the body? So NMN, nicotinamide mononucleotide, is a common NAD booster. I've recently done a lot of research about both NR and NMN. They both work in raising NAD. They're both generally safe, although the FDA currently is trying to, not ban, but take NMN off the market to potentially turn it into a prescription drug. We'll see how that turns out. But NMN does effectively raise NAD levels, and it does so pretty rapidly, like within hours, and it stays elevated as well, in a dose-dependent manner. So like 1,000 milligrams is going to raise NAD more than just 250 milligrams of NMN.