Are your longevity supplements harming your health? With an aging population, people are looking for ways to extend lifespan and boost health as they age. But four popular longevity supplements may actually be doing the opposite. In this article, we’ll look at the supposed benefits of each one and the clinical evidence that they may be doing more harm than good.
Table of Contents
Section 1: Resveratrol
We’ll start with the most popular supplement marketed for extending lifespan, resveratrol.
[1] How is it supposed to work? Scientists discovered an enzyme called SIRT1 which acts like a control switch for many important cell processes. It helps regulate stress response, inflammation, and the repair of damaged DNA. For these reasons, it’s linked to the aging process. Researchers have discovered that when SIRT1 levels are increased in various organisms, they live longer [2].
So they searched for something that could boost SIRT1 levels, hoping this might lead to longer lifespans in humans, too. One early study identified resveratrol as a possible match. The study claimed it extended the lifespan of yeast by 70% [3].
Those initial results caused a lot of excitement. There’s just one problem, though. In a subsequent study, researchers didn’t see the same benefits from resveratrol. They found the earlier results seemed to be based on a mistake. It wasn’t the resveratrol alone that was extending lifespan in yeast. Instead, it only had this effect when it was combined with a chemical dye used in the experiments [4]. When testing resveratrol without the dye, they found it had no effect on life span [5].
That should have been a serious blow to the early hype about resveratrol. But researchers kept looking for beneficial effects. So far, results have been disappointing.
In particular, when the meticulous Interventions Testing Program studied resveratrol, there was no effect. This program confirmed that the resveratrol was indeed absorbed into the bloodstream, so it’s not an absorption issue. It’s just that resveratrol doesn’t work [6].
Results have been disappointing for other claimed effects of resveratrol, too. For example, some have suggested it might help with type 2 diabetes. But a Cochrane analysis found the current research doesn’t support any such claims [7].
Does resveratrol have any effects at all? Yes, but not the effects that we want. A recent study returned to the question of whether it can stimulate SIRT1. Researchers used CRISPR technology to see exactly what was going on. Backing up the study we looked at earlier, they found resveratrol does not seem to activate SIRT1. Instead, resveratrol stressed the cells. It interfered with the process of copying DNA during cell division [8]. If the normal DNA copying process is like smoothly copying pages in a book, resveratrol makes the copying process slower and more difficult. It’s like trying to copy pages with a malfunctioning copier.
That doesn’t sound good. But maybe there’s a silver lining. It has to do with exercise.
Here’s the logic. When we exercise, this stresses our cells. But that works to our benefit. This signals them to become stronger and more efficient. So the thought was this: we could combine resveratrol and exercise to ramp up the cellular stress. Maybe this would also increase the benefits we get from exercise.
But it turns out the opposite happens. One study looked at 27 men who performed high-intensity exercise training. Resveratrol supplementation reduced the positive effect of exercise training on blood pressure, blood cholesterol, and how efficiently their bodies used oxygen [9].
A separate study confirmed these results. It also found resveratrol blunted the positive effects of exercise [10]. These effects are a big deal. If we’re taking a supplement that blunts the benefits of exercise, we’re undercutting one of our most effective tools for ensuring a healthier, longer life.
There’s also some clinical evidence that resveratrol can reduce testosterone levels [11]. Why is this a concern? Because lower testosterone levels are associated with a higher risk of death, especially among older men [12].
So at this point, we don’t have good evidence of beneficial effects of resveratrol in terms of living longer. But we do have evidence of harm. Taking resveratrol supplements isn’t a good strategy.
I’ve only scratched the surface of the resveratrol debacle here, and I’ll link to my full article outlining the research mess in the references below.
Section 2: Metformin
The next thing to avoid if we’re hoping to extend our lifespan is metformin. Now I want to be clear that not a day goes by at the clinic where I'm not prescribing metformin for my pre-diabetic and type 2 diabetic patients. What I'm referring to here is non-diabetic patients taking metformin as a way to live longer.
You’ll see claims that it can slow our aging and increase our life span [13]. And it costs just pennies a day. It sounds amazing. But is it true?
Metformin has raised some interest as a way to address aging because of several of its effects on the body. It can reduce inflammation, lower insulin levels, and may help protect against oxidative stress. But what does the research show about extending life?
Looking at the Interventions Testing Program again, they found no impact on lifespan [14].
What about human studies? A recent review of the evidence found no compelling evidence that it extends lifespan. It does, however, reduce early mortality due to diseases like diabetes [15]. In other words, the evidence doesn’t suggest metformin counters the effects of aging. It just helps prevent diseases that cause early death. That’s why it makes perfect sense for pre-diabetics or people with type 2 diabetes to take it. It’s also why it doesn’t make sense for someone without the conditions it targets to use it as a supplement.
Another large study followed adults at high risk for diabetes over 21 years. Researchers concluded taking metformin did not affect all-cause mortality or death rates from cancer or heart disease [16].
Just like resveratrol, we have solid evidence that metformin can reduce the benefits of exercise. In a 2019 study where both groups were exercising, the people who took metformin improved their cardiovascular fitness by only half as much as those who took a placebo [17]. That study was backed up by a 2022 study showing the same thing. Metformin use reduced the improvements in how well the body can use oxygen during exercise by half [18].
And also like resveratrol, metformin lowers testosterone levels [19].
Section 3: High-Dose Vitamin C
That brings us to the next supplement: high-dose vitamin C. The “high-dose” part is important. Let me explain.
Vitamin C is an essential nutrient. It’s a part of several body processes, like immune system function, iron absorption, and wound healing. It’s also a powerful antioxidant.
Antioxidants help prevent or slow damage to cells by neutralizing free radicals. Free radicals are unstable molecules produced naturally in the body. We used to think all free radicals were bad and we should do everything we can to lower them. But now we realize they play an important role. What we want is a balance. And that means having too high an intake of antioxidants isn’t a good thing.
With vitamin C, the recommended daily intake is only 90 mg. But you’ll see vitamin C supplements with more than 20 times that dose [20]. That can disrupt the balance between oxidants and antioxidants. For example, as explained earlier, exercise stresses our cells. This releases all sorts of oxidants. That's a good thing as it signals to our cells to become more efficient. But if we're taking high doses of vitamin C and antioxidant supplements, that can blunt those effects.
Here’s an example. In a study of 54 people who were exercising, half received 1,000 mg of vitamin C plus another antioxidant and the other half got a placebo. What they found is those taking the vitamin C supplements improved less from exercise than the group taking the placebo [21].
Similar results were found in another trial of strength training. Again, those taking the vitamin C supplement had less improvement in their strength compared to the placebo group [22].
So while it's important to reach the recommended daily intake of vitamin C, we don’t necessarily want to exceed it. That's why MicroVitamin, the low-dose multivitamin and mineral that I personally take, only has 50 percent of our recommended daily intake of vitamin C. It’s best to prioritize our diet as the primary source for this vitamin.
But just because I take a supplement in no way means you have to also
Section 4: Vitamin E
Now for the last one. It’s also an antioxidant and an essential vitamin. It’s found naturally in vegetable oils, nuts and seeds, and green leafy vegetables like spinach. Like vitamin C, it’s claimed that it can increase lifespan because of its antioxidant properties. It’s particularly active in protecting cell membranes. It has also been claimed to prevent cancer and heart disease.
For all these reasons, supplement manufacturers have been encouraging people to increase their intake of this vitamin. Which one are we talking about? Vitamin E.
But this is a bad idea. Here’s why.
First, vitamin E deficiency is rare except in individuals with unusual health conditions. That’s because it’s found in a wide variety of foods. So for most of us, we’re getting plenty of this vitamin already.
But, second, vitamin E, just like the antioxidant vitamin C, can interfere with the benefits from exercise if we’re getting too much of it [21].
Third, there’s the disturbing possibility that supplementing with vitamin E could actually be shortening our life span. An in-depth Cochrane analysis of clinical research looked at 78 trials with a total of almost 300,000 participants. They found no evidence to support antioxidant supplements to decrease mortality. Shockingly, the evidence suggested vitamin E supplementation might even increase mortality [26]. That’s the opposite of what we want.
And this same analysis highlighted one other popular antioxidant: vitamin A. At higher supplement doses, it also seems to be associated with increased mortality. And a separate study notes that too much vitamin A can weaken our bones, damage the liver, and cause birth defects [27].
Returning to vitamin E, it also appears the form matters. The vitamin comes in 8 forms: four tocopherols and four tocotrienols [23]. And it's the tocotrienols that appear to offer a greater antioxidant effect [24].
So I've seen other creators ignore the safety concerns of vitamin E because they say that those studies didn't look specifically at tocotrienols. That’s an interesting hypothesis, but it needs testing. We don't have any long-term safety data on tocotrienols. And besides, the tocopherols and the tocotrienols act in roughly the same way. They're both antioxidants. In the trials that we have so far there's not even a hint that vitamin E can extend lifespan. Instead, we're left with the concern it might increase mortality. Too much has even been shown to increase the risk of prostate cancer [25].
So before even considering supplementation with tocotrienols, we have to make sure that they're safe. And these concerns we’ve looked at for both vitamin E and vitamin A are the reason I don’t include them in MicroVitamin.
We can draw a general lesson from the four supplements we’ve looked at in this article. And supplement manufacturers want you to miss this point. Here’s the lesson: Just because a substance can be helpful in a certain form and in a certain amount doesn’t mean it’s helpful to supplement with it. Oftentimes, it can even be harmful.
Reference List
Below are the studies and sources referenced in this article, in the order they appeared:
1. https://www.lifeextension.com/vitamins-supplements/item02210/resveratrol
2. https://pubmed.ncbi.nlm.nih.gov/24011076/
3. https://pubmed.ncbi.nlm.nih.gov/12939617/
4. https://pubmed.ncbi.nlm.nih.gov/15684413/
5. https://pubmed.ncbi.nlm.nih.gov/15684413/
6. https://pmc.ncbi.nlm.nih.gov/articles/PMC3598361/
7. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011919.pub2/full
8. https://www.cell.com/molecular-cell/fulltext/S1097-2765(20)30476-7
9. https://pmc.ncbi.nlm.nih.gov/articles/PMC3810808/
10. https://pmc.ncbi.nlm.nih.gov/articles/PMC4001758/
11. https://pubmed.ncbi.nlm.nih.gov/27754722/
12. https://pmc.ncbi.nlm.nih.gov/articles/PMC9938530/
13. https://fortune.com/well/2023/05/04/metformin-anti-aging-longevity-risks-side-effects/
14. https://pmc.ncbi.nlm.nih.gov/articles/PMC5013015/
15. https://pubmed.ncbi.nlm.nih.gov/34421827/
17. https://pmc.ncbi.nlm.nih.gov/articles/PMC6351883/
18. https://pmc.ncbi.nlm.nih.gov/articles/PMC9321693/
19. https://pmc.ncbi.nlm.nih.gov/articles/PMC8740051/
21. https://ods.od.nih.gov/factsheets/ExerciseAndAthleticPerformance-HealthProfessional
22. https://ods.od.nih.gov/factsheets/ExerciseAndAthleticPerformance-HealthProfessional
23. https://www.bocsci.com/resources/vitamin-e-tocopherols-and-tocotrienols-and-their-derivatives.html
24. https://pmc.ncbi.nlm.nih.gov/articles/PMC1790869/
25. https://pmc.ncbi.nlm.nih.gov/articles/PMC4169010/
26. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007176.pub2/full
27. https://jamanetwork.com/journals/jama/fullarticle/2793446
