Evidence-Based Supplements and Drugs for Longevity and Anti-Aging

Jump To Section

• The Supplements and Longevity Market
• Alpha-Ketoglutarate Anti-Aging Research
• The Importance of Randomized Controlled Trials
• Other Promising Longevity Compounds
• Repurposed Drugs for Longevity
• Full Transcript

The Supplements and Longevity Market

Supplements are a popular and rapidly growing area within the longevity field. Dr. Andrea Maier, MD, notes that many people view them as an easy way to modify the aging process. The market is vast, encompassing everything from multivitamins to more specific amino acids like glycine.

However, Dr. Maier presents a critical perspective from evidence-based medicine. She states that for the majority of these supplements, there is only a tiny amount of data showing any benefit for humans at specific life stages. This significant evidence gap underscores the urgent need for more rigorous scientific research.

Alpha-Ketoglutarate Anti-Aging Research

One supplement under intense investigation is alpha-ketoglutarate. Dr. Andrea Maier, MD, explains that this compound appears to have multiple functions targeting several pillars of aging. Its potential mechanisms include reducing oxidative stress and improving mitochondrial function.

Research led by Professor Brian Kennedy has shown that alpha-ketoglutarate extends lifespan in mice. A recent initial human study yielded a remarkable finding. Participants taking the supplement showed a biological age, as measured by epigenetic clocks, that was approximately eight years younger than their baseline. Dr. Maier cautions that this study lacked a control group, a major limitation that highlights the need for more robust trial designs.

The Importance of Randomized Controlled Trials

Dr. Andrea Maier, MD, emphasizes that randomized controlled trials (RCTs) are the gold standard for building evidence. These studies are essential to establish a causal link between a supplement and its effects. In an RCT, participants are randomly assigned to receive either the active ingredient or an identical-looking placebo.

This blinding prevents bias, as neither the participant nor the researcher knows who is receiving the treatment. Dr. Maier points out that without a control group, any observed benefits could be attributed to other factors, such as concurrent positive lifestyle changes made by study participants. Her team is currently conducting RCTs with alpha-ketoglutarate in middle-aged individuals to verify its effects on biological age.

Other Promising Longevity Compounds

Beyond alpha-ketoglutarate, Dr. Andrea Maier, MD, discusses several other compounds being researched for their anti-aging potential. These include the amino acid glycine and a compound called spermidine, which is currently being tested in mouse models in her laboratory.

Nicotinamide mononucleotide (NMN) and other NAD+ precursors have also been available as supplements for some time. Dr. Maier estimates there is a list of 20 to 30 compounds that are currently attracting significant attention from longevity researchers and are entering human trials.

Repurposed Drugs for Longevity

The search for anti-aging interventions extends beyond supplements to include the repurposing of existing medications. Dr. Andrea Maier, MD, highlights that this approach can accelerate research, as the safety profiles of these drugs are often already well-established.

Notable drugs being investigated for their potential longevity benefits include Metformin, a common diabetes medication. ACE inhibitors and beta-blockers, typically used for cardiovascular conditions, are also being studied. Additionally, lithium is on a list of 20 to 30 drugs highly regarded for their possible neuroprotective effects. Dr. Anton Titov, MD, and Dr. Maier agree that rigorous randomized controlled trials are equally crucial for validating the efficacy of these repurposed drugs in slowing biological aging.

Full Transcript

Dr. Anton Titov, MD: But supplements and longevity are very hot topics. What supplements could affect the aging process? You published some data about the anti-aging properties of alpha-ketoglutarate. Could you please talk about your research on that?

Dr. Andrea Maier, MD: Absolutely. Supplements are thought to be an easy way to modify the aging process. There were lots of supplements already on the market. You can think about multivitamins. You can think about more specific ones, such as glycine. Specific amino acids are being given and sold already. So there's a huge market of supplements already.

There is a negative side of supplements from an evidence-based medicine perspective. For most of the supplements, there is a very little and tiny amount of data showing what benefits somebody would have of these supplements at certain stages in life. We need much more research on these kinds of supplements.

That's what we are doing at the Center for Healthy Longevity here in Singapore at the National University of Singapore. We shed light on which supplement has what effect. One of the examples is indeed alpha-ketoglutarate.

Alpha-ketoglutarate is a supplement having many functions on the pillars of aging. I think most of the supplements will have a spread of actions. Really trying to improve or reduce oxidative stress by improving mitochondrial function and protein folding to increase that and optimize it. These kinds of supplements might have the biggest effect on the biological aging process in humans.

Alpha-ketoglutarate is a supplement being investigated by Professor Brian Kennedy. It has already been shown that if you give alpha-ketoglutarate to mice, they are living longer. Still, it also might be that they are living longer and healthier, which is, of course, most important.

This is the first study being done giving alpha-ketoglutarate to humans. Quite recently it was shown that the biological age is being measured by epigenetic clocks. These individuals who took that supplement were about eight years younger compared to the baseline biological age.

The downside of that study was that there were no controls. As you might know, if you're in a study or taking something, you also might change other lifestyle habits. That's the reason why it's so important to have randomized controlled trials.

It means the randomization. You might get the active ingredient or you might be in the control. Still, you also get the same tablet with the same size, the same smell, the same taste, the same color. We can actually be in a blinded way to analyze what works, what supplement is causally related to that effect.

This is what we are doing at the moment. We do clinical trials with alpha-ketoglutarate in a randomized controlled way. We give it to middle-aged individuals to see if their biological ages are lower.

In summary, supplements are tackling lots of aging hallmarks. Very often we do not yet really know what is the mechanism of action. But we accept that. We are targeting a lot of hallmarks of aging, because it might have a greater benefit when measuring the biological age.

Dr. Anton Titov, MD: Apart from alpha-ketoglutarate, from your research, what are other compounds that might have actual human evidence that is active in longevity or affecting several pillars of human aging?

Dr. Andrea Maier, MD: Yeah, we are investigating glycine, for example. That's an amino acid. Other longevity compounds are spermidine. There are mice models in our lab to see if spermidine would work in anti-aging. But you also have NMN, NAD precursors being out there already for a long time, in terms of supplementation.

So there is a list of at least 20 to 30 compounds, which have the attention of researchers being in longevity trials now. For everybody who is maybe listening and saying, "Okay, I would like to be included in such studies," there is on the web a registration of all ongoing randomized control trials in humans, where anybody can find information on what's going on.

We build the evidence for supplements for longevity, but also by repurposing drugs, for example, Metformin. We also use ACE inhibitors, or beta-blockers, and lithium. And there's also a list of 20 to 30 drugs being highly regarded to have possible neuroprotective effects.

They are being studied in human randomized control trials. It's very important that I mention that we need randomized control trials because we have to control for other changes, such as lifestyle, that might be associated with lowering the biological age.