From Resveratrol to Rapamycin: A potential Longevity Stack
As the co-founder of a longevity focused VC, I’m often asked about my personal longevity regime — what lifestyle changes I’ve made, what I’m taking, and why.
While I think the most powerful longevity interventions will likely emerge from some of the exciting biotech companies working on cutting edge interventions to slow, delay or even reverse the effects of aging, I believe there is nothing out there at the moment that reverses aging. However, there are still plenty of potential options to consider when it comes to improving your healthspan today. We have collected strong research about interventions that may promote a longer, healthier life, and I’ve adopted a number of science-backed approaches that I’d like to share with you.
Before I reveal my personal longevity stack, let’s start with the basics. In order for a supplement or drug to make it onto my list, it needs to have animal data on health and lifespan, human data on health effects, and, of course, sufficient human safety data.
Okay, let’s get started!
Health monitoring and early detection
I think it’s important to mention that a fundamental principle of any personal longevity regime is to monitor your health closely. All of my longevity interventions and strategies are done alongside regular medical checkups.
One of the best ways to live a long and healthy life is to not get sick, so be sure to check your long-term risks for the biggest age-related diseases, such as cardiovascular disease, diabetes, high blood pressure, cancer, and so on. This means regularly checking things like cholesterol levels, blood sugar levels and blood pressure. Also think about any diseases your parents and grandparents have or had. Keep these in mind and tackle them early!
If you find, for example, you are at high risk and have a high biomarker for cardiovascular disease (e.g. high ApoB cholesterol), or diabetes (e.g. high HbA1c blood sugar), be sure to treat it early. If your cholesterol is too high, for example, consider taking a cholesterol-lowering medication. Most chronic diseases are very treatable in their early stages — just don’t wait until it’s too late.
In terms of cancer, I do annual screenings with GRAIL in the US and the PanTum Detect test in Germany. Both tests have their pros and cons, but I feel that doing both increases the chance of finding cancer at its earliest stage. I also do a preventive MRI scan and colonoscopy every 1–2 years. Cancer Research UK has some great data on the importance of early diagnosis. For example, only 10% of people diagnosed with late-stage bowel cancer survive for five years or more, but this rises to more than 90% if diagnosed at the earliest stage. So I‘m really doing my best to catch things early, if possible.
Now, onto my top longevity interventions, starting with the most obvious…
Food: the “no brainer”
Perhaps the most obvious longevity intervention today is diet. There is a huge body of research showing the link between food, health, and longevity. However, if you were hoping for a list of healthy foods, I have to disappoint you — I believe what you don’t eat is at least as important as what you eat. Therefore I will just focus on this topic.
My top three food-related things to avoid are:
Trans fat. Also called trans-fatty acid, trans fats are generally considered to be the worst type of fat to eat, so I do my best to steer clear of them. They are known to both raise “bad” cholesterol and lower “good” cholesterol, increasing the risk of heart disease, the leading killer of adults. And that’s not all — recent research shows that trans fats may be worse than sugar at causing high blood sugar.
Burned meat. I try to avoid burnt or well-done meat due to studies associating it with higher possibilities of pancreatic cancer and prostate cancer. While these links are hard to prove for certain, I think it’s better to be safe than sorry.
Glucose spikes. Whether caused by too much sugar or carbs in one meal, I try to watch what I eat to avoid the dreaded spikes that occur when your blood sugar rises and then falls sharply after you eat. Over time, this can lead to type 2 diabetes, so try using a continuous glucose monitor (CGM) to learn what foods and combinations of foods you should avoid. For more on avoiding glucose spikes, see the sections on fiber and diabetes drugs below.
And of course, there is also plenty of evidence that eating a diet rich in fruit and vegetables is good for longevity, and this links nicely with what I believe is one of the most overlooked elements of food consumption…
Fiber, fiber, fiber!
In my opinion, fiber is probably the most important element of the food I consume — no other part of our diet has so much evidence behind its beneficial effects. Fiber’s ability to reduce all-cause mortality in a dose-dependent manner, is compelling, and if you look in more detail at specific markers, you’ll also find that fiber reduces cholesterol and blood sugar, and helps with weight loss.
One of the best papers I’ve read on fiber was published in 2019 in The Lancet — it is a meta-analysis of 10 studies, spanning more than 80,000 subjects.
While the graphs show that 35g of fiber a day indicates a clear trend toward positive health outcomes, it looks like the trend continues, which is why I aim for a fiber intake of 50–60g per day. Of course, it’s hard to get all of that from food, so I also supplement to hit this mark.
The effects of fiber intake on the incidence of coronary heart disease are also very compelling, demonstrating an effect that is almost comparable to that of statins! I suspect this is probably because of the cholesterol lowering effects combined with positive effects on blood sugar and weight loss.
As you can see, it appears that cereal fiber is particularly beneficial. This is a conclusion also reached by other researchers in the field, which is why I try to get as much cereal fiber in my diet as possible. I prefer oat fiber, which I take as a supplement, adding about another 10g per day to my already fiber-rich diet.
I choose to supplement with oat fiber because it’s gluten free and my body handles it much better than psyllium husk, for example. In addition, oat fiber, which is also linked to reduced mortality, contains β-glucan, which seems to be the contributing factor to the cholesterol-lowering effect. British researchers found that just 3g of oat extract can help lower LDL cholesterol by around 10% and reduce the risk of heart disease by 20%.
My final point on oat fiber centers on this large study, which came to the conclusion that each additional intake of 5g/1000 kcal of dietary fiber was associated with a 9% relative reduction in all-cause mortality risk. That is huge! The study also favors soluble fibers, like the β-glucan found in oat fiber.
For those who don’t want to take fiber as a supplement, consider fiber-rich foods like avocados and others (a quick Google search will provide lots of ideas). For example, each avocado packs 13.5 grams of dietary fiber, of which 40% are soluble.
There are no real risks associated with increased fiber consumption. Note that adding too much fiber too quickly into your diet can result in side-effects, such as intestinal gas, bloating and cramping. To allow your digestive system to adjust, try increasing the fiber in your diet gradually over a few weeks. If a certain type of fiber doesn’t agree with you (e.g. psyllium husk), just try oat fiber or something else — there are so many options to choose from!
The supplements
Okay, technically I already told you about one supplement, oat fiber, but I also take a few others. Of course, the science behind longevity supplements is still evolving, and the effectiveness of supplements can vary from person to person, but here are the ones I take and the reasons why.
Glycine
Glycine, a non-essential amino acid, is one of 20 amino acids used to produce proteins in humans. Glycine is also the only over-the-counter product to improve lifespan in mice by around 5% in the Intervention Testing Program (ITP), a multi-institutional study investigating treatments that extend lifespan in mice. Check out our review of glycine and other ITP compounds here.
The most glycine-rich food is bone broth, however, in order to get the same concentration the animals had in the ITP, you would need to eat an awful lot of broth, which is why I am supplementing to achieve a higher dose.
While I would put glycine in the category of low benefit (5% lifespan extension in the ITP is on the lower end), there are also no reports of any long-term risks of supplementing with glycine, which gives me confidence in taking it on a daily basis.
Some studies suggest that a glycine supplement should be taken when you eat protein, but I supplement with glycine every mealtime, in one of two ways. When eating at home, I mix 5g of glycine powder (easily found on Amazon) in water. And if I eat out in a restaurant, I bring my glycine tablets, which are also an option if you don´t like the taste of the powder. Glycine tablets can also be found on Amazon, but make sure your pills contain 100% glycine and don’t have ‘fillers’ like silicon dioxide, or titanium dioxide, which can add up if you’re taking them every day.
Glycine is generally considered to be a safe supplement when taken in doses of up to 6g daily for 4 weeks. Only mild potential side effects are associated with its use, such as stomach upset.
NAC
N-acetyl cysteine (NAC) is a supplement form of cysteine, a conditionally essential amino acid. It is thought that NAC may stimulate the synthesis of glutathione, a powerful antioxidant that helps fight free radicals, unstable atoms that can cause inflammation and damage.
Many people choose to combine glycine with NAC to boost levels of glutathione, which are known to decrease as we age. Some doctors suggest starting supplementation once glutathione levels start to drop, typically around your mid-40s.
NAC has not been tested in the ITP but also showed lifespan effects in rodent studies (see here (male mice, 24%), here (male mice, ~15%) or here (female mice, ~5%)). Probably more importantly, NAC taken in combination with glycine was associated with beneficial effects in elderly patients in a placebo-controlled clinical trial.
It should be said that not everyone is convinced that NAC is the best supplement to take. Check out this perspective from Derek Lowe at Science.
Although it can be considered a safe supplement, there are some potential side effects associated with its use, especially if you have kidney disease or asthma. Also, side effects, which may include dry mouth, nausea, vomiting, and diarrhea, appear to be dose-dependent, so don’t overdo it! A typical daily dose of 100–200 mg works well for me, and the maximum daily dose of 600 mg should clearly not be exceeded.
Vitamin B
Homocysteine is an amino acid, which is broken down to create other chemicals your body needs. Homocysteine is a marker that can be easily measured with a blood test and should be part of any regular checkup.
Levels of homocysteine increase with age and are strongly correlated with all-cause mortality and increasing risk of dementia, heart disease and stroke. Check out this great article from Michael Lustgarten about homocysteine levels and all-cause mortality risks.
There is solid evidence that certain B vitamins can help lower homocysteine levels. Therefore, I take a low-dose vitamin supplement with every meal, three times a day.
Most supplements designed to lower homocysteine contain B6, B12, folate and TMG. Some also contain B2 or B9. I like this supplement from Germany because it doesn’t mega-dose the vitamins and take it, as recommended, with all bigger meals.
For our readers in the US, this supplement looks similar, but it also has very high doses of some of the vitamins. I prefer a lower dose, which allows me to take it with every meal, because homocysteine rises after meals.
Unfortunately, the homocysteine supplements do not contain vitamin B3 which I think is also interesting and promising from a longevity perspective. Some people might choose to take NMN, or NR (nicotinamide riboside), which is part of the Vitamin B3 family, but I personally feel it’s enough to just take Vitamin B3 (or Vitamin B complex) because they all act around the same mechanism.
In terms of the risk-benefit ratio, Vitamin B supplements are generally considered safe to take, and excess amounts are typically excreted in urine.
Of course, not everyone is so sure about the potential of B vitamins against homocysteine. Check out this commentary from Harvard Health.
Resveratrol
Resveratrol, a chemical mostly found in red grapes, has been the subject of keen interest, and controversy, ever since David Sinclair published on its life extension potential in yeast. Here Dr Sinclair talks about the potential impact of resveratrol on cardiovascular health.
However, resveratrol did not produce results in the ITP, and some scientists say it just doesn’t work, but I believe the effect was too small to be significantly positive. While life-extension results are limited to obese mice, there are mouse studies showing resveratrol’s benefit in neurodegeneration and cardiovascular disease.
In addition, Rafael de Cabo, an aging scientist I greatly respect, ran a large resveratrol study in monkeys and produced some convincing data that obese monkeys benefited from treatment with resveratrol.
As it didn´t show effects in some studies, resveratrol is probably the most controversial supplement in my longevity stack. But it also appears to do no harm, and I believe the evidence points more in the positive direction than the negative. David Sinclair also says that resveratrol should be taken with fat, which was not the case in the ITP. For that reason, I take 1g of trans-resveratrol with fat every morning.
Vitamin D and Omega 3
Vitamin D and omega 3 fatty acids are on many people’s longevity stack. My take is that I have not seen enough convincing data from a longevity perspective, so these supplements are not on my personal list. However, I’m also not aware of any adverse effects or reasons why people should not take them.
The pharmaceuticals
The nature of clinical trials and regulatory approvals means that we may be waiting for a long time before a drug is officially approved for longevity. But that doesn’t mean a longevity drug doesn’t already exist! There are many pharmaceutical products that have been approved for one indication or another but may also hold potential for potential healthspan benefits.
Of course, pharmaceuticals come with their own set of potential risks and rewards, and any decision to proceed with taking them should be carefully considered. Supplements and other over-the-counter products generally have good safety profiles but the beneficial effects may be limited in some cases. Pharmaceuticals may produce more significant beneficial effects but this may also come with higher risks of side effects.
Diabetes drugs
There are many diabetes drugs that have shown to prolong healthspan and lifespan in animals. Based on current evidence, I would say that taking a diabetes medication is likely to be helpful.
However, which diabetes drug one should take depends on your weight and BMI. If you’re at a healthy weight, then Acarbose seems to be the best choice. If you’re up to 10 lbs overweight, then Jardiance, which has good longevity data and promotes weight loss, looks interesting. If you’re more overweight, then a GLP-1 agonist such as Semaglutide, or Monjuvi might be an option.
SGLT-2 inhibitors, such as Jardiance, are older drugs used to treat diabetes. To my knowledge, no other drug has such compelling data on all-cause mortality as SGLT-2 inhibitors. Check out this meta-analysis, which shows that the drugs decrease all-cause mortality by around 14%.
Typical side effects are drug-specific and can vary from bloating and abdominal discomfort (Acarbose) to diarrhea, pancreatitis (GLP-1 agonists), and urinary tract infections (SGLT-2 inhibitors). Women appear to have a higher chance of getting SGLT-2 specific side effects.
It should also be noted that there are potentially serious side effects, such as acute kidney injury, and there is an FDA warning about the use of SGLT-2 inhibitors and severe urogenital infections.
The risk of side effects can potentially be reduced by lowering the daily dosage. For example, going from 25mg Jardiance to 10mg, which appears to have a similar effect, or even going down to 5mg.
Rapamycin
Those who want to take things to the next level may want to consider rapamycin, a drug currently used as an immunosuppressant in transplant patients to avoid organ rejection.
To date, no other drug has demonstrated the lifespan-enhancing effects of rapamycin, which still holds the record for the largest extension of lifespan in the ITP (a median increase of up to 26% for females and 23% for males), and has shown promising results in other species too.
Some doctors are prescribing rapamycin off label already, particularly in Alzheimer´s prevention and as an osteoarthritis treatment. However, there are only a few studies in humans so in contrast to all the other drugs and supplements I’ve mentioned here, human evidence is limited.
If you’re interested in learning more from the experts, check out Dr Matt Kaeberlein, who has studied rapamycin for years, or Dr Alan Green, a physician who has the most patients on rapamycin today.
Based on my own personal risk reward judgement, I have decided it is worth taking low dose rapamycin (6mg per week), and I know several other people in the biotech industry who do the same. Why do I consider this to be a low dose? Well, if you scaled up the mouse dose from the ITP study to a human, you’d end up taking 6mg per day, not per week!
Stay tuned
My longevity stack was compiled based on the latest available scientific data (October 2023). As evidence-based science is the guiding principle for my decisions on what to take and avoid, these are likely to change as new results come out. Stay tuned!
The information included in this article is for informational purposes only. Its purpose is to promote a broad understanding and knowledge of health topics. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. The use of information contained in this article is at the reader’s own risk. Always seek the advice of your doctor with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it.
