#59: 💊 Can We Outsmart Aging with Longevity Supplements?
How to boost longevity and what to watch out for
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💊 Can We Outsmart Aging with Longevity Supplements?
📚 The Fourth Wing
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💊 Can We Outsmart Aging with Longevity Supplements?
Before you reach for supplements, it’s best to optimize the foundations of a healthy lifestyle - sleep, diet, exercise, socialization and mental health.
With those in place, again before reaching for a pill bottle, try adjusting your diet to add the supplement through whole-foods. Fruits, vegetables and proteins contain more than just the supplement and many of these molecules support each other in the whole-food source.
For example, taking a vitamin C supplement versus eating an orange. When you take a vitamin C supplement, that is all you are getting. An orange however, is rich in vitamin C but also in folate, calcium, potassium, vitamin B1 and is even a great source of fiber.
Some nutrients may have to be supplemented because they are not part of our natural diet. Some people may suffer from deficiencies such as a lack of fiber, potassium, iron, glycine, etc. In either case, supplementation could be the right path forward to recovery.
In terms of longevity, the aging research community has been looking for drugs and supplements which extend lifespan and healthspan. Several have been identified and studied in laboratory model organisms, such as the fruit fly (Drosophila melanogaster), a clear nematode (C. elegans) and rodent models.
What are the Age-Fighting Drugs and Supplements?
Resveratrol
Resveratrol is a natural compound found in 70 plant species, especially in grapes, berries, and seeds. It acts similarly to an antioxidant, preventing the cells in the body from the damage of oxidation.
It has been studied for its potential anti-aging effects on skin, blood sugar stabilization, male infertility, cardioprotective effects and effect on cognition.
The easiest way to add resveratrol to your diet is through grapes, wine (yay!), blueberries, cranberries and pomegranates. It is also possible to take resveratrol supplements which contain much higher doses than a person can reasonably consume through diet.
The proper dose of resveratrol is unclear and more studies are needed to determine a safe and effective dose. Some studies have shown side effects of nausea, vomiting or diarrhea at doses of 2500mg, and positive effects on blood pressure were seen at 150mg.
NMN (Nicotinamide Mononucleotide)
NMN is a compound that is involved in the production of NAD+ (nicotinamide adenine dinucleotide) in the body. NAD+ is a coenzyme that plays a crucial role in various cellular processes, including energy metabolism, DNA repair and cellular repair processes.
As we age, NAD+ levels decline and this decline has been implicated in age-related health issues.
Supplementation with NMN aims to increase NAD+ levels in the body and potentially support cellular health and longevity.
There are some preclinical studies in mice indicating that NMN can increase NAD+ levels, improve mitochondrial function, enhance energy metabolism, and potentially ameliorate certain age-related conditions. NMN has also shown positive effects on metabolic health, cardiovascular function, cognitive function, and muscle endurance in animal studies.
It's important to note that the translation of these findings from animal studies to humans is still in progress. Clinical research on NMN supplementation in humans is ongoing but relatively limited. More research is needed to establish the safety, efficacy, optimal dosage, and long-term effects of NMN supplementation in humans. However, a review of the safety and antiaging effects of NMN in human clinical trials was published in August 2023.
Metformin
Although primarily used as a medication for type 2 diabetes, metformin has gained attention for its potential anti-aging effects as it appears to positively impact many key pathways of aging.
Epidemiological studies have suggested that metformin reduces cancer risk and mortality and preserves cognitive function. In an observational big-data study of 78,000 adult type 2 diabetics in their 60s, those who took metformin lived longer than healthy matched controls.
This study excited the medical and aging research community because Metformin is widely available, inexpensive and safe. Factors that allow for the mass adoption of such an aging intervention.
Millions of diabetics have been taking metformin since the 1960s, and the mild side effects are well-known. Metformin is available as a generic, costing just a few cents a dose.
Two clinical trials have been designed to assess the potential benefits of metformin as an anti-aging drug. The studies are the MILES (Metformin in Longevity Study) and the TAME (Targeting Aging with Metformin).
The TAME is designed to prove the concept that multi-morbidities of aging, such as cardiovascular disease, cancer, cognitive decline and overall mortality, can be delayed by metformin.
The study was designed in 2015 as a double-blind study of 3000 elderly people, half would get placebo and the other metformin, and is yet to begin. The status of the TAME trial can be followed online. They are currently looking for donors to support the cost of the trial and to recruit individuals between the ages of 65-79 to participate.
Omega-3 fatty acids
Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are found in walnuts, fatty fish, seed and plant oils.
Best known for their anti-inflammatory properties, Omega-3s are also associated with supporting cardiovascular health, cognitive function, skin hydration and joint health.
Make sure your supplements offer a balanced ratio of EPA to DHA, which maximizes the benefits of both omega-3s, and come from cold-water fish like salmon, mackerel or sardines.
Oil supplements can go rancid, so keep an eye on the expiration date and only take supplements which are fresh.
Coenzyme Q10 (CoQ10)
CoQ10 is an antioxidant that plays a vital role in mitochondrial energy production within cells. It has been studied for its potential benefits in cardiovascular health and age-related decline.
You can boost your coenzyme Q10 intake through meat, fish and seafood. Vegetables like soybeans, and broccoli are some of the highest coenzyme Q10 vegetable sources, however they contain much less coenzyme Q10 than meats and fish.
The recommended daily dose of CoQ10 is between 90-200mg, which is difficult to achieve through diet alone. CoQ10 supplements are generally well tolerated with limited side effects.
Rapamycin
Rapamycin is an immunosuppressant drug that has gained attention in the field of longevity research due to its potential anti-aging effects. It belongs to a class of drugs called mTOR inhibitors, which inhibit the mechanistic target of rapamycin (mTOR) pathway.
The mTOR pathway is involved in cellular processes such as growth, metabolism, and autophagy (the cellular recycling system). By inhibiting mTOR, rapamycin is thought to activate autophagy, which helps remove damaged cellular components and promote cellular rejuvenation.
Rapamycin is currently an FDA-approved drug used primarily as an immunosuppressant to prevent organ rejection in transplant patients. It is not specifically approved for anti-aging purposes.
Long-term use of rapamycin may have side effects and can suppress the immune system, so it should only be taken under the supervision of a healthcare professional.
Studies conducted on various organisms, including yeast, worms, flies, and mice, have shown that rapamycin can extend lifespan and improve healthspan. It has been observed to delay the onset of age-related diseases and improve several health markers.
The use of rapamycin for anti-aging purposes is an area of active research, and more studies are needed to determine its long-term effects, optimal dosing, and potential risks in humans.
What To Watch Out For
Incompatible Combinations
Supplementation can be complex because each of our bodies is unique and we have different needs. It may also be hard for some people to generalize a routine.
It is not always best practice to try to take all of the available supplements simultaneously.
I was recently at a longevity meetup where aging researcher, Dr. Diogo Barardo, shared his results from a study combining longevity supplements.
In ~50% of combinations of two or three longevity supplements, the effect on longevity either resulted in a mutual cancellation of the benefits or toxicity where the combination was actually worse on longevity than taking nothing or a single supplement alone.
In only 10% of cases were the effects additive, and synergistic effects only occurred in 21% of the tested combinations.
It is important to use measurements to gauge if something is working for you or not. What were your biometric measurements before the supplement? After 1 week? 4 weeks? 6 months after taking the supplement?
Metrics you can track include, resting heart rate, VO2max, weight, sleep quality and waist circumference. It is important to create a feedback loop where you try the intervention, evaluate your results, and track your progress. Then based on your results, you can choose to continue the supplement or try something new.
Quality
Since supplements are not regulated in the same way that drugs are by the FDA, it is important to be cautious and make sure you are buying from a reputable supplier.
A recent report shows that a number of NMN supplements sold on amazon inaccurately displayed the amount of NMN in the product with some containing no NMN at all. Additionally, it is always advisable to check with your doctor before starting a new supplement regime.
Look for supplements with the NSF International, US Pharmacopeia, Underwriters Laboratory or ConsumerLab seal. These organizations verify that the product actually contains the ingredients that the label says it does and that the product doesn’t have any potentially harmful ingredients.
Be wary of supplements made outside of the US and EU, as again, many are not regulated and have misrepresented their products on the labels.
Supplements do not last forever. Make sure to regularly check the expiration dates and discard those that are past their expiration.
If you buy them, make sure you keep them in a cool, dark and dry place. It is also important to note, as I just learned this, to avoid storing supplements in bathrooms and other damp areas. I was keeping all my supplements above my stove, which gets hit directly with steam from cooking 🤦🏽♀️.
Longevity Celebrity Supplement Routines
Since clinical trials for aging drugs and supplements are difficult to design, control and fund, many aging researchers are experimenting on themselves in order to demonstrate the effects as an N=1 (sample size of 1).
We see this type of experimentation from longevity enthusiasts like Dr. David Sinclair, Dr. Andrew Huberman, and Bryan Johnson, who have made their supplement stacks public.
Keep in mind that many of these longevity influencers have more resources than the average person and have a team of people in place to help them achieve their optimal health. Copying one of their routines may not be necessary or right for everyone.
Nonetheless, let’s check them out.
David Sinclair’s Supplement Stack
Dr. Sinclair never gives brand names of the supplements he takes, but he does share his routine. More notes on his longevity routine here.
NMN + Resveratrol: 1 g of NMN and 0.5 g of resveratrol every morning mixed in with some yogurt
Vitamin D + K2
Metformin: 1 g at Night
High Dose Statin (he has genetically driven high cholesterol)
Bryan Johnson’s Blueprint
Bryan Johnson is a billionaire software entrepreneur and longevity enthusiast, best known for Project BluePrint which outlines his personal anti-aging protocol.
His supplement stack is a staggering 52 different supplements intended to support his goal of ”not dying.”
While his protocol is extreme, he is a very visible personal experiment of all anti-aging treatments. He spends over $2 million a year on attaining the biological metrics of an 18-year old and with this team of doctors in place to measure the effects of any diet, supplement or medical intervention he tries.
It is hard to imagine taking 52 different supplements multiple times a day. View the whole list and the medical rationale behind it here.
Dr. Andrew Huberman’s Supplement Routine
Stanford professor, neuroscientist and host of the Huberman Lab podcast, Dr. Andrew Huberman, has an extensive routine of 27 supplements to promote healthspan and lifespan. Read the full list with rationale written up by Hone Health.
Highlights include:
Fish oil for EPA's antidepressant and lipid profile benefits
Alpha-GPC for cognitive enhancement
Garlic extract to manage cardiovascular risks
L-Tyrosine for focus and attention
Phenylethylamine (PEA) for cognitive function
Glutamine for immune and cognitive benefits
Creatine for brain function and focus
Ashwagandha for stress management
AG1 for nutrient needs and gut health
Multivitamin
Protein powder
Dr. Molly Maloof’s Supplement Stack
Dr. Molly Maloof is a healthspan medical doctor and author of The Spark Factor (Nina’s Notes Book of the Week on March 8, 2023, ★★★★☆). She is a mitochondrial expert who works with thousands of private clients to help boost your energy.
Her baseline supplements include:
Omega 3's, 2-4 grams daily
B Complex for metabolism and deficiency prevention
Vitamin D, K1, K2, 5000 IU if deficient
Magnesium, 400 mg daily
For Extra Optimization she uses:
Mineral complex personalized based on testing
Iron supplementation based on ferritin levels
She also lists supplements for digestion support, mitochondrial health, detoxification and immune support. All which can be found on her website.
If you are considering any supplementation consult with a healthcare professional who is knowledgeable about anti-aging interventions and can provide personalized advice based on your specific health circumstances. They can help you determine whether supplementation is appropriate for you and guide you through the potential benefits and risks.
📚 Book of the Week
The Fourth Wing by Rebecca Yarros
Rating: ★★★★★
If you loved How to Train Your Dragon and The Atlas Six, then you’ll love The Fourth Wing.
It’s basically dragon magic school and I’m here for it.
This one is also in my Top 5 for 2023.
The sequel, Iron Flame debuted on November 7, 2023.
⚡️ Check This Out
Cats are generally thought of as antisocial but the magnitude of their facial expressions shows quite the opposite.
Cats have nearly 300 facial expressions, as reported by a new study published last month in Behavioral Processes.
In comparison, humans have 44 facial expressions, dogs have 27 and chimpanzees have 357.
The study was completed over a year by studying 53 adult domestic cats at the CatCafé lounge in Los Angeles, CA.
Just FYI, this is likely the PhD work of a grad student and I can’t think of a better hack for grad school than studying cats in a cafe. Well done Lauren Scott, first author on the paper. Hats off to you.
Edited by Wright Time Publishing
Very useful breakdown of the current state of longevity supplements. Thank you for shedding light on this subject :)
Please share your top 5-10 books at some point too :) I love your book recommendations.