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3. Supplements – What to Believe?

As a doctor, I am cautious when it comes to supplements. They account for a huge commercial business, quality assurance and clinical validation are often questionable, and any scientific discussion of their health benefits must necessarily be highly complex. However, since no anti-aging drugs are currently on the market yet, supplements and healthy lifestyles are the only interventions available to us. There have been some quite exciting studies on supplements and anti-aging. We need to separate the hope from the hype.

The choice of supplements is a complex business.

The claimed health benefits of dietary or nutritional supplements have been a matter of controversy ever since the discovery of vitamins in 1912. Previously, supplements had been used in small amounts for the treatment of deficiency diseases. One example is the use of Vitamin D and calcium for rickets. With our ever-growing demand for fitness and wellness, supplements have been gradually taking on a more frontline role in disease prevention, immunity-boosting, and even therapeutic benefits. Because giving a general evaluation of supplements is beyond the scope of this document, our focus will be on supplements that have a direct impact on aging and lifespan.

3.1

The NAD+ booster and resveratrol

The NAD+ booster and resveratrol

What do they do?

From magical potions to the fountain of youth, humans have always been searching for something that can extend our life and youth. While we have managed to find certain supplements or therapies that can improve specific functions, such as heart function, eyesight, etc., it is only now that our understanding of longevity at a molecular level and our ability to design and discover compounds based on this ability have enabled us to discover the compounds directly targeting aging. Resveratrol, nicotinamide mononucleotide (NMN), and nicotinamide riboside (NR) are the first supplements that can be considered to be truly effective in preventing aging processes, based on the fact that they can bring about rejuvenation on the cellular level.

“The fountain of youth is in your mind.” – Sophia Loren

Sirtuins are a family of proteins that work as signals to modulate many physiological functions, such as energy metabolism, DNA repair, tissue regeneration, inflammation, neuronal signaling. They were found to extend lifespan in several species. Resveratrol is a natural compound that can be found in red wine. It is one of the most important sirtuin activators but has also been found to act through other mechanisms than sirtuins. It was made famous by the “French paradox,” the paradoxical phenomenon that French people on average have relatively low rates of coronary heart disease despite a diet that is relatively high in saturated fat.

Sirtuin activity can also be increased by nicotinamide adenine dinucleotide (NAD+) levels. NAD+ is a coenzyme essential for many critical processes in our body. The NAD+ level declines with aging, a change considered by many scientists as an important aging pathway. NMN and NR can transform into NAD+ through enzymatic reactions in our bodies.

One of the challenges is the practical application of scientific insights for real-life benefits. Based on the latest scientific studies, we provide suggestions on the best formulation and the most effective way of taking these supplements.

What to look for when buying them

Red wine is one of the sources of resveratrol

Resveratrol can be found in red wine, apples, berries, and other foods. Unfortunately, we can’t absorb sufficient levels only by drinking red wine. The current recommended daily intake of resveratrol is 1g, based on dosage conversion from animal studies. The average red wine contains around 1.9 ± 1.7 mg trans-resveratrol per liter. It is therefore impossible to get the recommended 1g/day dose by drinking wine or from dietary sources. 

Resveratrol is, however, commercially available as a dietary supplement. We have to look for two things in choosing the right form that can lead to the best health benefit. First, look for trans- rather than cis-resveratrol. The trans- form is considered biologically more active. A purity of 98 percent trans-resveratrol is ideal. Second, look for micronized resveratrol. The micronized form has a reduced particle size that increases bioavailability. 

Another thing about resveratrol is that it is light-sensitive. It is an off-white color and will turn brown if not stored properly. When you receive your resveratrol, you should make sure that it does not have a dark color, which means it is no longer active. The best way is to store it in a sealed bottle in the fridge.   

NMN/NR

NMN and NR are both NAD+ boosters. Since NR is a smaller molecule, it is traditionally considered to have higher efficiency. However, in animal trials, NMN has often been observed to boost the NAD+ level at a much lower dose. In his bestselling book Lifespan, anti-aging pioneer and researcher Dr. David Sinclair said that he takes NMN, based on his experiences with both molecules.

NMN is an expensive product, and a good NMN product could cost US$4-6 per gram and has a purity of at least 98 percent.

NMN and NR don’t have a long shelf life. It is best to store them in the fridge or freezer.

How to take

Resveratrol

There are no clear recommendations on how to take resveratrol. Resveratrol is soluble in fat. Dr. Sinclair mixes his resveratrol with yogurt. Other evidence suggests that taking resveratrol with breakfast, rather than with a high-fat meal, can increase resveratrol concentration in blood. Another way to increase absorption is through sublingual administration. A daily dose of 1g is recommended.

NMN/NR

Almost all of our knowledge regarding NMN comes from studies on mice. There is no standard recommended dosage for NMN. Converting the mouse dosage to a human scale human gives us a dosage of 8mg/kg/day. Another factor is age. Older people theoretically should take a higher dose than younger ones. In general, 500mg per day could serve as a baseline recommendation for someone with a 60-70kg body weight.

There have been a few human studies on NR. The recommended dose for NR is 300mg per day.

Timing and frequency of ingestion

Resveratrol

Resveratrol is taken daily. Some people prefer to take it in the morning, some in the evening. There have been some concerns that resveratrol may blunt the benefit of exercise. More studies have found that resveratrol correlates with exercise due to its positive effects on muscle function, antioxidant activity, and body metabolism. Since most of the studies were done on lower doses, it is reasonable to lower the resveratrol dose to 500mg on high-intensity training days.

NMN/NR

NMN and NR can be taken in a capsule. Some people claim sublingual administration can increase absorption. However, this has not been proven scientifically.

3.2

Other supplements

Other supplements

In the absence of real anti-aging drugs, our best options are supplements and healthy lifestyles.

From 1970 to early 2000, the “free radical theory of aging” took center stage in anti-aging studies. Vitamin C and Vitamin E have been promoted for their antioxidant effects. In early 2000, scientists realized that antioxidants did not make any difference in people’s mortality. There was some evidence that certain supplements may benefit specific organs or functions (e.g., Vitamin E is good for certain eye conditions and Coenzyme Q10 may prevent heart disease). There is no evidence that they can extend lifespan.

Omega-3 fatty acid (consisting of ALA, EPA, and DHA) is another popular supplement that is promoted commercially to prevent heart disease, stroke, cancer, etc. There are no scientific studies to support these claims.

There is some evidence, on the other hand, that oral collagen supplements can prevent skin aging. A few studies have found that oral collagen supplements are generally safe and can increase skin elasticity, hydration, and dermal collagen density.

In general, there is no evidence that a healthy person needs dietary supplements. The amount of vitamin and other nutrients required varies from one person to another. The golden rule is to make the decision based on vitamin levels in the blood.

3.3

Supertrends recommendations on anti-aging supplements

Supertrends recommendations on anti-aging supplements

  • Resveratrol: buy in the form of micronized trans-resveratrol, take at a dose of 1g per day, 500mg per day on days of high-intensity training, take with food or by sublingual administration.
  • NMN: buy products with more than 98 percent purity, take at a dose of around 500mg per day, either in a capsule or by sublingual administration.

It is important to know that regulations for supplements are less strict than medications. Most of the time, supplements are not likely to cause any health risks. However, they may interact with other medications or cause allergic reactions. It is advisable to discuss with your medical doctor before taking any supplements.

Sources

  • Bonkowski MS., Sinclair DA. 2016. Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nat Rev Mol Cell Biol. 17(11):679-690. https://doi.org/10.1038/nrm.2016.93
  • Weiskirchen S., Weiskirchen R. 2016. Resveratrol: How Much Wine Do You Have to Drink to Stay Healthy?. Adv Nutr. 7(4):706-718. https://doi.org/10.3945/an.115.011627
  • Smoliga J.M., Blanchard O., 2014. Enhancing the Delivery of Resveratrol in Humans: If Low Bioavailability is the Problem, What is the Solution? Molecules. 19,17154-17172; https://doi.org/10.3390/molecules191117154
  • Baltaci SB., Mogulkoc R., Baltaci AK. 2016. Resveratrol and exercise. Biomed Rep. 5(5):525-530. http://doi.org/10.3892/br.2016.777
  • Conze D., Brenner C., Kruger CL. 2019. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Sci Rep. 5;9(1):9772. https://doi.org/10.1038/s41598-019-46120-z.
  • Nicholls SJ., Lincoff AM., Garcia M., et al. 2020. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: the STRENGTH randomized clinical trial. JAMA. Published online. https://doi.org/10.1001/jama.2020.22258
  • FDA 101: Dietary Supplements. https://www.fda.gov/consumers/consumer-updates/fda-101-dietary-supplements#:~:text=The%20law%20defines%20dietary%20supplements,used%20to%20supplement%20the%20diet.