Supplements intended to increase NAD+

Vitamins and nutrients in foods are key to maintaining a healthy life. Research in many areas has converged on the idea that altered metabolism is a key factor in aging and aging-associated diseases. Consequently, there is great interest in identifying molecules in food that can support a youthful, healthy metabolism and thus reduce aging-associated disease and the effects of aging. When given as a supplement, such food-based molecules that promote health or have medicinal benefit, are called nutraceuticals. The two components of the supplement Basis made by Elysium Health are nicotinamide riboside (NR) and pterostilbene (Figure 1).

Figure 1. Chemical structures of pterostilbene (left), nicotinamide riboside (NR, middle), and nicotinamide adenine dinucleotide (NAD+, right). The top structures are 2D representations and the bottom are 3D representations. Visit PubChem for interactive versions of these molecules. Nicotinamide riboside is enzymatically converted into NAD+ in cells.

In short, through its conversion to the chemical NAD+, NR is intended to support healthy cellular metabolism and provide a required substrate for the enzyme SIRT1. Pterostilbene is intended to reduce oxidative stress and stimulate the activity of the enzyme SIRT1. NR is structurally related to the B 3 vitamins, niacin and nicotinamide. Unlike niacin and nicotinamide, which are found in many foods, NR is not present in sufficient quantities in most foods to be considered a vitamin. NR is detectable in cow’s milk, and it may also be present in very small amounts in foods that are naturally rich in Vitamin B 3 and in products made with yeast or that contain yeast in the product, such as beer or bread. Pterostilbene is a molecule found in plants, such as blueberries, red grapes and red wine, peanuts, and almonds. Neither NR or pterostilbene are vitamins with a recommended daily allowance. Their amounts in foods are very low.

The rationale for using NR, instead of niacin, as an anti-aging supplement is that high concentrations of niacin have negative side effects ranging from annoying facial flushing (due to dilation of blood vessels) to potentially life-threatening liver damage (due to effects on metabolism). The enzymes in cellular metabolic processes that rely on NAD+as a coenzyme are incredibly numerous and mediate hundreds of biochemical reactions in cells. The enzymes that consume NAD+as a substrate to mediate their reactions, such as SIRT1, are also numerous. SIRT1 is only one of 7 sirtuin enzymes that use the NAD+, and sirtuins are only one of several families of enzymes that use NAD+to regulate cellular behavior and metabolism. Thus, it is difficult to predict exactly how using NR as a nutraceutical will affect different people of various ages with different genetic backgrounds, diets, and microbiomes (the microbes that share our bodies with us).

Clinical Trials of NR-Based Supplements

Elysium Health funded an independently run clinical trial to test the safety and efficacy of the components in Basis in increasing NAD+in circulation. The 60-day trial involved 120 people (men and women between 60 and 80 years old) and included a placebo group. Two doses were tested. Interestingly, the higher dose regimen did not maintain a high amount of NAD+ in the blood. Both doses were leading to the same concentration of NAD+ in the blood at the end of the 60-day study, consistent with the body requiring an optimal amount of NAD+and inducing systems to limit the accumulation of the molecule (likely resulting in the excretion of its metabolites in the urine).

This study did not test health benefits. It was study to see if there were adverse effect from taking the supplement (safety) and a study to see if the supplement increased the amount of NAD+in circulation (efficacy). It was a very short study though, which would not reveal increases in cancer risk or metabolic adaptations that could be negative.

Another company developing and testing NR-based supplements in clinical trials is ChromaDex, who make Niagen. Many pterostilbene supplements are commercially available.

No data from adequately controlled clinical trials have shown convincing health benefits from taking these supplements.

Questions

Many questions remain about using Basis or its active components to stave off the effects of aging.

Are there health benefits to taking NR and pterostilbene supplements?

Is there an ideal time in life to start taking NR and pterostilbene supplements?

Are there risks to taking NR and pterostilbene supplements too early in life?

Do NR and pterostilbene supplements increase the risk of developing or the progression of some cancers?

Can NR and pterostilbene supplements trigger autoimmune disease by hyperactivating a subset of T cells?

Are there specific patients that would benefit from NR or pterostilbene or both if used as a prescription-based medical treatment for a defined treatment period?

Are there genetic factors that can identify those most likely to benefit from NR and pterostilbene supplements and those most likely to be harmed?

How do NR and pterostilbene supplements influence the activity or effects of medications, such as metformin? Are there contraindications with other supplements or medications?

Should patients be screened for NAD+or NAD+/NADH balance prior to taking such a supplement?

How does this supplement interact with different diets?

How does the body process the compounds, how long do they or their metabolites persist in the body, and how are they or their metabolites excreted?

If someone has sufficient NAD+, do these supplements just make expensive pee?

Related Reading and Resources

R. W. Dellinger, S. Roel Santos, M Morris, M. Evans, D. Alminana, L. Guarente, E. Marcotulli, Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: A randomized, double-blind, placebo-controlled study. NPJ Aging Mech. Dis. 3, 17 (2017). DOI: 10.1038/s41514–017–0016–9. PubMed

S. Johnson, S. Imai, NAD biosynthesis, aging, and disease. F1000Research 7 (F1000 Faculty Rev),132 (2018). DOI: 10.12688/f1000research.12120.1. PubMed

Nutraceutical Companies

Elysium Health (accessed 10 June 2018) https://www.elysiumhealth.com/

ChromaDex (accessed 10 June 2018) https://chromadex.com/

Nicotinamide riboside (accessed 10 June 2018) https://clinicaltrials.gov/ct2/results?cond=&term=Nicotinamide+riboside

Pterostilbene (accessed 10 June 2018) https://clinicaltrials.gov/ct2/results?cond=&term=pterostilbene

Nicotinamide riboside (accessed 10 June 2018) https://pubchem.ncbi.nlm.nih.gov/compound/nicotinamide_riboside

Pterostilbene (accessed 10 June 2018) https://pubchem.ncbi.nlm.nih.gov/compound/5281727

NAD+(accessed 10 June 2018) https://pubchem.ncbi.nlm.nih.gov/compound/5892

Cite as: N. R. Gough, Anti-Aging Supplements: The Basis for Basis. BioSerendipity (11 June 2018) https://www.bioserendipity.com/anti-aging-supplements-the-basis-for-basis/