Why It's Important to Methylate While Taking Nicotinamide Riboside - Thorne Asia

Why It's Important to Methylate While Taking Nicotinamide Riboside

When you supplement with nicotinamide riboside (NR), it’s also important to support your body’s methylation processes. But why? Before we answer that, let’s take a refresher on what methylation is and why it’s important.


What is methylation and why is it important?

Methylation is a simple biochemical process – it is the transfer of four atoms – one carbon atom and three hydrogen atoms (CH3) – from one molecule to another.

When optimal methylation occurs, it has a significant positive impact on many biochemical reactions in the body. These reactions regulate the activity of cardiovascular, neurological, reproductive, and detoxification processes, including those relating to:

  1. DNA production
  2. Neurotransmitter production
  3. Detoxification
  4. Histamine metabolism
  5. Estrogen metabolism
  6. Eye health
  7. Fat metabolism
  8. Cellular energy
  9. Liver health

Some of the important substances that are made in the body that depend on methylation include: 

  1. Glutathione
  2. Coenzyme Q10
  3. Melatonin
  4. Serotonin
  5. Nitric oxide
  6. Norepinephrine
  7. L-Carnitine
  8. Cysteine
  9. Taurine


The problem

Many U.S. adults – some estimates are as high as 60 percent – have a genetic defect in a critical enzyme involved in methylation – MTHFR. MTHFR is the enzyme that creates active folate from inactive folic acid obtained from food and supplements. Individuals with this genetic defect can have a significantly decreased methylation abilities. This situation can result in an increase in the undesirable amino acid metabolite homocysteine, a decrease in the creation of the important substances listed above, and subsequent decreased detoxification.


What does NR supplementation have to do with it?

Supplementation with NR, a vitamin B3 analog, has been demonstrated to increase the number of mitochondria and benefit their function, which ultimately increases NAD+ and the cellular energy molecule ATP.* NAD+ levels decline with aging and stress.

As NAD+ does its work, it is broken down to nicotinamide (also known as niacinamide), which is mostly converted to methylnicotinamide (MeNAM). So, the more NAD+ there is, the more MeNAM there is. The methyl group for this bioconversion must come from a methyl donor, but if the methyl group comes from the methyl pool in your body, then it puts stress on that pool. And, particularly in the case of specific genetic and/or lifestyle issues, there are fewer methyl groups for the other essential methylation functions. This can be particularly problematic for individuals with genetic mutations, such as in the MTHFR gene mutation.


What does the science say?

A clinical study of nicotinamide supplementation showed not only an increase in MeNAM, but also an increase in homocysteine levels, which is an independent risk factor for heart disease.* This study also showed a decrease in the detoxification of undesirable neurotransmitters.1


What’s the solution?

Eat foods that support methylation:

  1. Asparagus
  2. Avocado
  3. Broccoli
  4. Brussels sprouts
  5. Green, leafy vegetables
  6. Legumes (peas, beans, lentils)
  7. Rice

Make lifestyle changes that support methylation:

  1. Engage in regular physical exercise
  2. Avoid excessive alcohol consumption
  3. Don’t smoke
  4. Avoid excessive coffee consumption (not more than five cups daily)
  5. Avoid processed foods as much as possible


Essential nutrients that support methylation:

Several nutrients support methylation by directly donating a methyl group. For the most part, these are obvious because the word “methyl” is in the name of the nutrient – 5-methyltetrahydrofolate (5MTHF; active folate), methylcobalamin (active B12), dimethylglycine (DMG; derivative of the amino acid glycine), and trimethylglycine (TMG; betaine). TMG is one of the most important because, as the name implies, it has three methyl groups to donate. Other less obvious methyl donors include choline and methionine. Other nutrients that are necessary cofactors in methylation include vitamins B2, B6, and D, and magnesium.

Thorne has always been a leader in spreading awareness of and supplementing with methylation nutrients along with NR – including in ResveraCel.


  1. Sun W, Zhai M, Li D, et al. Comparison of the effects of nicotinic acid and nicotinamide degradation on plasma betaine and choline levels. Clin Nutr 2017;36:1136-1142.
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