This is an abstract image representing methylation. This is an abstract image representing methylation. This is an abstract image representing methylation.

The Importance of Balanced Methylation and Its Relationship to NAD+

Donors and Recipients—The Miracle of Methylation

Methylation is a vital cellular process, occurring one billion times per second and impacting nearly every essential function in the body. 

It is essential for the proper functioning of various substances including vitamins, amino acids, neurotransmitters, hormones, DNA, RNA, and antioxidants.

It also plays a significant role in cardiovascular, neurological, and reproductive health, along with detoxification and energy production. 

Suboptimal methylation, influenced by dietary, lifestyle, environmental, and genetic factors, can negatively affect overall well-being and lead to age-related disease. So understanding methylation is crucial for supporting health on a foundational, cellular level.

A Deeper Dive

Methylation is a chemical reaction that involves the transfer of a methyl group, a simple structure of one carbon and three hydrogen molecules (CH3), from one bioactive compound to another via DNA methyltransferases (DNMTs). These compounds must be methylated in order to function properly or to create other substances required by the body. 

In the process of methylation, the receiving molecule is said to be methylated. And the molecule that gives up the methyl group is called a methyl donor. 

DNA Methylation—Going Beyond Genes

The intriguing process of DNA methylation happens when a methyl group is added to a specific site on a DNA strand, tagging it, and effectively silencing a gene and locking it in the “off” position. Or DNA methylation can result in structural changes that make DNA more or less accessible by certain enzymes. Collectively, this process ends up telling a cell what it will become (blood, skin, etc.), what operations it will perform, and when. Known as epigenetics, the process influences gene expression, which is how and to what extent your genes are used in the body. 

A note on Epigenetics:

Epigenetics is a chemical process that modulates how our genes work without changing our DNA. In other words, your genes play an important role in your health, but so do your behaviors and environment. Epigenetics is the study of how your environment, nutrition, and lifestyle affect the way your genes work. These lifestyle factors can affect your health, immunity, the likelihood of developing certain diseases, and the speed at which you age.

The good news is that unlike genetic changes, epigenetic changes are reversible and do not alter your DNA. Proper nutrition and nutritional supplements, such as NAD+ (nicotinamide adenine dinucleotide) may indirectly or directly influence the way your genes work.

As in Life, in Methylation, Balance Is Everything

Since the methylation cycle influences many critical processes in the body, it cannot be overstated how important balanced methylation is for the regulation of bodily functions and optimal health.

An imbalance in methylation can be caused by genetics, stress, nutritional deficiencies, lifestyle, environment, and age itself. It can involve too few methyl donors (also known as hypomethylation), or too many methyl donors (hypermethylation).

When it comes to aging, the quality of methylation has become a more precise marker of age than telomeres.

DNA methylation biomarkers can be an indicator of the biological age of any tissue across the entire human lifespan, even during development.

Benefits of Balanced Methylation:

Healthy levels of homocysteine: Compromised methylation can cause an elevated level of homocysteine in your blood, which has been linked to elevated risk of various diseases. Methylation helps maintain a low level of homocysteine.

Glutathione production: Methylation plays a crucial role in converting homocysteine to glutathione, a master antioxidant in your body. It helps prevent the formation of free radicals, which cause cellular toxicity. Poor methylation can hinder glutathione production in your body, leading to weakened immunity, arterial damage, cognitive decline, and accelerated aging.

Protein synthesis: Methylation helps in protein synthesis. It also helps support muscle mass and fitness. 

Neurotransmitter synthesis: The methylation cycle is essential for the synthesis of serotonin and dopamine, which keep you relaxed and happy. It also helps support normal brain function.

Cardiovascular health: Homocysteine, an amino acid, has been linked to an elevated risk of blood clots and cardiovascular disease. People with genetic variants of the MTHFR gene are more vulnerable to this condition, as lowering levels of homocysteine can be difficult for them. The MTHFR gene mutation inhibits the way the body processes folic acid and other B vitamins, which serve as important methyl donors. Adapting levels of these nutrients is a potential focus in countering MTHFR mutation effects. Methylation helps convert homocysteine back to other health-friendly amino acids.

Hormone regulation: Methylation helps maintain a healthy balance of hormones such as estrogen by supporting liver function. 

Protection of telomeres: Telomeres are attached to DNA and chromosomes. Well-protected telomeres are associated with slower aging. Methylation protects the telomeres and hinders signs of early aging.

Mitochondrial health: Mitochondria are the major energy producers in your cells. Methylation may protect mitochondria, helping them to maintain adequate energy production. Methylation imbalances can cause severe and persistent fatigue. The methylation cycle helps in the production of coenzyme Q10, which is essential for heart health and energy production within mitochondria.

The Role and Importance of NAD+ in Methylation

Very simply, NAD+ is a coenzyme that helps build energy. Some enzymes build energy in your mitochondria. NAD+ activates these enzymes so they can do the job of powering your body. You can think of NAD+ as the coenzyme that allows mitochondria to do their job by activating the enzymes that create energy. And in this way, NAD+ helps generate over 90% of your body’s energy.

But NAD+ declines up to 65% between the ages of 30 and 70. This may contribute to a decrease in cellular energy, which can potentially lead to further health problems over time.

The relationship between declining NAD+ levels, abnormal DNA methylation, and aging is complex and not fully understood. However, replenishing NAD+ levels is being explored as a potential strategy to mitigate age-related changes in DNA methylation and promote healthier aging. Studies have shown that NAD+ counteracts epigenetic reprogramming, suggesting its role in nutritional-based therapies to combat age-related functional decline.

NAD+, an essential coenzyme for various enzymes involved in epigenetic pathways (including DNA methylation), holds promise as a potential anti-aging molecule as NAD+ is an essential coenzyme for this process. 

Because NAD+ activates the enzymes involved in epigenetic pathways, declining NAD+ levels have been associated with abnormal DNA methylation, which can lead to unwanted changes related to aging.  

Maintaining balanced NAD+ levels may have implications for preventing and managing aging associated with aberrant DNA methylation.

How to Support Methylation and NAD+ Levels

We can support healthy methylation and NAD+ by consuming foods that are rich sources of methyl donor nutrients, such as:

  • Dark leafy greens: Kale, spinach, collard greens, mustard greens, and escarole are rich in magnesium, folate, and other B vitamins. They support methylation and NAD+ levels.

  • Cruciferous vegetables: Brussels sprouts, cauliflower, broccoli, cabbage, and arugula are great sources of folate and support methylation and detoxification, and NAD+ levels.

  • Beets: Packed with betaine, beets are an excellent methyl donor food.

  • Shiitake mushrooms: While all mushrooms support methylation and other physiological systems, shiitake mushrooms are particularly beneficial to both methylation and NAD+. These mushrooms are packed with choline and a number of B vitamins such as riboflavin, niacin, pantothenic acid, B6, and B12. 

  • Turmeric: A methylation adaptogen, turmeric contains a phytochemical called curcumin that has anti-inflammatory and epigenetic modification properties.

  • Berries: These phytonutrient-packed fruits are considered methylation adaptogens.


A growing body of evidence indicates that exercise training modulates DNA methylation in muscles and adipose tissue. Some of these epigenetic markers were associated with a reduced risk of chronic diseases. 

On top of that, your mitochondria will notice if you are sitting around, not moving very much and basically leading a sedentary lifestyle and they’ll begin to reduce their numbers. Fewer mitochondria means less NAD+, and this may affect DNA methylation.

Reduce Exposure to Toxins

Methylation and detox pathways are linked, and metabolic stressors such as too much direct sunlight can also reduce NAD+ levels. So practicing healthy detoxification is a good way to support methylation and NAD+. 

Toxins include anything from alcohol and cigarettes to harsh chemicals found in cleaning agents, fragrances, and conventional beauty products, to excess UV light. Stressors on your cells, such as toxins or excess sun exposure, require DNA repair that can deplete your NAD+ levels. In other words, lifestyle choices can help keep your cells healthy, support methylation, and keep NAD+ levels intact. When it comes to your environment, filtering the air and water in your house is another great idea.

Benefits and Limitations of NAD-Boosting Supplements

Nutritional intake affects the human epigenome by directing epigenetic pathways in normal cell development, but the molecular mechanism is still unknown. What we do know is that imbalances in nutritional intake are able to dysregulate the epigenetic profile and drive cells toward unwanted transformation.

Studies indicate NAD+ as a novel epigenetic modulator that counteracts the widespread epigenetic reprogramming, providing important nutritional-based support for gene expression in human cells. One study bridges a nutritional intervention to a molecular observation: An increase of NAD+ levels results in local correction of DNA methylation. This data suggests adverse alterations of DNA methylation may potentially be linked to decreased NAD+ levels. Taking a NAD-boosting supplement is another way to combat cellular stress caused by poor diet, lack of exercise, excess alcohol, excess sun exposure, too little sleep, and aging in general. By taking Tru Niagen consistently each day, you can help protect your cells from the effects of aging. We all age. But we can choose to do so with higher levels of NAD+—and perhaps more balanced methylation.

Related Posts

food group pie chart food group pie chart food group pie chart

What Does Vitamin B3 Deficiency Look Like?

Vitamin B3 deficiency is rare but this nutrient is vital for your health. What happens when you don't have enough?
home chef in the kitchen home chef in the kitchen home chef in the kitchen

What Is Cellular Nutrition?

Proper nutrition has too many variables. Learn why cellular nutrition is different and what you can do to benefit the foundation of your health.
Man jumping over guard rail Man jumping over guard rail Man jumping over guard rail

7 Ways Your Body Makes Energy

Find out the different ways your body makes energy on a biological level.