Nitric Oxide, Methylation & Heart Health: What You Need to Know


Nitric oxide is one of the most important molecules in your body. It is a very important free radical that is responsible for dilating blood vessels and maintaining arterial elasticity. Maintaining optimal levels of nitric oxide is absolutely essential for anyone with heart disease, or anyone with an increased risk of cardiovascular disease. There are a number of potentially important nutritional therapies, including methylation protocols, for boosting nitric oxide synthesis to support optimal health.

3 Forms of Nitric Oxide & Lesser Known Functions

Nitric oxide is abbreviated as NO. There are 3 forms of nitric oxide:

  1. The inducible form (iNOS)
  2. The neuronal form (nNOS)
  3. The endothelial form (eNOS)

The 3 forms of nitric oxide combine to support many diverse and important functions of the body. Within the endothelium (cells that line the blood vessels) nitric oxide acts to "relax" smooth muscles, thereby dilating blood vessels. In these regards, nitric oxide plays a very important role in cardiovascular health.

Nitric oxide is also an important part of the immune system. Various immune cells such as macrophages, neutrophils and monocytes produce nitric oxide, which is cytotoxic to various pathogens such as bacteria and parasites.

Some of the other lesser known but important functions of nitric oxide:

  • Pancreatic function, inducing the release of the digestive enzyme amylase
  • Hypothalamic release of the hormone GRH (gonadotrophin releasing hormone)
  • Kidney function - nitric oxide improves glomerular filtration
  • Relaxes the smooth muscles of breathing airways of the lungs

There are 3 genes that are directly involved in nitric oxide synthesis: NOS1, NOS2 and NOS3. These gene mutations may predispose someone towards having sub-optimal nitric oxide levels.

Help Your Body to Make Nitric Oxide - Methylation

Nitric oxide is generated by a number of enzyme reactions. Most notably, this includes various enzymes found in the urea and methylation cycles. 3 amino acids are very important for nitric oxide synthesis. They are: Ornithine, citrulline and arginine. Even though arginine is the immediate cofactor for nitric oxide synthesis, supplementing with L-citrulline is more effective at raising arginine and nitric oxide levels (1).

Another very important component of nitric oxide synthesis is tetrahydrobiopterin, also known as BH4. This important molecule not only is important to make nitric oxide, it is also critical to synthesize neurotransmitters.

BH4 is synthesized in response to methylation. In fact, the enzyme that generates BH4 is known as DHFR (di-hydrofolate reductase). This enzyme is activated when there is proper folate methylation. In other words, deficiencies of 5-methylfolate (either caused by MTHFR gene mutations, or some other factor that depletes folate) can lead to BH4 deficiency. Methylation is a very important biochemical process, which not only effects nitric oxide, but also a number of very important functions.

Certain foods have been shown to boost nitric oxide levels. This is true of foods with high nitrates, such as beets, beet greens, and numerous green leafy vegetables such as spinach, chard, kale and parsley.

An effective way of testing your nitric oxide levels includes salivary nitric oxide testing strips. These are an effective and non-invasive method. Saliva nitric oxide testing is a valid way for individuals to monitor nutritional therapies that aim to boost nitric oxide levels.