Nitric oxide or NO is a signaling molecule that plays many roles in the body. It plays a role in oxygen delivery, blood flow, glucose uptake, power output, nutrient delivery, and muscle growth. Elevated levels of NO can improve muscle hypertrophy by increasing intramuscular blood flow for greater pumps, strength improvement, increased endurance, pain reduction, ATP production, and nutrient delivery. NO can also elevate gonadotroptin releasing hormone and adrenaline. Anecdotal reports also suggest that NO increases exercise induced vasodilation (pump due to physical activity) and cell volumization by routing water and nutrients preferentially to the muscle cell, while studies have shown that when NO synthesis is blocked, greatly reduced gains in muscle mass and muscle sarcomeres are observed.

So now the question is, how would one effectively and efficiently maximize nitric oxide levels in the body. Nitric oxide is created in the endothelium, which is located at the interface between the blood and the blood vessel wall. The endothelium has many functions. It plays a critical role in blood flow, coagulation, leukocyte adhesion, and vascular smooth muscle cell growth. Within the endothelium, the enzyme nitric oxide synthase converts the amino acid arginine to nitric oxide. Arginine is therefore an important substrate for the production of nitric oxide.

Arginine is a non-essential amino acid. In addition to being a substrate for the production of nitric oxide, arginine is also a substrate for the production of creatine, agmatine, glutamic acid, ornithine, proline, and polyamines. Two important metabolic pathways use the amino acid arginine: the nitric oxide synthase pathway and the arginase pathway. Arginine also appears to increase HGH levels by blocking the secretions of growth hormone inhibitor somatostatin. However, the problem with using arginine alone to increase NO is that arginine is a non-essential amino acid. Inside the gut arginine is hydrolyzed into peptide form and stripped down to it's carbon skeleton so it can be re-assembled into other non essential amino acids that may be needed at that time. Also, about 50% of ingested arginine is utilized by the small bowel, so not much arginine will make it to the endothelium to produce NO.

So how can we get the most arginine to the endothelium. Most NO supplements on the market mix L-arginine powder with alpha-ketoglutaric acid. Alpha-ketoglutarate (AKG) is a Krebs cycle intermediate. The Krebs cycle creates the fuel that runs every cell of your body. AKG is the fourth step in this 8-part cycle and therefore a vital part of the energy-creating mechanism for every cell. While AKG supplementation can certainly increase ATP production, it is not clearly understood how it increases nitric oxide production. One theory is that AKG inhibits the arginase pathway so more arginine is routed to the nitric oxide synthase pathway. However, even in the presence of AKG, arginine is still a non-essential amino acid and not much will make it past the gut to the endothelium. The arginine must be protected from the gut for maximum delivery to the endothelium.

Phospholipids are molecules that have a hydrophilic (water loving) head and a hydrophobic tail. When combined with the proper essential oils and emulsifiers, phospholipids will form a phospholipid bilayer or a micelle around various active ingredients. This phospholipid bilayer or micelle will then be able to protect that active ingredient from the ravages of the gut, enabling much more of the active ingredient to make it to the blood stream. So phospholipids would allow more arginine and AKG to make it to the endothelium, however there is still one problem.

NO production occurs with a single molecule of arginine. If the arginine has not been hydrolyzed down to peptide form, it cannot react with oxygen and NADPH to form NO. Amino acids are typically hydrolyzed in the gut, but since the phospholipids protect the arginine from the gut, the arginine must already be in peptide form. However, arginine peptides will rapidly produce NO, which only lasts for a few seconds, so NO levels will not remain elevated for an extended period of time. So we need a method for the arginine to slowly be released. Peptide bonding arginine to an AKG peptide will allow for that, so a peptide bonded or reacted arginine AKG protected by phospholipids will allow for sustained NO production while allowing for maximum delivery of arginine to the endothelium.

Since NO increases oxygen delivery, blood flow, glucose uptake, ATP production, gonadotroptin releasing hormone, adrenaline, nutrient delivery, exercise induced vasodilation, and cell volumization; working out with elevated NO levels will significantly improve nutrient and fluid delivery to the muscle for increased anabolism and recovery. And even without working out, increased NO levels will improve oxygen delivery and blood flow to the brain and "other areas" for improved mental and sexual function.

Ian Mathews is available for personal training at BodyTech Fitness Emporium in Tampa. He is also available for online nutritional consultation regardless of where you live. In addition to being a certified personal trainer and nutritionist, Ian is also Vice President of Sales for LMR Sports. You can contact Ian at ian@lmrsports.com.

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