UREA CYCLE AMINO ACIDS; Arginine; Ornithine

Arginine – Cholesterol Fighter

L-arginine is a basic amino acid involved primarily in urea or ammonia buildup and excretion, as well as DNA, polyamine and creatine synthesis. Arginine is an essential nutrient in cats, rats and other mammals. In man, arginine is essential only under certain conditions. Conditional deficiency of arginine occurs in the presence of excess ammonia, excess lysine, amino acid imbalances, rapid growth, pregnancy, trauma, protein deficiency or enzyme deficiency. As much as 20 g of arginine can be used to treat several inborn errors of urea cycle enzymes. Arginine deficiency is associated with rash, hair loss and breakage, poor wound healing, constipation, fatty liver, hepatic cirrhosis and hepatic coma.

Arginine supplementation is marked by many endocrine effects. Arginine in high doses given intravenously—20 to 35 g—releases growth hormone, glucagon and insulin. Doses as low as 1 g have been claimed to increase growth hormone quite significantly, although our studies have been unable to document this claim. Large doses of arginine given to rats increase collagen deposition, promote wound healing and positive nitrogen balance. Even larger levels in rats’ diet, 1 percent or more, protect the rats against thymus involution and provide anticancer effects. We have found that large doses of arginine can lower polyamines, which are elevated in various cancers. Arginine, like ornithine and aspartic acid, has a positive effect on viability of sperm and may have a role in the treatment of male infertility.

Metabolic arginine deficiency can be measured in blood, cerebrospinal fluid or by orotic acid excretion in urine. Several of our cancer patients have shown decreased arginine in blood and have been treated with amino acid supplements. We have characterized patients with low plasma arginine as being primarily women of small structure who have reduced protein mass, with a history of chronic disease or prolonged hospitalization. Many of these patients have multiple amino acids deficiencies and respond to multiple amino acid formulas. Arginine excess occurs in several inborn errors of metabolism and may be useful in treating cancer.

Doses greater than 40 g daily of arginine can result in dangerous hyperkalemia (high serum K) and hyperphosphatemia (high serum phosphorus) in patients with liver or kidney disease.

Arginine, like methionine, taurine and glycine, lowers cholesterol. We have found arginine loading doses of 6 g to reduce cholesterol by as much as 10 percent. The cholesterol lowering effect is enhanced by diets high in arginine and low in lysine, probably cereals as opposed to meat protein.

Arginine supplements may be of value in many disease conditions. As part of the body’s health maintenance system, this amino acid is just beginning to be understood.

Ornithine – Growth Promoter

L-Ornithine is a precursor of citrulline and arginine and when given orally, has very similar biological effects. It is a naturally occurring amino acid and is different from arginine in that it is not found incorporated into body proteins. Almost all recommendations given for therapeutic uses of arginine probably apply also to Ornithine.


Orally supplemented Ornithine can be converted by the body into arginine, glutamine or proline. Arginine is its primary end product and supplemental arginine is immediately converted back to Ornithine. Ornithine can also be converted into polyamines. Lysine, an antagonist of arginine, also prevents uptake of Ornithine.

Ornithine may enter the mitochondria more readily than arginine, so it is possible that L-Ornithine may be a better arginine supplement than arginine itself. L-Ornithine as 3000 mg tablets A.M. and P.M. is part of a recently formulated growth hormone-releasing supplement. We think that this dose may be too low to have a significant result.

L-Ornithine, 500 mg, is readily available. No toxicity has been reported. We have found doses as low as 1 g to cause insomnia in some individuals. Yet, in general, Ornithine supplementation is well tolerated, up to several grams daily and probably higher doses. The effect of mega Ornithine therapy, 10 g daily, for prolonged periods has not been investigated.

Arginine is an Ornithine agonist, while lysine inhibits Ornithine metabolism.

Ornithine supplements, like arginine may be useful in a variety of diseases. Ornithine releases growth hormone and may be of value for growth-impaired children and athletes in training.