Arginine, an essential α-amino acid, is used in the biosynthesis of proteins, increases blood flow, growth hormone (GH), improves memory, boosts immunity, detoxifies ammonia, and is involved in formation of creatine, agmatine, glutamate, polyamines (essential for muscle regeneration and growth), ornithine, and citrulline (2, 3). etc…
About 60% of the absorbed l-arginine is metabolized by the gastrointestinal tract, and only 40% reaches the systemic circulation intact, which is not very effective for increasing arginine levels in the blood. (5, 6) Plus high dose, 9g+ can cause quite some stomach upset.
However, it’s far from ineffective, let’s have a look.
Arginine boosts Growth hormone
Oral supplementation of arginine at doses ranging between 5-9g increases resting GH. The GH response increase in a dose-dependent manner and there is no further benefit past 9g. Most studies using oral arginine have shown that arginine alone increases the resting growth hormone levels at least 100%, while exercise can increase growth hormone levels by 300-500%. However, the combination of oral arginine plus exercise attenuates the growth hormone response, and only increases growth hormone levels by around 200% compared to resting levels. (7, 8)
A significant increase in GH and IGF-1 and a decrease in IGFBP3 was seen after 3 weeks of arginine and ornithine supplementation. (9)
It’s also shown that 1.2 to 1.5g of lysine with arginine each are able to increase growth hormone by 8 and 2.7 fold respectively, but there was no rise in GH when either one was administered alone. (10, 11)
Arginine helps Burn Fat
Arginine is able to improve oxidative metabolism, by increasing the body’s efficiency at transporting and utilization of fatty acids and glucose (glycolysis).
Arginine stimulates lipolysis and the expression of key genes responsible for activation of fatty acid oxidation to CO2 and water. It also prevents fatty acid synthesis from glucose by downregulating the enzymes malonyl-CoA decarboxylase (MCD), fatty acid synthase (FAS) and stearoyl coenzyme-A desaturase-1 (SCD1) in the liver.
Arginine upregulates enzymes that transport fatty acids (HSL, CPT1), increases mitochondria biogenesis (PCG-1alpha), improves insulin sensitivity, stimulates the growth of brown adipose tissue and reduces white adipose tissue. This leads to a great number of mitochondria, higher energy expenditure and thermogenesis and ultimately fat loss. (12)
Arginine lowers Ammonia
Arginine, with citrulline and ornithine, plays a crucial part of the urea cycle, which detoxifies ammonia and also converts ammonia back to glucose. (13)
Arginine increases Nitric oxide (NO) and circulation
Although arginine is the precursor to NO, some studies have shown that supplementation of L-arginine does not increase NO synthesis in healthy subjects at rest (2) or in response to exercise (3). Moreover, there is evidence demonstrating a significant increase in muscle blood volume after supplementation with 6 g of L-arginine orally (3). These results suggest that supplementation with L-arginine may promote vasodilatation via NO-dependent and independent mechanisms.
All in all, it’s very effective at lowering cholesterol, inducing vasodilation, preventing angina, help to reverse atherosclerosis, improve microcirculation, etc…
Arginine enhances Muscle protein synthesis & wound healing
Arginine activates the mTOR cell signaling pathway in skeletal muscle to enhances protein synthesis and whole-body growth (17). There is also indirect evidence that Arg inhibits proteolysis (protein breakdown) in skeletal muscle (18).
Arginine prevents the oxidation of BCAAs (which stimulate muscle protein synthesis and hypertrophy), thus ensuring that maximal leucine availability for the hypertrophy response.
Without arginine, testosterone cannot perform its anabolic functions in mice (21).
Human studies have concluded that Arg supplementation enhances hydroxyproline and ornithine content and tensile strength in wound tissues via a proline-dependent mechanism (22). Also, due to enhanced blood flow, arginine aids in supplying more oxygen and nutrients to the wound/tissue that needs growth and repair.
Arginine enhances Immunity
Arg stimulates T- and natural killer cell activity and influencing pro-inflammatory cytokine levels (23).
Arg, the same as glutamine, increases thymus weight, the number of thymic lymphocytes, T-lymphocyte proliferation, the cytotoxicity of specific cells (T lymphocyte, macrophages, and NK cells), IL-2 production, IL-2 receptor expression on T lymphocytes, and the delayed-type hypersensitivity response (24). Estrogen shrinks the thymus, so maybe Arg increases thymus weight by antagonizing estrogen.
Arg also prevents lipid peroxidation, which is the oxidation of polyunsaturated fatty acids, which causes inflammation. l-Arginine (1.6 g/day) in 16 elderly patients with senile dementia has been found to be effective in reducing lipid peroxidation and increasing cognitive function (25).
Arginine improves Exercise performance
Arg improves exercise performance and prolongs time to exhaustion by detoxifying ammonia (reduces it to urea via the urea cycle) and reduces lactate production.
Nitric oxide, synthesized by arginine, is responsible for mediating satellite cells activation, which stimulates muscle protein synthesis and repair, and can be very beneficial for reducing DOMS. (26)
However, it would seem that it has less benefit on trained men than for untrained men. (27)
Arg in combination with BCAA is beneficial for improving exercise performance of repeated sprints on consecutive days, preventing performance declines. As a side note, BCAAs also prevents tryptophan uptake in the brain (reducing serotonin), and arginine prevents BCAA oxidation, (28) making it a potent potential dopamine boosting ingredient. Just use phenylalanine and/or tyrosine with this combo.
I don’t think everyone should take Arginine
Certain conditions (increased endotoxins, gene mutations, etc) can increase nitric oxide production from arginine to excessive levels, which have been associated with:
- tumor promoting
- higher mortality. (29, 30)
- herpes virus (are able to let it resurface) (use lysine to counter this)
- increases prolactin (independent of NO) (31). More on lowering prolactin here…
- Intestinal inflammation
- enhanced COX activity which increases prostaglandin E2 (PGE2) production and therefore increases cortisol, inflammation, etc… (32).
Other benefits & additional information
a) Arginine inhibits gastric hyperacidity and protects gastric mucosa. (33)
b) Increase catecholamines such as dopamine, adrenaline, and noradrenaline. (34)
c) It’s a precursor to creatine, 2.3 g/day in a 70 kg man) are utilized for the production of creatine by it’s unlikely that additional arginine will raise creatine levels high enough to have an ergogenic benefit, as arginine is not the rate-limited step in creatine synthesis. (35)
d) Lysine competes with arginine for uptake in cells. The ratio of arginine:lysine should not exceed 1.5:1, so check your supplement intake.
e) Lactate inhibits arginine synthesis from proline. High lactate is common with impaired glucose metabolism such as diabetes, which makes it important to supplement with vitamin B1 (which lowers lactate) and arginine (or eat more protein sources), to increase low arginine levels.
f) Arginine and glutamine can have a synergistic effect in boosting the immune system, lowering inflammation and infection as well as have a BCAA sparing and glycogen resynthesis effect.
g) L-citrulline could rather be taken if you want to avoid potential gastrointestinal distress and to bypass the arginine degeneration in the intestine, as citrulline converts very effectively to arginine. Citrulline is also a neutral amino acid, meaning it doesn’t compete with other amino acids and doesn’t cause GI distress. However, you will lose out on the GH benefit this way.
h) Lysine inhibits arginase activity (the enzyme that converts arginine to ornithine). (36)
I personally would not use arginine pre or post-workout, but rather before bed, for its immune boosting, ammonia detoxifying and GH boosting effect, that will help me recover properly. My preferred dose is 5g.
- L-arginine – 1lb powder