Arginine

L-Arginine is a conditionally essential amino acid found in the diet. It is a dietary supplement used mostly by athletic people because it is the amino acid that directly produces nitric oxide via the nitric oxide synthase enzymes.

It's particularly important during periods of illness and chronic conditions like hypertension and type II diabetes, as these states tend to be characterized by an increase in the enzyme that degrades L-arginine (known as arginase) resulting in a transient deficiency; this precedes an increase in blood pressure in these states, and can be partially remedied by an increase in L-arginine intake or resolution of the illness/disease state.

L-arginine is a popular supplement for athletes as it is touted to increase nitric oxide activity in the body. Unfortunately, this effect appears to be unreliable in otherwise healthy adults. While there have been studies that have measured increased effects of nitric oxide (blood flow) they are paired with studies showing no net effects. As for the mechanism, there is reason to believe that this difference is in part due to poor absorption of L-arginine from the intestines before it can reach appreciable activity in the body.

L-Citrulline is another supplementation option because it is converted into arginine in the kidneys. It also has a better absorption rate. Citrulline is able to increase levels of plasma arginine more effective than arginine itself. For long-term health-related supplementation, L-citrulline may be a better supplementation option than L-arginine.

The standard pre-workout dose for L-arginine is 3-6g.

To maintain elevated arginine levels throughout the day, arginine can be taken up to three times a day, with a combined dose total of 15-18g. Note: L-Citrulline supplementation is more effective at maintaining elevated arginine levels for long periods of time.

Taking more than 10g of arginine at once can result in gastrointestinal distress and diarrhea.

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects arginine has on your body, and how strong these effects are.

Grade	Level of Evidence [show legend]
	Robust research conducted with repeated double-blind clinical trials
	Multiple studies where at least two are double-blind and placebo controlled
	Single double-blind study or multiple cohort studies
	Uncontrolled or observational studies only

Level of Evidence ? The amount of high quality evidence. The more evidence, the more we can trust the results.	Outcome	Magnitude of effect ? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.	Consistency of research results ? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.	Notes
	Blood Flow	Minor	Low See all 6 studies	May increase blood flow secondary to activating nitric oxide, but due to the unreliability of increasing nitric oxide there is also unreliability in how arginine increases blood flow
	Blood Pressure	Minor	Moderate See all 5 studies	Arginine has been implicated in reducing blood pressure, but the degree of reduction does not appear to be too remarkable and it is unreliable in doing so
	Growth Hormone	Minor	- See all 5 studies	Arginine has been implicated in increasing growth hormone (at rest) and suppressing an exercise-induced increase in growth hormone; both of these are short in duration, and it is unsure if there are any long lasting effects of such short a spike.
	Nitric Oxide	Minor	High See all 7 studies	Has been implicated in increasing nitric oxide formation in the body, but this does not appear to be a reliably occurring phenomena (despite arginine being required to make nitric oxide, it is not a good inducer thereof)
	Plasma Arginine	Minor	Very High See all 6 studies	Supplemental L-Arginine increases plasma L-Arginine. The spike in plasma L-arginine concentrations may be slightly more than that seen with L-citrulline, but the latter lasts longer and is thus more effective
	Asymmetric dimethylarginine (aka ADMA)	-	Very High See all 3 studies	Although there is some evidence for an increase in ADMA (a negative regulator of NOS that is derived from L-arginine), it does not appear to occur most of the time
	Heart Rate	-	Very High See all 4 studies	No significant influence on heart rate seen with supplemental L-Arginine
	Adiponectin	Minor	- See study	At least in persons with impaired glucose tolerance, an increase in adiponectin (and the adiponectin:leptin ratio) has been noted with supplemental L-arginine
	Anaerobic Running Capacity	Minor	- See study	May be able to increase anaerobic physical performance, but this is unreliable due to arginine not reliably increasing nitric oxide concentrations.
	Anti-Oxidant Enzyme Profile	Minor	- See study	At least in persons with impaired glucose tolerance and/or type II diabetes, L-arginine appears to have an indirect antioxidant role and increase superoxide dismutase concentrations
	Endothelial Function	Minor	Moderate See 2 studies	Unreliable improvements in endothelial function, notably in persons with impaired glucose tolerance/type II diabetes, associated with the supposed increase in nitric oxide
	Endothelin-1	Minor	- See study	A decrease in concentrations of endothelin-1 has been noted with supplemental L-arginine
	Fat Mass	Minor	- See study	A slight reduction in fat mass has been noted with long-term usage in persons with impaired glucose tolerance. No evidence supports the usage of arginine as a fat burner in otherwise healthy persons
	General Oxidation	Minor	- See study	A decrease in oxidation has been noted in persons with impaired glucose tolerance, thought to be associated with the increase in superoxide dismutase activity
	Insulin Secretion	Minor	- See study	An increase in insulin secretion has been noted with arginine supplementation. This is both due to arginine being a secretagogue (when used acutely), and prolonged usage in those with impaired glucose tolerance may regenerate pancreatic beta-cells
	Insulin Sensitivity	Minor	- See study	An increase in insulin sensitivity has been noted in persons with impaired glucose tolerance using arginine for long periods of time; this is thought to be secondary to increased pancreatic function
	Lean Mass	Minor	- See study	An increase in lean mass has been noted in persons with impaired glucose tolerance using L-arginine over a long period of time, where placebo experienced a decrease. It is unsure how this applies to otherwise healthy persons
	Oxygenation Cost of Exercise	Minor	Moderate See 2 studies	When nitric oxide is increased, the oxygenation cost of exercise appears to be decreased. This is unreliable with supplemental L-arginine as arginine is unreliable in increasing nitric oxide
	Symptoms of Intermittent Claudication	Minor	- See 2 studies	Both an improvement and an impairment have been noted on walking distance in persons with intermittend claudication, and it is not exactly known why this occurs (may be related to time, with prolonged usage being impairing)
	Ammonia	-	- See study	Although it is plausible that arginine could decrease ammonia (secondary to ornithine), it does not appear to reliably occur
	Blood Glucose	-	Very High See 2 studies	No significant influence on fasting blood glucose concentrations even in persons with impaired glucose tolerance
	Cortisol	-	- See study	No significant influence on circulating cortisol concentrations
	Glucagon	-	- See study	Does not appear to significantly influence circulating glucagon concentrations
	HbA1c	-	Very High See 2 studies	No significant influence on HbA1c concentrations in persons with impaired glucose tolerance, even when endothelial function is improved
	Lactate Production	-	- See study	No significant influence on lactate production associated with L-arginine supplementation
	Plasma Nitrate	-	- See study	There does not appear to be a reliable increase in plasma nitrate seen with arginine supplementation
	Power Output	-	Very High See 2 studies	No significant influence on power output
	Subjective Well-Being	-	- See study	In persons with peripheral artery disease (intermittent claudication), despite improving symptoms as assessed by a treadmill walking test there does not appear to be an improvement in self-reported well being
	Testosterone	-	- See study	No significant influence on circulating testosterone concentrations
	Urea	-	- See study	Although it is theoretically plausible that arginine can increase urea concentrations (secondary to the actions of ornithine), it does not appear to reliably occur
	Insulin	-	- See study	No significant influence on fasting insulin concentrations associated with arginine supplementation
	Somatomedin A	-	- See study	No significant effect of arginine on somatomedin A concentrations

Studies Excluded from Consideration

• Excluded due to also using L-citrulline supplementation^[1]

• Confounded with the inclusion of Lysine^[2]

• Also included the amino acids Glycine and α-Ketoisocaproic acid^[3][4]

• Investigating arginine for erectile dysfunction

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