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Arginine

L-Arginine is a conditionally essential amino acid. It is important for blood flow and nitric oxide levels, but oral supplementation may not reliably improve blood flow in humans.

Our evidence-based analysis on arginine features 175 unique references to scientific papers.

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Summary of Arginine

Primary information, health benefits, side effects, usage, and other important details

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.

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How to Take

Medical Disclaimer

Recommended dosage, active amounts, other details

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.

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Human Effect Matrix

Unlocked for Examine Plus members

The Human Effect Matrix summarizes human studies to tell you what effects Arginine has on your body, how much evidence there is, and how strong these effects are.

Full details are available to Examine Plus members.
Grade Level of Evidence
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
grade-b 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
grade-b 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
grade-b
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.
grade-b 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)
grade-b 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
grade-b - 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
grade-b - Very High See all 4 studies
No significant influence on heart rate seen with supplemental L-Arginine
grade-c 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
grade-c Minor - See study
May be able to increase anaerobic physical performance, but this is unreliable due to arginine not reliably increasing nitric oxide concentrations.
grade-c 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
grade-c 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
grade-c Minor - See study
A decrease in concentrations of endothelin-1 has been noted with supplemental L-arginine
grade-c 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
grade-c 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
grade-c 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
grade-c 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
grade-c 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
grade-c 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
grade-c
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)
grade-c - - See study
Although it is plausible that arginine could decrease ammonia (secondary to ornithine), it does not appear to reliably occur
grade-c - Very High See 2 studies
No significant influence on fasting blood glucose concentrations even in persons with impaired glucose tolerance
grade-c - - See study
No significant influence on circulating cortisol concentrations
grade-c - - See study
Does not appear to significantly influence circulating glucagon concentrations
grade-c - Very High See 2 studies
No significant influence on HbA1c concentrations in persons with impaired glucose tolerance, even when endothelial function is improved
grade-c - - See study
No significant influence on lactate production associated with L-arginine supplementation
grade-c - - See study
There does not appear to be a reliable increase in plasma nitrate seen with arginine supplementation
grade-c - Very High See 2 studies
No significant influence on power output
grade-c - - 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
grade-c - - See study
No significant influence on circulating testosterone concentrations
grade-c - - 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
grade-d - - See study
No significant influence on fasting insulin concentrations associated with arginine supplementation
grade-d - - 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]

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Things to Note

Is a Form Of

Other Functions:

Primary Function:

Also Known As

L-Arginine

Goes Well With

  • Anionic salts such as Alpha-ketoglutarate

  • High doses of L-arginine can cause gastrointestinal upset preceding diarrhea

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Click here to see all 175 references.