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Arginine

Your body makes nitric oxide (NO) out of arginine, but although NO widens blood vessels and improves blood flow, arginine supplementation may not improve blood flow in healthy people.

Our evidence-based analysis on arginine features 178 unique references to scientific papers.

Research analysis led by and reviewed by the Examine team.
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Summary of Arginine

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

Arginine is an amino acid. The enzyme nitric oxide synthase (NOS) uses it to make nitric oxide (NO), and the enzyme arginase uses it to make urea and ornithine[1] in a process that also disposes of excess ammonia.

Competing macrophage pathways for arginine metabolism
Source: Rath et al. Front Immunol. 2014 Oct[2]


Stress, illness, trauma, premature birth, hypertension, type 2 diabetes, and other health conditions may increase arginase production, and thus increase ornithine levels and decrease arginine and NO levels. This can lead to hypoxia, vascular and neurological complications, and increases in inflammation and reactive oxygen species.[1]

Because the body cannot always make enough arginine to compensate for an increase in arginase, arginine is considered a conditionally essential amino acid — meaning that, under certain conditions, you need to get some from your diet. Fortunately, nuts, seeds, dairy products, and meat (particularly white meat) are rich in arginine.

Although arginine is marketed for athletic performance, its supplementation in healthy adults has unreliable effects on NO production.[3][4][5] This may be due to arginine having poor bioavailability. The amino acid citrulline is more bioavailable and is converted into arginine in the kidneys; oral citrulline is better than oral arginine at increasing blood levels of arginine.

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How to Take

Recommended dosage, active amounts, other details

The standard preworkout dose for arginine is 3–6 grams.

Taking more than 10 grams of arginine at once can result in gastrointestinal distress and diarrhea, but it is possible to maintain elevated arginine levels throughout the day by taking three spaced doses (15–18 grams/day). However, citrulline supplementation is more effective at maintaining elevated arginine levels for long periods of time.

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Human Effect Matrix

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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.

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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 - 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 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 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 - - See study
No significant influence on lactate production associated with L-arginine supplementation
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
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[6]

  • Confounded with the inclusion of Lysine[7]

  • Also included the amino acids Glycine and α-Ketoisocaproic acid[8][9]

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Things to Note

Is a Form Of

Primary Function:

Other Functions:

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 178 references.