Arginine is an amino acid that plays many different important roles in the body. Among these are regulating blood pressure and circulation via nitric oxide and boosting immunity. Read more to find out how this amino acid may be critical to your health and if you need to be supplementing it.
What Is L-Arginine?
L-arginine is a conditionally essential amino acid that serves a variety of functions within the body. It is considered conditionally essential because healthy individuals can obtain enough of it from the diet and from synthesizing it within the body via the kidneys.
Nearly all protein-containing foods have arginine in them, with the only exception being gelatin. Particularly rich sources of arginine include fish and especially walnuts, with as much as 15% of the amino acids being comprised of L-arginine. L-arginine can also be made from citrulline via the proximal tubule cells in the kidneys.
The majority of L-arginine in the body is used to process ammonia into the less toxic urea, as well as to synthesize creatine and ornithine. A small portion is then used as a precursor to nitric oxide (NO), a compound that dilates blood vessels, lowers blood pressure, and helps maintain a healthy cardiovascular system [1].
Supplemental L-arginine is mainly used to achieve the benefits derived from converting this amino acid into nitric oxide.
L-Arginine Feedback Diagram
Source: [2]
Snapshot
Proponents
- Improves nitric oxide production, resulting in increased blood flow
- May prevent type 2 diabetes and its complications
- May boost immunity
- May help heal wounds
- Generally safe at food and normal supplemental doses
Skeptics
- Insufficient evidence for some benefits
- May trigger an autoimmune response
- May act as a laxative if taken on an empty stomach
Health Benefits of L-Arginine
Likely Effective for:
Improving Blood Flow
Nitric oxide is produced by cells in the body to reduce blood pressure and increase blood flow. It works to expand and relax blood vessels, thus helping prevent their clogging [3].
L-arginine increases the production of nitric oxide and stops its breakdown. Supplementation with L-arginine can, therefore, be useful in reducing blood pressure. This decreases the risk of hypertension and stroke [4].
L-arginine supplementation effectively reduced blood pressure in multiple clinical trials, as summarized in 2 meta-analyses of studies on adults with high blood pressure and pregnant women [5, 6].
The increased blood flow due to L-arginine may also help with erectile dysfunction, as seen in a clinical trial on 30 men [7].
Although not approved by the FDA, the evidence suggests that L-arginine supplementation improves blood flow and may help lower blood pressure and prevent heart disease. You may discuss with your doctor if it may help you as a complementary approach.
Possibly Effective for:
1) Preventing Diabetes and Diabetic Complications
In a study on 28 people, those with diabetes had lower L-arginine levels and disrupted metabolic pathways of this amino acid. Another study on 40 people found that those with type 2 diabetes produced less insulin in response to both sugar and L-arginine [8, 9].
In a long-term follow-up study on 144 people with metabolic syndrome, supplementation with L-arginine was associated with a reduced onset of type 2 diabetes [10].
In rats, L-arginine supplementation promoted the formation of insulin-producing cells in the pancreas [11].
Three clinical trials on over 100 people found that L-arginine supplementation can help decrease oxidative stress in type 2 diabetic patients by producing nitric oxide and activating antioxidant enzymes such as SOD. This may help prevent diabetic complications [12, 13, 14].
In people with type 2 diabetes, insulin resistance prevents the production of nitric oxide from L-arginine and increases the risk of heart disease. In 4 clinical trials on 50 diabetics, supplementation with L-arginine improved reduced oxidative damage to the blood vessels and improved their function, resulting in higher blood flow and reduced risk of heart disease [15, 16, 17, 18, 19].
In diabetic rats, L-arginine supplementation reduced fat mass and blood triglyceride levels by increasing fatty acid breakdown in diabetic rats [20].
All in all, limited evidence suggests that L-arginine may help prevent type 2 diabetes and its complications (especially heart disease). If you have type 2 diabetes or are at high risk of developing it, you may consult with your doctor if supplementing with L-arginine may be helpful in your case. Importantly, never take L-arginine in place of what your doctor recommends or prescribes.
2) Boosting Immunity
Nitric oxide can stimulate the immune system to act on and destroy pathogens. By increasing its production, L-arginine supplementation may boost immunity, especially in people with a weakened immune system [3].
Multiple studies have shown the immune-boosting effects of infused L-arginine (alone or in combination with RNA and omega-3 fatty acids) before and after surgical procedures. L-arginine increased immune cell counts, altered cytokine levels, and increased patient survival [21, 22, 23, 24, 25, 26, 27, 28, 29, 30].
Similarly, infused formulas with L-arginine improved immune response, reduced infections, and shortened ICU stay in 4 clinical trials on 130 severely injured or burned patients [31, 32, 33, 34].
L-arginine improved immune function (lymphocyte activity and response, migration of neutrophils to infection sites, and antibody levels) in 2 trials on 59 elderly people. In people with recurrent infections, it increased the levels of natural killer lymphocytes and antibodies [35, 36, 37].
A pilot trial on 11 people with HIV found that L-arginine supplementation increased natural killer cell counts. However, another trial on 55 people only found increased weight gain but no improvement in the immune function after supplementing with L-arginine and omega-3 fatty acids [38, 39].
In the only clinical trial done on healthy, non-elderly people (36 non-smoking volunteers), L-arginine increased lymphocyte production [40].
Again, limited evidence suggests that L-arginine may help improve immune function, especially in people recovering from surgery or severe injuries. You may discuss with your doctor if L-arginine may be helpful as an add-on to your treatment regime.
Insufficient Evidence for:
1) Wound and Sore Healing
Supplementation with L-arginine improved wound healing in a clinical trial on 30 elderly people. A diet with L-arginine and fish oil not only sped up the healing of burn injuries in a clinical trial on 23 people, but also increased the incidence of infections and other complications [36, 41].
In a small trial on 15 people, a topical L-arginine gel improved the healing of anal fissures [42].
However, neither oral nor injected L-arginine improves blood vessel formation, skin regrowth, and immune function in 2 clinical trials on 53 people undergoing skin autografting [43, 44].
In 4 clinical trials on over 250 people confined to bed, L-arginine (both alone and combined with zinc and vitamin C) improved the healing of bedsores [45, 46, 47, 48].
In mice, L-arginine supplementation improved wound healing by increasing nitric oxide, which promotes blood vessel development and collagen production [49, 50].
Because most studies were very small and there are some mixed results, we cannot consider the evidence sufficient to conclude for certain that L-arginine helps with wound and sore healing. More studies on larger populations are needed to draw conclusions.
2) Anxiety
In 2 clinical trials on 137 healthy people, supplementation with L-lysine and L-arginine (~3 grams each) reduced anxiety and modified stress hormone levels in response to stressful situations [51, 52].
Although the results are promising, 2 clinical trials are insufficient to support the use of L-arginine to curb anxiety. Further clinical research is needed.
3) Fertility
In women, low fertility is often caused by a poor ovarian response to hormones. In a clinical trial on 34 women undergoing assisted reproduction, L-arginine supplementation increased pregnancy rates by increasing ovarian response to hormones. However, another study on 32 women undergoing ovarian hyperstimulation came to opposite results [53, 54].
In men, low fertility is often caused by low sperm count and low sperm motility. In a clinical trial on 50 subfertile men, supplementation with L-arginine, L-citrulline, and pycnogenol increased sperm volume, concentration, viability, and mobility, possibly by increasing NO production [55].
Three small clinical trials (with mixed results) are clearly insufficient to claim that L-arginine helps with fertility issues. Larger, more robust human studies are needed to shed some light on this potential benefit.
Possible Negative Effects of L-Arginine Supplementation
This list does not cover all possible side effects. Contact your doctor or pharmacist if you notice any other side effects.
Call your doctor for medical advice about side effects. In the US, you may report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada, you may report side effects to Health Canada at 1-866-234-2345.
1) May Trigger An Autoimmune Response
Nitric oxide can react with hydrogen peroxide in the body to form free radicals, which may increase oxidative damage, cell death, and trigger an autoimmune response. By increasing nitric oxide levels, L-arginine may cause these adverse effects [3].
2) May Act as a Laxative
There have been reports of L-arginine causing diarrhea when taken on an empty stomach [56].
L-Arginine: Safety, Dosage, Side Effects, and Cautions
L-arginine is produced in the body but occurs at very low levels. For this reason, supplementation can sometimes be useful, especially in elderly people [57].
The average dietary intake of L-arginine is 5.4 grams per day. Arginine-rich foods include red meat, fish, dairy products, nuts, and poultry [3].
L-Arginine can be found in red meat, fish, dairy, nuts, and poultry.
It can be also taken as a supplement. Capsules typically contain 500 mg L-arginine. However, L-arginine supplements have not been approved by the FDA for medical use. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.
Studies have found very few adverse side effects from taking L-arginine at daily concentrations of 20 grams or below. Consult with your doctor if you notice any severe or mild, persistent adverse effects after supplementing with L-arginine [58].
As mentioned above, it is recommended to take it with food to avoid its potential laxative effects.
