Nitric oxide supplements have played an integral role in bodybuilding since 1996. These supplements help athletes and fitness enthusiasts alike improve circulation, build muscle, and boost immunity.
Interestingly enough, nitric oxide supplements don’t actually contain nitric oxide (N.O.), which is a gas produced naturally by the body. Rather, these supplements provide various amino acids and other ingredients to spur nitric oxide production.
“To make nitric oxide, enzymes in the body break down the amino acid, arginine,” explains Jim White, spokesperson for the American Dietetic Association.
Then, nitric oxide dilates blood vessels, increasing blood flow and circulation. Improved circulation increases the maximum amount of nutrients and oxygen available to the muscles. More nutrients and oxygen enables the muscles to work harder and longer with reduced fatigue and recovery time.
Nitric oxide supplementation can offer amazing results when the right ingredients are used. Arginine and citrulline (which converts into arginine) are some of the most effective ingredients in the industry.
However, using nitric oxide supplements is a double-edged sword. On one side, you have increased performance and enhanced results, but on the other, you have the risk of negative side effects.
Most Common Nitric Oxide Supplement Side Effects
The most common nitric oxide supplement side effects are primarily minor and include nausea, diarrhea, headaches and stomach problems but there are other potential side effects to be aware of before taking a nitric oxide supplement with some less concerning than others.
1. Increased Urge to Urinate
As mentioned earlier, the amino acid arginine is essential for nitric oxide production. However, consuming excess amounts of arginine often results in more frequent urination.
According to the Food Research International, “In order to produce urine, the body processes liquids into an intermediate stage which is high in the amino acid called arginine. Normally the liver produces enough of the enzyme arginase to convert and concentrate this liquid into urea (urine). When it does not, however, in some people this seems to cause the body to try to expel this high arginine liquid excessively, both day and night.” 
How to Regulate This Effect: To avoid this side effect, keep arginine dosages under 5,000 mg a day. Although this might sound like a lot, you could exceed this dosage in three to four servings of an average nitric oxide supplement.
2. Reduced Dopamine Levels
Another potential side effect is a decrease in dopamine. Effective nitric oxide releasers have an inhibitory effect on dopamine transporters, which decreases uptake by as much as 66% .
Dopamine, an organic neurotransmitter, is responsible for regulating the following:
- Motivation levels
- Healthy sleep cycles
- Short and long term memory
- Cognitive skills
By increasing your nitric oxide production, it could have a negative impact on any of the above functions.
How to Regulate This Effect: The amino acids used in nitric oxide supplements typically have little impact on dopamine production, so this side effect is rare. However, you can naturally increase dopamine levels via exercise, dieting, and even participating in sexual activities. Furthermore, the amino acid tyrosine is known to increase dopamine production (when used in safe doses between 250-500 mg daily).
3. Zinc Deficiencies
The amino acid histidine is often featured in nitric oxide supplements. When combined with the amino acid beta-alanine, it creates the compound carnosine. Carnosine is a natural substrate to nitric oxide synthase (the enzyme responsible for nitric oxide production).
However, studies show that high levels of histidine and carnosine are often associated with zinc imbalances and deficiencies. 
If you continue to lose zinc, you may suffer from any of the following:
- Impaired appetite
- Delayed sexual maturation
How to Regulate This Effect: The recommended dietary allowance for zinc is 8 mg daily for women and 11 mg daily for men. According experts at WebMD, “The typical North American male consumes about 13 mg/day of dietary zinc; women consume approximately 9 mg/day,” so consuming adequate zinc shouldn’t be problematic for most individuals.
However, if you’re concerned about eliminating too much zinc, then you may consider taking a zinc supplement. You can also consume zinc-rich foods like oysters, pumpkin seeds, peanuts, and crabs.
4. Nausea and Stomach Cramps
Perhaps the most common side effect of nitric oxide supplements is gastrointestinal distress. Many amino acids used to produce nitric oxide have a history of creating digestive problems, particularly arginine.
Experts at Medline Plus explain, “L-arginine is POSSIBLY SAFE for most people when taken appropriately by mouth short-term. It can cause some side effects such as abdominal pain, bloating, diarrhea, gout, blood abnormalities, allergies, airway inflammation, worsening of asthma, and low blood pressure.” 
How to Regulate This Effect: While this side effect isn’t too damaging in the long-run, it can make your workout experience unpleasant. To reduce this risk, be sure to follow the directions on your supplement carefully. Some formulas offer the best results with food, while others work best when taken on an empty stomach. Many products divide arginine doses throughout the day to keep side effects to a minimum.
Feel free to take smaller doses of your supplement and then work your way up to the full amount, allowing your body to adjust to the ingredients.
5. Blood Pressure Changes
As mentioned earlier, nitric oxide widens blood vessels to improve circulation and reduce blood pressure. According to the Centers for Disease Control and Prevention, about 1 in 3 US adults have high blood pressure , so this side effect may be desirable.
However, if you have mildly low blood pressure, or hypotension, this may result in chest pain, shortness of breath, loss of energy, and even seizures.
How to Regulate This Effect: If you already suffer from hypotension, you may want to think twice about trying a nitric oxide supplement, or at least consult with a doctor first.
Additionally, you should also be sure to increase your fluid intake, since low blood pressure can be exacerbated by mild dehydration.
6. Blood Sugar Changes
Similar to changes in blood pressure, nitric oxide supplements can also affect blood sugar.
According to a study published by the American Diabetes Association, nitric oxide increases glucose uptake during exercise.
“This mechanism is more important in individuals with type 2 diabetes…N.O.-mediated glucose uptake may compensate for impaired insulin action…The N.O. pathway therefore may represent a potential therapeutic target in patients with type 2 diabetes.” 
How to Regulate This Effect: Experts at MayoClinic.com exhort diabetics to exercise caution before supplementing with arginine or similar nitric oxide supplements. Blood glucose levels should be carefully monitored by a professional whether you have type 1 or type 2 diabetes.
Additional Arginine Ailments and Side Effects
Touted for its ability to boost nitric oxide levels, the amino acid arginine is one of the most common ingredients found in nitric oxide supplements. Arginine is regarded as safe, but ingesting large quantities may lead to gastrointestinal side effects such as bloating and stomach cramps.
According to the Mayo Clinic, additional side effects include an increased risk of bleeding, change in blood sugar levels, and increased risk of herpes simplex cold sores. 
If being treated for low nitric oxide levels via arginine injection, there are some additional side effects to be aware of. These include allergic reactions, itching, or shortness of breath.
Interactions With Medication
Always consult with a doctor before using any nitric oxide supplement as there are dangerous interactions with medications that can occur. Antihypertensive drugs combined with arginine, for example, might cause blood pressure to drop to dangerously low levels.
You should also avoid taking nitric oxide supplements with nitrates or other medications which increase blood flow to the heart. This might cause increased dizziness and lightheadedness. 
Are Nitric Oxide Supplements Safe?
While nitric oxide supplements pose a small risk to your health, many products are completely safe when taken as recommended. The above side effects are usually minimal and only affect a small portion of users. As long as you maintain a healthy diet and participate in regular exercise, you can enjoy the benefits nitric oxide has to offer.
However, if you are taking any medications, it’s always best to consult a doctor before adding supplements (nitric oxide or otherwise) to your diet.
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-  Kiss Jp, Zsilla G, Vizi ES. “Inhibitory effect of nitric oxide on dopamine transporters: interneuronal communication without receptors.” Neurochemicstry International. 2004 Sep;45(4):485-9.
-  Kaslow, Jeremy. “Zinc Deficiency and Metabolism.”
-  “Zinc.” WebMD.
-  “L-Arginine.” MedlinePlus.com.
-  “High Blood Pressure Facts.” Centers for Disease Control and Prevention.
-  Kingwell at al. “Nitric Oxide Synthase Inhibition Reduces Glucose Uptake During Exercise in Individuals With Type 2 Diabetes More Than in Control Subjects.” Diabetes. August 2002 vol. 51 no. 8 2572-2580.
-  “Arginine Safety.” Mayo Clinic.