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Which is Better: L-Arginine or L-Citrulline? A Comprehensive Comparison

Which is Better: L-Arginine or L-Citrulline?

L-arginine and L-citrulline are two popular supplements taken for their potential health and performance benefits. But which one is better? This comprehensive article will compare and contrast L-arginine and L-citrulline to help you decide which supplement may be right for you.

What is L-Arginine?

What is L-Arginine?

L-arginine is an amino acid that plays several important roles in the body. It is considered a semi-essential or conditionally essential amino acid because while the body can synthesize some L-arginine on its own, dietary intake is still required under certain conditions.
Some of the key functions of L-arginine include:
  1. Precursor for nitric oxide synthesis - L-arginine is converted into nitric oxide, a molecule that promotes vasodilation and blood flow. This is why L-arginine supplements are often taken for cardiovascular health.
  2. Protein synthesis - L-arginine is needed to make proteins and creatine. It supports muscle growth and development.
  3. Wound healing - L-arginine stimulates the release of growth hormone and insulin-like growth factor-1 (IGF-1), both of which aid tissue growth and repair.
  4. Detoxification - L-arginine helps remove ammonia from the body by converting it into urea. Ammonia is a waste product that is toxic at high levels.
  5. Immune function - L-arginine promotes lymphocyte replication and activity, strengthening the immune response.
Overall, L-arginine plays a multifaceted role in several bodily processes related to circulation, muscle growth, immunity, and more.

What is L-Citrulline?

What is L-Citrulline?

L-citrulline is another amino acid in the body that is closely related to L-arginine. Unlike L-arginine, L-citrulline is considered a non-essential amino acid since it does not need to be obtained from the diet.
Here are some of the main functions of L-citrulline:
  1. Precursor to L-arginine - L-citrulline gets converted into L-arginine in the kidneys. It is actually a more potent way to boost L-arginine levels than taking L-arginine directly.
  2. Nitric oxide production - By increasing L-arginine, L-citrulline further boosts nitric oxide levels and enhances blood flow.
  3. Detoxification - Like L-arginine, L-citrulline helps remove ammonia and metabolize waste products.
  4. ATP production - L-citrulline helps increase ATP production in the body, which provides cellular energy.
  5. Reduces muscle soreness - Some research shows L-citrulline can reduce post-exercise muscle soreness and fatigue.
While the two amino acids are related and share some roles, L-citrulline’s main mechanism of action relies on its ability to increase L-arginine levels more efficiently than L-arginine itself.

L-Arginine vs. L-Citrulline: Key Differences

Now that we have covered the basics of both supplements, let’s compare some of the key differences between L-arginine and L-citrulline:

Bioavailability

  • One major difference between L-arginine and L-citrulline is their bioavailability, or how well the body can utilize each nutrient.
  • L-citrulline has superior bioavailability compared to L-arginine. One study found that oral L-citrulline supplementation led to a 250% increase in L-arginine levels in the blood over the course of 3 hours.
  • Meanwhile, oral doses of L-arginine are subjected to extensive metabolism in the intestines and liver. This means only a fraction of the initial dose makes it into circulation.
  • Due to its improved bioavailability, L-citrulline is considered a better way to increase L-arginine levels and nitric oxide production than taking isolated L-arginine.

Effects on Arginine and Nitric Oxide Levels

Given the differences in bioavailability, it’s not surprising that L-citrulline has been shown to increase arginine levels more effectively than L-arginine itself.
  • One study gave participants a single dose of either 6 grams of L-citrulline or 6 grams of L-arginine. Plasma arginine levels were measured over the next 3 hours.
  • L-citrulline supplementation increased arginine levels by 129%, while arginine only increased by 105% with L-arginine supplementation.
  • Multiple studies also show greater nitric oxide production with L-citrulline compared to L-arginine.
Based on the research, L-citrulline appears more effective at increasing nitric oxide bioavailability thanks in large part to its superior bioavailability.

Exercise Performance

The increased nitric oxide production from L-citrulline has led to considerable interest in its effects on exercise performance. Several studies have found promising results:
  • In one study, L-citrulline supplementation allowed participants to perform more repetitions during resistance exercise compared to exercise with L-arginine supplementation.
  • Marathon runners exhibited lower times with L-citrulline compared to placebo, indicating an ergogenic effect.
  • Cyclists biking at 80% VO2 max saw improved oxygen kinetics with L-citrulline.
The results for L-arginine on exercise performance are more mixed. While some studies noted improved anaerobic power or tolerance, others found no benefit on performance measures or exercise capacity.
Based on the current research, L-citrulline seems to have a more consistent ergogenic effect compared to L-arginine.

L-Arginine or L-Citrulline Side Effects

When considering any new supplement, potential side effects are an important factor.
  • L-arginine is generally well tolerated, but abdominal pain and diarrhea are possible side effects at higher doses.
  • There are fewer reported side effects with L-citrulline. The most common side effect is stomach upset, though this is usually mild.
  • For healthy adults, both supplements appear relatively safe when used appropriately. However, it’s best to start with lower doses and avoid exceeding recommended intakes.

L-Arginine or L-Citrulline Dosage

  1. The standard supplemental dosage for L-arginine is around 3-6 grams per day, while L-citrulline doses range from 3-6 grams per day up to 8-10 grams per day.
  2. Due to differences in molecular weight, these similar gram doses equate to a greater molar concentration for L-citrulline compared to L-arginine.
  3. This means on an equal weight basis, L-citrulline provides higher amounts of the raw amino acid. This partly explains its superior effects despite similar dosing.
  4. Additionally, the research indicates there may be an optimal dose range for L-citrulline between 6-8 grams per day for athletic performance. In contrast, higher L-arginine doses do not appear to confer additional benefits.

L-Arginine vs. L-Citrulline: Which Is Better?

Based on all the available research, L-citrulline appears to be the superior supplement compared to L-arginine for increasing nitric oxide levels and boosting exercise performance.

L-citrulline:
  1. Has higher bioavailability when taken orally
  2. Is more effective than L-arginine at increasing plasma arginine levels
  3. Causes greater nitric oxide production
  4. Has been shown to enhance exercise performance and capacity
  5. Produces fewer side effects than L-arginine
The only area where L-arginine may have a slight edge is on wound healing. Due to L-arginine’s role in tissue repair, topical application to wounds can accelerate healing.
For systemic benefits related to circulation, performance, and heart health, L-citrulline is likely the better choice.
However, keep in mind that most research has used isolated L-citrulline or L-arginine supplements. Comparative studies directly testing the two supplements are still somewhat limited.
Additionally, some people do seem to respond better to L-arginine for exercise performance. So individual variation certainly plays a role.

Who Might Benefit More from L-Arginine?

While L-citrulline looks to be superior for most people, are there any circumstances where L-arginine may be more beneficial?
Here are some instances where L-arginine could have an advantage:
  1. Individuals with impaired kidney function - The conversion of L-citrulline into L-arginine occurs in the kidneys. Impaired kidney function reduces this conversion.
  2. Older adults - Aging is associated with a decrease in arginine synthesis and nitric oxide production. Older adults may derive more benefit from direct L-arginine supplementation (24).High oral doses - At very high single doses of 15-20 grams, L-arginine may produce higher transient spikes in nitric oxide compared to L-citrulline. However, these doses are associated with more side effects.
  3. Topical application - Applied topically to the skin, L-arginine boosts wound healing better than L-citrulline which is inactive when applied topically.
  4. Individual variation - A small percentage of people seem to respond better to L-arginine for reasons not fully understood. So L-arginine may end up being better for some individuals.
L-citrulline is likely the best first choice for most. But if it is not well tolerated or effective, L-arginine supplementation could be trialed to see if results differ.

Combining L-Arginine and L-Citrulline

Given their complementary mechanisms, some supplements combine both L-arginine and L-citrulline into one product.
In fact, evidence shows that L-citrulline can recycle L-arginine to further potentiate nitric oxide production. This suggests they work synergistically.
One study tested this by giving participants either L-citrulline alone, L-arginine alone, or L-citrulline + L-arginine together. The combination increased nitric oxide levels slightly more than either supplement alone.
Another study found that a lower dose of L-citrulline (2 grams) combined with L-arginine (2 grams) improved exercise performance similarly to a higher 6 gram dose of L-citrulline alone.
Based on the evidence, combining L-citrulline and L-arginine may offer benefits:
  • Increased nitric oxide production compared to either supplement alone
  • Amplifies the ergogenic effects for exercise performance
  • Allows lower doses of each to be used effectively
The combination approach makes sense biologically given the interrelated metabolic pathways. Just be cautious of higher doses that increase the likelihood of GI side effects.
Food Sources of L-Arginine and L-Citrulline
In addition to supplements, both amino acids can be obtained through dietary sources. Here are some of the top foods containing L-arginine and L-citrulline:

L-Arginine Food Sources

  1. Turkey and chicken
  2. Pork loin
  3. Pumpkin seeds
  4. Soybeans
  5. Peanuts
  6. Dairy products
  7. Seafood
  8. Whole grains
  9. Beans and lentils

L-Citrulline Food Sources

  1. Watermelon
  2. Cucumbers
  3. Garlic
  4. Onions
  5. Legumes
  6. Nuts
  7. Seeds
  8. Green peppers
While foods supply a slower release of these amino acids, eating arginine- and citrulline-rich foods daily can help maintain optimal levels in the body.

Who Should Avoid L-Arginine and L-Citrulline?

L-arginine and L-citrulline supplements are generally well tolerated but certain individuals should use them with caution or avoid them:
  1. Pregnant or breastfeeding women - Recommended to avoid due to lack of safety data.
  2. Children - Lack of research on safety and optimal dosing.
  3. Nitrate use - Both amino acids can amplify the blood pressure lowering effect, increasing risk of hypotension.
  4. Herpes - L-arginine may exacerbate herpes flare-ups in susceptible individuals. L-citrulline is preferred.
  5. Kidney disease - Impairs the conversion of L-citrulline into L-arginine. L-arginine may be safer.
  6. Liver disease - Impairs urea synthesis. Ammonia build-up may occur. Use with caution.
Anyone with significant medical conditions should consult a doctor before using to discuss appropriateness and dosage.

Conclusion
In summary, L-citrulline and L-arginine are two popular supplements taken for enhancing nitric oxide production, exercise performance, and overall health. The research indicates L-citrulline is superior in terms of bioavailability, effectiveness, and tolerability for most people. However, some may still derive greater benefits from L-arginine based on factors like age and kidney function. A combination approach with lower doses of both can also be effective. While promising, more research is still needed on the long-term efficacy and safety of high dose supplementation. Including sufficient whole food sources of both amino acids as part of a balanced diet remains the healthiest approach.
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