citrulline & arginine

What’s its purpose?

Citrulline and arginine both are part of a nitric oxide (NO) pathway. Nitric oxide functions to open up blood vessel diameter, ultimately for the goal of either reduction of blood pressure or improved delivery of oxygen and nutrients to the cells. Both are amino acids that are non-essential. Arginine is conditionally non-essential, and a low amount is used for NO synthesis, while citrulline is also conditionally non-essential but more readily available due to the fact it is an intermediate in the TCA cycle. If you’re a nutrition nerd, you’ll know what that cycle is, but if not don’t worry about it! Not important for this post.

Where can you find it?

Citrulline is found in the rind of watermelon, as well as pumpkins, and cucumbers. You can find it in higher amounts as a supplement. There are two forms: L-citrulline and citrulline malate. The former is by itself, and the latter is bound to malate. Both citrulline and malate have separate functions in the body, so it’s unclear in research if benefits are found in citrulline, or malate once they’re split in the body after digestion.
*If you’re supplementing with citrulline malate, make sure to account for just the citrulline grams, not the compound. To obtain 1 gram of citrulline, you’d need to take 1.76 grams of citrulline malate.
FUN FACT: in order to get 3 grams of citrulline from watermelon, you’d have to drink 44 oz.

(1) citrulline (+ malate) –> arginine –> nitric oxide (by eNOS – an enzyme by the name of nitric oxide synthase)

(2) antioxidants + nitrate –> nitrite –> nitric oxide

How should it be taken?

If the goal ultimately is nitric oxide production, arginine and citrulline should be taken together. Nitric oxide is very unstable and lasts in the bloodstream for a short while. Increased glutathione helps stabilize NO. Glutathione is synthesized from the amino acids: glycine, cysteine, and glutamic acid. These can be found in plant and animal protein sources.
While both are required for the pathway to NO, taking both ensures higher likelihood of NO synthesis. Citrulline is more readily absorbed, and arginine commonly causes GI distress. Additionally, because arginine takes a while to get to the bloodstream, ingesting a combination of the two can yield more NO and minimize GI distress.
**GI distress was seen with arginine doses greater than 10 grams per day. Due to how the amino acids are digested, peak benefits can be seen after 1 hour of taking.

Studies have shown 6-8 grams of L-citrulline having benefit by itself, as well as 3-6 grams of arginine. Refrain from taking more than 8 grams of citrulline and 10 grams of arginine to avoid GI distress.
Recommendation: 3-6 grams are taken of each, one hour before exercise.

Is it worth the hype?

And here is the part of the post where my opinion comes in. Arginine and citrulline do have benefits in improving blood flow and endothelial function. However, recent study in The Journal of Nutrition (https://doi.org/10.3945/jn.116.234740) demonstrated on average humans ingest 5 grams of arginine daily, for use of conversion into nitric oxide, among other uses. Based off current evidence, it’s apparent these supplements benefit a select few scenarios: metabolic syndrome, wound healing (arginine), and potentially anaerobic training (citrulline). If you seek a nutrition goal with one of these scenarios, consult with a physician, as well as a dietitian, to see if these can benefit your specific nutrition needs. There are few times when I would recommend citrulline by itself, and few times when I would recommend arginine by itself. Although the pathway is suggested for a purported mechanism, the evidence for increased vasodilation and skeletal muscle perfusion is scarce and inconsistent. If I was consulting with a client who wanted to increase NO synthesis, I would recommend nitrates (see other information that is useful below).

Other information that is useful:

Since we’re on the topic of nitric oxide, there is a more direct way to increase nitric oxide synthesis, which is by means of ingesting nitrates. Please refer to the second italicized pathway above!
Nitrates will peak in the blood as nitric oxide faster than the amino acids citrulline and arginine. You can take some nitrate supplements in as little as 30 minutes before peak levels are found in the blood.
FUN FACT:
– Beet Elite has 250 nmol/mL nitrates (NO3)
– Resync Recovery has 575 umol/mL nitrates (NO3) **or 575,000 nmol/mL nitrates
– Beet Juice (100%) ex: Lakewood has 50 umol/mL nitrates (NO3) **or 50,000 nitrates [with the slowest peak]

More nitrates are not always better. You can actually get hypotensive (too low of blood pressure) by ingesting too many nitrates. Think about what your goal of nitric oxide function will be (for example, are you wanting increased nutrient and oxygen delivery to muscles? or are you seeking improved recovery needing the nitrates to work for longer periods of time?). These are important questions you can ask to determine the right nutrition for your needs.

Citrulline in Athletic Performance:

[doi: 10.1519/JSC.0000000000003426] This article summarizes the latest research up to date (2020). Citrulline (8 grams of citrulline malate – 4.5 grams of L-citrulline) marginally reduces perceived muscle soreness and exhaustion compared to placebo [DOI: 10.1016/j.jshs.2020.02.003] – note subjects were untrained and trained. There also was a decrease in perceived exhaustion in a male soccer player study when 1.2 grams of arginine + 1.2 grams of citrulline were taken daily for 7 days [DOI: 10.1007/s00421-019-04097-7]. Overall, there needs to be consistency of supplementation observed in a research study, as well as chronic supplementation. In my humble opinion, there is stronger evidence for other supplements in terms of reducing muscle soreness and exhaustion.

Hope you loved the learning as much as I did… until next time! xo Lisa