If you’ve taken a pre-workout powder, chances are you’ve seen citrulline before. It’s a non-essential amino acid that’s commonly added to fitness supplements to enhance performance, but can easily be synthesized in the body. It’s also found in a staple summertime food—watermelon.

The primary role of citrulline is to act as a detoxifier for ammonia, but it’s also a powerful vasodilator, which is the main reason fitness fanatics love the stuff.

It’s known to enhance performance by increasing training volume and preventing fatigue, but it also supports other functions. Citrulline's role in the production of enzymes, arginine synthesis, muscle strength, and cardiovascular health means it has to be a staple in your supplement stack.

If you aren’t familiar with this power pump supplement, we’re giving you the ins and outs of supplementing with L-citrulline. We’ll cover what citrulline is, how it works, and the ultimate power duo to take your workout to the next level.

What You Need To Know About L-citrulline

L-citrulline is a non-essential amino acid that can be produced by the liver and intestines in the human body, but it's also found in foods like cucumber, squash, pumpkins, and watermelon. Unlike most other amino acids that are used to build proteins, citrulline is capable of forming peptide bonds but does not participate in protein synthesis.

Rather, it’s heavily involved in the urea cycle in the liver and kidneys, and is involved in metabolism and regulating the production of nitric oxide (NO); citrulline is the precursor for L-arginine, a substrate required for NO synthesis1.

Like other nitric oxide-boosting supplements, L-citrulline has gained popularity for its role in supporting cardiovascular health and its anti-hypertensive properties, as well as for its direct and indirect effects on skeletal muscle and adipose tissue metabolism 2.

But the primary reason citrulline has become such a popular supplement among the fitness community is because of its vasodilating properties. As the precursor to L-arginine and thus NO production, supplementing with citrulline can dilate blood vessels, increase blood flow, and promote the ‘pump’ that all lifters crave.

How Does It Work?

Although L-citrulline has a variety of functions that are key to optimal health and performance, there’s one we’re going to focus on—vasodilation.

Vasodilation refers to increasing the diameter of blood vessels to increase blood flow and reduce blood pressure 3. Upon consumption of citrulline, it’s converted into another amino acid, L-arginine, which is then converted into nitric oxide.

Nitric oxide is a small but ultra-powerful molecule. It's involved in virtually all cellular and organ functions, making it one of the most important chemical messengers in the body. That includes blood pressure regulation, cellular signal transmission, immune responses, and more 4.

Although some athletes may want to go crazy with NO, too much can damage host cells and cause neurotoxicity. However, in the vasculature, it’s a major regulator of vascular tone and blood flow via activation of soluble guanylate cyclase (sGC) in vascular smooth muscle 5.

That said, if you’re planning to consume arginine to boost NO production, it may not be super effective. Studies show that citrulline may increase levels of arginine more so than consuming arginine itself, largely due to how the body processes and absorbs arginine and citrulline 6.

This increase in NO and subsequent increase in blood flow are part of L-citrulline’s beneficial effects on exercise performance. And while it may not have a direct role in building proteins, it can enhance muscle protein synthesis by stimulating a key signaling pathway involved in muscle growth 6, 7.

What Is Citrulline Used For?

Athletic performance

You know that ‘pump’ that lifters chase? That’s NO hard at work.

Citrulline’s ability to dilate blood vessels and enhance blood flow to active muscle tissue is one of the main reasons why it’s big in the fitness industry. While it may not directly trigger muscle growth, it can help to improve the oxygen supply to muscles, which may lead to better performance 8, 9.

A 2015 study of 10 healthy male participants looked at the effects of L-citrulline and L-arginine supplementation on nitric oxide (NO) biomarkers, pulmonary oxygen uptake (V̇O2), and exercise performance 8. Participants completed moderate- and high-intensity cycling exercise on days 6 and 7 of a 7-day protocol using 6g/day each of arginine and citrulline or a placebo.

Results showed that citrulline supplementation improved tolerance to high-intensity exercise and increased the total amount of work; cyclists were able to work for 12% longer before exhaustion than participants taking a placebo.

Other research supports the use of citrulline for resistance training performance. One study found that participants saw a 53% increase in the number of repetitions performed after consuming citrulline malate, but it also attenuated muscle soreness, decreasing it by a whopping 40% 48-hours post-exercise 10.

Cardiovascular health

Because of its ability to dilate blood vessels and improve blood flow, short-term supplementation with citrulline appears to benefit cardiovascular health. Supplementation has been shown to reduce blood pressure in people with hypertension and prehypertension 11.

The mechanism of L-citrulline’s ability to improve endothelial dysfunction, in conditions like atherosclerosis, may be mediated through a direct reduction of free radical formation, direct action on vascular smooth muscle, and indirect action on nitric oxide production 11.

However, the exact source of oxidative stress—from either superoxide or hydroxyl radicals—plays a role in how effective L-citrulline is at attenuating endothelial damage and dysfunction.

Studies also show positive effects for L-citrulline on blood pressure, finding that just eight weeks of supplementation can lead to a 4 to 15% decrease in blood pressure 12, 13.

The Power Duo: L-citrulline + L-glutathione

But when it comes to supplementing L-citrulline to boost NO levels, there’s one thing you have to consider: stability.

Nitric oxide has powerful effects while in the vasculature, but breaks down relatively quickly in the bloodstream. So, to maintain the beneficial effects of NO, we need to extend its life—enter glutathione.

Glutathione is one of the body’s most powerful and important antioxidants. It plays a key role in the detoxification of endogenous metabolic products and buffers nitric oxide (NO) 14. Skeletal muscle is a highly active tissue that produces ROS and nitric oxide under various physiological conditions, especially during intense exercise.

As a result, the demand for antioxidants increases during and after exercise to neutralize radicals and prevent damage, as well as maintain NO levels in the blood.

A study published in the Journal of the International Society of Sports Nutrition looked at the effectiveness of L-citrulline and/or GSH supplementation on markers indicative of NO synthesis 15. These results show that oral supplementation with Setria® Glutathione and L-citrulline can increase blood levels of nitrite, nitric oxide, and cGMP compared to the placebo.

As such, when combined with L-citrulline, Setria® Glutathione not only enhances levels of NO, but it may sustain levels by preventing oxidation.

Long story short, if you want to maintain the beneficial effects that nitric oxide has to offer, adding glutathione to your citrulline stack provides massive benefit—even up to 30 minutes post-exercise.

The Best L-citrulline Supplement: Pre Lab Pro®

The purpose of a pre-workout supplement is to boost your energy and enhance focus, but they’re not all effective for driving the pump. If you want to shatter your limits and reach new heights in your training, you need a pre-workout that’s going to support that.

Pre Lab Pro® sparks a 2X muscle-pumping nitric oxide (NOx) turbocharge with afterburn for all-around performance and athletics. Moderate-dose smart caffeine, hydrating factors, restorative essentials, and more help you crush your workout.

With an exhilarating blood flow boost, physical and mental energy, peak muscle power and efficiency, and extended endurance, you get a laser intensity and calm clarity like you’ve never experienced.

Once you think you’ve reached maximum performance, feel the afterburner kick in—a second NOx surge that helps you go longer, finish stronger, and boost recovery.

Pre Lab Pro® features:

  • RedNite® red beetroot powder—Nitric oxide boosters with 25x more nitrate for a bigger muscle-pumping blood flow boost
  • Setria® performance blend—Protects NO against degradation for a more sustained blood flow and better muscle growth
  • Natural caffeine—Precision-tuned stimulation for laser intensity and sharper focus
  • Ajipure® L-tyrosine—Enhances focus under stress and maintains neurotransmitter levels depleted by caffeine and high-intensity exercise
  • Suntheanine® L-theanine—Bolsters caffeine benefits while minimizing the negative side effects for clean, calm stimulation and mental clarity


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