Fatigue is one of the most common complaints in today’s fast-paced world, but did you know it might be tied to your liver? The liver plays a major role in detoxifying the body, and when it's overburdened — say, after long-term alcohol use or a diet heavy in processed foods — you might notice a dip in your energy levels. A sluggish liver struggles to keep up with its many responsibilities, leaving you feeling drained and out of sync.
But let’s look at the bright side: your body has tools to help combat this cycle, and there are many ways to help it do so. When it comes to helping the body clear harmful substances and fight fatigue, citrulline is one that’s worth considering. This nonessential amino acid has been studied for its ability to improve energy levels, circulation, and detoxification.
What Is Citrulline and How Can It Help?
Discovered in watermelon (Citrullus vulgaris) in 1930, citrulline is a compound that has since been recognized for its multifaceted role in health. While it is most popular among athletes for improving endurance and reducing muscle fatigue, its benefits go far beyond sports performance.
One of citrulline's standout features is its ability to assist in clearing ammonia from the body. Ammonia is a byproduct of protein metabolism that can accumulate and contribute to muscle fatigue. Citrulline also plays a key role in the production of nitric oxide, a compound that dilates blood vessels and improves circulation.[1]
The most notable property of citrulline, however, has to do with its ability to give the liver a hand in clearing the body of toxins. Giving your liver a chance to repair itself can help you gain momentum on your alcohol reduction journey while providing you with that much-needed energy boost. Let’s take a closer look at what the most recent research has to say on the subject.
Citrulline and Liver Health: A Deep Dive Into Recent Findings
A 2021 study in Redox Biology explored the potential of L-citrulline to mitigate the progression of non-alcoholic fatty liver disease (NAFLD) — a condition often tied to poor dietary habits and liver dysfunction.[2] Using a mouse model, the researchers demonstrated how citrulline supplementation could help protect the liver from further damage by improving intestinal health and reducing inflammation.
While NAFLD was the focus of the study, the findings are also relevant to anyone whose liver has been compromised by alcohol use. NAFLD and alcohol-related liver problems share many of the same mechanisms. Both also share one major contributing factor: leaky gut. As NAFLD sets in, the intestinal barrier fails to block harmful toxins from entering the bloodstream and triggering inflammation. Alcohol, in turn, is also notorious for causing leaky gut and increasing inflammation throughout the body.
In both conditions, this gut-liver connection creates a vicious cycle: an inflamed gut leads to liver stress, which worsens gut health, and so on. The liver becomes overwhelmed trying to filter out toxins, leading to fatigue and systemic issues.
The study revealed that citrulline supplementation improved both gut and liver health in mice on a high-fat, high-fructose diet — one that’s known to accelerate NAFLD. Here’s what the researchers found:
- Citrulline strengthens the gut barrier. Citrulline helped prevent the loss of essential tight junction proteins (such as ZO-1 and occludin), which maintain the gut’s protective barrier. With a stronger barrier, fewer bacterial toxins leaked into the bloodstream and the inflammation in the liver was reduced as a result.
- It also boosts arginase activity. Arginase, an enzyme involved in detoxification and nitric oxide regulation, was found to be suppressed in mice with NAFLD. Citrulline reversed this suppression, restoring gut function and reducing inflammation. Interestingly, when researchers blocked arginase activity, citrulline’s benefits disappeared, showing that the two compounds work synergistically in the gut-liver connection.
- Citrulline reduces inflammation and oxidative stress. Citrulline supplementation lowered markers of liver inflammation, including levels of tumor necrosis factor-alpha (TNFα) and oxidative stress markers (like 4-HNE).
- It improves circulation. By supporting nitric oxide production, citrulline improved blood flow to both the gut and liver, aiding in the delivery of nutrients and removal of toxins.
What makes this research especially compelling is its focus on the intestinal-liver connection in combating liver problems. By targeting gut health with citrulline, the researchers showed a new pathway for preventing liver damage — without relying solely on drastic dietary changes.
Making Citrulline Part of Your Routine
While the study was conducted on mice, the results offer promising clues about how citrulline could benefit humans, particularly those experiencing fatigue or inflammation tied to liver issues. Let’s explore some ways to incorporate it into your routine.
1. Add Watermelon to Your Diet
Watermelon is the natural source of citrulline. And while you’d have to eat a whole lot of it to get a therapeutic dose, it’s a refreshing way to start.
- Snack on fresh watermelon daily to supply your gut with a steady intake of citrulline.
- Blend watermelon into smoothies for a hydrating and gut-friendly drink that supports liver health.
- Add watermelon cubes to your salads to pair citrulline with leafy greens rich in antioxidants, further reducing inflammation.
2. Add Citrulline-Containing Foods to Meals
While watermelon is the richest source, foods such as cucumbers and squash also contribute small amounts of citrulline. These foods also play a supporting role in improving gut health, which goes hand-in-hand with the health of your liver.
- Add cucumbers to your water or salads for a refreshing, gut-supportive snack.
- Spiralize zucchini or yellow squash as a base for your meals to improve gut health and reduce intestinal permeability.
3. Pair Citrulline Foods with Gut-Healing Nutrients
To take gut restoration to the next level, combine citrulline-rich foods with nutrients that support the intestinal barrier.
- Include fermented foods like yogurt, kimchi, or kefir alongside citrulline-rich snacks. These probiotics help support a healthy gut microbiota, reinforcing the protective effects of citrulline.
- Pair watermelon with a handful of walnuts, which contain omega-3s to further reduce inflammation.
At the same time, steer clear of foods that are known to disrupt gut health. Science shows that a high-fat, high-sugar diet exacerbates gut permeability and liver stress. Try to reduce fructose-heavy foods and replace sugary snacks with citrulline-rich options such as watermelon or cucumbers.
4. Consider Citrulline Supplements
While food sources are a great start, supplements can ensure consistent and therapeutic levels of citrulline. The Redox Biology study used specific doses for improving gut and liver health.
- Begin with 2 grams of L-citrulline per day and gradually increase based on your body’s response and guidance from a healthcare provider.
- Take citrulline supplements with a meal to support gut absorption and improve intestinal barrier function.
- Make sure to drink a glass of water with each dose of citrulline to support circulation and toxin removal. (You can also add watermelon or cucumber slices to your water for a hydrating, citrulline-infused beverage.)
Note of Caution
While citrulline is generally safe, it can interact with certain medications (particularly blood pressure-lowering drugs). If you have underlying health conditions or are taking medications, consult a healthcare professional before adding citrulline to your routine to ensure it’s the right fit for your needs.
Likewise, be sure not to mix citrulline with other nitric oxide-boosting supplements such as arginine or beetroot, as it may excessively dilate blood vessels, leading to low blood pressure, dizziness, or headaches. It can also interact with blood pressure-lowering supplements like hawthorn or magnesium, potentially causing blood pressure to drop too low, increasing the risk of lightheadedness or fainting.
Summing Up
Your liver is one of the most resilient organs in your body, capable of regenerating and repairing itself when given the right support. By focusing on a nutrient-rich diet, maintaining a healthy gut, and reducing factors that overburden the liver, you can help it restore balance and function. Small, consistent changes to your routine, paired with mindful choices, can make a big difference in your energy levels and overall well-being. Trust in your body’s natural resilience and give your liver the care it needs to thrive.
