Nitric Oxide Supplements for Better Blood Flow: What Actually Works? A Functional Medicine Physician's Take on L-Arginine, L-Citrulline, and Beetroot

By Yoon Hang Kim, MD, MPH

If you've spent any time researching supplements for cardiovascular health or exercise performance, you've probably come across nitric oxide boosters. They're everywhere—from beetroot powders at your local health food store to amino acid blends marketed to athletes.

But here's what I tell my patients: not all nitric oxide supplements work the same way, and choosing the right one depends entirely on what you're trying to accomplish.

Let me break down what we actually know about these supplements and help you figure out which approach might make sense for you.

Why Nitric Oxide Matters for Your Health

Nitric oxide is one of those molecules that quietly runs the show behind the scenes. It helps your blood vessels relax and dilate, which improves circulation throughout your body. It also plays a role in immune function, brain signaling, and how your cells produce energy.

Here's the catch: your body makes less nitric oxide as you get older. And if you're dealing with conditions like high blood pressure, diabetes, or heart disease, your nitric oxide production may already be compromised.

This decline has sparked a lot of interest in finding ways to boost nitric oxide levels through diet and supplementation—a approach that fits naturally within integrative and functional medicine, where we focus on supporting the body's own healing mechanisms rather than just managing symptoms.

The Two Pathways: Understanding How Your Body Makes Nitric Oxide

Before choosing a supplement, it helps to understand that your body produces nitric oxide through two different routes.

The L-Arginine Pathway: Your cells use an enzyme called nitric oxide synthase (NOS) to convert the amino acid L-arginine into nitric oxide. This is your body's primary production method.

The Nitrate-Nitrite Pathway: When you eat nitrate-rich foods like beets and leafy greens, bacteria in your mouth convert those nitrates into nitrites, which your body then transforms into nitric oxide. This backup pathway becomes especially important when the primary pathway isn't working well.

Why does this matter? Because different supplements target different pathways—and what works best for you may depend on which pathway needs the most support.

L-Arginine and L-Citrulline: The Amino Acid Approach

L-arginine seems like the obvious choice for boosting nitric oxide since your body uses it directly. But here's something that surprises many of my patients: when you take L-arginine by mouth, most of it gets broken down in your liver before it ever reaches your bloodstream.

L-citrulline, on the other hand, takes a different route. It bypasses your liver entirely and gets converted to L-arginine in your kidneys. This metabolic quirk means L-citrulline actually raises your blood arginine levels more effectively than taking arginine itself.

What the Research Shows

A well-designed study comparing these two amino acids found that seven days of L-citrulline supplementation (6 grams daily) did a better job of increasing nitric oxide markers than an equivalent dose of L-arginine. The citrulline group also saw improvements in blood pressure and exercise performance—benefits that didn't show up with arginine alone.

Even more interesting: combining L-citrulline and L-arginine at lower doses (about 1.2 grams of each) appears to work synergistically. Research on collegiate soccer players found this combination improved cycling performance and post-exercise nitric oxide levels.

The reason? Citrulline doesn't just turn into arginine—it also blocks the enzyme that breaks arginine down. So when you take them together, the citrulline protects the arginine from being destroyed before your body can use it.

Beetroot and Dietary Nitrates: The Vegetable-Based Strategy

If the amino acid pathway in your body isn't working optimally—which happens with aging, diabetes, and cardiovascular disease—beetroot and other nitrate-rich foods offer an alternative route to boosting nitric oxide.

This is where functional medicine's emphasis on food as medicine really shines. Rather than viewing beets as just another vegetable, we can understand them as a targeted intervention that bypasses a dysfunctional pathway.

Blood Pressure Benefits

The evidence for beetroot juice and blood pressure is probably the strongest we have for any nitric oxide supplement. Multiple studies have found that beetroot juice reliably lowers both systolic and diastolic blood pressure, with the most consistent benefits appearing in people who already have elevated blood pressure.

A systematic review from 2022 confirmed these findings, showing meaningful blood pressure reductions in adults with hypertension after beetroot juice supplementation.

Beyond Blood Pressure

Recent research has also shown benefits for vascular function that go beyond simple blood pressure readings. A 2024 study in postmenopausal women—a group with elevated cardiovascular risk after estrogen levels decline—found that one week of dietary nitrate supplementation significantly improved how their blood vessels function.

This kind of finding is particularly relevant for women navigating the cardiovascular changes that come with menopause.

So Which Supplement Should You Choose?

Here's my honest answer: it depends on your goals.

For blood pressure and cardiovascular support: Beetroot juice or standardized nitrate supplements have the most consistent evidence. Look for products providing about 300-500 mg of dietary nitrate—roughly equivalent to 500 mL of beetroot juice. The benefits are clearest in people who already have elevated blood pressure or signs of blood vessel dysfunction.

For exercise performance and physical energy: L-citrulline, either alone (3-6 grams daily) or combined with L-arginine (1-2 grams of each), has better support for improving exercise capacity and oxygen utilization. These benefits are most pronounced in recreational exercisers; elite athletes may see smaller improvements.

For impaired endothelial function: When the cells lining your blood vessels aren't working well—which happens with aging, diabetes, and established heart disease—combining both approaches makes physiological sense. Using L-citrulline/L-arginine alongside dietary nitrates addresses both pathways simultaneously.

I should note that we don't yet have large clinical trials testing this combined approach. The recommendation comes from understanding the mechanisms rather than definitive outcome data.

What About Those Proprietary Blends?

Several companies sell specialized nitric oxide formulas combining various ingredients. Some research suggests these products can increase nitric oxide markers in saliva or blood.

However, I approach these products with some caution. Many of the studies are industry-funded, and the evidence often stops at biomarker changes rather than demonstrating actual health improvements. That doesn't mean they're ineffective—just that the evidence is less mature.

Safety Considerations and Practical Tips

These supplements are generally well-tolerated, but a few things are worth knowing:

L-Arginine: High doses can cause GI upset. More importantly, some research has raised concerns about L-arginine supplementation in people who've recently had a heart attack. If you have established cardiovascular disease, definitely work with your physician.

Dietary Nitrates: The main practical consideration is mouthwash. Chlorhexidine-containing mouthwashes kill the oral bacteria that convert nitrate to nitrite, essentially blocking this pathway. If you're using beetroot supplements, skip the antibacterial mouthwash.

All Nitric Oxide Supplements: These can add to the blood pressure-lowering effects of antihypertensive medications or drugs like Viagra. Blood pressure monitoring during the initial period is wise if you're on vasoactive medications.

The Functional Medicine Perspective

In functional medicine, we think about supplements differently than conventional medicine often does. Rather than asking "what pill treats this symptom," we ask "what's the underlying dysfunction and how can we support the body's own repair mechanisms?"

For nitric oxide, that means:

• Assessing the whole person rather than just prescribing a supplement

• Considering dietary foundations first—leafy greens and beets should be part of a cardiovascular-supportive diet regardless of supplementation

• Choosing supplements based on the specific pathway that needs support

• Monitoring response and adjusting the approach based on what's working

The goal isn't to take a supplement forever. It's to support healing while addressing root causes—whether that's improving diet, managing blood sugar, optimizing sleep, or reducing inflammation.

Starting with Beetroot Powder: A Practical Guide

For patients new to nitric oxide supplementation, I often recommend starting with beetroot powder as an accessible entry point. Here's a reasonable approach:

Starting dose: 1-2 teaspoons daily, mixed in water, juice, or a smoothie

Timing: Many people take it in the morning or 2-3 hours before exercise

What to watch for: Blood pressure effects (especially if you're on medications), and the completely harmless but sometimes alarming red color it can give to urine and stool

Quality matters: Look for organic products from reputable companies. The nitrate content can vary significantly between products.

And as always, if you're taking medications or managing chronic conditions, work with a physician who understands both your health situation and how these supplements interact with your treatment plan.

The Bottom Line

Nitric oxide supplementation makes physiological sense for many people, particularly those dealing with cardiovascular concerns or looking to support exercise performance as they age.

But there's no universal "best" supplement. The choice between L-citrulline, beetroot, or a combined approach should be based on your specific goals, health status, and which nitric oxide pathway needs the most support.

The research continues to evolve, and I suspect we'll have more refined recommendations in the coming years. For now, the evidence supports a thoughtful, individualized approach—which is really what good integrative medicine should always be about.

References

Bailey SJ, Blackwell JR, Lord T, et al. L-citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. Journal of Applied Physiology. 2015;119(4):385-395.

Jones AM. Dietary nitric oxide precursors and exercise performance. Sports Science Exchange. 2016;29(156):1-6.

Kiani AK, Bonetti G, Medori MC, et al. Dietary supplements for improving nitric-oxide synthesis. Journal of Preventive Medicine and Hygiene. 2022;63(2 Suppl 3):E239-E245.

Morita M, Hayashi T, Ochiai M, et al. Oral supplementation with a combination of L-citrulline and L-arginine rapidly increases plasma L-arginine concentration and enhances NO bioavailability. Biochemical and Biophysical Research Communications. 2014;454(1):53-57.

Proctor S, Biggerstaff K, Pugh J. Seven-day dietary nitrate supplementation clinically significantly improves basal macrovascular function in postmenopausal women. Frontiers in Nutrition. 2024;11:1359671.

Suzuki I, Sakuraba K, Horiike T, et al. A combination of oral L-citrulline and L-arginine improved 10-min full-power cycling test performance in male collegiate soccer players. European Journal of Applied Physiology. 2019;119(5):1075-1084.

Wong SA, Rowlands D, Chan J, Bailey TG. Effect of dietary supplements which upregulate nitric oxide on walking and quality of life in patients with peripheral artery disease. Biomedicines. 2023;11(7):1859.

Zamani H, de Joode M, Hossein G, et al. Nitrate derived from beetroot juice lowers blood pressure in patients with arterial hypertension. Frontiers in Nutrition. 2022;9:823039.

Dr. Yoon Hang Kim is a board-certified preventive medicine physician and integrative medicine specialist. He practices telemedicine through Direct Integrative Care, serving patients in Iowa, Illinois, Missouri, Georgia, Florida, and Texas.

www.directintegrativecare.com