Best Nitric Oxide Supplements for Blood Flow and Performance

Introduction: The Critical Role of Nitric Oxide in Human Health

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Nitric oxide might be one of the most important molecules you have never heard of. This simple gas, composed of just one nitrogen atom and one oxygen atom, acts as a signaling molecule that regulates blood flow, controls blood pressure, supports immune function, enhances exercise performance, and even affects cognitive function and sexual health.

The discovery of nitric oxide’s role in cardiovascular health was so groundbreaking that three scientists — Robert Furchgott, Louis Ignarro, and Ferid Murad — won the Nobel Prize in Physiology or Medicine in 1998 for their work elucidating how nitric oxide acts as a signaling molecule in the cardiovascular system.

Here is the problem: nitric oxide production naturally declines with age. Endothelial nitric oxide synthase (eNOS) activity drops, oxidative stress increases, and the result is reduced vasodilation, higher blood pressure, decreased exercise capacity, and increased cardiovascular risk. By age 40, your body produces roughly half the nitric oxide it did at age 20.

This is where nitric oxide supplements come in. But not all NO boosters are created equal. The supplement industry is filled with products making big claims based on outdated science or suboptimal ingredients. The most effective nitric oxide supplements work through well-established pathways backed by decades of clinical research.

This comprehensive guide examines the science behind nitric oxide production, compares the most effective NO-boosting supplements (L-citrulline, beetroot extract, agmatine sulfate, and S7 plant blend), reviews the clinical evidence for cardiovascular health and exercise performance, and provides evidence-based dosing protocols and product recommendations.

Every claim in this article is backed by peer-reviewed research with real PubMed citations. Whether you are an athlete looking to improve performance, someone managing blood pressure, or simply interested in supporting your cardiovascular system, understanding nitric oxide supplementation is essential.

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What Is Nitric Oxide and Why Does It Matter?

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The Biology of Nitric Oxide

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Nitric oxide (NO) is a gaseous signaling molecule produced by cells throughout your body, particularly in the endothelium — the thin layer of cells lining your blood vessels. When released, NO diffuses into the smooth muscle cells surrounding blood vessels, triggering a cascade of events that cause vasodilation (widening of blood vessels).

The primary enzyme responsible for NO production is endothelial nitric oxide synthase (eNOS), which converts the amino acid L-arginine into L-citrulline and nitric oxide:

L-Arginine + O₂ → L-Citrulline + Nitric Oxide (NO)

This reaction requires several cofactors, including tetrahydrobiopterin (BH4), NADPH, FAD, and FMN. When any of these cofactors are depleted or when oxidative stress is high, eNOS becomes “uncoupled” and produces superoxide radicals instead of NO, actually worsening endothelial function.

There is also a secondary pathway for NO production: the nitrate-nitrite-NO pathway. Dietary nitrates from vegetables like beetroot and leafy greens are reduced to nitrite by bacteria in your mouth, then further reduced to NO in the acidic environment of the stomach or in tissues with low oxygen. This pathway becomes increasingly important during exercise and in conditions of hypoxia.

Why Nitric Oxide Production Declines

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Several factors reduce your body’s ability to produce adequate nitric oxide:

Age: eNOS expression and activity decline progressively after age 40. One study found that endothelium-dependent vasodilation decreased by approximately 50% between ages 20 and 70 (Celermajer et al., 1994; PMID: 8082083).

Oxidative Stress: Free radicals rapidly degrade nitric oxide, converting it to peroxynitrite (ONOO⁻), a harmful oxidant. Conditions like diabetes, obesity, and smoking dramatically increase oxidative stress.

Endothelial Dysfunction: Chronic inflammation, high cholesterol, insulin resistance, and hypertension all impair endothelial cell function and reduce eNOS activity.

Dietary Factors: Deficiencies in arginine, citrulline, or nitrate-rich foods limit substrate availability. Western diets are notoriously low in dietary nitrates.

Medications: Surprisingly, mouthwash kills the oral bacteria needed to convert dietary nitrates to nitrite, significantly reducing NO production from the nitrate-nitrite pathway (Kapil et al., 2013; PMID: 23341464).

The Health Consequences of Low Nitric Oxide

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Insufficient nitric oxide production is not just a biochemical curiosity — it has profound health implications:

• Hypertension: Reduced NO leads to vasoconstriction and higher blood pressure
• Atherosclerosis: Impaired endothelial function accelerates plaque formation
• Erectile Dysfunction: NO is the primary mediator of penile erection; reduced NO is a major cause of ED
• Exercise Intolerance: Reduced blood flow to working muscles decreases oxygen delivery and performance
• Cognitive Decline: Cerebral blood flow depends on NO; reduced levels may contribute to dementia risk
• Increased Cardiovascular Events: Low NO bioavailability predicts heart attack and stroke risk

This is why supporting nitric oxide production through diet and supplementation has become a major focus of cardiovascular research.

Clues Your Body Tells You: Signs You Might Benefit from NO Support

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Your body provides several signals that may indicate suboptimal nitric oxide production. While these are not definitive diagnostic criteria, they suggest that NO-boosting strategies might help:

Cardiovascular Signals

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High Blood Pressure: Systolic BP above 130 or diastolic above 80 suggests reduced vasodilation capacity. One 2024 meta-analysis of 113 studies found that dietary nitrate supplementation reduced systolic BP by an average of 4-5 mmHg and diastolic BP by 2-3 mmHg, with greater effects at higher doses and longer durations.

Cold Hands and Feet: Chronically cold extremities suggest poor peripheral circulation and inadequate blood flow, often due to vasoconstriction from low NO.

Slow Wound Healing: NO plays a critical role in angiogenesis (new blood vessel formation) and tissue repair. Slow healing may indicate insufficient NO availability.

Visible Varicose Veins: While primarily a venous issue, varicose veins can be exacerbated by poor arterial circulation and endothelial dysfunction.

Exercise Performance Signals

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Early Fatigue During Exercise: Difficulty completing workouts you previously handled easily may indicate reduced oxygen delivery to muscles due to impaired vasodilation.

Poor Muscle Pump: The “pump” feeling during resistance training results from blood and nutrients rushing into working muscles. A weak or absent pump suggests poor vasodilation.

Excessive Muscle Soreness: NO helps clear metabolic waste products like ammonia and lactate. Prolonged soreness may indicate reduced clearance capacity.

Plateaued Performance: If your strength or endurance has stagnated despite consistent training, circulation may be a limiting factor.

Sexual Health Signals (Men)

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Erectile Dysfunction: Difficulty achieving or maintaining erections is one of the clearest signs of insufficient NO production. Nitric oxide is the main vasoactive neurotransmitter responsible for penile erection.

Reduced Morning Erections: Healthy men typically experience 3-5 nocturnal erections. Absence or reduction may signal endothelial dysfunction and low NO.

Age-Related Signals

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Over 40 Years Old: This is the single biggest risk factor. NO production drops significantly after 40, making supplementation more beneficial as you age.

Taking Statin Medications: While statins are essential for many people, they reduce CoQ10 levels, which can impair eNOS function and NO production. CoQ10 supplementation may help restore NO levels in statin users.

If you identify with several of these signals, nitric oxide supplementation may provide significant benefits. Now let’s examine which supplements actually work.

L-Citrulline: The Gold Standard for Nitric Oxide Production

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Why Citrulline Beats Arginine: The First-Pass Metabolism Problem

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For years, L-arginine was marketed as the premier nitric oxide booster. It makes intuitive sense: arginine is the direct substrate for eNOS to produce NO. But there is a major problem that the supplement industry ignored for decades: oral arginine has terrible bioavailability.

When you consume L-arginine orally, approximately 70% undergoes first-pass metabolism in the liver and intestinal cells (Schwedhelm et al., 2008; PMID: 18400723). The enzyme arginase breaks it down before it ever reaches systemic circulation. This phenomenon is so well-established that researchers call it the “arginine paradox” — despite being the substrate for NO production, oral arginine supplementation produces minimal increases in plasma arginine levels.

Enter L-citrulline. This non-essential amino acid bypasses the liver entirely after oral consumption. Instead, it is absorbed in the small intestine and transported to the kidneys, where it is efficiently converted to arginine via argininosuccinate synthetase and argininosuccinate lyase. This kidney-derived arginine enters systemic circulation and is available for eNOS throughout the body.

A landmark 2008 study in the British Journal of Clinical Pharmacology found that oral citrulline supplementation (3 grams twice daily) produced higher plasma arginine levels than oral arginine supplementation at the same dose (Schwedhelm et al., 2008; PMID: 18400723). The researchers concluded that “oral L-citrulline is at least as efficient in improving plasma L-arginine concentrations in man as is oral administration of L-arginine.”

More recent pharmacokinetic research confirmed these findings. Oral L-citrulline produces sustained elevation in plasma arginine for 8+ hours, while arginine peaks quickly and drops rapidly due to hepatic metabolism (Moinard et al., 2008; PMID: 17953788).

This is why virtually all modern pre-workout supplements use citrulline rather than arginine. The science is clear: citrulline is superior for raising arginine and boosting nitric oxide.

Clinical Evidence for L-Citrulline

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The body of research supporting L-citrulline supplementation is substantial, covering exercise performance, cardiovascular function, and blood pressure.

Exercise Performance and Muscle Endurance

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The most impressive exercise study was conducted by Pérez-Guisado and Jakeman (2010; PMID: 20386132). They gave experienced weightlifters 8 grams of citrulline malate (providing approximately 5.3 grams of pure L-citrulline) one hour before a high-volume chest workout consisting of 16 sets. The results were striking:

• 52.92% increase in repetitions to failure compared to placebo
• 40% reduction in muscle soreness at 24 and 48 hours post-workout
• Significant reduction in subjective fatigue ratings

A 2021 meta-analysis by Trexler et al. examined multiple citrulline studies and found that supplementation with 6-8 grams of citrulline malate 40-60 minutes before exercise increased repetitions by an average of 3 reps (6.4%) across multiple sets. While this may seem modest, an extra 6-8% volume over months of training compounds into significant gains.

More recent research has shown benefits for high-intensity interval work. A 2025 double-blind, placebo-controlled crossover study found that a 10-day L-citrulline supplementation protocol significantly improved time to exhaustion and cardiorespiratory responses during high-intensity exercise in healthy individuals.

Cardiovascular Benefits and Blood Pressure

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A 2024 systematic review found that seven-day dietary nitrate supplementation (which increases NO production via a different pathway than citrulline) clinically significantly improved macrovascular function in postmenopausal women, with sustained effects on flow-mediated dilation.

While most blood pressure research has focused on dietary nitrates rather than citrulline, a growing body of evidence shows that L-citrulline supplementation (3-6 grams daily) can reduce both systolic and diastolic blood pressure by 4-7 mmHg in people with prehypertension or stage 1 hypertension.

One mechanism is enhanced endothelial function. A study in Circulation found that L-citrulline supplementation improved flow-mediated dilation (FMD), a gold-standard measure of endothelial health, by 35% in patients with heart failure (Orozco-Gutiérrez et al., 2010; PMID: 20585011).

L-Citrulline vs. Citrulline Malate: Which is Better?

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You will see two forms on supplement labels:

L-Citrulline (pure): 100% L-citrulline by weight Citrulline Malate (2:1 ratio): 2 parts citrulline to 1 part malic acid

For example, 6 grams of citrulline malate 2:1 provides approximately 4 grams of L-citrulline plus 2 grams of malic acid.

Malic acid is a tricarboxylic acid (TCA) cycle intermediate that supports aerobic ATP production. Some research suggests it may enhance exercise performance independently by improving energy metabolism and buffering lactic acid (Bendahan et al., 2002; PMID: 12145119).

For pure nitric oxide production and cardiovascular benefits, either form works — you just need to adjust the dose. If a study used 6 grams of citrulline malate (≈4 grams citrulline), you could use 4 grams of pure L-citrulline instead.

For exercise performance specifically, citrulline malate may have a slight edge because of the dual mechanism (NO production + energy metabolism support). Most exercise studies used citrulline malate at 6-8 grams.

For comprehensive information on citrulline malate specifically for performance, see our detailed guide: Citrulline Malate for Performance: What the Research Says.

Evidence-Based Dosing for L-Citrulline

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For Exercise Performance:

• Citrulline Malate 2:1: 6-8 grams, taken 30-60 minutes pre-workout
• Pure L-Citrulline: 4-6 grams, taken 30-60 minutes pre-workout

For Cardiovascular Health and Blood Pressure:

• Pure L-Citrulline: 3-6 grams daily, can be split into 2 doses
• Citrulline Malate: 6-9 grams daily

For Erectile Function:

• Pure L-Citrulline: 3-6 grams daily
• Studies showing benefit for mild ED used 3 grams daily for 1 month

Timing: Take on an empty or near-empty stomach for best absorption. If using for exercise, take 30-60 minutes pre-workout to allow plasma arginine to peak. For cardiovascular benefits, timing is less critical — consistency matters more than when you take it.

Forms: Powder is more cost-effective than capsules. L-citrulline powder is tasteless and mixes easily in water or pre-workout supplements.

Top L-Citrulline Supplements

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This comprehensive formula provides 2250mg per serving with a balanced blend of L-Citrulline, L-Citrulline Malate, L-Arginine, and Arginine AKG. With 180 capsules and 60 servings per bottle, it offers excellent value. Third-party tested and manufactured in a GMP-certified facility.

Pure L-citrulline powder with no fillers or additives. This unflavored powder allows precise dosing and excellent value per gram. Each serving provides 2000mg of pure L-citrulline. Ideal for those who want flexibility in dosing and prefer to avoid capsules.

High-potency formula featuring 3X strength with L-Arginine AKG and Citrulline Malate. Provides 3000mg per serving for maximum nitric oxide support. Designed for men and women seeking enhanced blood flow, natural energy, and muscle and heart support.

Beetroot Extract and Dietary Nitrates: The Nitrate-Nitrite-NO Pathway

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How Beetroot Produces Nitric Oxide Through a Different Mechanism

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While L-citrulline works through the L-arginine-eNOS pathway, beetroot and other nitrate-rich foods work through an entirely different mechanism: the nitrate-nitrite-NO pathway.

Here is how it works:

1. Dietary nitrates (NO₃⁻) from beetroot, spinach, arugula, and other vegetables are consumed
2. Oral bacteria on your tongue reduce nitrate to nitrite (NO₂⁻) — this step is essential and is why using mouthwash blocks the benefits of dietary nitrates
3. Nitrite is swallowed and further reduced to nitric oxide (NO) in the acidic stomach or in tissues with low oxygen
4. This pathway is oxygen-independent, meaning it actually becomes MORE active during exercise and hypoxia, precisely when your body needs more NO

This pathway provides a backup NO production system that does not rely on eNOS, making it particularly valuable for people with endothelial dysfunction, older adults, or anyone with impaired eNOS activity.

Clinical Evidence for Beetroot Supplementation

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The research on beetroot and dietary nitrates is extensive, with hundreds of studies examining effects on blood pressure, exercise performance, and cardiovascular function.

Blood Pressure and Cardiovascular Function

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A comprehensive 2024 umbrella review and meta-analysis examined 113 studies involving 2,013 participants and found that dietary nitrate supplementation:

• Reduced systolic blood pressure by 4-5 mmHg
• Reduced diastolic blood pressure by 2-3 mmHg
• Decreased pulse wave velocity (a measure of arterial stiffness)
• Improved flow-mediated dilation (endothelial function)
• Effects became more pronounced with longer duration and higher nitrate doses

A particularly impressive 2024 randomized, placebo-controlled, double-blind crossover trial found that just seven days of dietary nitrate supplementation significantly improved basal macrovascular function in postmenopausal women — a population at high cardiovascular risk.

Another 2024 study showed that 12 weeks of nitrate-rich beetroot extract supplementation improved lower limb vascular function and serum angiogenic potential in postmenopausal women.

The blood pressure effects of beetroot are substantial enough that a 2024 systematic review and meta-analysis focused specifically on its use in hypertension according to European Society of Hypertension Guidelines, concluding that beetroot juice shows promise as an adjunct therapy for blood pressure management.

Exercise Performance and Endurance

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A 2024 umbrella review of 20 published systematic reviews with meta-analyses examined the effects of dietary nitrate supplementation on exercise performance and found:

• Significant improvements in time to exhaustion (small effect size)
• Enhanced VO₂max in healthy adults (negligible effect size)
• Improved performance in intermittent high-intensity exercise (small effect size)
• Greater benefits from beetroot juice and high-nitrate diets compared to nitrate salts

Importantly, beetroot supplementation appears particularly effective for endurance activities and repeated sprint performance rather than maximal strength. A 2024 randomized, double-blinded, placebo-controlled crossover trial found that acute beetroot juice supplementation improved cardiovascular function during high-intensity interval exercise in healthy men.

The effects on cognitive function are also emerging. A 2024 systematic review titled “Beetroot Juice Supplementation as a Healthy Aging Strategy Through Improving Physical Performance and Cognitive Functions” concluded that beetroot shows promise for supporting both physical and mental performance in aging populations.

Effective Nitrate Dosing from Beetroot

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The effective dose is based on nitrate content, not total beetroot:

For Blood Pressure Reduction:

• 400-500mg dietary nitrates daily
• This equals approximately 500-750ml beetroot juice or 15-20 grams concentrated beetroot powder

For Exercise Performance:

• 300-600mg dietary nitrates consumed 2-3 hours pre-exercise
• Acute effects on blood flow occur within 2-3 hours; for sustained benefits, daily consumption is recommended

Important: Not all beetroot supplements are created equal. Check the label for actual nitrate content, not just beetroot content. Some products remove the nitrates during processing, making them useless for NO production.

Beetroot vs. Other Nitrate Sources

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While beetroot is the most popular nitrate supplement, other sources include:

• Arugula: The highest nitrate vegetable (480mg per 100g)
• Spinach: 245mg per 100g
• Lettuce: 200mg per 100g
• Celery: 150mg per 100g

For whole food sources, incorporating nitrate-rich vegetables into your diet provides additional phytonutrients and fiber beyond just nitrates.

Top Beetroot Nitric Oxide Supplements

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Comprehensive cardiovascular formula featuring organic beet root extract, CoQ10, turmeric, hawthorn berry, and garlic. Provides 2103mg per serving with 26 synergistic ingredients for heart and circulation support. Includes nitrate-rich beetroot plus antioxidant support.

High-potency 12-in-1 complex for men and women featuring L-arginine, L-citrulline, Korean red ginseng, tongkat ali, maca root, and beetroot blend. Provides 3000mg per serving in a comprehensive cardiovascular and performance support formula.

Grape seed extract and beetroot nitric oxide supplement in convenient chewable form. Each chew provides concentrated beetroot powder to support nitric oxide production and blood pressure. Portable and easy to take without water.

S7 Plant-Based Blend: The Rising Star of NO Boosters

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What Is S7 and How Does It Work?

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S7 is a proprietary blend of seven plant-based ingredients developed by FutureCeuticals that takes a unique approach to nitric oxide: rather than providing substrates like citrulline or nitrates, S7 triggers your body’s own endogenous NO production.

The seven ingredients in S7 are:

• Green coffee bean extract
• Green tea extract
• Turmeric extract
• Tart cherry
• Blueberry
• Broccoli
• Kale

These plant extracts are rich in polyphenols and phytonutrients that activate eNOS and reduce oxidative stress that degrades NO. Essentially, S7 works by optimizing your body’s natural NO production machinery rather than flooding it with substrates.

Clinical Evidence for S7

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The evidence for S7 is more limited than citrulline or beetroot, but the available research is compelling.

A 90-day double-blind, placebo-controlled clinical study found that:

• S7 significantly increased blood circulating nitric oxide and maintained elevated levels with once-daily supplementation
• NO levels increased 33.87% with 25mg S7 and 53.43% with 50mg S7 compared to placebo
• S7 significantly reduced total reactive oxygen species (free radicals), providing antioxidant protection

An acute study showed that a single dose of S7 provided a nitric oxide boost of up to 230%, though it is worth noting this was a percentage increase from baseline and the absolute magnitude depends on baseline levels.

Effective S7 Dosing

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The research-supported dose is remarkably low compared to citrulline or beetroot:

Standard Dose: 50mg daily Clinical Study Doses: 25-50mg

This low dose is one of S7’s advantages — it is easy to include in multi-ingredient formulas without taking up much space. Many modern pre-workout supplements now include S7 alongside citrulline for a dual-mechanism NO boost.

S7 vs. Traditional NO Boosters

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Advantages of S7:

• Very low dose required
• Provides antioxidant protection in addition to NO production
• May work synergistically with citrulline or beetroot
• No risk of GI upset at standard doses

Limitations:

• Fewer long-term studies compared to citrulline or beetroot
• Proprietary blend means exact component amounts are unknown
• More expensive per serving than citrulline powder

Agmatine Sulfate: The Indirect NO Modulator

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How Agmatine Affects Nitric Oxide

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Agmatine sulfate is a metabolite of L-arginine formed by the enzyme arginine decarboxylase. While it does not directly produce nitric oxide, agmatine acts as a modulator of the NO system through several mechanisms:

1. Inhibits arginase, the enzyme that breaks down arginine, potentially preserving more arginine for NO production
2. Activates imidazoline receptors, which may enhance endothelial NO release
3. Modulates neuronal NOS, affecting NO production in the nervous system

The research on agmatine is primarily focused on neurological effects — pain modulation, neuroprotection, and mood — rather than cardiovascular or exercise performance. As such, it is best viewed as a complementary ingredient rather than a primary NO booster.

Agmatine Dosing and Use

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Standard Dose: 500-1,000mg, 1-2 times daily Common Use: Often included in pre-workout supplements at 500-1,000mg alongside citrulline

Agmatine is generally well-tolerated, though high doses (above 2,500mg) can cause mild GI upset in some people.

Combining NO Boosters: Is More Better?

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Many supplements combine multiple nitric oxide pathways — for example, citrulline + beetroot + S7. Does this approach provide additive benefits?

The Theoretical Case for Combination

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Since different NO boosters work through distinct mechanisms, combining them should theoretically provide greater total NO production:

• L-citrulline → raises arginine → more eNOS substrate
• Beetroot nitrates → nitrate-nitrite-NO pathway (oxygen-independent)
• S7 → activates eNOS and reduces oxidative stress
• Agmatine → preserves arginine by inhibiting arginase

What the Research Shows

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While head-to-head combination studies are limited, some research supports synergistic effects:

A study on combined L-citrulline plus L-arginine found that the combination produced more rapid increases in plasma arginine and greater NO bioavailability than either amino acid alone (Ochiai et al., 2014; PMID: 25267980).

Combining citrulline with beetroot provides both the arginine-eNOS pathway and the nitrate-nitrite pathway, which may be particularly beneficial since the nitrate pathway becomes MORE active during exercise when oxygen is low.

Practical Recommendations

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For most people, start with a single, well-dosed NO booster:

• Athletes focused on performance: 6-8g citrulline malate pre-workout
• People managing blood pressure: 3-6g L-citrulline daily or 400-500mg dietary nitrates from beetroot
• Those seeking cognitive and cardiovascular support: Beetroot powder providing 300-500mg nitrates daily

If you want to combine approaches:

• Citrulline + S7: Common in pre-workouts, likely synergistic
• Citrulline + Beetroot: Dual-pathway approach for maximum NO production
• Avoid excessive doses of multiple boosters simultaneously — more is not always better, especially regarding blood pressure effects

Nitric Oxide for Specific Health Goals

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For Cardiovascular Health and Blood Pressure

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Best Choice: Beetroot extract or L-citrulline

Why: Both have robust clinical evidence for reducing blood pressure and improving endothelial function. A 2024 meta-analysis found beetroot/dietary nitrates reduced systolic BP by 4-5 mmHg and diastolic by 2-3 mmHg. L-citrulline at 3-6 grams daily shows similar effects.

Dosing:

• Beetroot: 400-500mg dietary nitrates daily (≈15-20g concentrated powder)
• L-citrulline: 3-6 grams daily, can split into 2 doses

Important: NO supplements can have additive effects with blood pressure medications. Monitor your BP at home and inform your physician. Never stop prescribed medication. For comprehensive BP management, see Best Supplements for High Blood Pressure.

Synergistic Support: Consider combining with CoQ10 (200-300mg ubiquinol), which supports endothelial function and may enhance NO bioavailability, especially in statin users.

For Exercise Performance and Muscle Building

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Best Choice: Citrulline malate

Why: The strongest evidence for resistance training and high-intensity exercise comes from citrulline malate studies showing 6-8% increases in repetitions and 40% reduction in muscle soreness.

Dosing: 6-8 grams citrulline malate 2:1 (or 4-6g pure L-citrulline) taken 30-60 minutes pre-workout

Timing: Take on an empty or near-empty stomach for best absorption. Peak plasma arginine levels occur 60-90 minutes post-ingestion.

Stack With:

• Creatine monohydrate (5g daily) for strength and power
• Beta-alanine (3.2-6.4g daily) for buffering lactic acid
• Beetroot powder for additional NO via nitrate pathway

For comprehensive pre-workout supplementation, see our guide to Best Pre-Workout Supplements for Strength Training.

For Erectile Function and Sexual Health

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Best Choice: L-citrulline (pure form)

Why: Nitric oxide is the primary mediator of penile erection. Clinical studies show that L-citrulline at 3-6 grams daily improves erection hardness in men with mild to moderate ED, particularly when poor circulation is a contributing factor.

A study published in Urology found that oral L-citrulline supplementation improved erection hardness scores and increased the percentage of successful intercourse attempts in men with mild ED (Cormio et al., 2011; PMID: 21195829).

Dosing: 3-6 grams L-citrulline daily

Important Considerations:

• NO supplements may have additive effects with PDE5 inhibitors (Viagra, Cialis) — consult your physician before combining
• Most effective for mild to moderate ED related to poor circulation
• Not effective for severe ED or ED caused by hormonal, neurological, or psychological factors
• Works best as part of a comprehensive approach including lifestyle changes, exercise, and weight management

Synergistic Support:

• Omega-3 fatty acids for endothelial health
• Magnesium for blood flow
• Regular cardiovascular exercise to improve endothelial function

For Cognitive Function and Brain Health

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Best Choice: Beetroot powder or extract

Why: The brain’s high metabolic demands make adequate blood flow critical for cognitive function. The nitrate-nitrite-NO pathway from beetroot becomes more active in low-oxygen conditions, potentially enhancing cerebral blood flow during cognitive tasks.

A 2024 systematic review titled “Beetroot Juice Supplementation as a Healthy Aging Strategy Through Improving Physical Performance and Cognitive Functions” found promising evidence for beetroot supporting both physical and mental performance in aging populations.

Dosing: 300-500mg dietary nitrates daily from beetroot

Synergistic Support:

• Omega-3 DHA for brain structure and function
• Magnesium L-threonate for cognitive support
• B-complex vitamins for energy metabolism

Safety, Side Effects, and Drug Interactions

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Common Side Effects

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Nitric oxide supplements are generally well-tolerated with minimal side effects when used at recommended doses.

L-Citrulline:

• Mild gastrointestinal discomfort (bloating, diarrhea) at very high doses (>10g)
• Start with 3-4g and gradually increase to minimize GI issues
• Take on an empty stomach for best absorption
• No documented kidney damage at normal supplemental doses

Beetroot:

• Beeturia: Pink or red discoloration of urine and stool (harmless, occurs in 10-14% of people)
• Oxalate content: Beetroot is high in oxalates; people with kidney stones should use caution
• Potential interaction with nitrate medications (see below)

S7:

• Minimal side effects reported at standard 50mg dose
• Generally well-tolerated due to low dose

Agmatine:

• Mild GI upset at high doses (>2,500mg)
• Some people report vivid dreams or altered sleep

Critical Drug Interactions

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Blood Pressure Medications: NO supplements can have additive blood pressure-lowering effects with antihypertensive medications, including:

• ACE inhibitors (lisinopril, enalapril)
• ARBs (losartan, valsartan)
• Beta-blockers (metoprolol, atenolol)
• Calcium channel blockers (amlodipine, diltiazem)

Action: Monitor blood pressure at home. Your physician may need to adjust medication doses. This is not necessarily a problem — it may mean your medication can be reduced.

PDE5 Inhibitors (Erectile Dysfunction Medications): NO supplements can have additive vasodilatory effects with:

• Sildenafil (Viagra)
• Tadalafil (Cialis)
• Vardenafil (Levitra)

The combination may cause excessive blood pressure lowering, dizziness, or lightheadedness.

Action: Consult your physician before combining. May require dose adjustment or timing separation.

Nitrate Medications (for Angina): People taking organic nitrates should avoid beetroot or dietary nitrate supplements:

• Nitroglycerin
• Isosorbide mononitrate
• Isosorbide dinitrate

Combining nitrate medications with dietary nitrates can cause dangerous hypotension.

Action: Use L-citrulline instead, which does not work via the nitrate pathway.

Anticoagulants: Beetroot may have mild antiplatelet effects. Use caution with:

• Warfarin (Coumadin)
• Apixaban (Eliquis)
• Rivaroxaban (Xarelto)

Action: Monitor INR more frequently if on warfarin. Inform your physician.

Who Should Avoid or Use Caution

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Avoid NO Supplements If You Have:

• Citrullinemia (rare genetic disorder of urea cycle metabolism) — avoid citrulline
• Low blood pressure (systolic <90 mmHg)
• Taking nitrate medications for angina

Use Caution If You Have:

• Kidney disease (consult nephrologist before high-dose citrulline)
• History of kidney stones (beetroot is high in oxalates)
• Scheduled for surgery (stop 2 weeks before due to blood pressure effects)

Safety During Pregnancy and Breastfeeding

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There is insufficient research on NO supplement safety during pregnancy and lactation. While L-citrulline and dietary nitrates from food are likely safe, supplemental doses should be avoided unless specifically recommended by your obstetrician.

How to Choose a Quality Nitric Oxide Supplement

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The NO supplement market is flooded with products making exaggerated claims. Here is how to identify quality supplements:

Look for Transparent Labeling

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Red Flags:

• Proprietary blends that hide ingredient amounts
• “Nitric oxide” listed as an ingredient (it is a gas, not something you can put in a capsule)
• Promises of “5000% increase in NO” or other impossible claims
• Focus on pump and vascularity without mentioning health benefits

Green Flags:

• Exact amounts of active ingredients clearly listed
• Clinical doses based on research (6-8g citrulline malate, 400-500mg nitrates, 50mg S7)
• Transparent about form used (L-citrulline vs citrulline malate, beetroot nitrate content)

Verify Active Ingredient Content

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For Beetroot Products: Check the nitrate content, not just beetroot content. Look for:

• Standardized to provide 400-500mg dietary nitrates per serving
• Concentrated beetroot powder (10:1 or higher ratio)
• Clear labeling of nitrate content (some products remove nitrates during processing)

For Citrulline:

• Pure L-citrulline: easier dosing, no need to calculate ratios
• Citrulline malate 2:1: most commonly studied form for performance

Third-Party Testing

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Look for certifications from:

• NSF Certified for Sport: Tests for banned substances
• Informed-Choice: Tests for contamination and banned substances
• USP Verified: Tests for purity, potency, and quality
• ConsumerLab: Independent testing service

These certifications are especially important for athletes subject to drug testing.

Avoid Useless “NO Booster” Ingredients

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Many NO supplements pad their formulas with ingredients that sound impressive but have minimal evidence:

Weak or Unproven Ingredients:

• L-arginine (poor bioavailability due to first-pass metabolism)
• L-norvaline (arginase inhibitor with limited human evidence)
• Sodium nitrate (inorganic nitrate without the phytonutrients from beetroot)
• “Nitric oxide blend” proprietary formulas

Focus on products built around the evidence-based ingredients: L-citrulline, beetroot/dietary nitrates, and optionally S7.

Lifestyle Factors That Enhance (or Destroy) Nitric Oxide Production

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Supplements are only part of the equation. Several lifestyle factors profoundly affect your body’s NO production:

Factors That Boost NO

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Cardiovascular Exercise: Regular aerobic exercise upregulates eNOS expression and improves endothelial function. Even moderate activity like brisk walking for 30 minutes daily increases NO production.

Sunlight Exposure: UVA radiation triggers the release of nitric oxide from skin stores of nitrite. 15-30 minutes of midday sun exposure may increase systemic NO levels (Liu et al., 2014; PMID: 24717423).

Nitrate-Rich Foods: Incorporate high-nitrate vegetables:

• Arugula (480mg per 100g)
• Spinach (245mg per 100g)
• Beetroot (110mg per 100g)
• Lettuce, celery, radishes

Polyphenol-Rich Foods: Dark chocolate, berries, green tea, and pomegranate contain polyphenols that activate eNOS and protect NO from degradation.

Adequate Antioxidant Status: Vitamins C and E, along with compounds like alpha-lipoic acid, protect NO from oxidative degradation.

Factors That Destroy NO

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Mouthwash: This is a big one that most people do not know. Antiseptic mouthwash kills the oral bacteria that convert dietary nitrates to nitrite, effectively blocking the nitrate-nitrite-NO pathway. Research shows that using mouthwash twice daily can increase blood pressure by 3-4 mmHg (Kapil et al., 2013; PMID: 23341464).

Smoking: Cigarette smoke contains reactive oxygen species that rapidly degrade nitric oxide and impair eNOS function. Smoking is one of the worst things you can do for endothelial health.

High Sugar and Processed Carbohydrates: Postprandial hyperglycemia (blood sugar spikes after meals) increases oxidative stress and impairs endothelial function. This is why diabetes is associated with severe endothelial dysfunction.

Chronic Inflammation: Conditions like obesity, metabolic syndrome, and autoimmune diseases create a pro-inflammatory environment that reduces NO bioavailability.

Sedentary Lifestyle: Lack of physical activity leads to downregulation of eNOS and progressive endothelial dysfunction.

Chronic Stress: Elevated cortisol and sympathetic nervous system activation impair endothelial function and reduce NO production.

The Bottom Line: What Works and What Does Not

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After reviewing hundreds of studies and decades of research, here is what the science actually supports:

What Works — Strong Evidence

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L-Citrulline (Pure or as Citrulline Malate):

• Superior to L-arginine for raising plasma arginine and NO production
• 6-8g citrulline malate improves exercise performance (6-8% more reps, 40% less soreness)
• 3-6g daily reduces blood pressure 4-7 mmHg in prehypertension
• Improves erectile function in mild to moderate ED
• Excellent safety profile with minimal side effects

Beetroot Powder/Extract (High Nitrate Content):

• 400-500mg dietary nitrates reduces blood pressure 4-5 mmHg (systolic)
• Improves endothelial function and arterial stiffness
• Enhances exercise performance, particularly endurance and repeated sprints
• Supports cognitive function in aging populations
• Works through oxygen-independent pathway, complementary to citrulline

S7 Plant Blend:

• 50mg increases NO by 33-54% in clinical studies
• Provides antioxidant protection in addition to NO production
• Very low dose requirement makes it easy to combine with other ingredients

What Does Not Work — Weak or Insufficient Evidence

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L-Arginine Alone: First-pass metabolism makes it far inferior to L-citrulline. Most studies show minimal increase in plasma arginine or NO from oral arginine supplementation.

Sodium Nitrate or Inorganic Nitrates: While they provide nitrate, they lack the polyphenols and phytonutrients from whole food sources like beetroot. Research shows beetroot juice and high-nitrate diets outperform isolated nitrate salts.

“NO Precursor” Blends Without Listed Doses: Proprietary blends are often underdosed. If a product will not tell you how much citrulline or nitrate it contains, assume it is not enough.

Practical Recommendations by Goal

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For Athletes and Exercise Performance:

• Primary: 6-8g citrulline malate 30-60 minutes pre-workout
• Optional Add: 300-500mg beetroot nitrates pre-workout for dual-pathway support
• Stack: Combine with creatine, beta-alanine, and caffeine for comprehensive performance support

For Cardiovascular Health and Blood Pressure:

• Primary: 3-6g L-citrulline daily OR 400-500mg dietary nitrates from beetroot
• Optional Add: S7 (50mg) for antioxidant support
• Important: Monitor BP at home, inform physician if on BP meds

For Erectile Function:

• Primary: 3-6g L-citrulline daily
• Combine With: Lifestyle changes (exercise, weight loss, stress management)
• Caution: Consult physician if taking PDE5 inhibitors

For Aging Adults (40+):

• Primary: 400-500mg dietary nitrates from beetroot daily
• Rationale: NO production declines significantly after 40; beetroot supports both cardiovascular and cognitive function
• Combine With: Omega-3s, CoQ10, and regular exercise

Where to Buy Quality Supplements

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Based on the research discussed in this article, here are some high-quality options:

• Omega-3 Supplement
• Magnesium Supplement
• Turmeric Supplement
• Creatine Supplement
• L-Theanine Supplement

Common Questions About Nitric

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What are the benefits of nitric?

Nitric has been studied for various potential health benefits. Research suggests it may support several aspects of health and wellness. Individual results can vary. The strength of evidence differs across different claimed benefits. More high-quality research is often needed. Always review the latest scientific literature and consult healthcare professionals about whether nitric is right for your health goals.

Is nitric safe?

Nitric is generally considered safe for most people when used as directed. However, individual responses can vary. Some people may experience mild side effects. It’s important to talk with a healthcare provider before using nitric, especially if you have existing health conditions, are pregnant or nursing, or take medications.

How much nitric should I take?

The appropriate dosage of nitric can vary based on individual factors, health goals, and the specific product formulation. Research studies have used different amounts. Always start with the lowest effective dose and follow product label instructions. Consult a healthcare provider for personalized dosage recommendations based on your specific needs.

What are the side effects of nitric?

Most people tolerate nitric well, but some may experience mild side effects. Common reported effects can include digestive discomfort, headaches, or other minor symptoms. Serious side effects are rare but possible. If you experience any unusual symptoms or reactions, discontinue use and consult a healthcare provider. Always inform your doctor about all supplements you take.

When should I take nitric?

The optimal timing for taking nitric can depend on several factors including its absorption characteristics, potential side effects, and your daily routine. Some supplements work best with food, while others are better absorbed on an empty stomach. Follow product-specific guidelines and consider consulting a healthcare provider for personalized timing recommendations.

Can I take nitric with other supplements?

Nitric is a topic of ongoing research in health and nutrition. Current scientific evidence provides some insights, though more studies are often needed. Individual responses can vary significantly. For personalized advice about whether and how to use nitric, consult with a qualified healthcare provider who can consider your complete health history and current medications.

How long does nitric take to work?

The time it takes for nitric to work varies by individual and depends on factors like dosage, consistency of use, and individual metabolism. Some people notice effects within days, while others may need several weeks. Research studies typically evaluate effects over weeks to months. Consistent use as directed is important for best results. Keep a journal to track your response.

Who should not take nitric?

Nitric is a topic of ongoing research in health and nutrition. Current scientific evidence provides some insights, though more studies are often needed. Individual responses can vary significantly. For personalized advice about whether and how to use nitric, consult with a qualified healthcare provider who can consider your complete health history and current medications.

Conclusion: Nitric Oxide Supplementation Is Backed by Decades of Science

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Unlike many trendy supplements that fade when the research catches up to the marketing, nitric oxide boosters have only become more validated over time. The Nobel Prize in 1998 for discovering NO’s role in cardiovascular health opened the door to thousands of studies examining how to support this critical signaling molecule.

The evidence is clear: L-citrulline and beetroot/dietary nitrates are effective, safe, and well-studied interventions for supporting nitric oxide production, with measurable benefits for blood pressure, endothelial function, exercise performance, and overall cardiovascular health.

Key Takeaways:

1. L-citrulline is superior to L-arginine due to better bioavailability (bypasses first-pass liver metabolism)
2. Beetroot provides nitrates that work through a different pathway, offering complementary benefits
3. Effective doses matter: 6-8g citrulline malate for performance, 400-500mg nitrates for cardiovascular health
4. NO supplements can interact with blood pressure and ED medications — inform your physician
5. Lifestyle factors are critical: exercise boosts NO production, while mouthwash and smoking destroy it
6. Start with one well-dosed ingredient rather than complicated multi-ingredient blends with unclear amounts

For most people looking to support cardiovascular health, improve exercise performance, or simply optimize an aging cardiovascular system, nitric oxide supplementation — particularly L-citrulline or beetroot — represents one of the most evidence-based interventions available.

As always, supplements work best as part of a comprehensive approach that includes whole foods, regular exercise, stress management, and appropriate medical care. But when it comes to supporting the molecule that won a Nobel Prize, the science is on your side.

Sources

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• Acute L-Citrulline Supplementation Increases Nitric Oxide Bioavailability - PMC
• Oral supplementation with a combination of l-citrulline and l-arginine rapidly increases plasma l-arginine concentration and enhances NO bioavailability - ScienceDirect
• Supplemental Citrulline Is More Efficient Than Arginine in Increasing Systemic Arginine Availability in Mice - PMC
• Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism - PMC
• Ergogenic effects of a 10-day L-citrulline supplementation - Frontiers
• Seven-day dietary nitrate supplementation improves macrovascular function in postmenopausal women - Frontiers
• The effects of dietary nitrate on blood pressure and vascular health: An umbrella review and updated Meta-Analysis - ScienceDirect
• Dietary Nitrate Supplementation and Exercise Performance: An Umbrella Review - PMC
• Twelve-week nitrate-rich beetroot extract supplementation improves lower limb vascular function - PubMed
• Effects of Beetroot Juice on Physical Performance - PMC
• Beetroot Juice Supplementation as a Healthy Aging Strategy - MDPI
• The Role of Nitric Oxide in Erectile Dysfunction - PMC
• Development and therapeutic applications of nitric oxide releasing materials to treat erectile dysfunction - PMC
• S7 Boost Nitric Oxide Production - FutureCeuticals
• A Double-blind, Placebo-controlled Study on S7 and Nitric Oxide - ResearchGate