Sodium Nitrate May Block Heart Benefits of Exercise in Women

Here’s a finding that complicates one of the supplement world’s biggest success stories. Researchers at Dalhousie University have shown that sodium nitrate — the active compound in beetroot juice and those concentrated shots sold to runners, cyclists, and gym-goers everywhere — may prevent, rather than promote, the heart’s healthy adaptation to exercise. And here’s the twist: the effect appears to be specific to females.

Published in Scientific Reports back in May 2026, the study gave female mice water laced with sodium nitrate at a concentration roughly equivalent to what a human might get from a daily beetroot shot. Those mice lost nearly all the beneficial cardiac remodeling that normally comes with regular running. Their male counterparts? Little change either way. Elise Bisset, a former PhD student in the lab of pharmacologist Dr. Susan Howlett at Dalhousie, led the paper. Howlett’s group has spent years digging into sex differences in cardiac aging.

“We expected nitrates and exercise to work together to improve heart health,” Howlett said. “Instead, in females, the supplement prevented many of the positive cardiac adaptations normally produced by exercise.”

A $15 billion assumption

This result isn’t just a lab curiosity. It lands smack in the middle of a supplement market that’s ballooned on the premise that dietary nitrate — typically consumed as concentrated beetroot juice — improves endurance, drops blood pressure, and makes exercise feel easier. Grand View Research pegs the global beetroot juice market at roughly $14.7 billion in 2023, growing 6.5 percent annually toward an estimated $22.7 billion by 2030. The International Olympic Committee counts nitrate among the few supplements with evidence backing its ergogenic effects. Walk into any running store or scroll through a fitness influencer’s Amazon storefront and you’ll find Beet It shots, SuperBeets powders, generic nitrate capsules — all marketed with the same core promise: more nitric oxide, better performance, for everyone.

To understand why the Dalhousie finding feels so counterintuitive — and why it matters — it helps to know what nitrate is supposed to do once it enters the body.

How nitrate becomes nitric oxide

The nitrate–nitrite–nitric oxide pathway works as a cascade of reductions. Dietary nitrate, whether from a handful of arugula or a two-ounce beetroot shot, gets absorbed into the bloodstream through the small intestine and then concentrated in saliva. Bacteria on the dorsal surface of the tongue reduce it to nitrite, which gets swallowed and re-enters circulation. When that circulating nitrite reaches tissues where oxygen tension is low — think skeletal muscle midway through a threshold interval — it gets reduced one final time, to nitric oxide.

Nitric oxide is a gas that functions as a signaling molecule. It relaxes the smooth muscle lining blood vessels, widening them and improving blood flow. It lowers the oxygen cost of muscular contraction by improving mitochondrial coupling efficiency — meaning you use less oxygen to produce the same amount of ATP. It also reduces the buildup of metabolites linked to fatigue. In theory, and in many published trials, more dietary nitrate means more circulating nitrite, and more nitrite means more nitric oxide available precisely where and when it’s needed most.

That theory has held up, at least partly, in human studies. A 2018 meta-analysis in Sports Medicine reported a moderate ergogenic effect across 80 trials. Endurance athletes, in particular, seemed to benefit. The mechanism was biologically plausible. The supplement was cheap and natural. By the early 2020s, beetroot juice had become the rare supplement that both scientists and coaches could agree on.

But here’s where things get complicated. Virtually all of that positive evidence came from studies done in men.

The sex-data gap

When researchers have looked specifically at women, the picture gets far murkier — and increasingly concerning. A 2019 review in Applied Physiology, Nutrition, and Metabolism by Kate Wickham and Lawrence Spriet, titled “No longer beeting around the bush,” flagged the near-total absence of female-specific nitrate data and called it “a substantial gap in the literature.” The review catalogued dozens of studies that had built nitrate’s ergogenic reputation and noted an uncomfortable pattern: nearly all the participants were male.

That warning was prescient. A 2020 meta-analysis re-examined those same 80 studies, this time breaking the data down by sex. The ergogenic effect of nitrate was present in male-only and mixed-sex studies — but it wasn’t statistically significant in the six female-only trials that existed at the time. The effect size for women was negligible (d=0.116, p=0.347). Small sample, sure, but the direction wasn’t encouraging.

Then the data got worse. In 2023, a study led by Ortiz de Zevallos and colleagues tested acute beetroot juice supplementation in healthy young women. Far from improving endurance, nitrate reduced time to exhaustion by about 48 seconds — a roughly 10 percent worsening of performance (P=0.04). The effect held independent of menstrual cycle phase, which ruled out a simple hormonal confound. A follow-up published in 2024 in the Journal of Applied Physiology confirmed that nitrate didn’t improve muscular power or endurance in either sex, but showed moderate-to-large effect sizes suggesting differentiated — and possibly opposing — responses between men and women.

What the Dalhousie study adds

The Dalhousie paper extends this picture from acute performance to chronic cardiac adaptation. Over 12 weeks, the researchers divided mice into four groups — male runners, female runners, male sedentary, female sedentary — and gave each group either plain water or water containing 1 mM sodium nitrate. The running animals had voluntary access to a wheel, and as expected, exercise alone produced measurable improvements in heart structure, ventricular function, and calcium handling. But when female runners also received nitrate, those improvements largely vanished. In males, the supplement had minimal effects on cardiac outcomes either way.

Elise Bisset and colleagues measured several parameters. Exercise increased heart mass and improved the heart’s ability to contract and relax — adaptations well-documented in the exercise physiology literature and linked to lower cardiovascular risk. Nitrate supplementation, when combined with exercise in female mice, prevented those adaptations from happening. The sedentary females given nitrate showed no cardiac changes, suggesting the effect is specific to the interaction between nitrate and exercise-induced signaling.

The mechanism isn’t fully understood yet, but the researchers suspect it involves crosstalk between nitrate-derived nitric oxide and estrogen signaling. Females have higher baseline nitric oxide bioavailability than males, likely due in part to estrogen’s role in upregulating endothelial nitric oxide synthase, the enzyme that produces nitric oxide from L-arginine. Add more nitric oxide precursors on top of an already-optimized system and you may push past a threshold where the signal stops being beneficial and starts interfering with the cellular pathways that drive exercise-induced cardiac remodeling — including calcium handling proteins and mitochondrial biogenesis pathways critical to the heart’s adaptive response to training.

This fits a broader pattern emerging from the nitrate literature. Women may not need supplemental nitrate because their endogenous nitric oxide production is already operating near its functional ceiling. Add more and it may not just fail to help — it may actively disrupt.

What this means, and what it doesn’t

Important limitations deserve a clear airing. This was a mouse study, not a human randomized controlled trial. The dose, while designed to be physiologically relevant, was delivered continuously in drinking water rather than as a pre-workout bolus — which is how most people actually consume beetroot juice. And the study measured cardiac structural adaptations in healthy mice, not hard performance outcomes or clinical cardiovascular events in athletes. Too early to say with any confidence that sodium nitrate blunts cardiac adaptation in exercising women. The finding needs replication — first in another animal model, then eventually in a human trial designed to track cardiac remodeling over months of training, ideally using echocardiography or cardiac MRI.

Yet the direction of the evidence, taken as a whole, gets harder to dismiss with each new study. A 2019 review warning of a data gap. A 2020 meta-analysis showing no benefit in women. A 2023 human trial showing a 10 percent worsening of endurance capacity. A 2024 follow-up suggesting sex-divergent responses. And now a 2026 mechanistic study showing that chronic nitrate supplementation blocks exercise-induced cardiac remodeling in female mice. These studies, from different labs using different methods and different species, converge on a message the supplement industry hasn’t yet incorporated into its labeling: nitrate may not work the same way in women.

Where the research goes next

Bisset, now a postdoctoral fellow at the Université de Montréal, and Howlett are among a growing group of exercise physiologists calling for mandatory sex-based analysis in supplement research. The Dalhousie news release notes the lab is continuing to investigate mechanisms — including the potential role of the oral microbiome (the tongue bacteria that perform the first reduction step) and the specific estrogen-nitric oxide crosstalk pathways that may underlie the sex difference.

Several other groups are contributing pieces to the puzzle. Researchers at Penn State published a 2025 paper in Food & Function examining the stability of nitrate-derived nitric oxide under different estrogen conditions. Groups in the UK and Australia are conducting the first female-only nitrate training studies with cardiac imaging endpoints. Results are expected within the next two to three years.

For now, the practical takeaway is modest but worth stating clearly. If you’re a woman who takes beetroot juice or nitrate capsules hoping to get more out of your workouts, the evidence base supporting that decision is thinner than the marketing suggests — and a small but growing body of research indicates it might, in some contexts, be working against you. The supplement industry doesn’t disaggregate its claims by sex, and the products lining the shelves at your local health food store were tested, if they were tested at all, mostly on men.

That doesn’t mean you should toss your beetroot shots. Dietary nitrate from whole foods — beets, spinach, arugula, celery — remains associated with lower blood pressure and improved vascular function in large epidemiological studies that include both sexes. The concern is specific to concentrated, supplemental doses taken chronically, particularly in the context of exercise training. Until the human trials catch up to the mouse data, women are making decisions about nitrate supplementation with incomplete information. If you’re unsure, the safest path is to prioritize whole-food nitrate sources and talk to your doctor before starting any supplement regimen.

References

1. Bisset E, Howlett SE, et al. Sodium nitrate supplementation prevents beneficial cardiac adaptations to running in female mice with few effects on male hearts. Scientific Reports. 2026. https://www.nature.com/articles/s41598-026-50082-4
2. Wickham KA, Spriet LL. No longer beeting around the bush: a review of potential sex differences with dietary nitrate supplementation. Appl Physiol Nutr Metab 44(9):915-924. 2019. https://pubmed.ncbi.nlm.nih.gov/31348674/
3. Ortiz de Zevallos J, et al. The effects of inorganic nitrate supplementation on exercise economy and endurance capacity across the menstrual cycle. J Appl Physiol. 2023. https://pubmed.ncbi.nlm.nih.gov/37732374/
4. Lundberg JO, Weitzberg E, Gladwin MT. The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov 7(2):156-167. 2008. https://pmc.ncbi.nlm.nih.gov/articles/PMC13003460/