Research Spotlight: Dietary nitrate is powerful stuff

Research Spotlight articles share concise breakdowns of interesting studies. The study reviewed is "Effect of Dietary Nitrate on Human Muscle Power: A Systematic Review and Individual Participant Data Meta-Analysis" by Coggan et al. (2021)

I know that title sounds like a brazen exaggeration, so please allow me to clarify: that title is a pun – this Research Spotlight is about the effects of dietary nitrate on power outcomes. While I’d rather protect my credibility than overstate the effects of dietary nitrate, it’s no secret that I am quite intrigued by nitrate. It was a major focus of my dissertation research, and I’ve written about it in MASS several times (onetwothreefour – subscription required to view). Ingested dietary nitrate can be converted to nitrite, which can then be converted to nitric oxide. Nitric oxide is generally known for its ability to increase vasodilation and blood flow, but evidence also suggests that increasing nitric oxide availability can reduce the energy cost of exercise, enhance the contractile function of muscle, increase cellular glucose uptake, and attenuate muscle fatigue. When looking more closely at mechanisms related to muscle function, it appears that nitric oxide can primarily impact contractility by increasing ryanodine receptor nitrosylation and guanylyl cyclase activity. This should result in increased calcium release from the sarcoplasmic reticula and greater myofibrillar calcium sensitivity, and should ultimately lead to increased force production, shortening velocity, and power output during explosive muscle actions.

For the presently reviewed meta-analysis, the researchers systematically searched for randomized, double-blind, placebo-controlled, crossover studies to determine if acute (single-dose) or chronic (5-6 days) nitrate supplementation significantly impacts maximal power outcomes. However, this wasn’t just any old meta-analysis. When performing a meta-analysis on “within-subject” data (such as studies with a pre-test and a post-test, or crossover studies in which each participant completes both the experimental condition and the placebo condition), it’s very advantageous to mathematically account for the within-subject correlation. It’s rarely feasible to account for this correlation for every single study within a meta-analysis, because the within-subject correlation is rarely reported directly in studies, and many studies report their results in a way that makes it impossible to back-calculate this value. In this scenario, the meta-analyst has three options: ignore the correlation, assume its value, or track down the authors to either obtain the value of the correlation or the raw, participant-level data. These researchers chose the latter option, and only included studies where they could calculate the actual within-participant correlation or obtain the raw data for all study participants. This falls under the umbrella of individual participant data meta-analyses; they’re unequivocally better than traditional, summary data meta-analyses, and aggregation of participant-level data can lead to some very cool insights, but they’re uncommon because they’re logistically hard to complete.

The analysis included data from 268 participants (218 men, 50 women) across 19 studies. Nitrate doses ranged from 6.4mmol (~400mg) to 15.9mmol (~1000mg), and were generally consumed in the form of concentrated beetroot juice. Effect sizes naturally varied from study to study, and there were plenty of non-significant findings in the mix, but it’s interesting to note that all 19 studies reported a positive effect size (favoring nitrate over placebo). Acute nitrate supplementation led to a statistically significant increase in maximal power production (effect size [ES] = 0.54, p < 0.0001; Figure 1), and chronic supplementation did as well (ES = 0.22, p = 0.004; Figure 2). Combining them together, this results in an overall effect size of ES = 0.42 (if you prefer the fixed-effect model) or ES = 0.45 (if you prefer the random-effects model), with a statistically significant average improvement of around 5%. Statistical heterogeneity was low, despite the fact that the participant pool ranged from heart failure patients to older adults to Olympic athletes. Nonetheless, two of the three smallest effect sizes came from studies sampling highly trained sprinters, and previous reviews have noted that effect sizes tend to be a bit smaller (but still generally positive) in participants of advanced training status. 

Subgroup analyses found that results were not significantly impacted by age, sex, or test modality (muscle actions of small versus large muscle groups), but the effect size for chronic dosing was significantly smaller than the effect size for acute dosing (p = 0.021). This contradicts other nitrate research, which generally indicates that chronic dosing protocols lead to effects that are similar or better than acute protocols. I wouldn’t get too carried away with this particular finding in the current meta-analysis, as only four studies with chronic dosing strategies met inclusion criteria, and the largest of the four (which carries the most weight for the analysis) included several participants of very advanced training status. At this point, the preponderance of the evidence across varied exercise outcomes suggests that chronic supplementation yields effects that are as good, if not better, than single-dose nitrate supplementation strategies.

Overall, this meta-analysis was conducted quite rigorously, and indicates that nitrate increases maximal power output by around 5% on average, which can be practically meaningful depending on the context. Nitrate is not a complete game changer, but there’s now some pretty good evidence that dietary nitrate can modestly enhance strength, strength endurance, and power output, so it’s a nutrient of interest for lifters. I still have reservations about quality control among commercially available nitrate and beetroot supplements, and the few beetroot supplements that repeatedly stand up to third-party verification of nitrate content tend to be pretty costly (in many contexts, costly enough to meaningfully impact the individualized cost-benefit analysis that should always precede supplementation decisions). As such, I think the best way to seek out the potential ergogenic effects of nitrate is to aim for a daily intake of 400-800mg from nitrate-rich fruits and vegetables (such as celery, beets, spinach, rocket [arugula], pomegranates, and more). If you wish to add some supplementation into the mix, there’s reason to believe that consuming 4-6g of citrulline (or 6-9g of citrulline malate) about an hour before workouts would complement this strategy quite nicely.

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