About the original paper
Angelia M. Holland, Ahmed S. Qazi, Kristen N. Beasley, and Hannah R. Bennett (2019) published Blood and cardiovascular health parameters after supplementing with ketone salts for six weeks as Original Research in the Journal of Insulin Resistance. The paper is available in full at the publisher’s site under a Creative Commons Attribution 4.0 license. All four authors are affiliated with the Department of Kinesiology at Augusta University in Augusta, Georgia. The paper runs ten pages and follows a standard randomized double-blinded placebo-controlled design.
The study tested a commercial exogenous ketone salt supplement (KETO//OS MAX, manufactured by Prüvit Ventures, Inc., Melissa, Texas) against a flavor- and calorie-matched placebo (maltodextrin-based, also from Prüvit) in 23 healthy adults aged 18 to 35 years (11 women and 12 men who completed the study). Participants consumed two servings per day for six weeks. Each serving of the KS supplement contained 7 grams of β-hydroxybutyrate combined with erythritol, L-Taurine, fermented L-Leucine, citric acid, natural flavour, vegetable juice colour, stevia, xanthan gum, beta carotene, and approximately 920 mg of sodium. Each serving provided 41 kcal, matched between supplement and placebo.
Measurements included resting blood pressure and heart rate, body mass index, venous blood draws for a comprehensive metabolic panel, lipid panel, and complete blood count, urinalysis, and questionnaires assessing mood and energy. Blood β-hydroxybutyrate levels were measured at baseline and 30 and 60 minutes after acute supplement consumption at both the baseline and post-intervention visits to confirm that the supplement raised circulating ketone levels.
The results were specific. Body mass index did not change in either group. Resting heart rate did not change. The lipid panel, complete blood count, comprehensive metabolic panel, and urinalysis all remained within normal ranges with no clinically significant changes attributable to the supplement. Acute ketone supplementation raised blood β-hydroxybutyrate levels significantly at 30 and 60 minutes post-consumption, confirming that the supplement produced the expected metabolic signal. The headline cardiovascular finding was a statistically significant reduction in systolic blood pressure in the KS group (118.8 ± 8.9 mmHg at baseline to 110.9 ± 9.7 mmHg post-intervention) with no change in the placebo group.
The authors framed the findings as supporting two conclusions: that chronic ketone salt supplementation appears safe in healthy young adults across the measured lab results, and that the systolic blood pressure reduction warrants further investigation in hypertensive populations where the effect might have clinical relevance.
The funding disclosure is central to interpreting the study. The paper states that Prüvit Ventures provided input regarding the study design and that financial support was provided by Prüvit Ventures, Inc. and the College of Education at Augusta University. Prüvit Ventures is the manufacturer of the exact ketone salt supplement tested. Industry funding of research on the manufacturer’s own product is a well-documented risk factor for outcome-reporting bias, even when individual studies are conducted with good intent. The acknowledgments section indicates that the funders did not directly collect or analyze data or write the manuscript, but the broader study design input from the manufacturer is disclosed.
What has been validated since publication
The general claim that exogenous ketone supplementation safely raises circulating β-hydroxybutyrate levels in healthy adults has been substantially confirmed by subsequent research. Acute and chronic supplementation studies consistently document the expected pharmacokinetic signal — ketone salts and ketone esters both raise blood β-hydroxybutyrate, with ketone esters typically producing larger and more sustained elevations than ketone salts (Stubbs et al., 2017; Falkenhain, Islam, & Little, 2023). The basic premise that exogenous ketones produce a measurable metabolic signal is uncontested.
The safety profile observed in the Holland study has held up in subsequent research. Multiple studies of acute and short-duration exogenous ketone supplementation in healthy adults have not identified concerning adverse effects across standard clinical laboratory measures, mirroring the Holland study’s safety findings. The 2023 Falkenhain et al. review in Experimental Physiology summarized the safety literature and identified gastrointestinal tolerance as the most common limitation rather than significant biomarker abnormalities.
Research on the metabolic effects of exogenous ketones has expanded substantially. Walsh, Neudorf, and Little (2021) reported that 14-day ketone monoester supplementation lowered glucose and improved vascular function in adults with overweight or obesity — a different study population and outcome measures than the Holland study, but pointing to potentially meaningful effects of exogenous ketones in specific clinical contexts. Mechanistic research has further established β-hydroxybutyrate as a signaling molecule (Newman & Verdin, 2017) with effects on inflammation, oxidative stress, and gene expression that may have downstream cardiovascular relevance.
The underlying physiological mechanism the Holland study invoked — that β-hydroxybutyrate interacts with sympathetic nervous system receptors and may reduce sympathetic activity, thereby reducing blood pressure — has support in the basic science literature (Kimura et al., 2011). The mechanism is plausible. The clinical question is whether the mechanism produces blood pressure effects of the magnitude the Holland study reported, in populations beyond the small healthy cohort the original study tested.
What has been criticized or remains contested
The headline blood pressure finding has not replicated in subsequent larger pooled analysis. Marcotte-Chénard and colleagues (2024) conducted a systematic review and meta-analysis published in the Journal of Dietary Supplements examining the effects of acute and chronic ingestion of exogenous ketone supplements on blood pressure. The analysis pooled 10 studies with 187 total participants and concluded that exogenous ketone supplementation produced no significant change in systolic or diastolic blood pressure. The pooled analysis is more robust than any individual small study and represents the strongest available evidence on the specific blood pressure question.
The industry funding relationship matters substantially for interpreting the Holland study. Prüvit Ventures funded the research on its own product (KETO//OS MAX). The company also provided input on the study design. Industry funding of research on the funder’s own product is the most reliable predictor of favorable outcome reporting in the broader nutrition supplement literature. The Holland study findings should be read with awareness that the broader category of industry-funded supplement research tends to overstate effect sizes relative to independently funded research, and that the specific finding (blood pressure reduction) did not replicate when pooled with other exogenous ketone research.
The small sample size and short duration limit the conclusions. The KS arm contained 11 participants. The placebo arm contained 12. The intervention lasted six weeks. These parameters are appropriate for a preliminary safety and feasibility study; they are not appropriate for drawing strong conclusions about cardiovascular efficacy. The original paper acknowledged the sample size limitation and called for larger studies in hypertensive populations, which is the appropriate framing for a preliminary finding. Subsequent research has not produced those larger studies in hypertensive populations specifically.
The chosen study population — young, healthy, non-hypertensive adults — limits the clinical generalizability of any blood pressure finding. Healthy young adults typically have well-controlled blood pressure and limited room for clinically meaningful reduction. A finding of approximately 8 mmHg systolic reduction in a small group of young healthy adults is a research observation, not a clinical recommendation that translates directly to hypertensive populations where the actionable question is whether ketone supplements should be considered as part of blood pressure management.
The sodium content of the ketone salt supplement is worth noting in any cardiovascular interpretation. Each serving of KETO//OS MAX provides approximately 920 mg of sodium. Two servings per day add 1,840 mg of sodium. This is a substantial sodium load — close to the AHA-recommended upper limit of 2,300 mg per day from a single supplement. The Holland study reported no change in serum sodium levels and framed this as evidence of metabolic safety. The broader question is whether a supplement contributing this much sodium can simultaneously lower systolic blood pressure — a question that would be relevant if the blood pressure finding had replicated, but is moot since it did not.
Adherence verification was based on patient self-report through a supplement log. The Holland study acknowledges this limitation directly. Self-reported adherence in supplement trials is known to be incomplete, which adds noise to any effect estimate. In a small study with a meaningful effect on systolic blood pressure, this noise may have affected the apparent magnitude of the finding.
The broader exogenous ketone supplement industry has accumulated a research base that the Holland study sits inside. Most of that research has been industry-funded or industry-adjacent, like the Holland study. Independent research on exogenous ketones is comparatively limited. The Marcotte-Chénard 2024 meta-analysis represents an attempt to synthesize the available evidence, including industry-funded studies, into a more reliable estimate of effect sizes. The result of that synthesis on the blood pressure question — no significant effect — is the appropriate primary takeaway in 2026.
What this means for readers in 2026
The headline finding has not held up. The broader exogenous ketone research is more interesting than this specific study.
If you have hypertension and are considering exogenous ketone supplementation specifically for blood pressure management, the available evidence does not support this use. The 2024 Marcotte-Chénard meta-analysis pooled the available exogenous ketone research and found no significant effect on systolic or diastolic blood pressure. The Holland 2019 study’s finding of approximately 8 mmHg systolic reduction has not replicated. The first-line evidence-based interventions for hypertension — dietary changes (DASH or Mediterranean patterns, moderate sodium reduction), regular aerobic exercise, weight management where appropriate, alcohol moderation, and antihypertensive medications where indicated — remain the appropriate management approach.
If you are considering exogenous ketone supplements for performance, weight loss, or general metabolic health (the more common consumer-facing claims for the product category), the broader exogenous ketone research is mixed. Ketone supplementation reliably raises blood β-hydroxybutyrate. The downstream metabolic and performance effects are smaller and more variable than the marketing for these products often suggests. Ketone esters appear more pharmacologically active than ketone salts at comparable doses. The sodium load in ketone salt supplements is meaningful and worth weighing if you take blood pressure medications or have hypertension. Discuss with your physician before adding any supplement to existing medical management.
If you are pursuing a ketogenic diet for type 2 diabetes management (the application supported by stronger clinical evidence — see our reviews of the Fung 2017 case study and Cucuzzella 2017), dietary ketogenesis is not the same as exogenous ketone supplementation. Dietary ketogenesis produces ketones through endogenous fat metabolism in the context of carbohydrate restriction. Exogenous ketones provide circulating ketones without the underlying metabolic shift. The clinical evidence for dietary ketogenesis in T2D management is meaningfully stronger than the evidence for exogenous ketone supplementation for any specific clinical purpose.
If you are evaluating industry-funded supplement research more generally, the Holland 2019 study is a useful example. The study itself was conducted with apparently good intent and reported its findings honestly, including a substantial set of unchanged lab measurements — the standard blood chemistries, cholesterol panel, complete blood count, and urinalysis — alongside the headline positive finding. The industry funding does not invalidate the work. It does mean that the specific finding warrants additional skepticism until replicated by independently funded research — and in this case, subsequent meta-analysis has not replicated the headline finding. The pattern is consistent with the broader nutrition supplement research literature, where industry-funded studies often produce favorable initial findings that do not generalize when pooled with broader evidence.
If you have already been using ketone salt supplements and want to make an evidence-based decision about continuation, the safety profile for short-duration use in otherwise healthy adults is reasonable based on the available evidence. The expected benefits beyond raising circulating ketones are uncertain. The sodium content of ketone salts is worth tracking against your overall sodium intake. The cost is substantial and the evidence base for specific health benefits is thin. The decision is yours and your physician’s; the editorial framing here is that the evidence does not support strong claims about benefit.
The Holland 2019 study captured a moment when interest in exogenous ketone supplements was expanding and industry-funded research was producing preliminary findings that the broader research community had not yet pressure-tested. The blood pressure finding did not survive that pressure test. The broader exogenous ketone research field has continued to advance, with meaningful work on vascular function, glucose responses, and ketones as signaling molecules. The specific cardiovascular claim from this paper has been superseded by stronger pooled evidence. The honest 2026 framing is that the exogenous ketone supplement category has interesting research happening in it, that the Holland blood pressure finding was an early observation that did not match what subsequent research into blood pressure and exogenous ketones has concluded, and that consumers and clinicians should weight the broader meta-analytic evidence above any individual small industry-funded study when making decisions.
References
ElSayed, N. A., Aleppo, G., Bannuru, R. R., et al. (2025). Standards of Care in Diabetes—2025. Diabetes Care, 48(Suppl 1).
Falkenhain, K., Islam, H., & Little, J. P. (2023). Exogenous ketone supplementation: An emerging tool for physiologists with potential as a metabolic therapy. Experimental Physiology, 108(2), 177–187.
Holland, A. M., Qazi, A. S., Beasley, K. N., & Bennett, H. R. (2019). Blood and cardiovascular health parameters after supplementing with ketone salts for six weeks. Journal of Insulin Resistance, 4(1), a47. https://doi.org/10.4102/jir.v4i1.47
Kimura, I., Inoue, D., Maeda, T., et al. (2011). Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proceedings of the National Academy of Sciences USA, 108(19), 8030–8035.
Marcotte-Chénard, A., Tremblay, R., Falkenhain, K., et al. (2024). Effect of acute and chronic ingestion of exogenous ketone supplements on blood pressure: A systematic review and meta-analysis. Journal of Dietary Supplements, 21(3), 408–426.
Newman, J. C., & Verdin, E. (2017). β-Hydroxybutyrate: A Signaling Metabolite. Annual Review of Nutrition, 37, 51–76.
Stubbs, B. J., Cox, P. J., Evans, R. D., et al. (2017). On the metabolism of exogenous ketones in humans. Frontiers in Physiology, 8, 848.
Walsh, J. J., Neudorf, H., & Little, J. P. (2021). 14-day ketone supplementation lowers glucose and improves vascular function in obesity: A randomized crossover trial. The Journal of Clinical Endocrinology & Metabolism, 106(4), e1738–e1754.