On this page
Key takeaways
• No human trial has measured blood pressure changes with fisetin supplementation. The evidence is entirely preclinical.
• Preclinical data suggest mild vasorelaxant effects — the 2025 Mahoney preprint reported that intermittent fisetin partially reversed age-related endothelial dysfunction in 27-month-old mice (2).
• Related flavonoids (quercetin, kaempferol) have shown modest blood pressure reductions in meta-analyses of human trials (4) — suggesting a class effect that may extend to fisetin.
• The Krishnakumar 2022 pharmacokinetic study reported no significant blood pressure changes after single doses of unformulated fisetin in 15 healthy adults (3).
• Fisetin is not a substitute for antihypertensive medication. Patients with hypertension should continue their prescribed regimen; any blood pressure effects of fisetin are modest at best.
• Patients on antihypertensives should discuss fisetin with their prescriber and monitor home blood pressure in the first month after starting.
Quick answer
No human clinical trial has directly measured blood pressure changes with fisetin supplementation. The preclinical data suggest fisetin has mild vasorelaxant effects, consistent with the broader flavonoid class. The Krishnakumar 2022 human pharmacokinetic study reported no significant blood pressure changes after single doses (3). If fisetin lowers blood pressure in humans at all, the effect is likely modest — comparable to the small BP reductions seen with dietary flavonoid interventions, on the order of 2–5 mmHg. Fisetin should not be used as an antihypertensive treatment and should not substitute for prescribed medication. Patients on antihypertensives should discuss fisetin with their prescriber before starting. This article walks through the preclinical evidence, the human data gap, and the practical guidance. For the broader safety picture, see our side effects and safety article.
The two reader questions
This article is written to answer two questions that arrive in reader emails with roughly equal frequency.
"Can fisetin raise my blood pressure?" Usually asked by patients with well-controlled hypertension worried about adding a supplement that might destabilise their regimen. The short answer: no established mechanism or clinical evidence supports this concern.
"Can fisetin lower my blood pressure?" Usually asked by patients who have seen marketing claims about flavonoid benefits for cardiovascular health and are wondering if fisetin can substitute for or supplement antihypertensive treatment. The short answer: preclinical evidence supports a mild vasorelaxant effect, but no controlled human trial has demonstrated a meaningful BP reduction, and fisetin should not be used as antihypertensive treatment.
The honest picture is that fisetin’s effect on human blood pressure has not been characterised in any published randomised trial. The claims in both directions rest on extrapolation from preclinical data and from related flavonoids, not on direct evidence.
The preclinical case for vasorelaxant effects
Fisetin has documented activity on several vascular pathways in preclinical models, and the 2025 Mahoney preprint made the most specific case yet for a fisetin-endothelium link (2).
The 2025 Mahoney preprint — endothelial dysfunction reversal
Mahoney and colleagues (bioRxiv, 2025) reported that intermittent fisetin at the mouse equivalent of the human pulsed protocol partially reversed age-related endothelial dysfunction in 27-month-old mice (2). The mechanism they identified was suppression of the SASP factor CXCL12 in aged vascular tissue. This is a mechanistically coherent story: aged vascular endothelium accumulates senescent cells that secrete inflammatory factors, which impair nitric oxide production and produce the endothelial dysfunction underlying much age-related hypertension. Fisetin’s senolytic activity clears the senescent cells; the vascular tone improves; the mice show improved endothelium-dependent vasodilation.
This is a preprint. It has not yet been peer reviewed, and its conclusions may change on peer review. It is also a mouse study — the human vascular biology may respond differently. But it is the most specific mechanistic case for a fisetin blood pressure effect, and it aligns with the general senolytic hypothesis being tested in the ongoing Mayo Clinic trials.
The broader flavonoid class
Fisetin’s closest chemical relatives — quercetin, kaempferol, myricetin — have been more extensively studied for blood pressure effects. Meta-analyses of quercetin supplementation trials have reported small but statistically significant systolic BP reductions of roughly 3–5 mmHg, more pronounced in hypertensive patients than in normotensive volunteers (4). The mechanism appears to involve mild endothelial nitric oxide enhancement, mild ACE inhibition, and modest antioxidant activity in vascular tissue (6). Whether fisetin produces a similar class effect at supplement doses in humans is unstudied but plausible.
The human data — what has and has not been measured
Direct measurement of blood pressure effects of fisetin in a controlled human trial has not been published. Three data points are worth naming.
The Krishnakumar 2022 pharmacokinetic study
The 15 healthy adults who received single doses of 1,000 mg fisetin (unformulated) or 192 mg fisetin (hydrogel) did not experience clinically significant blood pressure changes during the 12-hour observation period (3). This was not the primary endpoint of the study, and the sample size was small, but it provides preliminary evidence that single-dose fisetin at these levels does not produce acute blood pressure effects in healthy adults.
The COVID-FIS trial
The COVID-FIS trial in nursing home residents captured routine vital sign monitoring, including blood pressure. Preliminary safety data (posted to ClinicalTrials.gov in August 2025) reported no blood pressure signals of concern in the fisetin-treated arm compared to placebo. Full published analysis is pending (1). This is the closest available human evidence for blood pressure safety.
AFFIRM and other ongoing trials
The AFFIRM trial protocol includes cardiovascular endpoints as secondary outcomes, including some vascular function measures. When AFFIRM publishes, it will provide the first randomised, controlled data specifically on how fisetin affects cardiovascular parameters in frail older women (5).
Practical guidance for patients on antihypertensives
For patients with hypertension who are considering fisetin supplementation, the practical guidance is straightforward.
Continue your prescribed antihypertensive regimen unchanged. Fisetin is not a substitute for prescribed medication, and any potential BP effect is likely too small to justify medication adjustment.
Discuss fisetin with your prescriber before starting. They may want to know the specific supplement, the dose, and the intended purpose. Some prescribers will have no concern; others may prefer you defer starting until BP is stable.
Monitor home BP for the first four weeks after starting fisetin. If your BP drifts meaningfully in either direction, inform your clinician. Modest reductions may be beneficial and welcomed; substantial reductions in a patient already on antihypertensive treatment could indicate additive hypotensive effect and warrant dose adjustment.
Avoid combining fisetin with new-onset antihypertensive treatment in the same week. If you are starting a new BP medication, wait until your regimen is stable (typically 2–4 weeks) before adding fisetin, so any BP changes can be clearly attributed.
Be aware of postural hypotension. If you experience lightheadedness after starting fisetin, particularly on standing, this may reflect mild additive hypotensive effect. Slow position changes, adequate hydration, and clinician discussion are the sensible responses.
What we still don't know
• Whether fisetin produces measurable blood pressure changes in humans at any dose. No RCT has directly measured this.
• Whether the endothelial-dysfunction reversal seen in the Mahoney 2025 mouse preprint translates to human vascular biology. The preprint has not yet been peer reviewed (2).
• Whether pulsed versus continuous fisetin dosing produces different blood pressure effects. Different pharmacokinetic profiles may yield different vascular responses.
• Whether fisetin’s theoretical BP effect is additive with antihypertensive medications or independent. Not characterised in any interaction study.
• Whether specific patient subgroups (older adults, patients with baseline endothelial dysfunction, patients with metabolic syndrome) respond differently. The AFFIRM population, when it publishes, will begin to address this.
Bottom line
Fisetin has preclinical evidence supporting mild vasorelaxant effects and endothelial function improvement, most recently in the Mahoney 2025 mouse preprint (2). No human trial has directly measured blood pressure changes with fisetin supplementation. If fisetin lowers BP in humans, the effect is likely small — comparable to what is seen with dietary flavonoid interventions. Fisetin is not a substitute for prescribed antihypertensive treatment. Patients on antihypertensives should discuss fisetin with their prescriber before starting and should monitor home BP in the first month. Patients with well-controlled hypertension can typically add fisetin without concern; patients starting new BP medication should defer fisetin until their regimen is stable. For the broader safety picture, see our side effects and safety article and drug interactions article.
Frequently asked questions
Can fisetin raise my blood pressure?
No known mechanism or clinical evidence supports this concern. Fisetin’s general vascular activity is vasorelaxant rather than pressor.
Does fisetin lower blood pressure?
Preclinically, mild vasorelaxant effects have been described. No human RCT has demonstrated meaningful BP reduction. Any effect is likely small.
Can I take fisetin if I have hypertension?
Yes, generally — but continue your prescribed medication, discuss with your prescriber before starting, and monitor home BP for the first month.
Should I take fisetin instead of my BP medication?
No. Fisetin is not a substitute for prescribed antihypertensive treatment. Stopping prescribed medication in favour of a supplement risks poorly controlled BP and cardiovascular complications.
Does fisetin affect heart rate?
No documented effect on heart rate in the Krishnakumar 2022 study (3) or in COVID-FIS safety monitoring. Some flavonoids modestly modulate autonomic tone; fisetin’s specific effect on heart rate is not characterised.
Can fisetin cause palpitations?
Very rare anecdotal reports exist. Not established as a fisetin-specific effect. Anxiety, caffeine, and general flavonoid stimulant-like effects are more common explanations.
Is fisetin safe with beta blockers or ACE inhibitors?
No documented interaction. Combination has been used without concerning reports. Monitor BP after adding fisetin to an established antihypertensive regimen.
References
1. Verdoorn BP, Evans TK, Hanson GJ, et al. Fisetin for COVID-19 in skilled nursing facilities: senolytic trials in the COVID era. J Am Geriatr Soc. 2021;69(11):3023-3033. https://pmc.ncbi.nlm.nih.gov/articles/PMC8447437/
2. Mahoney SA, Mazan-Mamczarz K, Tsitsipatis D, et al. Senolytic treatment with fisetin reverses age-related endothelial dysfunction partially mediated by SASP factor CXCL12. bioRxiv (preprint). 2025. https://doi.org/10.1101/2025.08.13.670216
3. Krishnakumar IM, Jaja-Chimedza A, Joseph A, et al. Enhanced bioavailability and pharmacokinetics of a novel hybrid-hydrogel formulation of fisetin orally administered in healthy individuals. J Nutr Sci. 2022;11:e74. https://doi.org/10.1017/jns.2022.72
4. Larson AJ, Symons JD, Jalili T. Therapeutic potential of quercetin to decrease blood pressure: review of efficacy and mechanisms. Adv Nutr. 2012;3(1):39-46. https://pmc.ncbi.nlm.nih.gov/articles/PMC3262612/
5. AFFIRM: Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Women (NCT03430037). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT03430037
6. Khan N, Syed DN, Ahmad N, Mukhtar H. Fisetin: a dietary antioxidant for health promotion. Antioxid Redox Signal. 2013;19(2):151-162. https://pmc.ncbi.nlm.nih.gov/articles/PMC3689181/
7. Kim JA, Lee S, Kim DE, et al. Fisetin, a dietary flavonoid, induces apoptosis of cancer cells by inhibiting HSF1 activity through blocking its binding to the hsp70 promoter. Carcinogenesis. 2015;36(6):696-706. https://pubmed.ncbi.nlm.nih.gov/25896443/
8. Ivey KL, Hodgson JM, Croft KD, et al. Flavonoid intake and all-cause mortality. Am J Clin Nutr. 2015;101(5):1012-1020. https://pubmed.ncbi.nlm.nih.gov/25948669/