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What are the potential interactions between HMB and ACE inhibitors in older adults?
Executive summary
HMB (β‑hydroxy‑β‑methylbutyrate) is a nutritional supplement studied for preserving muscle in older adults, while ACE inhibitors are widely used first‑line antihypertensives in the elderly with specific renal and cardiovascular considerations (ACE inhibitors are recommended first‑line alongside CCBs and thiazides) [1] [2]. Available sources in the provided set do not mention direct pharmacologic interactions between HMB and ACE inhibitors; they describe HMB’s role in muscle outcomes and ACE inhibitors’ benefits/risks in older adults but do not report documented drug–supplement interactions [1] [3].
1. Why this question matters: muscle preservation and polypharmacy in older adults
Sarcopenia and frailty are clinical priorities in older adults, and HMB is being evaluated as an adjunct to resistance training to improve muscle quality, body composition and function in that population [1]. At the same time, ACE inhibitors are commonly prescribed to older patients for hypertension, heart failure, and chronic kidney disease and are endorsed among first‑line antihypertensive classes in recent guidelines [2] [3]. Because older patients frequently take multiple medicines and supplements, clinicians and patients rightly worry about interactions that could alter blood pressure control, kidney function, or muscle effects [2] [1].
2. What the reviewed evidence says about HMB itself
A recent systematic review/meta‑analysis in older adults examines HMB combined with resistance training vs resistance training alone and focuses on muscle quality, body composition, and physical function; this body of research positions HMB as a nutritional adjunct rather than a prescription drug [1]. The available summary in the provided sources emphasizes exercise‑nutrition synergy but does not discuss systemic pharmacodynamics that would plausibly interact with RAAS‑modulating drugs like ACE inhibitors [1].
3. What the reviewed evidence says about ACE inhibitors in older adults
Multiple guideline and review sources show ACE inhibitors are an important, often first‑line class for treating hypertension and related conditions in the elderly; they improve organ perfusion and have class benefits across cardiovascular and renal indications [4] [5] [2] [3]. The 2025 AHA/ACC guideline explicitly lists ACE inhibitors among first‑line agents and discusses their effects on renin and aldosterone physiology—ACE inhibitors can stimulate renin and suppress aldosterone—which is clinically relevant when interpreting biochemical testing or monitoring electrolytes and renal function [2] [6].
4. Direct interaction data: what is — and is not — reported
None of the provided sources report a direct pharmacokinetic or pharmacodynamic interaction between HMB and ACE inhibitors. The HMB systematic review/meta‑analysis does not describe safety signals or interaction data with ACE inhibitors in its summary [1]. The ACE inhibitor literature and guidelines in the supplied set detail drug interactions relevant to ACE inhibitors (e.g., with diuretics, potassium‑sparing agents, or NSAIDs) and physiological effects (renin/aldosterone changes, renal monitoring), but they do not mention HMB [2] [6] [3]. Therefore, available sources do not mention direct HMB–ACE inhibitor interactions.
5. Plausible interaction pathways clinicians consider despite absent direct evidence
Even when specific interaction studies are lacking, clinicians consider general mechanisms: ACE inhibitors can affect renal function and potassium balance, so any supplement that alters renal perfusion, potassium, or fluid status could theoretically modify ACE inhibitor safety or efficacy [6] [3]. HMB is a metabolite of leucine primarily studied for anabolic effects on muscle; the provided sources do not document effects on renal hemodynamics, aldosterone/renin axis, or potassium handling, so there is no mechanistic signal in these references to predict a harmful interaction [1] [3]. Available sources do not mention HMB affecting blood pressure control or RAAS hormones [1].
6. Practical takeaways and recommended precautions
Given the absence of documented interactions in the provided literature, clinicians may reasonably consider HMB as unlikely to directly interfere with ACE inhibitor pharmacology based on current reporting, but they should monitor the usual ACE inhibitor safety parameters—blood pressure, renal function (eGFR/creatinine), and serum potassium—after starting any new supplement in an older patient because guidelines highlight these monitoring needs for ACE inhibitors [2] [6]. If patients have chronic kidney disease, heart failure, or polypharmacy concerns, individualized review is necessary because ACE inhibitor dosing and monitoring are especially important in those groups [2] [3].
7. Where reporting gaps remain and what to watch for
The supplied literature does not include targeted pharmacovigilance or clinical trial data on concomitant HMB plus ACE inhibitor use; therefore, absence of evidence is not proof of no risk. Future randomized trials or post‑marketing safety reports that explicitly collect concomitant supplement use would be needed to confirm safety. Until then, clinicians should document supplement use, counsel patients to report any new symptoms (lightheadedness, muscle pain, changes in urine output), and check routine labs after changes in therapy [6] [1].
If you want, I can draft a short conversation script for clinicians to use when asking older patients about HMB or other supplements and what specific labs to consider monitoring after initiation.