What doses and formulations of propolis or honey were used in human studies and what safety concerns exist for older adults?
Executive summary
Human trials of propolis have used widely varying doses and formulations: common oral ranges run from 250 mg twice daily (500 mg/day) to 900 mg/day, with some trials and meta-analyses reporting practical study doses between ~400–1,500 mg/day and effects at ≥1,000 mg/day for certain biomarkers [1] [2] [3] [4]. Safety discussions point to an often-cited “safe” extrapolated level of about 70 mg/day for general humans but also note clinical studies using much higher doses with acceptable tolerability; potential risks for older adults include allergic reactions, renal perfusion concerns from CAPE (a propolis constituent), interactions with drugs (including warfarin/CYP enzymes), and contamination/adulteration issues [5] [6] [7] [4].
1. What human studies actually used — doses and formulations
Clinical trials and reviews show no single standard. Randomized trials have used tablet extracts of propolis at 250 mg twice daily for 12 weeks (total 500 mg/day) in metabolic‑syndrome participants [1]. A high‑profile COVID-19 randomized trial used a standardized Brazilian green propolis extract (EPP‑AF®) at 900 mg/day and reported compositional details (flavonoids/phenolics) alongside clinical outcomes [2]. Systematic reviews and meta‑analyses compile studies whose practical dosing spans roughly 400–1,500 mg/day; one meta‑analysis found MDA reductions notably at doses ≥1,000 mg/day [3] [4]. Reviews also describe diverse extract types (ethanolic, aqueous, standardized green propolis, country‑specific propolis) and non‑oral uses (topical dental/dermal preparations) without uniform active‑component standardization [8] [9].
2. Formulation matters — standardization and geographic variation
Propolis composition varies by geography, plant sources and extraction methods; Brazilian green and Chinese propolis are repeatedly named in human and animal studies, and some trials use standardized extracts (for example EPP‑AF®) to ensure batch reproducibility and report flavonoid/phenolic content per dose [2] [9]. Reviews emphasize the challenge this poses for comparing trials and for dose translation because “500 mg” of one extract can differ chemically from “500 mg” of another [8] [4].
3. What the evidence says about efficacy at studied doses
Randomized evidence and meta‑analyses show biomarker effects (oxidative stress, some inflammatory markers, glycemic indices) but heterogeneity is high. A 2025 meta‑analysis of RCTs on inflammation/oxidative stress highlighted substantial heterogeneity and found that neither dose nor duration fully explained differences between trials, though individual analyses showed greater oxidative marker change at higher doses in some studies [10] [3]. Single RCTs report clinical endpoints using 500–900 mg/day regimens [1] [2].
4. Safety signals and older‑adult considerations
Primary safety concerns in the literature: allergic contact dermatitis and hypersensitivity to bee products; potential interaction with drug‑metabolizing enzymes and specific drugs like warfarin; theoretical nephrotoxicity via CAPE‑mediated iNOS inhibition affecting renal perfusion in at‑risk patients; and the reality of varied toxicology data leading some reviewers to cite an extrapolated “safe” level of ~70 mg/day while clinical trials commonly use much higher doses without acute severe toxicity [5] [6] [7]. For older adults, these translate into concrete risks because they are more likely to have polypharmacy (interaction risk), decreased renal reserve (CAPE concern), prior allergies, and comorbid conditions excluded from trials (for example severe heart failure, end‑stage renal disease) [2] [5] [7].
5. Honey — formulations, medical use, and elderly safety context
Honey use differs: medical‑grade honey is sterilized and standardized for wound care and is preferred in elderly wound management; general dietary honey is considered safe for most adults but must be distinguished from “mad honey” (contains grayanotoxins) and from unregulated or adulterated products that can carry contaminants [11] [12] [13]. Several practical guides state raw honey is generally safe for older adults but flag immune‑compromised status and contaminated/unregistered products as concerns [14] [12] [15]. For topical wound care in elderly patients, medical‑grade honey is recommended because it meets sterilization and pollutant standards [11].
6. How clinicians and older adults should approach use
Given compositional variability, documented drug interactions, and specific constituent concerns (CAPE), clinicians should treat propolis as a bioactive supplement: ask about product type and dose, consider vendor standardization (e.g., EPP‑AF®), review concomitant medications (anticoagulants, drugs metabolized by CYPs), and assess renal and hepatic status before endorsing higher‑dose regimens used in trials [2] [7] [5]. For honey, prefer medical‑grade products for wounds in older adults and verify product registration/sterility for therapeutic use [11] [15].
Limitations: available sources document many human trials and reviews but do not provide a single authoritative dosing guideline; the 70 mg/day “safe” figure is an extrapolation cited in several reviews while many clinical studies used hundreds to thousands of mg/day with variable monitoring and exclusion criteria [5] [4] [3].