Dosage exploration of the effects of honey and its derivatives on cardiometabolic outcomes: an overview of systematic reviews and GRADE-assessed updated meta-analysis

Nutrition & Diabetes REVIEW ARTICLE www.nature.com/nutd OPEN Dosage exploration of the effects of honey and its derivatives on cardiometabolic outcomes: an overview of systematic reviews and GRADE-assessed updated meta-analysis Mostafa Norouzzadeh 1,2,3, Sanaz Barazandeh1,3, Minoo Hasan Rashedi1,3, Sanaz Jamshidi4, Fatemeh Hatamifar1,3, ✉ ✉ Zohreh Maghsoomi5, Farshad Teymoori 1 and Mojtaba Malek5 1234567890();,: © The Author(s) 2025 Cardiovascular diseases and diabetes are associated with significant mortality, morbidity, and economic burden, highlighting the need for alternative preventive strategies. Honey bee products, including honey, royal jelly, and propolis, are considered potential interventions for managing cardiometabolic risk factors. This umbrella review aimed to compare the effectiveness of these products in cardiometabolic health. PubMed, Scopus, and Web of Science databases were systematically searched from inception through 21ST October 2024 to identify eligible meta-analyses and primary randomized controlled trials (RCTs). Random-effect pairwise analysis combined trial findings, while dose-response and influence analyses assessed result robustness. Evidence quality and certainty were evaluated using AMSTAR-II, ROB, GRADE, and ICEMAN criteria. Analysis of 69 RCTs with 3544 participants revealed that 10 g of honey daily may lower Hemoglobin A1C but adversely affect systolic blood pressure, Aspartate transferase, triglycerides, fasting blood glucose, and high-sensitive C-reactive protein. Royal jelly improved blood pressure, lipid profiles, glycemic indices, and total antioxidant capacity. Propolis demonstrated reductions in anthropometric measures and improvements in lipid profile, glycemic control, liver enzymes, and inflammation and oxidative stress markers. While long-term or high-dose honey consumption in individuals with health concerns warrants caution, RJ and propolis demonstrated dose-dependent benefits for cardiometabolic health with proper certainty. Future research should focus on population-specific characteristics and optimized dosages. Nutrition and Diabetes (2025)15:48 ; https://doi.org/10.1038/s41387-025-00403-9 INTRODUCTION Non-communicable diseases (NCDs) are responsible for an estimated 43 million deaths annually, disproportionately affecting low- and middle-income countries where nearly 73% of global NCDs-related mortality was recorded [1]. In high-income countries like the United States, an NCDs-related death occurs every 33 seconds, highlighting their pervasive impact [2]. The World Health Organization (WHO) Sustainable Development Goal 3.4 aims to reduce premature NCDs mortality by 30% by 2030 to address this burden [1]. Complementary and alternative medicine may contribute to this target; however, robust, well-designed research is essential to establish effective interventions [3]. A variety of pharmaceutical and nutraceutical agents are used to manage NCDs, yet their inconsistent efficacy and potential side effects have led to growing interest in complementary strategies [4]. Dietary components with therapeutic potential are of interest, as they are commonly consumed and may have notable effects on cardiometabolic outcomes [3]. Such interventions can help refine dietary and clinical guidelines, especially for individuals at high risk of NCDs [4]. Among natural alternatives, honey bee (Apis mellifera) products, namely honey, royal jelly (RJ), and propolis have a long history of medicinal use dating back to 2000 BC [5–7]. Honey is rich in fructose, trace elements, and bioactive compounds [8, 9], showing promise in preventing and managing NCDs [10–12]. RJ, a nutrientdense bee secretion, offers antioxidant, anticancer, neuroprotective, and cardioprotective benefits [13–19]. Propolis, a resin-like material collected from plant sources, contains over 300 phytochemicals, including polyphenols, amino acids, vitamins, and aromatic compounds, and is recognized for its potent antiinflammatory and immune-modulating effects [20–24]. Recent systematic reviews and meta-analyses (SRMAs), and trials underscor honey bee products nuanced and sometimes contrary effects on cardiovascular health. A 2023 meta-analysis reported that honey improved blood glucose and lipid parameters but also increased pro-inflammatory markers [25], whereas a 2021 SRMA found no significant effect on lipid profiles [26]. Hadi et al. observed no overall impact of RJ on serum lipids. However, longer-duration studies (>90 days) showed lipid improvements [27, 28]. While RJ had no significant overall effects on liver 1 Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran. 2The Persian Gulf Tropical Medicine Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran. 3Student Research Committee, Iran University of Medical Sciences, Tehran, Iran. 4 Imam Ali Hospital, Shiraz University of Medical Sciences, Kazerun, Iran. 5Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran. ✉email: ; Received: 16 February 2025 Revised: 25 September 2025 Accepted: 14 October 2025 M. Norouzzadeh et al. 2 enzymes or glycemic indices, subgroup analyses noted reductions in blood glucose in non-healthy individuals treated for ≥8 weeks [29]. Vajdi et al. found no general effect on anthropometric indices, but RJ at doses <3000 mg/day significantly improved anthropometric indices [30]. Regarding propolis, a 2024 SRMA showed significant improvements in serum cholesterol, though not in triglyceride (TG) [31]. Nazari Bonab et al. reported increases in antioxidant markers, but significant effects were only seen at higher doses (≥1000 mg/day) and shorter durations (<11 weeks) [32]. Another SRMA found propolis to significantly reduce glycemic markers, inflammatory indicators, and liver enzymes while showing no notable effect on insulin resistance, oxidative stress markers, lipid profile, or anthropometric outcomes [33]. These findings highlight the variability in outcomes based on dose, duration, and population characteristics, underscoring the need for comprehensive evaluations. To address this, we conducted an umbrella review of existing SRMAs to compare the effects of honey, RJ, and propolis on cardiometabolic factors. To strengthen the validity of our results, we performed doseresponse, influence, and subgroup analyses. Additionally, we assessed the certainty and credibility of the evidence using established tools, including GRADE, ICEMAN, and AMSTAR. METHODS The study protocol has been registered in PROSPERO with the registration number CRD42024601377. We conducted the review following the Cochrane Handbook for Systematic Reviews of Interventions [34]. We also adhered to the Preferred Reporting Items for Overviews of Reviews (PRIOR) statement (Supplementary Table 1) [35]. In addition, we followed (...truncated)