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Hesperidin Extract

Also known as: Hesperidin, Hesperetin-7-rutinoside, Citrus bioflavonoid

Overview

Hesperidin is a flavonoid glycoside predominantly found in citrus fruits like oranges and lemons, especially in the peel and membranes. It's used as a dietary supplement primarily for its potential cardiovascular health benefits, metabolic syndrome support, antioxidant properties, and anti-inflammatory effects. Hesperidin is water-soluble and known for its antioxidant and anti-inflammatory capabilities, which contribute to its potential cardiometabolic benefits. Research on hesperidin is moderately mature, with several randomized controlled trials (RCTs) and meta-analyses available, although more extensive, long-term studies are necessary to fully understand its effects. The available evidence suggests robust short-term cardiometabolic and anti-inflammatory benefits, but long-term safety and efficacy data remain limited. It is metabolized into hesperetin by gut microbiota, which enhances its absorption.

Benefits

Hesperidin supplementation has demonstrated several evidence-based benefits, particularly in cardiometabolic health. A 2025 RCT showed significant reductions in fasting blood sugar (FBS), triglycerides (TG), total cholesterol (TC), LDL-C, systolic blood pressure (SBP), and TNF-α. Meta-analyses have also indicated significant anti-inflammatory effects, with studies showing a reduction in CRP, IL-6, and IL-4. Animal studies suggest antioxidant and radioprotective effects, including reduced DNA damage and improved wound healing after radiation exposure. However, a systematic review and meta-analysis found no significant effect on weight or BMI in clinical trials. The benefits are most pronounced in individuals with cardiometabolic disorders, with moderate effect sizes observed in reducing LDL-C and SBP. Most studies report benefits within 8–12 weeks of supplementation.

How it works

Hesperidin exerts its effects through several biological pathways. As an antioxidant, it scavenges free radicals, reducing oxidative stress. Its anti-inflammatory action involves inhibiting pro-inflammatory cytokines such as TNF-α, IL-6, and IL-4, and reducing CRP. In terms of cardiometabolic function, hesperidin improves lipid metabolism, endothelial function, and insulin sensitivity. It primarily affects the cardiovascular, metabolic, and immune systems. Molecular targets include NF-κB, Nrf2, AMPK, and various cytokine pathways. Hesperidin has moderate oral bioavailability, and its absorption is enhanced by gut microbiota, which metabolizes it into hesperetin.

Side effects

Hesperidin is generally well-tolerated in clinical studies. Common side effects are rarely reported, though some individuals may experience mild gastrointestinal discomfort. Uncommon side effects are not frequently reported in clinical trials. Rare side effects, such as allergic reactions, are possible but infrequent. No major drug interactions have been reported, although there is a theoretical interaction with CYP3A4 substrates, the clinical significance of which is unclear. There are no established contraindications, but caution is advised for individuals with citrus allergies. The safety of hesperidin during pregnancy and lactation has not been established, and there is limited data on its use in children. Overall, hesperidin appears to have a favorable safety profile at recommended doses, but further research is needed to fully assess its long-term effects and potential interactions.

Dosage

The minimum effective dose of hesperidin is 500 mg/day for cardiometabolic and anti-inflammatory effects. The optimal dosage range, based on clinical trial data, is 500–1000 mg/day. Up to 1000 mg/day is generally well-tolerated in clinical studies, but safety data for higher doses is lacking. Hesperidin can be taken with or without food, as there is no strong evidence for timing-specific effects. A standardized extract is preferred for consistency. Absorption is enhanced by gut microbiota, and bioavailability may vary between individuals. No specific cofactors are required, but a healthy gut microbiome may enhance its effects. It's important to adhere to the recommended dosage range to minimize the risk of potential side effects.

FAQs

Is hesperidin safe?

Hesperidin is generally safe for most adults at recommended doses. However, individuals with citrus allergies should exercise caution. Safety during pregnancy and lactation is not well-established.

When should I take hesperidin?

No specific timing is required; hesperidin can be taken daily, with or without food. Consistency is key for observing potential benefits over time.

What results can I expect from taking hesperidin?

Modest improvements in cardiometabolic and inflammatory markers may be observed within 8–12 weeks. It is not a substitute for pharmaceutical interventions in severe disease.

Can hesperidin help with weight loss?

Systematic reviews and meta-analyses have found no significant effect of hesperidin supplementation on weight or BMI.

Are there any side effects?

Hesperidin is generally well-tolerated. Some individuals may experience mild gastrointestinal discomfort. Allergic reactions are rare but possible.

Research Sources

https://pubmed.ncbi.nlm.nih.gov/39038797/ – This randomized controlled trial (RCT) investigated the effects of hesperidin supplementation on cardiometabolic markers. The study found significant reductions in fasting blood sugar (FBS), triglycerides (TG), total cholesterol (TC), LDL-C, systolic blood pressure (SBP), and TNF-α with hesperidin supplementation, suggesting potential benefits for cardiometabolic health.
https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.14120 – This study investigates the anti-inflammatory and antioxidant response to hesperidin. The research provides insights into the mechanisms through which hesperidin may exert its beneficial effects, highlighting its role in modulating inflammatory pathways and reducing oxidative stress.
https://www.mdpi.com/1648-9144/55/7/370 – This research explores the radioprotective effects of hesperidin in animal models. The findings suggest that hesperidin may reduce DNA damage and improve wound healing after radiation exposure, indicating its potential as a radioprotective agent.
https://www.tandfonline.com/doi/abs/10.1080/09603123.2022.2093841 – This meta-analysis of 18 studies examined the effects of hesperidin on inflammatory markers. The results showed a significant lowering of CRP, IL-6, and IL-4 with hesperidin supplementation, supporting its anti-inflammatory properties.
https://publish.kne-publishing.com/index.php/JNFS/article/download/14019/13161/ – This systematic review and meta-analysis of RCTs assessed the effects of hesperidin supplementation on anthropometric indices. The study found no significant effect on weight or BMI, suggesting that hesperidin is not effective for weight loss.