MD, PhD, FMedSci, FRSB, FRCP, FRCPEd.

Hesperidin is a flavonoid found in citrus fruits, especially orange and grapefruit. It is said to have antioxidant and anti-inflammatory effects. Research into hesperidin began in the 1940s but only recently interest turned buoyant, and all sorts of benefits have been suggested. Here are just three recent clinical studies:

  1. This study investigated the effects of chronic intake of an orange extract (2S-hesperidin) or placebo on non-oxidative/glycolytic and oxidative metabolism markers and performance markers in amateur cyclists. A double-blind, randomized, placebo-controlled trial was carried out between late September and December 2018. Forty amateur cyclists were randomized into two groups: one taking 500 mg/day 2S-hesperidin and the other taking 500 mg/day placebo (microcellulose) for eight weeks. All participants completed the study. An incremental test was used to evaluate performance, and a step test was used to measure oxygen consumption, carbon dioxide, efficiency and oxidation of carbohydrates and fat by indirect calorimetry. The anaerobic power (non-oxidative) was determined using Wingate tests (30 s). After eight weeks supplementation, there was an increase in the incremental test in estimated functional threshold power (FTP) (3.2%; p ≤ 0.05) and maximum power (2.7%; p ≤ 0.05) with 2S-hesperdin compared to placebo. In the step test, there was a decrease in VO2 (L/min) (-8.3%; p ≤ 0.01) and VO2R (mL/kg/min) (-8.9%; p ≤ 0.01) at VT2 in placebo. However, there were no differences between groups. In the Wingate test, there was a significant increase (p ≤ 0.05) in peak and relative power in both groups, but without differences between groups. Supplementation with an orange extract (2S-hesperdin) 500 mg/day improves estimated FTP and maximum power performance in amateur cyclists.
  2. In this clinical trial with a parallel-group design, 49 patients with MetS received either 500-mg hesperidin or placebo, twice daily, for 12 weeks. Number of participants with treated MetS was considered as a primary end point. Anthropometric parameters, dietary intake, physical activity, lipid profile, glucose homeostasis parameter, tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP) were assessed at the beginning and at the end of the study. Compared with the placebo group, hesperidin decreased fasting glucose level (- 6.07 vs. – 13.32 mg/dL, P = 0.043), triglyceride (- 8.83 vs. – 49.09 mg/dL, P = 0.049), systolic blood pressure (- 0.58 vs. – 2.68 mmHg, P = 0.048) and TNF-α (- 1.29 vs. – 4.44 pg/mL, P = 0.009). Based on the within-group analysis, hesperidin led to significant decrease in serum levels of glucose, insulin, triglyceride, total cholesterol, low density lipoprotein cholesterol, TNF-α and hs-CRP, while in control group only glucose and insulin significantly decreased. The results indicate that hesperidin supplementation can improve metabolic abnormalities and inflammatory status in patients with MetS.
  3. In this study, 64 patients were randomly allocated to receive 500 mg/day hesperidin or placebo capsules for 6 weeks. Data on systolic blood pressure (SBP), diastolic blood pressure, serum total antioxidant capacity (TAC), tumor necrosis factor alpha, interleukin 6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) were collected at the baseline and at the end of the study. In the hesperidin group, SBP (122.7 ± 8.5 vs. 119.0 ± 7.4; p = .005), mean arterial blood pressure (94.2 ± 5.5 vs. 91.8 ± 5.5; p = .009), IL-6 (8.3 ± 2.1 vs. 7.4 ± 1.8; p = .001), and hs-CRP (1.9 ± 1.2 vs. 1.1 ± 0.9; p < .000) decreased whereas TAC increased (0.74 ± 0.1 vs. 0.82 ± 0.1; p < .000) in comparison to the baseline values. There was a significant difference in mean percent change of SBP, diastolic blood pressure, mean arterial blood pressure, serum TAC, and inflammatory markers (tumor necrosis factor alpha, IL-6, and hs-CRP) between hesperidin and control groups following intervention in adjusted models (p < .05). These results suggest that hesperidin may have antihypertensive and anti-inflammatory effects in type 2 diabetes.

The latest suggestion for Hesperidin is – how could be be otherwise? – that it helps against COVID-19: Hesperidin can block coronavirus from entering host cells through ACE2 receptors which can prevent the infection. Anti-viral activity of hesperidin might constitute a treatment option for COVID-19 through improving host cellular immunity against infection and its good anti-inflammatory activity may help in controlling cytokine storm. Hesperidin mixture with diosmin co-administrated with heparin protect against venous thromboembolism which may prevent disease progression. Based on that, hesperidin might be used as a meaningful prophylactic agent and a promising adjuvant treatment option against SARS-CoV-2 infection.

According to one source, Hesperidin can cause several problems:

  • abdominal pain,
  • diarrhea,
  • contact dermatitis,
  • nausea,
  • interactions with medications (including anticoagulants, blood pressure drugs, and calcium channel blockers),
  • increased risk of bleeding.

No doubt, Hesperidin is an interesting substance. Yet, I feel that much more research is needed until we can be reasonably sure that it is clinically effective for any condition, particularly COVID-19.

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