Hesperidin: An anti-inflammatory and immune boosting citrus flavonoid

In a nutshell, the anti-inflammatory flavonoid found in citrus called hesperidin may help with cardiovascular health and prevent neuroinflammation.

What is hesperidin?

Hesperidin is a flavonoid found in citrus fruits. Its active metabolite is hesperetin, and you will see both mentioned almost interchangeably in studies.

Orange juice contains 200-600 mg/L of hesperidin, making up about 90% of the flavonoid content.[ref]

The benefits of hesperidin include:

  • reduced inflammation
  • decreased neuroinflammation
  • better vascular function
  • enhanced immune response

Let’s dig into the details on these benefits:

Hesperidin Reduces Neuroinflammation

One aspect of neurodegenerative diseases, such as Alzheimer’s or Parkinson’s, is inflammation in the brain cells. This neuroinflammation involves certain cell types, such as astrocytes and glial cells, which protect the neurons from insults.[ref]

There are several possible causes of neuroinflammation, including pathogens and oxidative stress.  Sources of oxidative stress can include heavy metals, pollution, smoking, mold exposure, viral infections, and more.

An in vivo and in vitro study investigated hesperidin’s effects on neuroinflammation. The lipopolysaccharide-induced neuroinflammation was decreased with hesperidin, which was shown to modulate TLR4 and NF-kB signaling. [ref]

Recent animal studies and cell studies show that hesperetin protects neurons in the brain from pathogens and oxidative stress. Specifically, hesperetin decreased TNF-α and LR4 (inflammatory cytokines). It reduced reactive oxygen species (ROS) in the hippocampus and cortex.[ref]

Several studies on Parkinson’s disease show promise for hesperidin in animal models.[ref]

A clinical trial of hesperidin-enriched orange juice (vs an orange-flavored drink) improved cognitive function in older adults.[ref]

Cardiovascular benefits of hesperidin

Animal studies clearly show that hesperetin decreases blood pressure and is anti-inflammatory, thus benefiting the heart.[ref][ref]

As usual, human studies aren’t quite as clear-cut.

  • One study using orange juice with increased flavonoids found that it helped vascular function after a meal.[ref]
  • Another placebo-controlled study found that hesperetin increased vascular function and decreased inflammatory biomarkers.[ref]
  • A double-blind clinical trial in people with diabetes found that hesperidin (500 mg/ day) decreased blood pressure, IL-6, and CRP levels.[ref]
  • A 12-week trial of hesperidin in orange juice showed  that it decreased blood pressure and also downregulated proinflammatory genes.[ref]

Metabolic syndrome studies using hesperidin

Hesperidin supplements (500 mg, 2x a day) reduced fasting glucose, blood pressure, triglycerides, and TNF-α in a placebo-controlled trial on people with metabolic syndrome.[ref]

Another clinical trial using 1g/day of hesperidin also showed decreased triglycerides and lower blood pressure.[ref]

Fatty liver disease (NAFLD)

A 12-week trial of 1g/day of hesperidin resulted in lower triglycerides, decreased liver fat, and lower inflammatory cytokine markers.[ref]

Immune system modulation

Hesperidin in animal studies has been shown to enhance immune response while at the same time preventing excess cytokine production.[ref][ref]

Additional animal studies show that hesperidin also decreases pro-inflammatory cytokines in the lung after lung injury.[ref]

Preliminary studies in chronic rhinosinusitis show that hesperidin increases mucosal clearance. This is being looked at for people with cystic fibrosis mutations.[ref]

Cancer proliferation inhibition

Numerous studies (mostly animal and cell studies) show that hesperidin inhibits cancer cell proliferation. There are current studies underway investigating the addition of hesperidin to chemotherapy regimens.[ref][ref][ref]

SARS-CoV-2 and SARS-CoV inhibition: Hesperidin studies

In silico studies can look at how the structure of the SARS-CoV-2 virus interacts with compounds (drugs, natural supplements, etc).

These computational models show hesperidin binding to the main protein needed for replication of the SARS-CoV-2 virus. Additionally, hesperidin counteracts the oxidative stress created by the infection.[ref]

Studies on SARS-CoV from 2005 also show that hesperetin is a potent inhibitor.[ref]

Traditional Chinese medicine herbal blends containing hesperidin also show promise against SARS-CoV-2.[ref]

Clinical trials are needed to see how effective hesperidin is against SARS-CoV-2 in vivo and at what dosage.

Being investigated for Pelvic organ prolapse:

A recent preprint study looked at gene expression in vaginal epithelial cells in women with pelvic organ prolapse (POP). The results showed that inhibiting TGFB1 signaling may be a target to explore for POP. Hesperidin has been shown to decrease TGFB1 signaling.[ref]


Bioavailability and Metabolism:

Absorption: Hesperidin is ranked as one of the most bioavailable flavonoids. When you eat foods containing hesperidin (or take it as a supplement), it isn’t broken down very well in the stomach or small intestines. Instead, your colon’s microbiome converts it to the more bioavailable aglycone hesperetin for easier absorption in the colon. It is thought that the metabolites are what give the health benefits, rather than the original hesperidin molecule.[ref]

Safety: Animal safety studies show that it is non-toxic and non-mutagenic.[ref] Talk with your doctor if you have any questions about your particular situation.

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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.