Hesperidin, found in orange peels, has a wide range of benefits. They include protecting the heart and brain, reducing diabetes symptoms, and preventing cancer. Listed below are the other noted health benefits of this glycoside.

Introduction

Hesperidin is a bioflavonoid glycoside. This means that it is a plant nutrient. It is a sugar-bound form of the flavonoid hesperetin (R).

Citrus fruits, mainly oranges, and tangerines contain hesperidin (R).

After consumption, hesperidin must progress to the colon before it can be readily absorbed into the body and circulate through the blood (R).

Another form of this flavonoid is hesperitin. Many studies use hesperitin instead of hesperidin. This is because drug administration is more efficient than consuming very high amounts of hesperidin.

Health Benefits Of Hesperidin

1) Hesperidin Works as an Antioxidant

https://doi.org/10.1002/ptr.5256

https://doi.org/10.1002/ptr.5256

Oxidants, such as hydrogen peroxide, and other chemicals can cause oxidative stress. Oxidative damage can cause disorders such as cancer and heart disease. Antioxidants can help protect against oxidative stress (R).

Both hesperidin and hesperitin can function as antioxidants. They both have radical scavenging activity. This means that they stop free radicals from damaging cells (R).

Hesperidin neutralizes reactive oxygen species. This protects DNA, proteins, and tissues from radiation, inflammation, and toxins. It also protects against oncogenes. Oncogenes are genes that can cause cells to transform into tumor cells (R).

Hesperidin had significant radical scavenging activity in red blood cells. It stopped hydrogen peroxide from damaging the cellular membranes of blood cells. It also protected against DNA damage (R).

2) Hesperidin Helps Prevent Cancer

Reactive oxygen species and oxidative damage are involved in cancer development and progression (R).

The antioxidant activities of hesperidin can help prevent cancer. It neutralizes reactive oxygen species to protect against oncogenes. Oncogenes are genes that can cause cells to transform into tumor cells (R).

Radiation can also be toxic. It can directly damage DNA. It may also produce free radicals to alter proteins, which can cause cancer. Hesperidin significantly reduces oxidative stress induced by radiation. In rats, hesperidin injection protected them from gamma-radiation (R).

In rats, satsuma mandarin juice enhanced with hesperidin significantly reduced the incidence of colon cancer in rats (R).

Orange and satsuma mandarin juice also reduced lung cancer by 29% in rats (R).

In male rats suffering from colon cancer, hesperidin administration stopped cell formation. It also increased cancer cell death in the colon (R).

Additionally, hesperidin stopped tumor growth and invasion in lung cancer cells. It stopped blood vessel formation, which contributes to tumor growth (R).

3) Hesperidin is Anti-Inflammatory

Chronic inflammation can increase in pro-inflammatory mediators. Such mediators include iNOS and COX-2. The levels of inflammatory cytokines also increase (R).

Hesperidin and its metabolites can lower inflammation. In cellular models of inflammation, hesperidin administration suppressed iNOS protein levels. It also lowered COX-2 enzyme levels (R).

It also reduced inflammatory cytokine production in rats (R).

4) Hesperidin Protects the Heart

Many factors can affect heart health. Oxidative stress, high fat, high blood pressure, and high cholesterol can all contribute to an unhealthy heart. Hesperidin administration can help with all these symptoms and protect the heart.

Daily oral hesperidin administration at 100mg/kg to old rats for 90 days benefitted heart tissue. Hesperidin protected against oxidative stress and increased the antioxidant levels. It also lowered inflammation (R).

Diabetes also contributes to heart disease. You can protect the heart by lowering your glucose levels (R).

Hesperidin may increase adiponectin, a protein hormone that helps control glucose and fat metabolism. Increasing adiponectin can help reduce fat accumulation. This can help improve blood vessel conditions and improve circulation in the heart (R).

Over the course of 4 weeks, a combination of hesperidin and orange juice helped lower blood pressure levels in overweight males (R).

In rats fed a high cholesterol diet, hesperidin supplementation reduced total cholesterol levels. It may help prevent high cholesterol by inhibiting the formation and absorption of cholesterol (R).

However, hesperidin does not show the same effects in humans. In men and women with high cholesterol levels, hesperidin and naringin (another citrus flavonoid) administration did not lower cholesterol levels (R).

5) Hesperidin Prevents Obesity

Hesperidin may increase adiponectin, a protein hormone that helps control glucose and fat metabolism. Increasing adiponectin can help reduce fat accumulation. This can help prevent obesity (R).

Hesperidin and p-synephrine (part of bitter orange extract) also increase the metabolic rate. Metabolic rate is the rate at which the body burns calories (R).

Glucosyl hesperidin (G-hesperidin) is a water-soluble form of hesperidin. A combination of G-hesperidin and caffeine reduces body fat in humans. It significantly reduced abdominal fat, body weight, and BMI in people with a moderately high BMI. This combination can help treat or prevent obesity (R).

6) Hesperidin May Protect Against Diabetes

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High glucose levels can cause diabetes, and eventually diabetic retinopathy. It is a disease of the retina that causes vision impairment and loss (R).

Protein kinase C-β (PKC-β) and VEGF can damage blood vessels. They also contribute to leakage in the retina (R).

Daily oral administration of hesperidin for twelve weeks mildly decreased blood glucose levels in streptozotocin-induced diabetic rats. It also stopped PKC-β and VEGF activity. This protected the rats from vision impairment (R).

7) Hesperidin Protects the Brain

Hesperidin neutralizes reactive oxygen species. Its antioxidant properties can protect the brain from oxidative damage (R).

D-galactose is a sugar that causes oxidative stress in the brain. It disrupts mitochondrial function and causes nerve cells to die. In rats, pretreatment with hesperidin and curcumin protected the brain. It reduced cognitive problems by preventing nerve cell death (R).

In mice models of Alzheimer’s disease, hesperidin administration reduced symptoms of the disease. 100 mg/kg per day of hesperidin reduced learning and memory problems. It also improved locomotor activity (R).

Finally, hesperidin may be able to protect the brain during strokes. 50 mg/kg of hesperidin daily for 15 days helped with brain function in male rats. It reduced inflammation. It also lowered the number of free radicals in the brain (R).

Hesperidin can also help protect against memory loss in rats that suffered from a stroke. Pretreatment with hesperidin and L-arginine slightly protected against memory loss (R).

8) Hesperidin Works as an Antidepressant

In the rat model of stress-induced depression, hesperidin may be able to reduce depression symptoms. Three weeks of oral administration improved the rats’ behaviors. This may due to the regulation of the HPA axis, which is a stress response system (R).

The opioid system is also a contributing factor for major depression. Hesperidin possessed anti-depressant-like properties and positively interacts with the opioid system. It works with opioid receptors to reduce depression symptoms in mice (R).

Hesperidin also has an anti-depressant effect in diabetic rats. By lowering glucose and inflammation levels, it enhanced brain function and reduced depression symptoms (R).

9) Hesperidin Reduces Stress and Anxiety

Stress can cause health problems. It can increase oxidative damage in the body. It also activates the HPA axis and causes changes in the body’s homeostasis (balance). Chronic stress can cause anxiety and mood disorders (R).

Hesperidin’s antioxidant activity can help reduce stress and protect your health. It prevents oxidative damage and can help stop anxiety (R).

10) Hesperidin Relieves Pain

Nervous system dysfunction can cause a condition called neuropathic pain. Injured nerve cells can contribute to pain and inflammation (R).

Hesperidin administration helped reduce pain in mouse models of prolonged inflammation and pain.  It inhibited inflammatory cytokine production. This reduced inflammation (R).

Additionally, it also reduced oxidative stress. It also stopped NF-κB activity, which also contributes to inflammation (R).

Hesperidin and diosmin (another flavonoid) administration also decreases pain in rats. The combination of these flavonoids helps protect nerve cells (R).

11) Hesperidin Helps Treat Allergies

Immunoglobulin E (IgE) can provoke allergic reactions by release histamine and cause inflammation. In humans, administration of both hesperidin and hesperitin can suppress IgE’s effects. It inhibits histamine release and stops Th2 cytokine secretion (R).

Oral ingesting of hesperidin in mice can help stop allergic reactions. It reduces the responsiveness of the airways to antigens. This suggests that it may help reduce asthma symptoms (R).

12) Hesperidin Can Treat Hemorrhoids

A mixture of three different flavonoids can help treat hemorrhoids. Hesperidin, diosmin, and troxerutin helped reduce hemorrhoid symptoms (R).

Hemorrhoid patients reported less pain, swelling, and bleeding after 12 days of treatment. They also used fewer painkillers after the flavonoid administration (R).

13) Hesperidin Enhances Skin Health

Topical hesperidin treatment in mice helped with skin health. It kept the skin barrier at a balance. It also stimulated skin cell production (R).

Additionally, hesperidin can protect the skin from radiation. A compound called hesperidin methyl chalcone helped stop oxidative damage in mouse skin cells. It reduced free radicals in a mouse model of UV radiation. It also reduced inflammatory cytokine production (R).

Topical hesperetin may also be an effective skin whitening agent (R).

14) Hesperidin Promotes Bone Health

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Hesperidin administration enhances osteoblast formation. Osteoblasts are cells that help with bone formation (R).

Hesperitin-7-glucuronide is the main circulating form of hesperidin. Its administration in rats helped increase bone cell formation (R).

Estrogen deficiency during menopause can cause bone loss and osteoporosis. Estrogen replacement therapy can prevent bone loss. However, can cause adverse effects like bleeding and cancer (R).

Hesperidin may improve bone metabolism. It can also prevent bone loss caused by estrogen deficiency (R).

In female mice, hesperidin supplementation prevented bone loss in all three areas of the femur. Osteoclasts are bone cells that break down bone tissue to release minerals. Hesperidin decreased the number of osteoclasts in the bones (R).

In addition to preventing bone loss, hesperidin did not have any negative effects on the uterus. However, the dose of hesperidin used in the study was much higher than the usual daily intake. It is unlikely for someone to consume that high of an amount in a normal diet (R).

Androgen deficiency can also cause bone loss. Male mice fed a diet with hesperidin had less bone loss compared to mice fed a normal diet (R).

15) Hesperidin May Have Sleep-Enhancing Properties

Hesperidin administration may help enhance sleep. It also has sedative properties. Its sedative properties might come from its ability to activate opioid receptors (R).

However, its sedative properties are only significant if it is injected into the body at a high level. Oral intake of hesperidin might not have the same effects (R).

16) Hesperidin May Increase Blood Flow

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Oral administration of both hesperidin and hesperitin may increase blood flow. Daily intake of 500mg of hesperidin daily for three weeks in metabolic syndrome patients increased blood flow. This is due to the widening of their blood vessels (R).

Additionally, 150mg of a water soluble form of hesperidin can improve blood flow in women (R).

17) Hesperidin Helps Treat Chronic Venous Insufficiency

High blood pressure in the veins can cause fluid leakage. During Chronic Venous Insufficiency, the lymphatic system becomes overwhelmed and causes edema (swelling) and ulcer formation (R).

This activates a white blood cell inflammatory response. The inflammation causes further deterioration to the veins (R).

Daflon is a mixture that contains 10% hesperidin and 90% diosmin (another flavonoid). Daflon administration inhibits the inflammatory response and decreases fluid leakage from the veins (R).

Diosmin and hesperidin inhibited free radical synthesis. It reduces swelling and accelerated ulcer healing. All of these contributed to the treatment of chronic venous insufficiency (R).

Sources of Hesperidin

1) Citrus Fruit (R, R)

  • Oranges
  • Tangerines
  • Lemons
  • Limes
  • Citrus fruit hybrids
  • Sundried tangerine peels

2) Various Herbs and Plants

  • Boehmeria nivea (R)
  • Dangshen (Codonpsis pilosula) (R)
  • Japanese catnip (Schizonepeta tenuifolia) (R)
  • Valeriana wallichii (R)
  • Honeybush (Cyclopia subternata ) (R)
  • Byrsonima crassifolia (R)
  • Peppermint (Mentha × Piperita) (R)

Warnings and Side Effects

Hesperidin can slow blood clotting and increase blood flow. It may make bleeding disorders worse (R).

Daflon (a mixture of hesperidin and diosmin) does not have any major side effects and is safe for daily use (R, R).

Many studies use very high amounts of hesperidin to get the health benefits. It would be nearly impossible to consume the required amount of hesperidin-containing food to get the same benefits as supplementation.

Technical

  • 50 mg/kg hesperidin administration led to higher total protein and albumin levels in mice after irradiation (R).
  • Hesperidin inhibited NF-kB activity and TNF-α, IL-1β, IL-6, and IL-10 production (R).
  • Hesperitin has estrogenic effects in cell culture. Its neuroprotective effects may also depend on estrogenic signaling (R).
  • Also, hesperitin can inhibit various intestinal bacteria (R).
  • Hesperidin works with other orange phenols (myricetin, chlorogenic acid, and naringenin) (R).

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