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Red clover is a natural source of bioidentical estrogen and many beneficial antioxidants. It helps with menopause, diabetes, skin problems, and cancer. However, it is not without side effects. Read more to learn about all of red clover’s health benefits and whether it’s safe for you to use.

Introduction

Red clover

Red Clover (Trifolium pratense) is a flowering plant, which blossoms, leaves, and stems can be used as medicine [R].

People have put blossoms in ointments or boiled them to treat fungal infections, burns, wounds, gout, and eye diseases. Red clover flower teas helped treat fevers, whooping cough, measles, asthma, and other diseases [R].

The isoflavones in red clover are similar to estrogen, so red clover is often used as a source of bioidentical hormones [R].

Most of the red clover studies are in post-menopausal women. Its many health benefits include reducing menopause symptoms and hair loss, protecting against cancer, and preventing skin diseases [R].

It is available for purchase in the following forms:

Red Clover Components

Isoflavones

Source: https://www.ncbi.nlm.nih.gov/pubmed/14601839

Red clover contains many different isoflavones (daidzein, genistein, formononetin, and biochanin A), which are a type of polyphenols with antioxidant and other health benefits [R, R].

There are also other isoflavones in clover – 26 in the flowers, 25 in the roots, and 31 in the leaves and stems. The leaves have the highest concentration of formononetin and biochanin A [R].

Isoflavones also act like estrogen in the body, lowering the risk of certain cancers, heart disease, and menopause symptoms [R].

Other Isoflavones and Polyphenols

  • Afrormosin
  • Calycosin
  • Irilin
  • Irilone
  • Methylorobol
  • Pratensein
  • Pseudobaptgenin
  • Clovamide
  • Maackiain [R].

Environmental factors, such as UV light, ozone, and pathogens can change polyphenol concentration in the plant [R].

Red clover harvested in the summer has higher phenolic concentration compared to autumn-harvested. Additionally, pot-grown roots have a significantly higher amount of phenolics than field-grown plants [R].

Mechanisms

Red Clover Contains Bioidentical Estrogen

Red clover isoflavones act like estrogen [R].

In red clover extract, daidzein and genistein are the most active components. Cytochrome P450 makes daidzein and genistein from formononetin and biochanin A [R].

Daidzein and genistein increase Estrogen Receptor β (ERβ) activity [R, R].

At higher concentrations, red clover isoflavones also bind to Estrogen Receptor α (ERα). However, they bind to ERβ more [R].

  • ERα controls estrogen signaling in the uterus, mammary gland, and skeleton. In the presence of estrogen, ERα increases cell formation, especially in breast cancer cells [R, R].
  • ERβ controls estrogen signaling in the ovary, immune system, prostate, gut, and brain (hypothalamus). ERβ activation balances the ERα response by inhibiting cell duplication. Through this mechanism, it may stop cancer growth and help with menopausal symptoms [R, R, R].

The estrogen-like activity of red clover depends on the isoflavone concentration [R].

Red Clover Activates Opiate Pathways

In hamster cells, compounds from red clover extract potently activated opiate receptors [R].

The opiate receptor system helps control female sex hormone levels, mood, temperature, and menopausal symptoms [R].

Red Clover’s Anti-Inflammatory and Antioxidant Activity

The isoflavones daidzein, genistein, formononetin, and biochanin A all inhibit COX enzyme activity. This suppresses prostaglandin synthesis; prostaglandin helps UV radiation cause sunburn and immunosuppression [R, R].

Genistein also protects against oxidative damage from UV radiation both in mice and cell-based studies [R].

In mice, genistein stimulated internal antioxidants and helped benefit the skin and small intestine [R].

Health Benefits of Red Clover

1) Red Clover Reduces Menopause Symptoms

By acting like a bioidentical hormone, red clover helps reduce unpleasant symptoms and improves overall health during menopause. Its isoflavones can:

  • Lower anxiety and depression [R].
  • Reduce triglycerides (fat) and increase HDL (good) cholesterol levels [R].
  • Prevent bone loss [R].
  • Reduce inflammation [R].
  • Alleviate hot flashes [R].
  • Improve overall quality of life [R].

2) Red Clover Helps Prevent Male Pattern Hair Loss

A combination of red clover flower extract and biomimetic peptides (man-made short proteins similar to growth factors) improved hair quality and quantity in 30 male pattern hair-loss patients [R].

The combination reduced inflammation and stimulated protein production near the hair follicle leading to an increase in hair growth and hair density [R].

3) Red Clover Extract Improves Bone Health

Daily red clover extract consumption benefited bone health in menopausal women (DB-RCT). After 12 weeks, red clover extract stopped osteoclasts, which are cells that break down bone tissue [R].

Red clover also increased bone mineral density and bone formation by promoting osteoblast activity [R].

4) Red Clover Isoflavones Protect the Heart

In menopausal women, red clover isoflavone supplementation reduces heart disease risk by:

  • Reducing artery stiffness [R].
  • Reducing plaque [R].
  • Increasing HDL (good) cholesterol levels [R].

5) Red Clover Isoflavones May Stop Cancer Growth

Compared to American men, Asian men who consume a diet with high amounts of isoflavones have lower risks of prostate cancer [R].

Consuming of 160 mg/day of red clover-derived isoflavones also stopped the progression of prostate cancer by killing cancer cells (apoptosis) [R].

6) Red Clover Extract May Improve Diabetes Symptoms

In type 2 diabetic mice, red clover extract treatment helped lower glucose levels. It activates the PPARγ gene, which improves insulin sensitivity and balances blood sugar levels [R].

Additionally, red clover helped balance fat levels in diabetic mice [R].

Unfortunately, in humans, red clover isoflavones do not improve insulin resistance [R].

7) Red Clover Isoflavones Stop Inflammation

Red clover isoflavones reduce inflammatory proteins (IL-6, TNF-a, NF-kB, and COX-2) [R].

A lotion with red clover isoflavones helped stop UV exposure from suppressing the immune system and causing inflammation on mouse skin [R].

The main red clover isoflavones also inhibited inflammation in chicken eggs [R].

8) Red Clover Extract Improves the Skin

In a study (DB-RCT) of 109 postmenopausal women, red clover extract supplementation improved their skin condition (better texture and more moisture) compared to placebo [R].

9) Red Clover May Help with Pain

Low estrogen levels can change pain perception and make individuals feel more pain. In rats, red clover extract helped return their pain threshold to normal levels [R].

By activating opiate receptors, and inhibiting COX enzymes, red clover isoflavones also help with pain and increasing pain threshold (in rats) [R, R].

10) Red Clover Compounds Are Antimicrobial

In cell-based studies, red clover extract stopped the growth of and killed the bacteria Clostridium sticklandii. The isoflavones in red clover worked together to increase their antimicrobial effects [R].

Side Effects of Red Clover

GIven its similarity to estrogen, red clover should not be used during pregnancy [R].

Red Clover Reduces Fertility

The phytoestrogen/isoflavone concentration in red clover can potentially cause problems with reproduction and fertility. Since phytoestrogens are similar in structure to estradiol, they can interfere with normal estrogen fluctuations required for fertility [R].

Studies in sheep and cows showed that red clover feeding reduced fertility. However, no human studies are available [R].

Reported Side Effects

Caveats

Although red clover has shown several health benefits, there are still not many studies available. Even though it can have beneficial effects in animals, more human trials are needed before any conclusions can be reached.

As with all studies, individual variations in patients influences the results of clinical studies. Aging, weight loss, hormones, and metabolic rate all influence study outcomes [R].

Dosage

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771774/

A standard dose of red clover supplement is 40 mg [R].

Different red clover supplements also vary widely in their effects. Each product has a different isoflavone concentration, which affects their activity and effectiveness in the human body [R].

Drug Interactions

Red clover interacts with the CYP450 gene, which produces the protein that breaks down drugs [R].

Red clover supplements contain compounds that can cause blood thinning and prevent blood clots formation. It might interact with blood thinners, like NSAIDs, and increase the risk of bleeding [R].

In one case study, the combination of red clover supplements and methotrexate (a drug that treats cancer and rheumatoid arthritis) caused methotrexate toxicity. The patient experienced severe toxicity and chest and stomach pain [R].

Gene Interactions

CYP450

Cytochrome (CYP) 450 encodes a group of enzymes that are involved in drug metabolism (breakdown of drugs into active substances in the body). Red clover can reduce decrease CYP450 enzymes [R].

The isoflavone biochanin A (from red clover) inhibits CYP19 enzyme activity and cellular production of the enzyme. CYP19 is an enzyme responsible for a step in the formation of estrogen [R].

Red clover inhibits the liver enzymes CYP1A1, CYP1B1, and CYP2C9. This may increase the blood levels of drugs that are metabolized via these pathways [R].

In rats, red clover increased the activity of two CYP enzymes, CYP2C13 and CYP3A2. CYP3A2 is similar to the human CYP3A4. Activation of this enzyme speeds up drug elimination, which decreases the length and intensity of drug’s effects [R].

Other Genes

  • Red clover isoflavones activate PPARy, which helps with fat cell production (differentiation) and insulin sensitivity [R].
  • High APOC3 levels may increase fat. Red clover decreases APOC3 activity [R].

Reviews

  • “I had severe P.T.L.S. from my tubal ligation surgery, causing me to go through menopause at age 28!! This is the first time in years I haven’t been completely immobilized by cramps and PMS. Red clover phytoestrogens are far safer than soy-based ones, so go with this product instead” [R].
  • “Red clover has an antibacterial and anti-allergic effect, heal wounds and ulcers, cleanses the skin from rashes, helps fight acne, psoriasis, eczema and other skin diseases” [R].
  • “I take two daily and they have greatly alleviated my gout” [R].
  • “I am taking Red Clover Blossoms & Herbs by Nature’s Way to help balance my hormones and hope it helps with my fibroid. So far it has helped with heavy bleeding”.
  • “Should be avoided by anyone with low blood pressure or on blood thinners and suggest caution if allergic to aspirin” [R].

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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