Red clover is a source of estrogen-like plant compounds and antioxidants. Supplement manufacturers claim it helps with menopause, diabetes, and hair growth. However, scientific evidence paints a different picture. Read more to learn whether red clover has health benefits and if it’s safe to use.
What is Red Clover?
Overview
Red Clover (Trifolium pratense) is a flowering plant. The blossoms, leaves, and stems are traditionally used [1].
People traditionally put blossoms in ointments or boiled them for fungal infections, burns, wounds, gout, and eye diseases. Red clover flower tea was historically used for fever, whooping cough, measles, and asthma [2].
The isoflavones in red clover are similar to estrogen and red clover is often used as a source of bioidentical hormones [2].
Most of the existing red clover studies were in post-menopausal women. This plant is said to help with menopausal symptoms, hair loss, and skin problems [2].
However, red clover has not been clearly shown to be helpful for any health condition.
Additionally, red clover supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.
What do we know?
According to the National Center for Complementary and Alternative Medicine, studies of red clover in people haven’t provided clear evidence of any beneficial effects [3].
Most research suggests that red clover does not relieve menopause symptoms such as hot flashes [3].
Ongoing research is focused on identifying active components in red clover and their possible interactions with medications.
Components
Isoflavones
Red clover contains different isoflavones (daidzein, genistein, formononetin, and biochanin A) [4, 5].
Other isoflavones have also been identified (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 [4].
Other Isoflavones and Polyphenols
- Afrormosin
- Calycosin
- Irilin
- Irilone
- Methylorobol
- Pratensein
- Pseudobaptgenin
- Clovamide
- Maackiain [6]
Environmental factors, such as UV light, ozone, and pathogens can change polyphenol concentration in the plant [6].
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 [6].
Mechanisms
Estrogen-like Activity
Isoflavones mimic estrogen in the body, which is why they are being researched in women experiencing symptoms of menopause [4].
In red clover extract, daidzein and genistein are the most active components. Cytochrome P450 makes daidzein and genistein from formononetin and biochanin A [7].
Daidzein and genistein may increase Estrogen Receptor β (ERβ) activity [7, 8].
At higher concentrations, red clover isoflavones may also bind to Estrogen Receptor α (ERα). However, they bind to ERβ more [8].
- ERα controls estrogen signaling in the uterus, mammary gland, and skeleton [9, 10].
- ERβ controls estrogen signaling in the ovary, immune system, prostate, gut, and brain (hypothalamus). ERβ activation balances the ERα response by inhibiting cell duplication [9, 8, 10].
The estrogen-like activity of red clover depends on the isoflavone concentration [8].
Pain Pathways
In hamster cells, compounds from red clover extract activated opioid receptors [1].
The opioid receptor system is involved in female sex hormone balance, mood, temperature, and menopausal symptoms [1].
Other
The isoflavones daidzein, genistein, formononetin, and biochanin A inhibit COX enzyme activity, which may suppress prostaglandin synthesis [11, 12].
Genistein may protect against oxidative damage from UV radiation both in mice and cell-based studies [12].
In mice, genistein stimulated internal antioxidants in the skin and small intestine [12].
Purported Health Benefits of Red Clover
Possibly Ineffective For:
1) Bone Loss
Based on the available evidence, red clover probably doesn’t improve bone health.
In early studies, red clover seemed to help prevent bone loss in menopausal women [13].
Daily red clover extract consumption benefited bone health in menopausal women. After 12 weeks, red clover extract stopped osteoclasts, which are cells that break down bone tissue [13].
Scientists suspect that red clover may increase bone mineral density and bone formation by promoting osteoblast activity [13].
However, later trials show that this herb probably doesn’t improve bone health. Red clover supplements do not affect bone mineral density in menopausal and postmenopausal women, according to a large analysis of clinical trials [14].
Insufficient Evidence For:
The following purported benefits are only supported by limited, low-quality clinical studies.
There is insufficient evidence to support the use of red clover for any of the below-listed uses. Remember to speak with a doctor before taking red clover supplements. Red clover should never be used as a replacement for approved medical therapies.
2) Menopausal Symptoms
Proponents state that red clover can reduce symptoms of menopause, but there is insufficient evidence to back up these claims.
Limited studies suggest that red clover may have the following effects in menopausal women:
- Lower anxiety and depression [15].
- Reduce triglycerides (fat) and increase HDL (good) cholesterol levels [16].
- Reduce inflammation [2].
- Alleviate hot flashes [17].
- Improve overall quality of life [18]
These findings remain to be confirmed in large-scale trials.
3) Male Pattern Hair Loss
Insufficient evidence supports the use of red clover for 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 [19].
The combination reduced inflammation and stimulated protein production near the hair follicle leading to an increase in hair growth and hair density [19].
More research is needed.
4) Heart Health
Insufficient evidence supports this purported health benefit.
In menopausal women, red clover isoflavone supplementation had potentially beneficial effects on the heart by:
However, purified red clover isoflavones did not improve cholesterol status or insulin resistance — both of which are risk factors for heart disease–in another trial of healthy premenopausal women [22].
5) Skin Health
In a study of 109 postmenopausal women, red clover extract supplementation improved their skin condition (better texture and more moisture) compared to placebo [23].
No other studies have been carried out.
Therefore, evidence is lacking to say red clover improves skin health.
6) Cancer Research
Red clover has not been shown to treat or prevent cancer.
Limited research looked at associations between cancer risk and isoflavone consumption. No health-related conclusion can be drawn from their findings. Additionally, no large-scale studies looked at red clover specifically.
Compared to American men, Asian men who consume a diet with high amounts of isoflavones have lower risks of prostate cancer [24].
In one study, the prostate tissues of men who consumed 160 mg/day of red clover-derived isoflavones showed less signs of progression (and higher levels of apoptosis) [24].
However, this study looked at prostate cancer tissue after surgery. Though men included in this study took red-clover-derived supplements prior to surgery, their health and overall symptoms were not assessed
No proper clinical trials have been done and the effects of red clover on cancer in humans are still unknown.
Lacking Evidence For:
No valid clinical evidence supports the use of red clover for any of the conditions listed in this section.
Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
7) Diabetes
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 [25].
Red clover helped balance fat levels in diabetic mice [25].
8) Inflammation
Red clover isoflavones may reduce inflammatory proteins (IL-6, TNF-a, NF-kB, and COX-2) [11].
A lotion with red clover isoflavones helped stop UV exposure from suppressing the immune system and causing inflammation on mouse skin [12].
The main red clover isoflavones also inhibited inflammation in chicken eggs [26].
9) Pain
According to one experimental hypothesis, low estrogen levels may change sensory perception and make individuals feel more pain. In rats, red clover extract helped return their pain threshold to normal levels [27].
Scientists are investigating if red clover isoflavones can activate opioid receptors and inhibit COX enzymes in rats, which may help relieve pain [27, 1].
10) Antimicrobial
In cell-based studies, red clover extract stopped the growth of and killed the bacteria Clostridium sticklandii. The isoflavones in red clover may have synergistic effects. The effects of red clover on infections in humans are unknown [28].
Limitations & Caveats
Although red clover is widely used, few clinical studies are available. More human trials are needed before any conclusions can be reached.
Red Clover Side Effects & Precautions
Reported Side Effects
No serious side effects have been reported in studies that evaluated red clover for various health conditions for up to a year.
Other possible side effects reported across the scientific literature included:
- Breast tenderness
- Swollen neck glands
- Migraines/headaches
- Dizziness
- Acne, rash, psoriasis
- Bloating
- Constipation
- Diarrhea
- Nausea [2]
Pregnant Women and Children
Given its similarity to estrogen and lack of safety data, red clover may not be safe for women who are pregnant or breastfeeding, for children, or for women who have breast cancer or other hormone-sensitive cancers [2, 3].
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 may interfere with normal estrogen fluctuations that affect fertility [29].
Studies in sheep and cows showed that red clover feeding reduced fertility. However, no human studies are available [29].
Drug Interactions
The following drugs may interact with red clover:
- Birth control pills
- Estrogen
- Medications changed by the liver (CYP1A2, CYP2C1, CYP2C9, CYP3A4 substrates)
- Drugs that slow blood clotting
- Tamoxifen (Nolvadex)
Red clover interacts with the CYP450 gene, which produces the protein that breaks down drugs [30].
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 [31].
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 [32].
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 the decrease of CYP450 enzymes [30].
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 [33].
Red clover inhibits the liver enzymes CYP1A1, CYP1B1, and CYP2C9. This may increase the blood levels of drugs that are metabolized via these pathways [2].
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 the drug’s effects [30].
Other Genes
- Red clover isoflavones activate PPARy, which may affect fat cell production (differentiation) and insulin sensitivity [34].
- High APOC3 levels may increase fat. Red clover decreases APOC3 activity [25].
Supplementation
Dosage
The appropriate dose of red clover depends on factors such as a person’s age, health, and other conditions.
Currently, there is insufficient scientific information to determine an appropriate range of doses for red clover.
The typical dose of red clover in clinical trials was 40 mg [35].
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 [36].
User 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. I think red clover phytoestrogens are far safer than soy-based ones, so I go with this product instead”.
- “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”.
- “I take two daily and they have greatly alleviated my gout”.
- “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”.
The opinions expressed in this section are solely those of the users who may or may not have medical or scientific training. Their reviews do not represent the opinions of SelfHacked. SelfHacked does not endorse any specific product, service, or treatment.
Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice from your doctor or another qualified healthcare provider because of something you have read on SelfHacked. We understand that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
Takeaway
Red clover is a flowering plant rich in isoflavones, compounds that mimic estrogen activity in the body.
Although women commonly take it to reduce menopausal symptoms, no proper evidence supports this use. Early studies point to red clover’s potential to improve mood, hot flushes, and blood fats in menopausal women. More evidence is needed to rate its effectiveness and safety.
Importantly, red clover can interact with many medications. It’s also not safe to use in children, breastfeeding or pregnant women, and people trying to conceive. Remember to talk to your healthcare provider before supplementing.
