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Red Clover Extract

Red Clover Extract (Promensil or Menoflavon) are isoflavones including the soy isoflavones in low amounts and some similar structures such as Biochanin A; used as a therapy for menopause, red clover appears to have minor yet unreliable benefits in improving health and reducing hot flashes.

Our evidence-based analysis on red clover extract features 85 unique references to scientific papers.

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Summary of Red Clover Extract

Primary Information, Benefits, Effects, and Important Facts

Red Clover Extract (RCE) refers to any extract that is taken from the red clover plant, known botanically as trifolium pratense which is a good natural source of isoflavone molecules. There are a few brand name products of RCE (Promensil, Menoflavon, etc.) which isolate the isoflavones that are thought to be bioactive, and this mainly refers to two of the soy isoflavones which are also found in this plant (genistein and daidzein) and two structurally similar methylated isoflavones known as biochanin A and formononetin. Specifically, biochanin A is just methylated genistein (and can produce genistein in the body when it is ingested) whereas formononetin is methylated daidzein (can also produce daidzein in the body after ingestion). RCE, and its brand name products, are recommended for the treatment of menopause or asthmatic symptoms.

When looking at research on RCE and menopausal symptoms, there are indeed benefits in isolated studies relative to placebo but there are also many failures indicating that supplementation is pretty unreliable in benefitting symptoms; this may be in part due to differences in absorption or simply due to potential industry bias (since many studies using the brand name products are partially funded by the producers of the products, and the independent studies tend to be more likely to report no significant benefit). There may be a minor reduction in anxiety however, which would be a percievable benefit and needs to be further evaluated. It should also be noted that most studies do reported great benefit with supplementation, but the placebo effect per se is very prominent in studies on menopausal symptoms (case in point, studies on black cohosh where the placebo effect sometimes halves symptoms of menopause alone).

Beyond the above possible anxiolytic property of red clover that needs to be investigated further and a possibly benefit to asthma and cough (also needs to be investigated further), there does not appear to be any significant benefit associated with red clover extract.

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How to Take

Medical Disclaimer

Recommended dosage, active amounts, other details

Supplementation of Red Clover Extract tends to be 40mg of total isoflavones taken once a day, or two doses totalling 80mg a day. This can be reached through:

  • Supplementing pure isoflavones (in which case the range is 40-80mg)

  • Supplementing brand name products such as Promensil, which confer 40mg isoflavones per 500mg capsule (so, around 8% isoflavones by weight)

  • Approximately 5 grams of the whole plant without any particular extraction techniques

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Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects red clover extract has on your body, and how strong these effects are.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-a - High See all 13 studies
Similar to other lipid parameters, despite an increase (10-20%) being noted in a few studies the best evidence to date does not support this conclusions and the benefits, when they occur, are unreliable.
grade-a - High See all 11 studies
Although a minor effect may occur in those with high blood cholesterol concentrations, the majority of evidence does not support a role of Red Clover Extract in reducing LDL-C when supplemented.
grade-a - Moderate See all 12 studies
While isolated studies have noted some benefits, the best evidence at this moment in time (Independently conducted and larger, better conducted, studies) tend to note no significant influence on the main climacteric symptoms such as hot flashes with supplementation.
grade-a - Very High See all 14 studies
The majority of evidence does not support a role for reducing total cholesterol with supplementation of red clover extract, except perhaps a minor (less than 10%) reduction in overweight postmenopausal women.
grade-a - High See all 11 studies
Isolated reports have noted minor (less than 10%) reductions in triglycerides in overweight or hyperlipidemics mostly, but overall there is not a significant reduction in triglycerides noted with Red clover extract.
grade-b - High See all 4 studies
A large decrease has been noted in one study in overweight postmenopausal women, although three other studies failed to replicate this decrease.
grade-b - Very High See all 7 studies
The one study in diabetics found a reduction in blood pressure, and due to no studies in hypertensives all other studies have failed to find an influence on blood pressure.
grade-b - High See all 4 studies
Beyond a small (less than 5%) attenuation in the rate of lumbar bone mineral density losses, standard supplementation does not appear to significantly influence bone mass or the rate of bone loss.
grade-b - Very High See all 6 studies
Regardless of any direct estrogenic effects (which also do not appear to occur) there are no changes in circulating estrogen seen with oral supplementation of red clover extract.
grade-b - Very High See all 6 studies
No significant influence on FSH seen with oral supplementation of red clover to postmenopausal women
grade-b - Very High See all 3 studies
No influence of supplementation on circulating concentrations of any measured IGF binding protein (IGFBP-1, IGFBP-2, IGFBP-3) in any tested population.
grade-b - Very High See all 3 studies
Supplementation does not appear to significantly influence circulating IGF-1 concentrations, although equol (a possible metabolite of formononetin) has been associated with a reduction not observed to a significant degree in most trials on red clover extract.
grade-b - Very High See all 3 studies
Luteinizing hormone does not appear to be significantly influenced with oral supplementation of red clover extract in postmenopausal women.
grade-b - Very High See all 6 studies
There are no significant alterations in the circulating levels of SHBG seen with red clover supplementation.
grade-b - High See all 3 studies
The majority of evidence has suggested no significant influence of red clover supplementation on the testosterone concentrations in postmenopausal women
grade-b - Very High See all 7 studies
No studies, even those using up to 120mg total isoflavones for up to a year, have noted significant weight loss associated with Red Clover supplementation in postmenopausal women.
grade-c Notable Very High See 2 studies
A minor reduction in anxiety (associated with menopause) has been noted in one independent trial while it was much more significant (near 80%) in a study with a potential conflict of interest; requires more research.
grade-c Notable - See study
Depression as a side-effect of menopause has been noted to be decreased to quite a significant level (around 80%) which needs to be replicated due to possible funding issues.
grade-c Minor Very High See 2 studies
Short term supplementation of red clover isoflavones appears to reduce arterial stiffness in a manner independent of changes in blood pressure or flow.
grade-c Minor - See study
Isolated formononetin has been noted to reduce circulating VCAM-1 levels by approximately 11% in one study.
grade-c Minor - See study
The complaint of 'dry eyes' appears to be slightly reduced in postmenopausal women given 80mg of the isoflavones as a supplement.
grade-c Minor Moderate See 2 studies
While one study has noted no significant effect, another has noted a minor reduction in sensitivity as assessed by QUICKI; reasons underlying this are unknown.
grade-c
Minor
- See study
The lone study to assess cognition in older women in menopause has noted an increase in visuospatial processing yet a reduction in digit span and verbal memory tests; uncertain implications.
grade-c Minor - See study
There appears to be an overall increase in skin texture and moisture content associated with oral supplementation of the isoflavones, and a depigmenting activity should also apply (not yet shown in humans)
grade-c Minor - See study
In post menopausal women, there appears to be an increase in self reported sleep quality that was quite notable, reaching 70-73 points of improvement on a 0-100 rating scale (placebo at 10-16) although this needs to be replicated (independently) to assure quality of data.
grade-c - - See study
No significant influence on attention processing in older women in a postmenopausal state with supplementation of red clover isoflavones.
grade-c - Moderate See 2 studies
The reduction in arterial stiffness (increase in arterial compliance) sometimes seen with supplementation of red clover extract does not necessarily coincide with improved blood flow.
grade-c - Very High See 2 studies
No significant influence on fasting blood glucose concentrations are known with supplementation of red clover extract.
grade-c - Very High See 2 studies
Breast density, as a measure of estrogenicity, has failed to be significantly influenced with supplementation of red clover extract in postmenopausal women.
grade-c - Very High See 2 studies
No known changes to circulating fibrinogen concentrations.
grade-c - - See study
There does not appear to be a significant influence on oxidative parameters seen with supplementation of red clover isoflavones.
grade-c - - See study
No significant changes in HbA1c seen with supplementation of red clover in diabetics.
grade-c - - See study
No significant influence on resting heart rate is seen with supplementation of red clover extract.
grade-c - - See study
There do not appear to be changes to circulating homocysteine in premenopausal women given supplementation of red clover extract.
grade-c - Very High See 2 studies
Fasting blood insulin concentrations do not appear to be significantly influenced with supplementation of red clover extract.
grade-c - - See study
No known interactions with serum MDA concentrations, a biomarker of lipid peroxidation.
grade-c - - See study
Liver function does not appear to be significantly altered with supplementation of red clover.
grade-c - - See study
Circulating osteocalcin does not appear to be influenced with supplementation of red clover extract.
grade-c - - See study
Circulating levels of PAI-1 (plasminogen activation inhibitor 1) have not been altered with supplementation of red clover isoflavones.
grade-c - - See study
There do not appear to be any significant changes to circulating folate seen with supplementation of red clover extract.
grade-c - Moderate See 2 studies
Two differing studies have noted either no improvement of well being in menopausal women, or a significant (near 80%) improvement; more research is needed to refine the actual effect, but the study noting no effect is considered higher quality.
grade-d Minor - See study
One preliminary study has noted a reduction in Apolipoprotein B concentrations with supplementation of a Formononetin rich red clover supplement.

Studies Excluded from Consideration

Note: The brand name products Promensil® and Rimostil® are included in the above table due to exclusively containing isoflavones found in Red Clover

  • Excluded due to being used alongside a peptide[1]

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Things to Note

Primary Function:

Also Known As

trifolium pratense, biochanin A, Formononetin Promensil (brand name), Menoflavon (brand name)

Caution Notice

Has been noted to interact with Drug Metabolism

  • Can potentially increase retention of methotrexate, a pharmaceutical with a relatively low therapeutic index (more prone to adverse drug-drug interactions)

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