ERr 731® (Rheum rhaponticum extract)

Rheum rhaponticum
Evidence Level
Moderate
3 Clinical Trials
5 Documented Benefits
3/5 Evidence Score

ERr 731® is a standardized extract of Siberian rhubarb (Rheum rhaponticum) root produced by Chemisches Laboratorium Dr. Kurt Richter and used as the active ingredient in branded menopause products such as Estrovera. It contains a defined profile of hydroxystilbene glycosides (rhaponticin, desoxyrhaponticin, and their aglycones rhapontigenin and desoxyrhapontigenin) that, in laboratory cell studies, switch on estrogen receptor beta much more than estrogen receptor alpha. In a 12-week randomized, placebo-controlled trial in 109 perimenopausal women, one tablet a day lowered total Menopause Rating Scale II scores significantly more than placebo. All of the published human research on this extract comes from a single research group linked to the manufacturer, and no independent team has repeated it. It is used by women looking for a non-hormone option during the menopausal transition, though switching on an estrogen receptor is still estrogen-like activity, not the absence of it.

Studied Dose One enteric-coated tablet daily standardized to 4 mg ERr 731 extract.
Active Compound Hydroxystilbene glycosides rhaponticin and desoxyrhaponticin (with aglycones rhapontigenin and desoxyrhapontigenin); in laboratory cell studies these switch on estrogen receptor beta rather than estrogen receptor alpha.

Benefits

Helps reduce menopausal hot flashes

In a 12-week randomized, placebo-controlled trial in 109 perimenopausal women (54 on the extract, 55 on placebo), one tablet a day lowered total Menopause Rating Scale II scores, including the hot flush and sweating items, significantly more than placebo. The trial was run by a research group linked to the extract's maker and has not been repeated by an independent team.

Supports overall menopausal symptom relief

In the 12-week trial, the total Menopause Rating Scale II score, which combines hot flush, mood, and physical complaint items, improved more than with placebo. That score is a symptom questionnaire, not a measure of hormone levels, and the results come from women who already had bothersome menopausal symptoms rather than from the general population.

Helps maintain mood and emotional balance

The anxiety, irritability, and depressed mood questions inside the Menopause Rating Scale improved during the 12-week trial in perimenopausal women. These are single items within a menopause symptom questionnaire, not a test of depression or anxiety treatment, and no study has looked at this extract as a stand-alone mood supplement.

May help the sleep item on menopause symptom scores

The sleep problems question inside the Menopause Rating Scale was among the items that improved in the 12-week trial. No study has measured sleep with a dedicated sleep questionnaire or in a sleep lab, so this is a single self-reported item within a menopause symptom score rather than evidence of a sleep aid.

Selectively activates estrogen receptor beta in lab studies

In laboratory cell studies the extract switches on estrogen receptor beta but not estrogen receptor alpha. That is receptor-selective estrogen activity, not an absence of estrogen activity, so describing it as non-estrogenic is misleading. In the 12-week trial, gynecological findings including endometrial biopsies showed no differences from placebo, which is reassuring but covers only 12 weeks in 109 women. Women with a history of breast or endometrial cancer, and women taking hormone therapy or tamoxifen, should talk to their doctor before using this or any other phytoestrogen.

Mechanism of action

1

Selective ER-beta activation

In cell-based laboratory studies, the aglycones rhapontigenin and desoxyrhapontigenin switch on estrogen receptor beta but not estrogen receptor alpha. This work was done in cells, not in people. Researchers think this receptor pattern may explain the symptom changes seen in the trials, but that link has never been demonstrated directly in humans.

2

Modulation of hypothalamic thermoregulation

Estrogen receptor beta activity in the brain's temperature control center may help steady the body's thermostat. This is a proposed explanation borrowed from general estrogen biology; nothing in the studies of this extract measured brain or temperature regulation.

3

Lack of uterotrophic ER-alpha signaling

Because the extract did not switch on estrogen receptor alpha in cell studies, researchers expected no thickening of the uterine lining. In the 12-week trial, gynecological findings including endometrial biopsies showed no differences between the extract and placebo. That is short-term data in 109 women and does not establish long-term uterine safety.

4

Serotonergic and mood-related signaling

Estrogen receptor beta activity can influence serotonin signaling, which is involved in mood. This is offered as a possible explanation for the mood questions that improved on the menopause symptom questionnaire, but no study of this extract measured serotonin or brain activity.

Clinical trials

1
12-week RCT in perimenopausal women

Randomized, double-blind, placebo-controlled trial; one enteric-coated ERr 731 tablet daily for 12 weeks, with 54 women on the extract and 55 on placebo.

109 perimenopausal women with climacteric complaints (Menopause Rating Scale II baseline).

Compared with placebo, the extract lowered the total Menopause Rating Scale II score significantly more (P less than 0.0001), along with the hot flush and other symptom items. Gynecological findings, including endometrial biopsies, showed no differences between the two groups over the 12 weeks. The authors are affiliated with a research group linked to the extract's manufacturer.

2
Follow-up efficacy report from the same research group

Multicenter, randomized, double-blind, placebo-controlled confirmatory trial; one ERr 731 tablet daily for 12 weeks.

112 perimenopausal women with menopausal symptoms.

This report describes reductions in the Menopause Rating Scale total score and in hot flush number and severity versus placebo, with no relevant safety signals. It is indexed in PubMed both as a randomized trial and as a meta-analysis, so it may partly re-analyze the earlier data rather than being a fully independent second trial, and it comes from the same manufacturer-linked research group.

3
Long-term observational extension

Two consecutive 48-week observational, open-label follow-up periods (up to 96 weeks total) in roughly 39 to 51 women. There was no placebo group and no randomization in these periods, so this is not a controlled trial.

Perimenopausal women previously enrolled in the 12-week RCT who continued with open-label ERr 731.

Menopause Rating Scale II scores stayed improved across the 96 weeks and no adverse events were attributed to the extract. Because every participant knew she was taking it and there was no comparison group, these results cannot show that the extract caused the continued improvement, and the group was small (roughly 39 to 51 women).

Side effects and drug interactions

Common Potential side effects

Mild gastrointestinal complaints such as stomach discomfort or nausea have been reported.
Occasional headache or dizziness was noted in clinical trial users.
Allergic-type skin reactions are uncommon but possible in sensitive individuals.
Breast tenderness has been reported infrequently during use.
No estrogenic endometrial thickening was observed but unscheduled bleeding warrants evaluation.

Important Drug interactions

May theoretically interact with hormone replacement therapy or oral contraceptives via ER signaling.
Women taking tamoxifen or aromatase inhibitors, and women with a personal history of breast or endometrial cancer, should talk to their doctor before using this or any other phytoestrogen, because the extract activates an estrogen receptor.
Concurrent use with other phytoestrogen supplements may compound estrogenic activity.
Theoretical interaction with anticoagulants such as warfarin warrants medical supervision.

Frequently asked questions about ERr 731® (Rheum rhaponticum extract)

What is ERr 731?

ERr 731® is a standardized extract of Siberian rhubarb (Rheum rhaponticum) root produced by Chemisches Laboratorium Dr. Kurt Richter and used as the active ingredient in branded menopause products such as Estrovera.

What is ERr 731 used for?

ERr 731 is researched primarily for Women's Health, Menopause Support, and Mood & Mental Health. In a 12-week randomized, placebo-controlled trial in 109 perimenopausal women (54 on the extract, 55 on placebo), one tablet a day lowered total Menopause Rating Scale II scores, including the hot flush and sweating items, significantly mor…

What is the recommended dosage of ERr 731?

The clinically studied dose is One enteric-coated tablet daily standardized to 4 mg ERr 731 extract. Always follow the product label and check with a healthcare provider for personal advice.

Is ERr 731 safe, and does it have side effects?

For most healthy adults, ERr 731 is well tolerated at studied doses. Reported effects can include: Mild gastrointestinal complaints such as stomach discomfort or nausea have been reported. Occasional headache or dizziness was noted in clinical trial users. It may also interact with some medications. ERr 731 is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does ERr 731 interact with any medications?

Possible interactions include: May theoretically interact with hormone replacement therapy or oral contraceptives via ER signaling. Women taking tamoxifen or aromatase inhibitors, and women with a personal history of breast or endometrial cancer, should talk to their doctor before using this or any other phyto… If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for ERr 731?

NutraSmarts rates the evidence for ERr 731 as Moderate (3 out of 5). It is backed by 3 clinical trials and 4 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(4 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Heger M, Ventskovskiy BM, Borzenko I, Kneis KC, Rettenberger R, Kaszkin-Bettag M, Heger PW. Efficacy and safety of a special extract of Rheum rhaponticum (ERr 731) in perimenopausal women with climacteric complaints: a 12-week randomized, double-blind, placebo-controlled trial. Menopause. 2006;Menopause. 2006 Sep-Oct;13(5):744-59..PubMedUsed to support: Original 12-week RCT showing ERr 731 significantly reduced MRS II total score and hot flashes vs placebo in 109 perimenopausal women.
  2. Kaszkin-Bettag M, Ventskovskiy BM, Solskyy S, Beck S, Hasper I, Kravchenko A, Rettenberger R, Richardson A, Heger PW. Confirmation of the efficacy of ERr 731 in perimenopausal women with menopausal symptoms. Alternative Therapies in Health and Medicine. 2009;Altern Ther Health Med. 2009 Jan-Feb;15(1):24-34..PubMedUsed to support: Follow-up report from the same manufacturer-linked research group showing significant MRS reductions versus placebo; PubMed indexes it both as a randomized trial and as a meta-analysis, so it may partly re-analyze the earlier dataset.
  3. Hasper I, Ventskovskiy BM, Rettenberger R, Heger PW, Riley DS, Kaszkin-Bettag M. Long-term efficacy and safety of the special extract ERr 731 of Rheum rhaponticum in perimenopausal women with menopausal symptoms. Menopause. 2009;Menopause. 2009 Jan-Feb;16(1):117-31..PubMedUsed to support: Two 48-week observational, open-label follow-up periods (up to 96 weeks, roughly 39 to 51 women, no control group) reporting sustained MRS scores and no long-term safety signals. Not a randomized controlled trial.
  4. Wober J, Möller F, Richter T, Unger C, Weigt C, Jandausch A, Zierau O, Rettenberger R, Kaszkin-Bettag M, Vollmer G. Activation of estrogen receptor-beta by a special extract of Rheum rhaponticum (ERr 731), its aglycones and structurally related compounds. Journal of Steroid Biochemistry and Molecular Biology. 2007;J Steroid Biochem Mol Biol. 2007;107(3-5):191-201..PubMedUsed to support: Laboratory (in vitro) cell study showing that ERr 731 and its aglycones switch on ER-beta but not ER-alpha. Not a human study.