After the 12 week treatment period, the Kupperman index for the red ginseng group significantly reduced from 18.93 to 13.32 compared with the placebo from 15.21 to 15.10. The Menopause Rating Scale score dropped significantly from 12.45 to 8.32 in the ginseng group compared with 10.23 to 9.26 in the placebo group. The hot flash score also reduced significantly in the red ginseng group.

Red ginseng also elicited a significant decrease in total cholesterol from 138.11 to 108.82 compared with the placebo, from 128.52 to 128.03. The drop in LDL was also significant in the red ginseng group compared to placebo but there were no significant differences between the two groups for HDL cholesterol or C-reactive protein. The estrogen levels were not considered to be affected by red ginseng. On the other hand, the carotid intima-media thickness was significantly reduced in the red ginseng group compared with the placebo group.

Commentary: This is not the first randomized, controlled trial using ginseng in menopause symptoms but it is the first double-blind randomized controlled trial to investigate the effect of red ginseng for 12 weeks on menopausal symptoms in postmenopausal women. In the previous trial published in 1999, there were no clear effects on hot flashes but there was an effect on quality of life. In the current study however, there was a clear effect in reducing the menopause symptoms rated on the Kupperman Index and the Menopause Rating Scale, including hot flashes. These are two of the most common research tools in evaluating menopause symptoms.

The positive results of red ginseng for hot flashes in the current study versus the negative results in the previous trial could be explained by the difference in ginseng used. Red ginseng has physiologically active components that are not present in raw white ginseng or the plain Panax ginseng. Another significant difference in the two studies is the 3gmper day of the red ginseng versus the 200 mg of ginseng in the previous study.

Reference

Young Kim S, Kyo Seo S, Mi Choi Y, et al.  Effects of red ginseng supplementation on menopausal symptoms and cardiovascular risk factors in postmenopausal women: a double-blind randomized controlled trial.  Menopause 2012;19(4):461-466

The incidence of type A influenza was significant and widespread in Japan through the study period of November 2008 to February 2009. A total of 2050 schoolchildren were included in the final analysis. The number of episodes of clinical influenza that were reported was 241, and 204 of those were confirmed by an antigen test. There were 185 cases of influenza A, 18 of influenza B and 1 case of combined.

More than 50% of the 2050 respondents drank green tea more than 6 days/week and 77.3% of the students drank < 1 cup a day and 1 to < 3 cups per day with approximately equal numbers of students in each group.

The consumption of 1-5 cups of green tea on an almost daily basis of 6 or more days/week was inversely associated with the incidence of influenza in this group of elementary schoolchildren. There was no evidence that more than 5 cups per day had any benefit for some reason.

Commentary: I am aware of six other studies on the prevention of influenza with green tea, including the previous blog posting in February, on my blog site. Collectively, these studies show that green tea inhibits the influenza virus in the laboratory, enhances systemic immunity in humans, and prevents the occurrence of cold and flu symptoms in adults. Drinking green tea and gargling with green tea are the methods that have been studied but for those of you who do not like or do not want to take the time to drink green tea, green tea capsules are another way to get the potential benefits of green tea.

Reference

Park M, Yamada H, Matsushita K, et al. Green tea consumption is inversely associated with the incidence of influenza infection among schoolchildren in a tea plantation area of Japan. J Nutrition 2011;141:1862-1870.

About two hundred health care workers in three different healthcare facilities in Japan were randomized to receive either a placebo or a combination of green tea catechins and theanine that contained 378 mg/day of catechins and 210 mg/day of theanine, both constituents found in green tea.

Of these eligible health care workers, 98 received the green tea and 99 received the placebo. The incidence of clinical signs and symptoms of influenza infection was significantly lower in the green tea (4.1%) group compared with the placebo group (13.1%).

Commentary:

The catechins and theanine in green tea have shown previous promise as a strategy for preventing influenza infections. In the laboratory, experiments have shown that green tea catechins can prevent influenza infection. A small study was then done that reported that gargling with tea catechins extracts was effective in preventing influenza infection in the elderly individuals in nursing homes. Green tea extracts have also been shown to enhance systemic immunity and prevent upper respiratory infections and influenza symptoms in adults. Based on this preliminary research, the more substantial randomized, double-blind study was done on the effectiveness of green tea catechins and theanine in preventing influenza infections. This is an extremely useful, simple, safe method of reducing the incidence of influenza. I will be advising my patients to take a standardized extract of green tea capsule regularly and/or drinking green tea liberally, especially during flu season.

Reference

Matsumoto K, Yamada H, Takuma N, et al. Effects of green tea catechins and theanine on preventing influenza infection among healthcare workers: a randomized controlled trial. BMC Complementary and Alternative Medicine 2011; 11:15

A statistically significant change was reported in the quality of the sleep in the valerian group when compared to the placebo group. The average scored on the sleep scale before valerian was 9.8 and after valerian it was 6.02. The placebo group had an initial average sleep scale score of 11.1 and after placebo, 9.4. Overall, 30% of the women taking valerian and 4% taking placebo reported an improvement in their sleep quality.

Commentary:

Approximately 61% of postmenopausal women have sleep problems, which then of course can lead to other consequences including impaired function, fatigue, depression and reduced quality of life. In addition, hot flushes and night sweats, which affect 75% to 85% of postmenopausal women, can also affect sleep quality.

Valerian is the most commonly used herb for individuals suffering from insomnia and is in the top 10 herbal supplements most commonly used in general. Quite a few studies have been done on valerian and insomnia in the last 20 years but few have studied older adults and no previous studies in postmenopausal women and over a longer period of time such as the current study. Results have been inconsistent and quite varied in the design of the study. Several previous studies have reported improvement in sleep quality in individuals using valerian over time but there are only a few studies with significant improvement in sleep outcomes when compared to placebo. Fortunately, the current study has shown that valerian improves the quality of sleep in postmenopausal women with insomnia, and can add to our treatment options in a much needed area of medicine.

Reference

Taavoni S, Ekbatani N, Kashaniyan M, Haghani H. Effect of valerian on sleep quality in postmenopausal women: a randomized placebo-controlled clinical trial. Menopause 2011; 18(9): 951-955.

The Maitake extract tablets contained 18 mg of an extract called “SX-fraction” (MSX), a water-soluble glycoprotein, and 250 mg of dried Maitake mushroom powder. Each patient was given 3 tablets, 3 times a day. For those who received the CC, they were given 50 mg/day from days 5 to 9 of menses and repeated up to 3 cycles. For patients who then took the combination, the same dosing regimen was used.

Twenty-six patients in the MSX group and 31 in the CC group were evaluated for ovulation with pelvic ultrasounds. The ovulation rate for MSX was 76.9% (20/26) and 93.5% (29/31) for CC. For the combination treatment, 7 of 7 patients who failed the MSX monotherapy and 6 of 8 patients who failed the CC monotherapy demonstrated ovulation.

Commentary: This study demonstrated the ability of a Maitake extract to induce ovulation in patients with PCOS and can be used as a monotherapy or as an adjunct to clomiphene citrate. The ovulation rate of 76.9% is quite impressive, even though the clomiphene citrate rate was much better at 93.5%.

Maitake extract is reported to modulate serum glucose levels, reduce blood pressure, optimize serum lipids and enhance insulin sensitivity in animal studies, all important core issues in women with PCOS.

Reference

Chen J, Tominaga K, Sato Y, et al. Maitake mushroom (Grifola frondosa) extract induces ovulation in patients with polycystic ovary syndrome: a possible monotherapy and a combination therapy after failure with first-line clomiphene citrate. J Alternative and Complementary Medicine 2010;12(12):1295-1299

A systematic review was done to assess the clinical evidence for or against the efficacy of maca for sexual dysfunction. The review included only randomized clinical trials comparing maca to a placebo in men or women with sexual dysfunction. Four randomized controlled trials (RCT) met the inclusion criteria. Two of these trials suggested a positive effect of maca on sexual dysfunction or libido in menopausal women or adult. One other RCT did not show effect of maca in cyclists. The fourth study assessed the effects of maca in men with erectile dysfunction and did show significant effects.

While the evidence is limited, there does appear to be some effectiveness of maca in improving sexual function.

Reference

Shin B, Soo Lee M, Jin Yang E, Lim H, Ernst E. Maca (L. meyenii) for improving sexual function: a systematic review. BMC Complementary and Alternative Medicine 2010;10:44

A study of St John’s wort liquid extract showed a statistically decline in hot flashes severity, duration and frequency in the SJW group compared to placebo at week 8.[1]

Another double blind randomized clinical trial demonstrated that after 3 months of treatment, women in the St. John’s wort group reported significantly better quality of life scores, and significantly fewer sleep problems compared to placebo. [2]

About ten years ago, a non placebo controlled, drug monitoring study was conducted in women with menopause symptoms using 900 mg of St. Johns wort for 12 weeks. About three quarters of the women experienced improvement in both the self-rating scale and the physician rating, and significantly improved in psychological and psychosomatic symptoms as well as a feeling of sexual well-being.[3]

The first of three studies using St. John’s wort and black cohosh was published in 1999. This double-blind, randomized, placebo-controlled trial used St. John’s wort and black cohosh made by the makers of Remifemin.[4] The Kupperman index for the combination product decreased from 31.4 to 18.7 compared with a decrease in the placebo group from 30.3 to 22.3. Psychological symptoms also improved significantly in the black cohosh/St. John’s wort combination group.

A double-blind randomized placebo-controlled study was done using a combination trial of black cohosh and St. John’s wort. The mean Menopause Rating Scale score decreased 50% in the treatment group and 19.6% in the placebo group.[5] The Hamilton Depression Rating Scale score decreased 41.8% in the treatment group and 12.7% in the placebo group. In both testing measures the St. John’s wort + black cohosh group was significantly superior to the placebo group.

Another black cohosh/St. John’s wort trial was carried out in peri or postmenopausal Korean women, and was published in 2007.[6] Mean Kupperman index scores at 4 and 12 weeks were significantly lower in the treatment group (P < 0.002). At the end of the study, the average decrease in the Kupperman Index was 20 points in the treatment group and only 8.2 points in the placebo group (P < 0.001). Vaginal dryness and low libido were two symptoms that did not improve, but the average hot flash scores were significantly lower in the black cohosh/St. Johns wort group.

Finally, a study was done in which a combination of black cohosh with or without St. John’s wort was used in 6141 women at 1287 outpatient gynecologists in Germany in a prospective, controlled open-label observational study.[7] The greatest changes occurred with the combination therapy for nervousness/irritability and mood swings, but in the area of depression, there was a reduction in both treatment groups.

St. John’s wort is emerging as an important clinical tool in treating perimenopausal/menopausal women—for hot flashes and/or depression and/or mood swings, as a single agent, or in combination with other therapies.

References

[1] Abdali K, Khajehei M, Tabatabaee R. Effect of St. John’s wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause 2010;17(2): 326-331.

[2] Al-Akoum M, Maunsell E, Verreault R, Provencher L, Otis H, Dodin S. Effects of Hypericum perforatum (St. John’s wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause. 2009 Mar-Apr;16(2):307-14.

[3] Grube B, Walper A, Whatley D. St. John’s wort extract: Efficacy for menopasual symptoms of psychological origin. Adv Ther 1999;16:177.

[4] Boblitz N, Schrader E, Henneicke-Von Zepelin H, et al. Benefit of a fixed drug combination containing St. John’s wort and black cohosh for climacteric patients-results of a randomised clinical trial )poster presentation from 6^th Annual Symposium on Complementary Health Care, Exeter, England, December 2-4 1999). Focus Alt Comp Ther 2000;5(1):85-86.

[5] Uebelhack R, Jens-Uwe Blohmer, et al. Black cohosh and St. john’s wort for climacteric complaints. Obstet Gynecol 2006;107:247-255.

[6] Chung D, Kim H, Park K, et al. Black cohosh and St. John’s wort (GYNO-Plus) for climacteric symptoms. Yonsei Med J 2007;48(2):289-294.

[7] Briese V, Stammwitz U, Friede M, et al. Black cohosh with or without St. John’s wort for symptom-specific climacteric treatment- Results of a large-scale, controlled, observational study. Maturitas 2007;57:405-414.

Results: The total MRS II score for women while on black cohosh treatment reduced from 17.6 to 13.6, a statistically significant reduction. Symptoms of hot flashes, sweating, sleep problems, and anxiety improved, but vaginal dryness and body aches/pains did not change. Twenty two patients reported adverse events, but none were linked with the black cohosh; 90% of the women reported the tolerability of the black cohosh extract as very good or good.

Commentary: This is one more positive study using black cohosh extract for menopausal symptoms and even more meaningful, women on tamoxifen can have more problematic menopause symptoms and so a significant benefit of black cohosh is especially needed. Readers will also want to be reminded that we do have safety data on black cohosh in breast cancer patients—there is no estrogen in black cohosh, no phytoestrogens in black cohosh, no ability to stimulate breast cancer cells and laboratory data showed that black cohosh inhibited proliferation of estrogen receptor positive breast cancer cells and augmented the anti-estrogen effect when using black cohosh with tamoxifen. Black cohosh is clearly the first choice herb for menopause symptoms in breast cancer patients, and in breast cancer patients on tamoxifen.

Reference:

Rostock M, Fischer J, Mumm A, et al. Black cohosh (Cimicifuga racemosa) in tamoxifen-treated breast cancer patients with climacteric complaints – a prospective observational study. Gynecol Endocrinol. 2011 Jan 13;

While taking the cranberry extract, none of the women had a UTI over the course of the 6 months and almost all of the urine cultures were sterile (normal). Three women reported mild gastrointestinal problems and their dose was reduced to 2 capsules per day and as a result, their gastrointestinal problems subsided.

Commentary: Cranberries, in the form of juice and capsules have been shown to be effective in previous prevention and treatment of bladder infections. Both cranberries and blueberries belong to the Vaccinium species which are rich sources of dietary flavonoids, including anthocyanins and proanthocyanidins. While the exact mechanism of the benefits of cranberries has not been clearly established, it is thought that the inhibition of adherence of the main bacteria causing infection, Escherichia coli, to the uroepithelial cells that line the wall of the bladder is the main action.

Reference:

Karefilakis C, Mazokopakis E. Efficacy of cranberry capsules in prevention of urinary tract infections in postmenopausal women. J Altern Complement Med 2009;15(11):1155.

After 8 weeks, both the hops group and the placebo group had significant improvement in outcome measures compared to the baseline and actually higher average reductions in the placebo group. After 16 weeks however, only the group that was on the hops extract in the second 8 weeks had a reduction in all outcome measures whereas the placebo group in the second 8 weeks had an increase for all outcome measures. Although the overall treatment efficacy of the hops treatment compared with the placebo did not show a significant effect, the time specific uses did indicate significant reductions in the KI and the VAS for the hops group, and a marginal reduction in symptoms for the MRS after 16 weeks.

Commentary: This is the second study on an oral hops extract for menopause symptoms that I am aware of. The German Commission E (the German agency similar to our FDA), has approved hops for mood issues such as anxiety and restlessness, and for sleep disruptions. In the previous randomized, double-blind, placebo-controlled study, 67 menopausal women were given either a placebo or a 100 mcg or 250 mcg standardized hops extract for 12 weeks.[i] At 6 weeks, the 100 mcg dose was significantly superior to placebo, but not after 12 weeks. Even so, there was a more rapid decrease in menopause symptoms scored for both doses of hops extract , especially the hot flush score. The higher dose was not any better than the lower dose. Both the current study and this previous study, used a standardized hops extract at 100 mcg 8-prenylnaringenin. The current study used the lower 100 mcg dose.

This hops standardized extract may provide a useful herb for women suffering from common menopause symptoms such as hot flashes/night sweats. I have been using it in my clinical practice for approximately two years, usually along with one or more of the following: Black cohosh, St. John’s wort, Maca extract or a combination botanical of Dong Quai/burdock root/ wild yam root/ licorice root/motherwort. Hops do contain phytoestrogens and this is the likely mechanism of action.

Reference:

[i] Heyerick A, Vervarcke S, Depypere H, et al. A first prospective, randomized, double blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts. Maturitas 2006;54:164-175.