Study: The role of an herbal supplement in reducing breast cancer biomarkers

reference

Laidlaw M, Cockerline CA, Sepkovic DW. Effects of an herbal breast health supplement on estrogen metabolism in pre- and postmenopausal women not taking hormonal contraceptives or dietary supplements: a randomized controlled trial.Breast cancer. 2010;4:85-95.

design

Prospective, double-blind, placebo-controlled parallel study. Subjects were recruited for one of two study arms. One arm consisted of premenopausal women who did not use hormonal contraceptives, while the other consisted of postmenopausal women who did not use hormone replacement therapy (HRT). Each part of the study was conducted simultaneously and in a phase without a washout period.

Participant

Forty-seven premenopausal and 49 postmenopausal women were recruited for the study, and data from 68 subjects were used in the statistical analysis.

intervention

Subjects were randomly divided into treatment and placebo groups. The treatment supplement (femMED Breast Health) contained 200 mg indole-3-carbinol, 10 mg HMR lignan, 100 mg milk thistle, 75 mg calcium glucarate, 75 mg Schisandra chinensis, 50 mg nettle, and 10 mcg each of vitamin D. The woman took 2 capsules daily for 28 days as either treatment or placebo.

Target parameters

On day 0 and day 28, blood samples and first morning urine samples were collected and analyzed. Blood samples were analyzed for serum enterolactone concentrations. Random urine samples were collected on the first morning and analyzed for creatinine and estrogen metabolites. Repeated measures ANOVA statistical tests were performed to compare the treatment group with the placebo group.

Key findings

femMED Breast Health significantly increased estrogen C-2 hydroxylation. In both pre- and postmenopausal women, treatment supplementation resulted in a statistically significant increase (P<0.05) in 2-hydroxyestrone (2-OHE) concentrations in urine. In the premenopausal group, treatment resulted in an increase in the estrogen to metabolite ratio of 2:16α-OHE. In premenopausal and postmenopausal women, treatment supplementation together resulted in a significant increase in urinary 2-OHE concentrations. There was also a trend (P=0.074) towards an increased 2:16α-OHE ratio in the combined group. There was no significant increase in serum enterolactone concentrations in the treatment or placebo groups.

Effects on practice

It is estimated that in 2011, 230,480 women will be diagnosed with breast cancer and 39,520 women will die from it.¹Several of the known risk factors for breast cancer are related to estrogen exposure, namely early menstruation, late menopause, late or absent pregnancy, and use of oral contraceptives or hormone replacement therapy. Alcohol, which can impair the liver's ability to metabolize estrogen, is considered a risk, and the magnitude of the risk increases as the amount of alcohol consumed increases. Consuming alcohol can cause an increase in levels of both natural and synthetic estrogens. Being overweight or obese is associated with an increased risk of breast cancer, especially in postmenopausal women. Since fat tissue is the body's main source of estrogen after menopause, more fat tissue means higher estrogen levels, which can increase the risk of breast cancer. It is estimated that approximately 80% of breast cancers are estrogen receptor positive.²Avoiding known risk factors for breast cancer, such as alcohol consumption and the use of oral contraceptives and HRT, as well as maintaining a healthy body weight and regular physical activity, are important breast cancer prevention measures. Dietary supplements can play a supportive role in risk reduction.

Estrogen-metabolite ratio and risk reduction

Studies have found that two specific metabolites of estrogen metabolism influence susceptibility to breast cancer. When urine levels of 2-hydroxyestrone (2-OHE) increase and levels of 16-alpha-hydroxyestrone (16α-OHE) decrease, the risk of breast cancer decreases because 16α-OHE is an independent risk factor for breast cancer. In most human studies, results are presented as a ratio of urinary 2-OHE to urinary 16α-OHE. The higher the ratio, the better the risk reduction for breast cancer. The optimal ratio of 2-OHE to 16α-OHE in urine is 2:1, while a ratio of 1:1 is associated with an increased risk of cancer. This ratio is commonly referred to as the estrogen metabolite ratio (EMR).^3-6

In a prospective study, 10,786 Italian women were followed for 5.5 years and EMR was measured in all of these women at baseline. The number of diagnosed breast cancer cases that occurred during the study period was compared to baseline EMRs. Among premenopausal women, women with a higher ratio had an average breast cancer risk of 0.58 compared to women with a lower ratio.³

In a postmenopausal case-control study, there was a strong inverse association between EMR and breast cancer and a strong positive association between 16-α-OHE and breast cancer.⁴In another prospective study, researchers reported that postmenopausal women who developed breast cancer over the eight years of the study had, on average, a 15% lower EMR than matched controls. Additionally, women in the highest third had a 30% lower risk of developing breast cancer than women in the bottom two-thirds of the EMR.⁷

Mechanism of action

The ingredients of the dietary supplement used in this clinical study may modulate estrogen metabolism and estrogen levels in various ways. To apply this study and formulation to clinical practice, it is important to understand the mechanism of action of the ingredients and their influence on estrogen levels.

The most commonly studied component, indole-3-carbinol, helps maintain healthy estrogen levels in the body by balancing estrogen metabolites. In vitro studies have shown that indole-3-carbinol can alter microsomal estrogen metabolism in the liver. In particular, indole-3-carbinol can upregulate phase I and phase II enzymes, resulting in increased capacity to detoxify and inhibit carcinogens. Thus, indole-3-carbinol can shift the metabolic pathway of estrogens. Many of the indole-3-carbinol metabolites have antiestrogenic activity and compete with estrogen for binding sites. There is also evidence that indole-3-carbinol can inhibit cell proliferation and induce apoptosis in tumors.^8-13

Milk thistle exerts phytoestrogenic properties. It contains compounds that act as estrogen agonists, blocking estrogen receptors for endogenous estrogen and preventing estrogen from passing its message to breast tumor cells so that they divide and multiply. Phytoestrogens may also inhibit the local production of estrogens from circulating precursors in breast tissue. Milk thistle is also well researched for its liver protective effects and ability to promote detoxification.^14-17

Calcium D-glucarate has anticarcinogenic properties and has been shown to inhibit carcinogenesis in both the promotional and initiation phases. Its anticarcinogenic properties are attributed in part to its ability to increase glucuronidation and excretion of potentially toxic compounds. Specifically, it inhibits beta-glucuronidase activity, which allows the body to excrete hormones such as estrogen before they can be reabsorbed. This reduces endogenous estrogen in the body, which helps maintain a healthy estrogen balance.^18-20

Schisandra chinensiscontains dibenzo[a,c]cyclooctadiene lignans, a type of phytoestrogen. In general, phytoestrogen consumption is associated with a lower risk of breast cancer. In addition, schisandra can also reduce exposure to endogenous sex hormones by increasing the excretion of their metabolites.^15.21

The use of dietary supplements that can improve estrogen balance should be considered as part of an overall approach to breast cancer prevention.

The HMR lignans are spruce polyphenols that have a number of structural similarities to mammalian estrogens. Epidemiological and experimental studies show that a diet rich in lignans can reduce the risk of breast cancer in humans. Serum enterolactone, a metabolite of HMR lignan with phytoestrogenic properties, is inversely correlated with breast cancer risk. In rat studies, HMR lignans have been shown to reduce both tumor volume and tumor growth.^14,16,22-27

There is increasing research on the role of vitamin D in reducing breast cancer risk. In particular, 1,25-OH D3, the biologically active form of vitamin D, has been shown to act as a strong negative regulator of breast cancer cells.^28-30Vitamin D acts through the vitamin D receptor, a nuclear transcription regulating factor that signals the synthesis of proteins involved in cell cycle regulation. Many of these proteins regulate breast cancer cell proliferation, differentiation, and survival. When vitamin D status is not optimal, these activities are impaired.^31.32Research has also shown that vitamin D can downregulate estrogen receptors to reduce the growth of breast cancer cells.³³Several well-researched and designed cohort studies have reported a reduction in breast cancer risk in women with higher dietary or supplemental vitamin D intake.^34-37

Effects on practice

The ingredients of the nutritional supplement formula examined have been proven to have positive effects on estrogen balance with different mechanisms of action. However, this is the first human clinical trial to examine the effects and potential synergistic value of a combination formula on estrogen metabolism and breast cancer risk. While further research with larger numbers of subjects is warranted, the results obtained in this clinical trial are promising.

The use of dietary supplements that can improve estrogen balance should be considered as part of an overall approach to breast cancer prevention, along with dietary and lifestyle changes known to reduce risk, such as: B. Exercise, maintaining a healthy body weight, not smoking, and limiting alcohol consumption and avoiding estrogen.

Although there is no way to test the effectiveness of many of our interventions, supplements that can modulate estrogen metabolites have a distinct advantage in this area. Doctors can assess the effect of the procedure through urine tests of 2-OHE and 16-OHE, which should provide confidence for both patients and doctors.

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