Study: Inositol, Betaine and Boswellia for Breast Health

This article is part of the 2017 Women's Health special issue. Read the full issue or download it here.

Relation

Pasta V, Dinicola S, Giuliani A, et al. A Randomized Pilot Study of Inositol Associated With Betaine and Boswellia in the Treatment of Mastalgia and Benign Breast Lumps in Premenopausal Women.Breast cancer (Auckl). 2016;10:37-43.

Draft

A 6-month double-blind, placebo-controlled, randomized clinical trial was conducted to evaluate the safety and effectiveness of boswellic acid, betaine, and myo-inositol in the treatment of mastalgia and benign breast lumps.

Participant

A total of 76 premenopausal women aged 22 to 51 years with mild to severe mastalgia for more than 6 months were included in the study. Those who had received treatment for mastalgia, were taking hormonal contraceptives, or undergoing other endocrine treatments within 4 months of the study were excluded. Further exclusion criteria included the presence of breast nodules diagnosed as breast cancer, atypical lobular hyperplasia, sclerosing adenosis, anemia or metabolic disorders.

After randomization, the type of mastalgia (cyclic, noncyclic, or extramammary) and the degree of breast density (almost completely fat, scattered fibroglandular densities, heterogeneously dense, or extremely dense) were determined for each woman.

intervention

Participants in the control group received oral capsules each containing vitamin B6 (2.1 mg), riboflavin (2.1 mg), folic acid (300 µg), vitamin B12 (3.75 µg), and N-acetylcysteine ​​(100 mg). The experimental group received a dietary supplement called Eumastós, which contained the same combination with the addition of myo-inositol (200 mg).Boswellia Serrata(50 mg) and betaine (175 mg). All participants were instructed to take 2 capsules twice daily.

Target parameters

The primary endpoint was improvement in mastalgia as measured by patient questionnaires obtained at randomization, Month 3 and Month 6. Secondary endpoints included reduction in benign breast nodule size (greater than 20% of original diameter) and overall breast density measured by mammography. Additional measures mentioned included relief of the following common accompanying symptoms: anxiety, menstrual pain, nipple discharge, headaches and nausea.

Key insights

Of the 76 women enrolled, 62 completed the study. Four participants were lost to follow-up; However, 2 of the 4 reported improvement during a telephone interview.

Among those who classified their pain as cyclical, 56.2% of the experimental group experienced improvement compared to 16.6% of the control group. In addition, 36.8% of the former reported almost complete disappearance of pain after completing the study. Of those with noncyclic pain, 61.5% of the experimental group reported relief, compared to 16.6% of the control group. Relief of both cyclic and non-cyclic chest pain reached statistical significance (cyclic,P=0.025; non-cyclic,P=0.29).

Supplementation with split doses of Myo-Inositol (800 mg),Boswellia Serrata(200 mg) and betaine (700 mg) may be a valuable new therapy in the treatment of patients with mastalgia, benign breast diseases and/or high breast density.

Reductions in nodule size occurred at a rate of 40.7% in the experimental group, while only 16% of the control group showed improvement (P=0.07). A deterioration (increase in dimensions) was not observed in any group.

Twenty-five of 32 (78%) women in the experimental group and 22 of 30 (73%) women in the control group had extremely dense breast tissue at baseline. No changes were reported in the control group at study completion; However, 15 of the 25 (60%) in the experimental group had a significant reduction in density (P=0.001).

Relief of anxiety occurred regardless of treatment; However, significantly higher rates of improvement in menstrual pain were noted in those who took boswellia, betaine, and myo-inositol. Improvement in all other symptoms was not significant in any group.

Practice implications

These results suggest that moderate doses of several commonly used nutritional supplements may improve the symptoms that affect many of our premenopausal patients.

Despite the fact that breast pain (mastalgia) is usually benign in nature and results from cyclical hormonal fluctuations or benign breast diseases, it is a symptom that often causes considerable concern to patients until further investigation is performed.¹In addition to emotional distress, mastalgia has been reported to interfere with activities of daily living such as sexual activity and sleep.²Therefore, a low-risk intervention is required to alleviate this symptom.

Several studies suggest that high breast density is a genetic but potentially modifiable risk factor for breast cancer.^3.4Antiestrogen medications such as tamoxifen have been successful in reducing density and relieving mastalgia; However, accompanying side effects often outweigh the benefits.⁵The formulation used in this study is promising as it offers the same results without the unwanted side effects.

The design of the present study shows that not all ingredients (B vitamins etcN-Acetylcysteine) are essential for achieving the documented benefits. However, previous literature demonstrating the individual therapeutic effects of boswellia, betaine, and myo-inositol helps us understand how these may be effective in treating mastalgia and other breast-related conditions. Boswellia has been shown to be effective in the treatment of various chronic inflammatory diseases due to its ability to modulate inflammation, particularly by inhibiting 5-lipoxygenase.⁶Betaine, commonly known for its use in treating hypochlorhydria, has also been shown to improve breast health. Several previous papers have reported an inverse association between betaine intake and breast cancer risk.^7.8Myo-inositol, a chemical mediator of insulin, has been found to improve hormonal and metabolic parameters, especially in women with polycystic ovary syndrome (PCOS).⁹There is also evidence that myo-inositol can modulate inflammatory and oxidative processes.^10,11

Given the popularity of myo-inositol for the treatment of PCOS, this raises the question of whether the creators of Eumastós took into account the possible correlation between PCOS and the prevalence of benign breast disease (BBD) when formulating their product. There was no mention of such an association by them or the paper's authors; however, several, but not all, studies suggest a relationship.

In 2000, D'Amelio et al. via BBD in approximately 7% of women with normal-appearing ovaries, 57% of women with ovarian cysts, and 92% of women diagnosed with PCOS.¹²In a similar study (n = 93) conducted in 2009, Gumus et al. also found that BBD occurs significantly more frequently in women with PCOS (40%) than in women without (12.5%).¹³These studies show a clear correlation, but a 2005 clinical trial (n=240) by Soran et al suggests otherwise. In this study, the rates of fibrocystic breast disease, nodule thickening, fibroadenoma, calcification, pain, redness, discharge, and hyperplasia were equally present in both the experimental and control groups.¹⁴

In 2012, Ozkaya et al. a study to determine whether hyperandrogenemia (HA) acts as a protective factor against fibrocystic breast disease. Participants were categorized by PCOS phenotype (Group 1: PCO anovulation; Group 2: HA anovulation; Group 3: HA-PCO; Group 4: HA-PCO anovulation) and then assessed on various metabolic and hormonal parameters. Individuals in group 3 had the lowest rates of fibrocystic breast disease, while those in group 1 had the highest rates.^fifteenThese findings demonstrate an inverse correlation between hyperandrogenism and fibrocystic breast disease.

The authors of this present study (Pasta et al.) conducted a very similar clinical trial just one month after the publication of this first (pilot) study. In the second study, 64 women with fibroadenomas aged 30 years or younger were recruited and randomized into 2 groups; One group received the same placebo as in the pilot study and the second group received the same proprietary formula (Eumastós). After 6 months, the reduction in mean fibroadenoma volume was found to be more frequent (38.88% vs. 17.85%) and significant (17.86% vs. 5.96%) in the experimental group.⁵

These results further support the hypothesis that myo-inositol, boswellia, and betaine are beneficial for breast health when used in combination.

According to the results of both clinical trials by Pasta et al. supplementation with divided doses of myo-inositol (800 mg),Boswellia Serrata(200 mg) and betaine (700 mg) may be a valuable new therapy in the treatment of patients with mastalgia, BBD and/or high breast density. Additionally, this combination may be particularly effective in treating patients with PCOS and concurrent BBD.