Pasta V, Dinicola S, Giuliani A, et al. A randomized pilot study of inositol in association with betaine and boswellia in the management of mastalgia and benign breast lump in premenopausal women. Breast Cancer (Auckl). 2016;10:37-43.
A 6-month double-blind, placebo-controlled, randomized clinical trial was conducted to assess the safety and efficacy of boswellic acid, betaine, and myo-inositol in the treatment of mastalgia and benign breast lumps.
A total of 76 premenopausal women, aged 22 to 51 years, with mild to severe mastalgia for longer than 6 months were enrolled in the study. Those who had received treatment for mastalgia within 4 months of the trial, were on hormonal contraceptives, or were undergoing other endocrine treatments were excluded. Further exclusion criteria included the presence of breast nodules diagnosed as breast cancer, atypical lobular hyperplasia, sclerosing adenosis, anemia, or metabolic disorders.
Once randomized, type of mastalgia (cyclic, noncyclic, or extramammary) and level of breast density (almost entirely fat, scattered fibroglandular densities, heterogeneously dense, or extremely dense) was determined for each woman.
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 a day.
Primary outcome measure was improvement of mastalgia measured by patient questionnaires obtained at randomization, month 3, and month 6. Secondary outcome measures included reduction in benign breast nodule dimension (greater than 20% of initial diameter) and overall breast density measured by mammography. Additional measures noted were relief of the following common concomitant symptoms: anxiety, menstrual pain, nipple discharge, headache, and nausea.
Of the 76 women enrolled, 62 completed the trial. Four participants were lost to follow-up; however, 2 of the 4 reported improvement during a phone interview.
Among those who classified their pain as cyclic, 56.2% of the experimental group experienced improvement, compared to 16.6% of the control group. Furthermore, 36.8% of the former reported a nearly complete resolution of pain upon completion of the trial. Of those with noncyclic pain, 61.5% of the experimental group reported relief, compared to 16.6% of the control group. Relief in both cyclic and noncyclic breast pain reached statistical significance (cyclic, P=0.025; noncyclic, P=0.29).
Supplementation with divided doses of myo-inositol (800 mg), Boswellia serrata (200 mg), and betaine (700 mg) may be a valuable new therapy in treating patients with mastalgia, benign breast disease, 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 demonstrated improvement (P=0.07). Worsening (increase in dimension) was not observed in either group.
Twenty-five of 32 (78%) women in the experimental group and 22 of 30 (73%) in the control group had extremely dense breast tissue at baseline. No changes were reported in the control group at the completion of the trial; 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 greater rates of menstrual pain improvement were noted in those taking boswellia, betaine, and myo-inositol. Improvement of all other symptoms was not significant in either group.
These results suggest that moderate doses of several commonly used supplements may improve symptoms that concern many of our premenopausal patients.
Despite the fact that breast pain (mastalgia) is commonly benign in nature, resulting from cyclic hormonal fluctuations or benign breast disease, it is a symptom that often raises significant concern for patients until further evaluation has been done.1 In addition to the emotional burden, mastalgia has been reported to affect activities of everyday living such as sexual activity and sleep.2 Therefore, there is need for a low-risk intervention to alleviate this symptom.
Several papers suggest that high breast density is a genetic, but potentially modifiable, risk factor for breast cancer.3,4 Antiestrogenic drugs, such as tamoxifen, have been successful in decreasing density and relieving mastalgia; however, accompanying adverse effects often outweigh the benefits.5 The formulation used in this study is promising because it offers the same outcomes without the unwanted side effects.
The design of the present study reveals that not all of the ingredients (B vitamins and N-acetylcysteine) are essential for achieving the documented benefits. However, previous literature revealing the individual therapeutic effects of boswellia, betaine, and myo-inositol helps us understand how each may be effective in the treatment of mastalgia and other breast-related disorders. Boswellia has proven effective in the management of various chronic inflammatory diseases due to its ability to modulate inflammation, most notably by inhibition of 5-lipoxygenase.6 Betaine, commonly known for its use in treating hypochlorhydria, has also been shown to improve breast health. Several earlier papers have reported an inverse association between betaine intake and breast cancer risk.7,8 Myo-inositol, a chemical mediator of insulin, has been found to improve hormonal and metabolic parameters, especially in women with polycystic ovary syndrome (PCOS).9 There is also evidence that myo-inositol can modulate inflammatory and oxidative processes.10,11
Given the popularity of myo-inositol for the management of PCOS, it raises the question of whether the creators of Eumastós considered the possible correlation between PCOS and the prevalence of benign breast disease (BBD) when formulating their product. There was no mention of such association by them or the authors of the paper; however several, but not all, studies suggest a relationship.
In 2000, D’Amelio et al reported BBD in approximately 7% of women with normal-appearing ovaries, 57% of women with ovarian cysts, and 92% of women with diagnosed PCOS.12 In a similar study (n=93) conducted in 2009, Gumus et al also found BBD to be significantly more prevalent among women with PCOS (40%) compared to those without (12.5%).13 These studies demonstrate a clear correlation, but a 2005 clinical trial (n=240) by Soran et al suggests otherwise. In this study, rates of fibrocystic breast disease, lump thickening, fibroadenoma, calcification, pain, redness, discharge, and hyperplasia were equally present in both the experimental and control group.14
In 2012, Ozkaya et al designed a study to determine if 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 evaluated using 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.15 These 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 a month after this first (pilot) study was published. In the second study, 64 women with fibroadenomas, aged 30 years or younger, were recruited and randomized to 2 groups; one group received the same placebo used in the pilot study and the second group received the same proprietary formula (Eumastós). After 6 months, it was found that reductions in fibroadenoma median volume were more prevalent (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 to breast health when used in combination.
According to the findings 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 treating patients with mastalgia, BBD, and/or high breast density. Furthermore, this combination may be particularly effective in treating those with PCOS and concomitant BBD.