Reviewed: Huseini HF, Kianbakht S, Mirshamsi MH, Zarch AB. Effectiveness of topical Nigella sativa seed oil in the treatment of cyclic mastalgia: a randomized, triple-blind, active, and placebo-controlled clinical trial [published online November 19, 2015]. Planta Med. doi: 10.1055/s-0035-1558208.

Mastalgia, or breast pain, may interfere with quality of life and can occur as a non-cyclic phenomenon or as cyclic mastalgia, which occurs during the premenstrual phase of the cycle. Although there are a few standard treatments for severe mastalgia, including nonsteroidal anti-inflammatory drugs (NSAIDs), these common therapies can cause adverse side effects. Traditionally, black cumin (Nigella sativa, Ranunculaceae) seed and preparations thereof have been used both internally and externally as an analgesic, galactagogue, digestive stimulant, and antibacterial for a variety of ailments, including gastrointestinal problems, bacterial infections, dysmenorrhea, and hypertension. In Iranian traditional medicine, black cumin seed oil is used topically for mastalgia. This randomized, triple-blind, placebo-controlled trial compared the topical use of black cumin seed gel with diclofenac gel (an NSAID) and placebo.

The study included Iranian women (aged 25-45 years) with regular menstrual cycles who had cyclic mastalgia during at least three previous consecutive menstrual cycles, who experienced pain for at least seven days per month, and who had mastalgia severity scores greater than 4 on a visual analog scale (VAS; 0 = no pain to 10 = severe pain), requiring medical treatment. Those taking NSAIDs, hormones, or a hormone-based contraceptive, and those who had irregular menstrual cycles, cancer, a hysterectomy, or an oophorectomy (the surgical removal of ovaries) in the past were excluded. Patients who were pregnant, lactating, planning to become pregnant, or had severe health issues also were excluded.

Treatments consisted of cold-pressed black cumin seed oil gel (30% seed oil by weight; Barij Essence Pharmaceutical Company; Mashhad-e Ardahal, Iran), diclofenac gel (1% diclofenac by weight; Darou Pakhsh Pharmaceutical Company; Tehran, Iran), and placebo gel. The same gel base was used for all three treatments. Patients applied 2 g black cumin seed oil gel (equivalent to 600 mg of black cumin seed oil), 2 g diclofenac gel (equivalent to 20 mg of diclofenac), or 2 g placebo gel topically at the mastalgia site twice daily for two menstrual cycles.

The study’s primary endpoint was pain improvement based on VAS scores during three baseline cycles and two treatment cycles at the late luteal phase (post-ovulation). Patients also reported any adverse side effects (the secondary endpoint). Returned treatment containers and patient self-reporting were used to measure compliance. Fatty acid concentrations, as well as fixed and volatile compounds in the black cumin seed oil, were measured using gas chromatography-mass spectrometry.

From a total of 181 patients screened, 159 were randomly assigned to black cumin seed oil gel, diclofenac gel, or placebo gel (n = 53 for each). In the black cumin seed oil and diclofenac groups, one and two patients, respectively, were lost to follow-up for “personal reasons,” leaving a total of 156 for the analysis. Patients reportedly “fully complied” with the study protocol.

No significant differences were noted in baseline pain scores between groups. Following the second treatment cycle, those in the black cumin seed oil group experienced a significant decrease in pain scores compared to baseline (P < 0.001). A significant decrease in pain scores was also seen in those using diclofenac (P < 0.001). A nonsignificant reduction in pain scores between baseline and endpoint was observed in the placebo group (P > 0.05).

The pain scores of those in the black cumin seed oil and diclofenac groups during both treatment cycles were significantly less than those of the placebo group (P < 0.001 for both comparisons). Additionally, no significant differences were noted between scores of the black cumin seed oil and diclofenac groups after either treatment cycle. Patients (98% of the black cumin seed oil group and 95% of the diclofenac group) reported more than 50% pain relief, with relief occurring 10-15 minutes following topical application. None of the patients reported any adverse side effects.

In the phytochemical analysis, the unsaturated fatty acids linoleic acid (58.24%), oleic acid (22.58%), and palmitoleic acid (0.28%) were prominent fixed compounds in the black cumin seed oil. The phytochemicals -cymene (51.62%), thymoquinone (14.48%) and carvacrol (0.96%) were detected as volatile components.

In this study, both black cumin seed oil gel and diclofenac gel were effective in treating mastalgia compared with placebo. The data suggest that black cumin seed oil may be as effective as diclofenac, since no significant differences were noted between pain scores in treatment cycles of these groups. Since there were no adverse side effects reported during the treatment period, black cumin seed oil appears safe for use.

Thymoquinone and carvacrol have previously been shown to have analgesic effects, and may contribute to the pain-reducing effects seen with the topical application of black cumin seed oil gel. However, since these compounds were not directly tested, no conclusion can be drawn as to their bioactivity, and the pain modulation may be due to other undetected compounds. Further studies should investigate the potential mechanisms of action of black cumin seed oil.

The results of this trial suggest that topical black cumin may be a candidate for the list of evidence-based natural therapies for cyclic mastalgia, which includes chaste tree (Vitex agnus-castus, Lamiaceae) berry, evening primrose (Oenothera biennis, Onagraceae) seed oil, vitamin E, and molecular iodine.

—Amy C. Keller, PhD