Title: The effectiveness of vitamin B6 in reducing mastalgia: a systematic review and meta-
analysis
Version: 1 Date: 22 Jun 2025
Reviewer's report:
Comments to author
This is a systematic review and meta-analysis of the effects of vitamin B6 on mastalgia, with
the inclusion of three randomized controlled studies. As can be seen from the results of the
forest plot, vitamin B6 did not have a significant ameliorative effect on mastalgia. However,
the article's conclusion that vitamin B6 has potential benefits for reducing mastalgia, which
could easily be misleading to readers. In addition, this manuscript contains more errors in the
description of sentences.
Abstract:
1.“This study presents a meta-analysis of interventional studies that compare the effects of
vitamin B6 to a placebo in healthy women with Mastalgia.” It might be better to replace
“presents” with “is”.
2.“there were no differences between the two groups of vitamins B6 and placebo in a reduction
of pain intensity (SMD = 3.57, 95% CI: -2.01 to 9.15)”.According to figure 3, the result is
SMD=-3.57, 95%CI: -9.15 to 2.01. Please check it.
3.“This meta-analysis suggests that vitamin B6 may have a potential beneficial effect on
reducing mastalgia severity”. Based on the results, I’m afraid you can’t draw that conclusion.
Background:
4.Paragraph 2: “however, it is proposed that hormonal fluctuations including elevated estrogen
levels, progesterone deficiency, and hyperprolactinemia may play a significant role in the onset
of this form of pain”. This sentence is incorrectly structured, please change it to a subordinate
clause or add commas in the appropriate place.
5.Paragraph 4: “however, its effects have not been thoroughly analyzed in any comprehensive
meta-analysis.” The first letter of each sentence should be capitalized.
Study inclusion and exclusion criteria
6.Paragraph 1: “Mastalgia was defined as breast pain, regardless of its association with the
menstrual cycle or underlying breast conditions. Specifically, studies were included if they
involved women experiencing cyclic mastalgia (breast pain related to the menstrual cycle)……”
The definition of mastalgia suggests that it is not related to the menstrual cycle, while the
subsequent section mentions the included studies of breast pain related to the menstrual cycle.
Is this contradictory?
7.With regard to the handling of disagreements, why were some of them decided through
discussion and others through the participation of a third author?
Data Analysis
8.“……50 to 75% as high heterogeneity, and more than 75% as heterogeneity”. What level of
heterogeneity is I2 over 75%?
9.The authors state in the Methods section that 6 databases (Web of Science, Embase, Cochrane
Library, Scopus, PubMed, and Google Scholar) will be searched, but only 5 are described in the
Results section, what about the search results from the Cochrane Library?
10.In Figure 1, 602 records were retrieved from the database, 27 records were obtained from
other sources, and when 292 duplicate studies were eliminated there should have been 337
records remaining instead of 301. Please check it.
Study characteristics
11.“We conducted four clinical trials [24-26, 34] with a control group.” The “conducted” is not
appropriate here and it is suggested that it be changed to included or acquired.
Quality assessment (Risk of bias)
12.“The risk of bias due to the lack of blinding participants and assessors was low in all four
studies [24-26, 34].” This sentence is misstated: low risk of bias due to lack of blinding? Please
correct it.
Primary outcome meta-analysis
13.“The combined meta-analysis of three studies [24-26] showed between-group differences
in mean change scores for mastalgia intensity post-treatment using vitamin B6 compared to
placebo (SMD= -3.57, 95% CI: -9.15 to 2.01).” I think the authors misunderstood the results of
the meta-analysis, as can be seen in Figure 3, which shows that there is no difference between
the data of the experimental and control groups.
14.“however, when considering the confidence interval, the reduction in pain intensity in
the intervention group was not statistically significant.” This sentence is misstated. The
interpretation of the results should have been that vitamin B6 had a non-significant effect on
reducing mastalgia compared to the control group.
Sensitivity analysis
15.“A sensitivity analysis using the one-out removal method showed that the removal of the
Ghazanfarpour study caused significant changes in the results (Figure 5). ” By significant change
here, the authors mean a change in SMD and confidence intervals, but this change did not alter
the results of the meta-analysis, which remained statistically insignificant.