Discussion
swelling, premenstrual disorders, water retention symptoms, lower extremity complaints, psychiatric, Premenstrual Disorders, PMS
ADVERSE EVENTS, FLUID RETENTION, PMS
To the best of our knowledge, this is the first report of γ-Toc intake alleviating physical and psychiatric symptoms in women with water retention symptoms during the luteal phase. Studies have mainly examined the antioxidant and anti-inflammatory effects of γ-Toc [Regarding PMS symptoms, Takeda et al. reported that > 80% of Japanese women aged 20–49 years present some physical symptoms, including those related to water retention [During the follicular phase, there were biphasic variations in lower extremity symptoms (“swelling of the legs” and “heavy legs”) and thigh circumference, with peaks in the evening and dips in the next morning. This could be attributed to the fact that water stored in the lower limbs due to gravity-induced downward water movement during the day is excreted as urine due to position changes during sleep. Contrastingly, during placebo intake, there was a lesser decrease in lower extremity complaints during the luteal phase than during the follicular phase, even in the morning when the lower extremities were least affected by gravity. Specifically, water retention symptoms in the morning could be a characteristic phenomenon of some women in the luteal phase, which could be treated through γ-Toc intake.In our study, there were lower and higher plasma ANP and aldosterone levels, respectively, in the luteal phase than in the follicular phase. The observed variations in aldosterone levels are consistent with a previous report by Rosenfeld et al. of increased plasma renin activity and aldosterone levels during the late luteal phase of the menstrual cycle in women with PMS, which contributed to increased fluid retention [In the post hoc analysis, there was decreased 24-h urinary sodium excretion during placebo intake in the luteal phase than in the follicular phase. Additionally, γ-Toc intake significantly increased sodium excretion compared with placebo intake. These results suggest that γ-Toc moderately mitigates the accumulation of excessive sodium levels in humans, including during the premenstrual period, as reported by Uto et al. in rats [Regarding the safety of γ-Toc ingestion, γ-Toc intake resulted in the menstrual delay in one participant; however, no other adverse events were observed. There were no significant between-supplement differences in blood hemoglobin and hematocrit levels, which suggests that γ-Toc intake does not affect circulating blood volume. Therefore, ingesting 360 mg γ-Toc for 7 days was considered safe.The strength of this study is that this is the first study to examine the PMS-reducing effects of γ-Toc in a randomized, double-blind, placebo-controlled crossover design. In addition, we prospectively assessed the severity of symptoms during the screening visits and subsequently evaluated the efficacy of the test supplement using the VAS and MDQ scores. Regarding PMS symptoms, there is frequently a mismatch between retrospective complaints and actual symptom patterns; additionally, the ACOG diagnostic criteria require a prospective symptom survey for at least two cycles [This study had some limitations. First, there was an insufficient sample size. Second, given the relatively complex protocol, we could not confirm the phases using the hormone levels. Third, the number of days until the onset of menstruation following the evaluation period could not be strictly aligned across the individuals or between the groups. Fourth, although we evaluated the efficacy of γ-Toc within a single menstrual cycle, the International Society for Premenstrual Disorders recommends 3 months of interventions for placebo-controlled, parallel-group trials on premenstrual disorders, including PMS [For future recommendations, since there are only two reports regarding the efficacy of γ-Toc intake against water retention during the luteal phase, there is a need for future studies covering multiple cycles with adequate sample size to confirm its efficacy in daily life. Finally, we did not consider the effect of season on the symptoms related to water retention, which should be considered in future studies.