Dietary vitamin D intake, 25-hydroxyvitamin D₃ levels and premenstrual syndrome in a college-aged population

Abstract

High dietary intake of vitamin D may reduce the risk of premenstrual syndrome (PMS), perhaps by affecting calcium levels, cyclic sex steroid hormone fluctuations, and/or neurotransmitter function. Only a small number of previous studies have evaluated this relationship and none have focused on young women. We assessed this relationship in a cross-sectional analysis within the UMass Vitamin D Status Study. Between 2006 and 2008, 186 women aged 18–30 (mean age = 21.6 years) completed a validated food frequency questionnaire, additional questionnaires to assess menstrual symptoms and other health and lifestyle factors, and provided a fasting blood sample collected during the late luteal phase of their menstrual cycle. Among all study participants, results suggested the possibility of an inverse association between intake of vitamin D from food sources and overall menstrual symptom severity, though were not statistically significant; mean intakes in women reporting menstrual symptom severity of none/minimal, mild, and moderate/severe were 253, 214, and 194 IU/day, respectively (P = 0.18). From among all study participants, 44 women meeting standard criteria for PMS and 46 women meeting control criteria were included in additional case–control analyses. In these women, after adjustment for age, body mass index, smoking status and total calcium intake, higher intake of vitamin D from foods was associated with a significant lower prevalence of PMS. Women reporting vitamin D intake from food sources of ≥100 IU/day had a prevalence odds ratio of 0.31 compared to those reporting <100 IU/day (95% confidence interval = 0.10–0.98). Late luteal phase 25-hydroxyvitamin D₃ levels were not associated with prevalent PMS. Results from this pilot study suggest that a relationship between vitamin D and PMS is possible, though larger studies are needed to further evaluate this relationship and to investigate whether 25-hydroxyvitamin D₃ levels in the follicular or early luteal phases of the menstrual cycle may be related to PMS risk.

Introduction

Moderate-to-severe premenstrual syndrome (PMS) affects up to 20% of reproductive age women and is associated with substantial levels of impairment [1]. The most common symptoms of PMS include irritability, mood swings, anxiety, depression, breast tenderness, bloating, and headaches. While many pharmaceutical treatments for PMS have been evaluated, all have significant limitations and none has a reported efficacy greater than 60–70%. Because of the substantial limitations of available treatments, it is important to identify ways to prevent the initial development of this disorder.

While the etiology of PMS remains largely unclear, evidence from multiple sources suggests that vitamin D may play a role in its development and/or the experience of symptoms. Both diet and sunlight contribute to circulating levels of plasma vitamin D metabolites. Dietary intake of fortified dairy foods and cereals, some types of fish, multivitamins and calcium/vitamin D supplements contribute importantly to vitamin D in elderly populations and those with low ambient sunlight exposure [2]. In populations with ample sun exposure, cutaneous conversion of 7-dehydrocholesterol to previtamin D after exposure to solar UV radiation provides the greater source. Previtamin D from both diet and cutaneous production is hydroxylated in the liver into 25-hydroxyvitamin D₃ (25(OH)D₃), the metabolite circulating in the greatest concentration. 25(OH)D₃ is then further hydroxylated to 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), in the kidney and in target tissues including the brain, breast and endometrium. 1,25(OH)₂D₃ is the biologically active metabolite that binds to nuclear vitamin D receptors in target tissues.

It has been suggested that women with luteal phase symptoms consistent with PMS may be experiencing vitamin D deficiency, or related conditions of calcium dysregulation and hyperparathyroidism [3] but few studies have addressed this. In a sub-study within the prospective Nurses’ Health Study II (NHSII), high total vitamin D intake was associated with a significant 41% lower risk of PMS, while high vitamin D from food sources only was associated with a significant 31% lower risk [4]. Results from this study are provocative and raise several questions. For example, it is unknown whether vitamin D may be associated with overall severity of menstrual symptoms in a general population, and whether serum 25(OH)D₃ levels, which better reflect vitamin D status than dietary intake alone, are associated with PMS. Therefore, we have evaluated these relationships in a pilot study of college-aged women in Massachusetts, USA.