The effect of nutritional supplementation on premenstrual syndrome

Premenstrual syndrome (PMS) occurs during the luteal phase of ovulatory menstrual cycles characterized by disrupting psychological and physical symptoms, which are relieved during menstruation. Around 20% of women experience PMS across social, ethnic and cultural groups. The aim of this thesis was to investigate the therapeutic potential of nutritional supplements for mild to moderate PMS. The aetiology of PMS remains obscure; genetic and environmental vulnerabilities have been identified yet no specific pathophysiology has been established. Neurotransmitter systems with their reciprocal relationship to the hypothalamic-pituitary-gonadal axis, are implicated in PMS. The catecholamine, serotonergic and GABA systems each modulate aspects of the synthesis, release and inhibitory feedback mechanisms involved in the menstrual cycle. Progesterone, its metabolites and oestrogen also act as neurosteroids modulating neurotransmitter systems. A role for the serotonergic system in PMS is supported in a proportion of sufferers. A transitory dysfunction in homeostasis is thought to account for the on/off nature of PMS symptoms. One hypothesis suggests that a dysfunction in calcium metabolism involving a lack of sensitivity to parathyroid hormone and a transitory deficiency in extra and intracellular calcium ions, leads to disruptions in receptor site activity, giving rise to symptoms. This thesis supports elements of this theory. Micronutrient cofactors are intrinsic to neurotransmitter synthesis and receptor site function and adequate provision of micronutrients for these functions provides one rationale for their use in the treatment of PMS. A systematic review of methodologically sound clinical trials of nutritional interventions in PMS found evidence for the efficacy of calcium, tryptophan, magnesium, pyridoxine and a micronutrient formula. The effect of two complexes on symptoms of mild to moderate PMS were investigated. Methodological considerations specific to the study of PMS include appropriate assessment and interpretation of definitions. A mixed-methods study of three PMS assessment instruments informed the choice of instrument used in the trials. A double-blind clinical trial with parallel groups investigated a multivitamin complex compared to placebo. Healthy participants recorded symptoms for two menstrual cycles allowing confirmation of PMS prior to randomization and a four menstrual cycle intervention stage. Daily symptom recordings were maintained. A hierarchical regression model was fitted to the natural logarithm of the data. Women taking the micronutrient complex experienced a highly significant reduction in symptoms of PMS compared to placebo (p\u3c0.000). A second trial with similar methodology had three arms; calcium complex alone, calcium complex with the multivitamin complex and a placebo arm. The groups taking the calcium alone and combined with the multivitamin experienced significant reduction in symptoms compared to placebo, p It was postulated a dysregulation of calcium metabolism might be reflected in reduced bone density in PMS. A pilot study used densitometry to compare women with and without PMS. However no significant difference was found. PMS may be better understood as subsyndromes with separate characteristics and etiologies. Were this hypotheise proven, it would substantially impact the direction of future research into nutritional therapy