PMS and Dietary Factors

Various reports, many of a preliminary nature, or based on clinical experience, suggest that women suffering from PMS consume more sugar, refined carbohydrate, and dairy products and less fiber, B complex vitamins, iron, zinc, and magnesium than normal women.

Carbohydrate

Carbohydrate-rich meals have been shown to improve mood in women with premenstrual depression. The reason for this has been indicated in animal studies: The availability of tryptophan to the brain increases following such meals. As tryptophan is a substrate for the synthetic pathway to serotonin, levels of this neurotransmitter rise, while levels of other neurotransmitters are maintained. Hence premenstrual craving has been suggested as a compensatory response to deal with a relative lack of serotonin during this phase of the cycle. Indeed, PMS symptoms of craving, particularly for sweet foods, may be a useful indicator of the cyclical changes that occur in brain neurotransmitters in women.

Increased energy intake due to craving has been shown to range from 380 to 2000 kJ per day (90-500 kcal per day) during the luteal phase compared with the follicular phase in women with PMS. However, there is no obvious pattern of macronu-trient intake. Some women consume more carbohydrate, some more fat, and some more protein. As might be expected, the increase in energy intake is accompanied by an increase in certain nutrients, such as magnesium, vitamin D, potassium, phosphorus, and riboflavin. Enhanced intake of several of these nutrients has been linked to alleviation of PMS symptoms (see below).

Magnesium

Magnesium deficiency has been proposed as a causative factor in PMS. Magnesium has a sedative effect on neuromuscular excitability and is involved as an enzyme cofactor in many reactions in the body. In the metabolism of essential fatty acids it also acts as a cofactor, working together with vitamin B6, zinc, niacin, and vitamin C. At the cell membrane, magnesium acts as a regulator of both membrane rigidity and ion exchange, helping to maintain electrolyte balance. In addition, it moderates the action of calcium in stimulating cell functions such as hormone secretion.

Modern Western diets high in refined cereals lack magnesium. Many dietary surveys, including those sponsored by governments throughout the Western world, have shown that the mean intake of magnesium for women is below recommended dietary standards, with subgroups having exceptionally low intakes. Decreased intake or absorption or increased renal excretion may lead to a reduced intracellular magnesium. Indeed, perhaps the most consistent physiological abnormality yet found for PMS subjects has been the reduced magnesium level in red blood cells compared with controls.

While severe magnesium deficiency is characterized by a progressive muscle weakness, failure to thrive, neuromuscular dysfunction, and tachycardia, symptoms of marginal deficiency are more subtle. Nevertheless, there is accumulating evidence to suggest that magnesium supplementation of the diet can alleviate a variety of conditions in which there is an element of muscular overcontraction, such as hypertension and tension headaches. The stress of modern living plays a part by enhancing magnesium excretion in the urine even in otherwise normal subjects. This sets up a vicious circle, as magnesium deficiency itself increases susceptibility to stress by increasing the secretion of ACTH-mediated adrenal androgen, which is a central nervous system depressant.

Several mechanisms proposed for the development of PMS symptoms have been claimed to be promoted by magnesium deficiency. Low magnesium status may also be responsible not only for exacerbating gonadal hormone imbalance in women, but may promote an increase in the aldosterone-to-oestrogen ratio. Enhanced aldosterone levels promote potassium and magnesium excretion and sodium retention, thus inducing fluid retention as found in PMS-H. In addition, deficient levels of magnesium decrease blood glucose control in two ways: by decreasing the ability of the liver to metabolize glucose and by increasing insulin secretion in response to glucose. Hence, changes in appetite and craving, both common PMS symptoms, may be closely linked to magnesium deficiency through loosening of blood glucose control. A low blood glucose supply to the brain may cause craving as a signal for increased energy intake. Even the decreased brain dopamine levels postulated to be responsible for anxiety and irritability of PMS (see above) may be exacerbated by magnesium deficiency.

In support of some of these hypotheses, several scientific reports have demonstrated a role for magnesium supplementation in relieving symptoms of PMS. In particular, Italian workers have shown that in 32 women, who were given 360 mg magnesium or placebo per day from the 15th day of the menstrual cycle to the onset of menstrual flow, magnesium supplementation was an effective treatment for low mood in PMS.

Vitamin B6

Vitamin B6, in the form of pyridoxal phosphate (PLP), is a cofactor in a large number of important enzymic reactions throughout the body. Therefore it is a cofactor in serotonin and dopamine production in the hypothalamus. High oestrogen levels may lead to a relative deficiency in vitamin B6 by altering tissue distribution and by inducing hepatic enzymes which increase the rate of vitamin B6 breakdown. An oestrogen-induced deficiency in vitamin B6 may reduce the synthesis of both serotonin and dopa-mine, an action that may alter the delicate balance between the two, normally maintained by adequate synthesis and breakdown. Adequate intakes of vitamin B6 are also thought to be necessary for the maintenance of normal intracellular magnesium levels, as this vitamin plays a fundamental role in the active transport of magnesium through the cell membrane. Thus, a synergetic role for magnesium and vitamin B6 has been suggested, although this remains to be tested.

High doses of vitamin B6 have been found to be effective in treating most of the most common symptoms of PMS in several double-blind, placebo-controlled trials. For this reason administration of dietary supplements is a popular therapy for PMS used by many medical practitioners. However, as large doses have been associated with dependency and sensory neuropathy, doses higher than 50 mg per day should be avoided.

Essential Fatty Acids

Gamma-linolenic acid (GLA) is thought to be the major active constituent of evening primrose oil (EPO), which is self-administered by many women for the relief of PMS symptoms. GLA is a fatty acid belonging to the n-6 essential fatty acid family. It is formed in the body from linoleic acid (from seed oils such as sunflower). In the body linoleic acid is elongated and further desaturated in a several-step process leading to arachidonic acid. GLA is one of the intermediates in this pathway, which, in response to a stimulus, can act as a substrate for a series of enzyme reactions giving rise to series 1 eicosanoids (biologically active substances, including prostaglan-dins), which have a broad range of activities in the body.

Under similar circumstances arachidonic acid present in the cell membrane gives rise to series 2 eicosanoids, which tend to be proinflammatory unless moderated by the presence of series 1 and 3 eicosa-noids (series 3 are from n-3 fatty acids, which are high in fish oils). In people consuming a Western diet, it is common to find that when cell membranes are stimulated (e.g., stressed), production of series 2 eico-sanoids is dominant. This is because arachidonic acid can be provided in the preformed state in the diet in meat, and body status of GLA and w-3 fats can be low. Although low status of the latter may derive from poor diet choice, low GLA status may result because of the slow action of the enzyme 6-6-desatur-ase, which is involved in the first desaturation step in the metabolism of linoleic acid. Its action is further slowed by viral infection, age, alcohol, stress, and lack of magnesium or zinc in the diet.

The suggestion that PMS may be caused by eico-sanoid imbalance is based on the assumption that failure of the normal conversion of linoleic acid to GLA results in low levels of prostaglandin E1 (PGE1)

eicosanoids in relation to the other eicosanoids, and this sensitizes tissues so that they respond abnormally to normal levels of oestrogen and progesterone. In support of this hypothesis, studies from Japan, Finland, and the UK have shown that women suffering from PMS have lower blood levels of GLA and DGLA (dihomo-7-linolenic acid, a compound related to GLA), although linoleic acid levels are higher. Additional support for a therapeutic role of GLA in PMS comes from six double-blind, placebo-controlled studies which have shown a significant improvement in symptoms from a daily supplement of GLA in the form of EPO, although one further study carried out in Australia showed no benefit.

Cyclical mastalgia, or breast pain, in the premenstrual phase may or may not be accompanied by other symptoms of PMS. In any case, similar abnormalities in n-6 fatty acid profile of cell membranes to that described above for PMS have been found in this condition and good response to GLA supplementation has been reported. Indeed, EPO is commonly prescribed by breast surgeons as the firstline treatment for the condition. In one study nearly half of hospital outpatients with this condition showed a benefit of EPO treatment without side effects, although doses of at least 4 g per day are required.

Other Nutrients

Apart from those already discussed, a role for deficiency of other nutrients in the etiology of PMS has been suggested, although few well-designed studies have been reported. Studies in vitamin E-deficient animals suggest that vitamin E supplementation may enhance the production of eicosanoids of series 1 and reduce the release of arachidonic acid from phospho-lipids. Hence, this combined action would reduce the inflammatory tendency implicated in some forms of PMS. Two double-blind, placebo-controlled studies in the 1980s indicated that supplementation with vitamin E may alleviate PMS symptoms, but at least one other study reported no effect. In one of the positive studies, daily supplements of 300 IU significantly alleviated PMS symptoms of anxiety after 2 months, while 600IU per day was required for the same duration to reduce PMS symptoms of craving and depression. These levels of vitamin E are far greater than can be obtained through diet.

Zinc deficiency may be involved in the etiology of PMS. This suggestion stems from observations of low luteal-phase zinc levels in women suffering from PMS. Several mechanisms for involvement of zinc deficiency in PMS have been proposed. Zinc is involved in the regulation of pituitary hormone secretion, influencing, in particular, prolactin and luteinizing hormone activity, which may affect predisposition to PMS. Zinc is a modulator of endogenous opiate-receptor binding in the central nervous system, a system also implicated in the condition. Zinc also takes part in the synthesis of PGE1 by its involvement in the release of DGLA and hence may influence eicosanoid balance (see above). Nevertheless, no placebo-controlled study has been carried out to show the effects of supplementary zinc as therapy for PMS.

Women with PMS have been reported to have higher intakes of calcium than normal women owing to excessive intake of dairy products. Foods in this group are characterized by having very high calcium-to-magnesium ratios and PMS sufferers have been reported to have diets with higher ratios than normal women. As a high intake of calcium is known to reduce magnesium absorption, a high calcium intake has been proposed to result in a chronic magnesium deficiency and PMS. It has also been postulated that excessive calcium intake may cause the behavioral changes of PMS by calcium interference with glucose breakdown as a source of energy to the brain. However, a controversial placebo-controlled study on 33 women showed that daily supplementation of 1 g of calcium for 3 months significantly reduced PMS symptoms of depression and fluid retention.

Caffeine

Several surveys of unselected women have shown that those who consume large amounts of beverages containing caffeine are more likely to suffer from PMS. Although constant consumption of low doses of caffeine may exacerbate the stress reaction and tendency to PMS, paradoxically, acute, high-dose consumption has been used to treat migraine headaches, although it was not reported whether these headaches were present premenstrually.

Botanicals

There has been renewed interest in recent years in the therapeutic applications of herbal medicine for a wide range of conditions. The active phytochemicals of the majority of commonly used herbs and their physiological effects are well reported. It is only recently, and mostly in Germany, that clinical studies of efficacy in treatment have been undertaken. There is no doubt from the clinical experience of practitioners that phy-totherapy has much to offer for treatment of hormone imbalance syndromes in women, including PMS, but more research-based evidence is required.

An important herb used by phytotherapists to treat PMS is the chaste tree (Vitex agnus-castus L.). Extracts of the berries have been shown to reduce the abnormally high prolactin secretion of PMS via the ability of certain of its phytochemicals to mimic the action of dopamine by binding to dopamine receptors in the pituitary. Other herbs traditionally used in phytotherapy for PMS contain phyto-oestrogens. These molecules may have oestrogen-like action, either due to the steroidal nature of their active constituents (false unicorn root, Chamaelirium luteum A. Gray) or to the spatial similarity of active groups in their constituents, which allow them to bind to oestrogen receptors. Among the latter group are isoflavonoids and lignans, which appear to have 'adaptogenic' properties: They are weakly oestrogenic at low circulating oestrogen concentrations and antioestrogenic at high oestrogen concentrations. Isoflavonoids are present in soya bean and its products and in medicinal herbs such as black cohosh (Cimicifuga racemosa Nutt.); these show a beneficial effect in reducing symptoms of PMS and the menopause. Lignans are present in high concentration in seed coats, including wheat, and are especially high in linseed (Linum ussitatissimum L.). The presence of lignans may explain why women who eat high quantities of whole grains, fruit, and vegetables are less likely to suffer from PMS.

See also: Appetite: Psychobiological and Behavioral Aspects. Behavior. Brain and Nervous System. Carbohydrates: Regulation of Metabolism. Cofactors: Inorganic; Organic. Hunger. Magnesium. Phytochemicals: Epidemiological Factors. Supplementation: Dietary Supplements. Vitamin B6.

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