Pre-menstrual Syndrome and Diet

The purpose of this review is to collate and evaluate critically recent reports on the effect of diet and nutritional supplements on the symptoms of pre-menstrual syndrome (PMS). Evidence is provided of a poor dietary intake and vitamin and mineral deficiencies in subjects with PMS. The review explains `the four-phase dietary treatment for PMS' used at the University College London Hospital's PMS Clinic, and the author's own experience derived from seeing many PMS patients over 6 years is briefly presented. From the available evidence, it appears that the diet advocated in the Health of the Nation document is also the best approach to treating PMS. As regards supplements, there is certainly, evidence that magnesium and vitamin B6 are helpful to some women. Evening primrose oil seems most effective when used to treat mastalgia. Evidence is emerging that calcium supplementation may also lessen some PMS symptoms. Beneficial effects (ire usually noticed only after following specific dietary advice for 3-4 months. This may cause some sufferers to lose patience with the dietary approach. Nutritional guidelines should be advocated (is the first-line approach for PMS. It is cheap, effective and puts the woman in control of her own treatment. Evidence is accumulating for I he role of neurotransmitters in PMS. It is known that diet can affect neurotransmitter metabolism but more research needs to be focused on this area.

Keywords: pre-menstrual syndrome. neurotransmitter, vitamin B6, magnesium, calcium, evening primrose oil.

INTRODUCTION

Pre-menstrual syndrome (PMS) can have a destructive effect on an individual, her family and society. It occurs frequently: approximately 95% of women of reproductive age suffer to some degree, 5% of them to such an extent that their lives are totally disrupted for 2 weeks out of 4 weeks [ 1, 2]. A safe, efficient and acceptable therapy for PMS therefore needs to be sought and, for many. in particular those whose diet is poor, good nutrition offers an efficient way of tackling this problem. It allows the woman to participate in her own treatment and it is relatively cheap.

THE DIET AND VITAMIN STATUS OF PMS SUBJECTS

It is claimed that PMS subjects consume more refined sugar, refined carbohydrates and dairy products, but fewer B vitamins. iron, zinc and manganese than healthy controls [ 2, 3].

Several experts have found a significantly reduced erythrocyte and/or lymphocyte magnesium level in PMS sufferers compared to controls [ 4-10]. Adults consume an average of only 237 mg of magnesium daily and this is below the daily recommendation for women of 270 mg [ 11]. Magnesium deficiency can occur if the diet is high in refined foods and phosphorus, or if there is a high consumption of dairy products or fibre and insufficient consumption of vegetables and wholegrain cereals [ 3, 12].

It is believed that approximately 16% of all women have below normal levels of vitamin B6, particularly those who have been taking the oral contraceptive pill [ 13, 14]. However, there seems to be no difference between the level in PMS sufferers and non-sufferers [ 6, 15]. Some studies have found no evidence of significant deficiencies of several vitamins and minerals in PMS subjects, including vitamins A, D, B6 and E, and magnesium [ 16, 17]. However, Chuong and Dawson [ 15] did find significantly lower levels of zinc and calcium.

The failure to relate peripheral measures of vitamins and minerals and clinical manifestations of PMS might be explained on the basis that they do not reflect the levels in the central nervous system which in turn influence neurotransmitter activities [ 15, 18].

As will be alluded to later, supplemental doses of some vitamins and minerals at higher than the dietary reference value (DRV) do seem to improve PMS symptoms in some cases. It may be that pharmacological doses ensure higher target tissue concentrations, thereby proving more effective. When nutrients are recommended above DRVs, great care should be taken to ensure that the evidence for their benefit has been well researched and they should only be prescribed by experienced nutritional practitioners.

DIETARY MANIPULATIONS TO RELIEVE PMS

Healthy Eating Guidelines
Stewart et al. [ 19] showed that adopting a healthy diet could significantly reduce PMS symptoms. This diet was low in fat but supplied a good intake of lean animal proteins; it was high in fresh fruit and vegetables but contained little tea, alcohol, salt, sugar and refined carbohydrates. Similarly, Abraham [ 3] advocated a low-fat, high-carbohydrate diet as a first approach to PMS treatment, based on evidence of its effectiveness in reducing symptoms.

Brush [ 18] showed that reducing saturated fats in the diet, such as processed meat products and using a good quality polyunsaturated soft margarine, significantly reduced PMS symptoms in many patients.

A high consumption of saturated fats, trans fatty acids (found in many processed foods including some margarines) and cholesterol can hinder the production of certain prostaglandins (see below). These prostaglandins are believed to make the tissues less sensitive to the female hormones and, thus, may lessen PMS symptoms [ 18, 20].

PMS subjects appear to have a decreased blood level of serotonin during the luteal phase [ 15]. Tryptophan is a precursor of serotonin and its uptake by the brain is increased by carbohydrate consumption. A high-carbohydrate diet is believed to increase serotonin production and diminish 'negative effects' in patients with PMS, seasonal adjusted disorder (SAD) and carbohydrate craving obesity [ 21, 22]. However, it is believed that refined carbohydrates should be kept to a minimum as they may cause a rise in insulin secretion, which in turn leads to increased fluid retention [ 15, 16, 23, 52]. An excess of refined sugars also leads to increases in the urinary excretion of magnesium [ 15].

One of the popular reasons given for avoidance of refined sugar among PMS sufferers is to prevent 'rebound hypoglycaemia'. However, a review of the literature fails to show any evidence that true hypoglycaemia occurs in PMS subjects.

Boyd et al. [ 24] claimed that the incidence of cyclical mastopathy is as high as 40% in all women and that it is often accompanied by other symptoms of PMS. After 6 months of following a high-complex carbohydrate and low-fat diet, participants lost weight, reduced their cholesterol levels and significantly reduced their breast tenderness. Boyd et al. [ 24] concluded that dietary interventions rather than drugs should be used as a first-line approach to breast tenderness.

A lack of fibre in the diet is known to cause a slower transit time. This in turn may increase the reabsorption of oestrogen into the blood stream which may disturb the oestrogen-progesterone balance and lead to PMS [ 3]. An increased level of oestrogen is also believed to raise aldosterone levels which may cause water and salt retention, thereby giving rise to bloating [ 3, 13, 23]. Many women become constipated before menstruation and so increasing the fibre and fluid in the diet will help to alleviate this.

Salt and Fluid Intake
Bloatedness is a common symptom of PMS. Drinking plenty of fluid will encourage the excretion of excess fluid and, hence, may reduce PMS bloating. At least eight cups of fluid a day are recommended [ 25].

Abraham [ 3] believed that lowering salt to 3 g a day (a low-salt diet) may help to relieve bloating and breast tenderness.

Some research has discounted the role of sodium and water retention: most women who develop bloatedness and abdominal distension in the luteal phase do not show increases in weight, total body water, extracellular fluid volume, total exchangeable body sodium or plasma volume [ 1].

Eliminating Potential Toxins
Coffee and other caffeine-containing beverages act as stimulants and this property may exacerbate PMS symptoms such as irritability, tension and headaches [ 3, 14, 25, 26, 32]. Coffee and tea are also believed to aggravate breast tenderness and cause a reduction in certain blood nutrients [ 13, 15, 27]. Thus, owing to such evidence, PMS sufferers may be wise to limit themselves to two cups of tea a day and one cup of coffee. Herbal teas and decaffeinated coffee may be drunk instead.

In one longitudinal study, women with PMS reported greater alcohol use than controls [ 28, 29]. It is believed that alcohol and drugs may worsen the psychological symptoms of PMS. In addition, alcohol inhibits gluconeogenesis and promotes a fall in plasma glucose [ 15].

Allergies and Intolerances
Women who suffer from allergies will frequently list PMS as one of their symptoms. Testing for and treating the underlying allergy may well minimize their PMS [ 14, 18, 30].

Eliminating wheat from, some people's diets seems to alleviate PMS symptoms. This approach has been recommended in patients in whom abdominal bloating and irritable bowel syndrome are prominent PMS symptoms [ 7, 14, 30].

It has been suggested that PMS may be totally or partially caused by dysfunctional gut syndrome. This occurs when yeast organisms, such as Candida and other pathogenic microorganisms normally present in the gut, are allowed to over-colonize the gut. This can result from antibiotic treatment, the use of female hormones such as the pill or reduced immunity [ 31-33]. The hypothesis is that yeasts which are multiplying in the gut produce toxins which are absorbed systemically and can cause an array of symptoms, including irritable bowel syndrome, chronic fatigue and PMS. To rid the body of these yeasts the sufferer must follow a sugar- and yeast-free diet, possibly along with antifungal medication [ 14]. Individuals who suffer from this condition may also fail to absorb B vitamins and minerals adequately, which in turn exaggerates their PMS symptoms. Thus, they may require supplementation [ 34]. It is claimed that yeast infections can also be reduced by using an assortment of nutritional 'medicines' which include garlic and evening primrose oil. These supposedly enhance the sufferer's immune system [ 14].

Crook [ 35] had success using antifungals to treat PMS but unfortunately he did not placebo control his trial. Schinfield [ 36] found that 60% of a sample of 30 women with PMS had a history of recent vaginal candidiasis. These patients responded to treatment with oral antifungal therapy and a yeast-free diet.

The Role of Vitamins
A deficiency of B vitamins may be implicated in PMS. One of their functions is to facilitate the hepatic metabolism of oestrogens, thereby helping to lower their level premenstrually [ 23]. The most important B vitamin involved in the treatment of PMS seems to be vitamin B6. although to work effectively vitamin B6 requires all the other B vitamins to be adequate in the diet [ 37].

The active form of vitamin B6 (pyridoxine) is pyridoxal-5-phosphate which is an essential co-factor in the formation of the neurotransmitters dopamine (derived from the amino acid tyrosine) and serotonin (derived from the amino acid tryptophan). A shortage of these neurotransmitters has been shown to give rise to changes in mood [ 38]. PMS is believed by some to be triggered in the luteal phase of the menstrual cycle by a rise in prolactin, but it has been found that an adequate supply of dopamine has the effect of inhibiting the action of prolactin [ 3, 15, 39]. Thus, adequate provision of vitamin B6, encourages an adequate supply of dopamine, thereby lessening PMS symptoms [ 4].

Vitamin B6 also has a role in prostaglandin synthesis 16]. Prostaglandins have many actions in the body, for example they can affect neurotransmitter sensitivity and alter the cerebral blood flow. They are present in most organs of the body and may play a role in lessening PMS symptoms (see later).

Although there have been some papers which refute the benefit of vitamin B6 in the treatment of PMS [ 40, 41], there have been several placebo-controlled trials which show the positive benefits of vitamin B6 in alleviating some PMS symptoms.

( 1) In a double-blind trial which involved giving subjects 200-800 mg of vitamin B6 per day, Abraham [ 3] found that the blood levels of progesterone increased while those of oestrogen decreased and PMS symptoms improved. However, levels of vitamin B6 above 50 mg should never be taken without medical supervision owing to potential toxic effects such as nerve damage and gastric irritability [ 42-44].

( 2) Brush [ 45] claimed that vitamin B6 is particularly effective when used to treat mood swings, breast tenderness and headaches. He reported effectiveness in up to 70% of cases. However. this trial was not placebo controlled but was based on several years' experience at St Thomas' PMS Clinic, London.

( 3) Barr [ 46] showed a significant improvement in PMS symptoms above the placebo effect using 100 mg of vitamin B6 per day. At this dose, there were no reported side-effects. The improvements included a reduction of bloating, breast tenderness, depression, irritability and headaches.

( 4) There is little evidence that 100 mg of vitamin B6 per day reduces cyclic mastalgia [ 39]; the evidence points more to a beneficial effect on the mental and emotional symptoms. For example, Doll et al. [ 47] found significant benefits in using 50 mg of' vitamin B6 for the emotional symptoms of PMS but not for anything else. This again was believed to be due to its role in the regulation of brain tryptophan metabolism [ 47].

Vitamin B6 and magnesium work closely together: Vitamin B6 increases cell membrane transfer and the use of magnesium, and this in turn leads to an increased metabolism of oestrogen. Magnesium is also required in serotonin production. Taking a supplement of magnesium along with the vitamin B6 is believed to lessen the likelihood of neurological damage, and both nutrients enhance each other's action [ 3].

It should be noted that the high-dose use of vitamin B6 is not based on the DRV; this is only 1.2 mg/day on average (depending on protein intake) and is the amount necessary to prevent deficiency disease. The beneficial effects of a high dose of pyridoxine used in PMS may be either due to pharmacological effects or it may be correcting a local deficiency in a specific organ or tissue such as the hypothalamus [ 48, 49]. To date, most trials on vitamin B6 use and PMS have been weak and further research is needed in this area.

Machlin [ 50] showed an improvement in PMS in subjects taking 300-600 IU a day of vitamin E per day. In a double-blind, placebo-controlled trial, vitamin E had a significantly greater effect than placebo in improving all PMS symptoms except oedema and bloating [ 50]. Others claim that supplemental doses of approximately 400 IU of vitamin E per day are effective in increasing appetite, reducing headaches, reducing breast tenderness, alleviating symptoms of anxiety and depression, and improving hormone balance [ 3, 7, 13, 15, 51]. Vitamin E may improve PMS symptoms through its role in prostaglandin E1 (PGE1) production (see later) and it may also affect neurotransmitter activity [ 15].

Unsubstantiated reports have claimed that vitamin A can reduce PMS symptoms by rectifying aberrations in oestrogen metabolism and by its diuretic properties [ 15]. One study demonstrated that vitamin A and zinc supplements were found to be effective in controlling 85%, of premenstrual flare-up of oily skin and acne [ 15].

Gamma-Linolenic Acid
Some workers believe that an inability to convert omega-6 essential fatty acids (Omega-6 EFAs) into Gamma-linolenic acid (GLA) is the main cause of PMS [ 6, 20, 52]. GLA becomes further metabolized into prostaglandins, one of which is believed to reduce PMS (see later). The enzyme involved in the production of GLA is called Delta-6-desaturase (see Table 1). This enzyme is inhibited by a number of factors, including the following:

Ageing [ 6, 20, 53].

Insulin deficiency [ 20, 52, 53].

Deficiency of protein [ 20].

Deficiency of vitamin B6, magnesium and zinc [ 20, 53, 54].

Hypercholesterolaemia [ 20].

Excessive saturated fat intake (found mainly in animal fats) [ 15, 18, 20].

Excessive trans fatty acid intake (found in dairy products, processed foods and most margarines) [ 20].

Excessive omega-3 fatty acids without sufficient GLA intake: the Delta-6-desaturase enzyme has a priority for working on the 3 rather than the 6 series of fatty acids. Therefore. those women taking fish oil supplements should also supplement with GLA in order to achieve a favourable prostaglandin balance [ 20].

Excessive alcohol consumption [ 32, 53].

O'Brien [ 6] found a significant difference in GLA and its metabolites between controls and PMS subjects, being lower in the latter. lie put this down to a deficiency in the Delta-6-desaturase enzyme or one of its co-factors. A deficiency in the GLA metabolite PGE1 may permit undue sensitivity to the luteal phase rise in ovarian hormones [ 6, 20].

Administering GLA provides the missing precursors for the production of PGE1 and can lead to clinical improvement without the need to alter hormone levels. Dietary sources of GLA include breast milk, borage, comfrey and blackcurrants. However, women wishing to augment their dietary intake of GLA have to take it as evening primrose oil or starflower oil.

Many claims have been made on the ability of GLA to relieve PMS [ 7, 20, 53]. Barber reported that GLA was as effective as bromocriptine in 45% of patients with cyclical mastalgia and Mansel [ 55] demonstrated similar significant benefits in the treatment of cyclical breast pain.

Not all reports have shown an effect of GLA on the treatment of PMS, for example Collins et al. [ 56], in a double-blind, cross-over trial, found that treatment with Efamol (which contains GLA) had no significant effect on PMS symptoms [ 52].

The Which? Consumer Group [ 57] reported that the trials done on GLA were badly designed and the amount of evening primrose oil capsules used in the trials was always more than the dose indicated on the bottles. However, the Which? Consumer Group [ 57] accepted that there was some good evidence that GLA Could help to reduce PMS breast pain. A review by Kleijnen [ 58] drew similar conclusions, i.e. there was evidence for a beneficial effect of GLA in PMS but the evidence was sparse. He recommended further rigorous trials, particularly for the treatment of mastalgia.

Evening primrose oil is available on prescription for the treatment of mastalgia and the recommended prescription dose is three to six 500 mg capsules twice daily taken throughout the cycle. Each capsule provides 40 mg of GLA. A clinical response is said to occur after 3-4 months and to last for several months. It is recommended that a lower maintenance dose is taken once there is clinical improvement [ 53, 58, 59].

Evening primrose oil seems to be safe but there are a few reported side-effects including depression, indigestion, nausea, loose stools, bloatedness, skin rashes and headaches [ 53, 58]. Epileptics are advised not to take evening primrose oil. Most medical experts agree that women can be allowed to self-medicate, the main problem being its cost [ 1].

The Role of Minerals
Much recent research has focused on the involvement of magnesium in PMS. There are several possible explanations why magnesium deficiency could play a role in PMS:

( 1) Magnesium is a co-factor which works with vitamin B6 in the conversion of cis-linoleic acid to GLA. A lack of magnesium may reduce the amount of PGE1 produced and, hence, trigger PMS (see earlier) [ 15, 18].

( 2) Magnesium has the general effect of increasing the biological activity of vitamin B6. Conversely, vitamin B6 can help to improve the body's use of magnesium by improving its intracellular transport [ 3].

( 3) It is known that magnesium deficiency can have adverse effects on neurochemistry metabolism, adrenal function and glucose metabolism [601. Magnesium is believed to modulate glucose-induced secretion of insulin by the Beta-cell of the pancreas [ 3, 15]. Abraham [ 3] found that women with reactive hypoglycaemia premenstrually tended to have low red cell magnesium levels and, with supplementation, 50% of these women significantly improved. Abraham [ 3] concluded that increasing the magnesium to calcium ratio in the diet will decrease the insulin response to a glucose load and, hence, lower the likelihood of pre-menstrual reactive hypoglycamia [ 61].

( 4) Magnesium deficiency can lead to an increase in the level of circulating aldosterone which may lead to fluid retention [ 15]. Any diuretics taken to counteract this problem may merely serve to lower magnesium levels even more [ 3].

A study carried out in a London PMS clinic showed that magnesium supplementation was more effective than many popular pharmacological interventions. The study showed that 38.5% of women improved on magnesium, which proved more effective than supplementation with zinc, evening primrose oil or vitamin B6 [ 62]

Similarly, Facchinetti et al. [ 8] found a significant improvement in PMS-induced mood change and menstrual migraine in a double-blind, randomized trial using 360 mg of magnesium daily. They believed that this added weight to the argument that magnesium exerted its effect through its influence on neurotransmitter activity.

There is evidence that the zinc status is reduced in women who suffer from PMS. Zinc is involved as a co-factor along with vitamin B6 in many metabolic pathways, e.g. in reducing prolactin levels and PGE1 synthesis. It is also believed to modulate opiate receptor binding in the central nervous system [ 15]. Thus, there are several mechanisms whereby zinc may have an effect on the hormonal and neurotransmitter secretion related to the mental and emotional states of women. There is evidence that zinc is particularly helpful in reducing PMS acne [ 4].

It is believed that chromium can become depleted if the diet is high in refined sugars [ 23]. Giving a supplement of 200 mcg of trivalent chromium daily may help to alleviate sugar cravings [ 3].

Thys-Jacobs et al. [ 63] and Alvir and Thys-Jacobs [ 64] in randomized, double-blind, cross-over trials using 1000 mg of calcium found that negative effects, such as mood swings, irritability, pain and water retention, were significantly improved.

In a later report, Thys-Jacobs [ 65] produced evidence that a combined supplement of elemental calcium and vitamin D reduced the severity of menstrual migraine headaches, as well as general PMS symptoms, within 2 months of therapy.

Supporting the previous workers' results, Penland and Johnson [ 66] conducted a double-blind trial on healthy women and found that a high calcium diet (1336 g) as opposed to a low calcium diet (587 g) significantly improved mood, concentration and behavioural symptoms. Pre-menstrual water retention and menstrual pain were also significantly improved. The same authors found that lowering dietary manganese levels, even with adequate calcium, caused significant worsening of pre-menstrual moodiness and pain. The workers agreed with Thys-Jacobs et al. that manganese and calcium may be acting via neurotransmitters, or they may be influencing smooth muscle responsiveness or hormone secretion [ 63].

In contradiction to this work, others believed that high calcium intakes exacerbate PMS symptoms, either by inhibiting magnesium absorption or by directly influencing the brain's ability to use glucose [ 15]. Some PMS experts therefore recommend a diet low in dairy products [ 3]. However, recent work has not demonstrated a worsening of PMS symptoms by increasing calcium in the diet. Furthermore, osteoporosis is a very real threat to women and milk products contribute many nutrients besides calcium to women of child-bearing age. Thus, it seems prudent not to restrict the intake of dairy products unless for intolerance reasons, in which case dietetic advice should be sought.

Multi-vitamin and Mineral Supplements Used to Treat PMS
Multi-vitamin and mineral supplements specifically designed for the treatment of PMS are available on the market. They contain varying proportions of vitamins and minerals, for some of which there is evidence of usefulness in treating PMS. Care should be taken that too high a dose of certain vitamins and minerals is not taken, in particular if several different supplements are taken together. Furthermore, high doses of one micronutrient may lessen the absorption of other equally important nutrients, for example zinc competes for the absorption of iron. Conversely, some supplements have too low a level of a certain mineral or vitamin so that no benefits can be expected. These supplements are usually costly and may leave women with the impression that they do not have to bother about healthy eating. In fact, supplements are more effective if taken with a healthy diet, but the expense of some supplements may leave women with less money to spend on nutritious food.

CONCLUSIONS

At University College London Hospital, all women attending the PMS clinic are screened using a simple questionnaire to ascertain whether they need dietary intervention. If the screening tool indicates that the diet of a PMS patient is inadequate, dietary changes are the first-line treatment. Moreover, if the diet is optimum, other therapeutic measures are more likely to be effective. However, an approach that works for one individual may not work for another. At the least, dietary changes will improve general health and self-esteem. It may increase a woman's tolerance to pre-menstrual changes and thereby reduce the impact of PMS on her daily life.

In treating PMS patients the author uses a four-phase dietary approach: at first the sufferer is advised on a healthy diet which includes, if appropriate, advice on cutting down on fats, simple sugars, salt. alcohol and caffeinated beverages, and increasing the consumption of starch and fibre.

It takes approximately 3 months for the diet to have a significant effect. If there has been little or no improvement, phase 2 involves excluding refined sugar as much as possible and trying to leave no more than 3-4 h between meals. Each meal or snack should be based on a starchy food. Although there is little evidence that true hypoglycaemia occurs in PMS subjects. many do experience hypoglycaemic-type symptoms such as faintness, shakiness, severe hunger with sugar cravings, anxiety and irritability. Experience has shown that these symptoms can be relieved by regular complex carbohydrate consumption.

If after a month there is still no significant improvement, phase 3 is started. This entails recommending the following vitamin and mineral cocktail: 50 mg of vitamin B6 [ 47], one to two capsules of 500 mg of GLA twice daily or two to four capsules twice daily if there is breast pain [ 59, 67] and 250-300 mg of magnesium [ 5, 67]. Occasionally other supplements, e.g. calcium, vitamin D and zinc, are recommended.

It takes approximately 3-4 months for any benefit of the supplements to be felt. However, if the supplements have brought no relief after 4 months, they should he discontinued and another approach considered. Supplements will only be effective if the diet is healthy first.

The fourth stage involves ensuring that underlying medical problems such as allergies and intolerances, diabetes, anaemia and irritable bowel syndrome are being treated appropriately. The control of such conditions often contributes further towards alleviating PMS misery.

The PMS dietary guidelines just outlined are based on widely accepted evidence. It is also reassuring to note that they exactly fit the Department of Health's [ 68] guidelines in The Health of the Nation. Patients should be made aware of the fact that the results of dietary manipulations are not immediate. However, those with patience and the will-power to persevere with their treatment for several months will often be rewarded, not only by relief of their PMS but with an improvement in their general well-being.

More funding needs to be poured into critical scientific research into PMS. Currently, evidence suggests that an aetiology for PMS may at least in part be found in neurotransmitter metabolism. Research should therefore be concentrated in this area. To be well conducted, they should ideally be placebo-controlled, randomized double-blind and crossover studies.

DIAGRAM: TABLE 1. The biochemical pathway of omega-6 essential fatty acids

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By GAYNOR BUSSELL BSc SRD University College London Hospital's Pre-menstrual Syndrome Clinic, United Elizabeth Garrett Anderson Hospital and Hospital for Women, 144 Euston Road, London NW1 2AP, UK

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