Magnesium and Hypertension

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Zinc, hydrochlorothiazide and sexual dysfunction

This study was designed to test the hypothesis that hydrochlorothiazide a diuretic used to treat hypertension depletes body zinc and thereby cause sexual dysfunction. Serum zinc and sexual dysfunction were measured in 39 middle aged hypertensive men who had been taking hydrochlorothiazide in average daily doses of between 25 and 50 mg daily for at least six months, and a control group of 27 unmedicated middle aged normotensive men. The medicated group had a higher incidence of sexual dysfunction (56 pc) as compared to 11 pc in the control group. The use of hydrochlorothiazide did affect serum zinc levels significantly in 20 patients. Sexual dysfunction occurred more often in older and overweight patients (p < 0.004). Three of the normotensive men experienced sexual dysfunction probably related to old age. Twenty two of the 39 on hydrochlorothiazide and experiencing sexual dysfunction were divided into two groups of 11 patients. Bloods were taken from the 27 normotensive and 22 hypertensive men receiving hydrochlorothiazide for the analyses of zinc. Subsequently one group of the patients were supplemented with zinc 500 mg daily for 30 days while the other group was supplemented with magnesium chloride 1 g daily for 30 days. The normotensive men were not treated. After 30 days, bloods were again taken from the three groups of analyses for zinc and magnesium. Serum zinc was significantly decreased (p < 0.05) by hydrochlorothiazide and a non significant decrease in serum magnesium (p = ns) was observed. After supplementation with zinc, the serum zinc levels returned to normal only in eight patients. There was improvement in the symptoms of sexual dysfunction in five patients. Two patients gained weight. Hydrochlorothiazide decreased serum zinc levels (p < 0.05) and was unchanged with magnesium supplementation but the serum magnesium returned to normal values. Improvement of symptoms of sexual dysfunction was positive in one patient. This study shows that low serum zinc levels may be associated with sexual dysfunction but the definitive role of zinc in the pathogenesis of sexual dysfunction will remain controversial.

Khedun-SM; Naicker-T; Maharaj-B
Cent-Afr-J-Med. 1995 Oct; 41(10): 312-5

Combinations of potassium, calcium, and magnesium supplements in hypertension

Dietary intakes of potassium, calcium, and magnesium have each been reported to lower blood pressure, but the extent of blood pressure reduction in epidemiological studies and clinical trials has tended to be small and inconsistent. We hypothesized that combinations of these mineral supplements would lower blood pressure and that the reductions would be greater than that usually reported in studies of each cation alone. One hundred twenty-five patients 82 men and 43 women) with untreated mild or borderline hypertension were randomly assigned to daily treatment with one of the following four regimens: 60 mmol potassium and 25 mmol (1000 mg) calcium, 60 mmol potassium and 15 mmol (360 mg) magnesium, calcium and magnesium, or placebo. Standardized clinic blood pressure measurements were obtained on 3 days at baseline and after 3 and 6 months of treatment. At baseline, systolic and diastolic blood pressures (mean +/- SD) were 139 +/- 12 and 90 +/- 4 mm Hg, respectively, and dietary intakes of potassium, calcium, and magnesium were 77 +/- 32, 19 +/- 13, and 12 +/- 52 mmol/d, respectively. The mean differences (with 95% confidence intervals) of the changes in systolic and diastolic blood pressures between the treatment and placebo groups were not significant: -0.7 (-4.3 to +2.9) and -0.4 (-2.9 to +2.1) for potassium and calcium, -1.3 (-4.4 to +1.8) and 0.4 (-2.5 to +3.3) for potassium and magnesium, and +2.1 (-1.8 to +6.0) and +2.2 (-1.0 to +5.4) for calcium and magnesium. In conclusion, this trial provides little evidence of an important role of combinations of cation supplements in the treatment of mild or borderline hypertension.

Sacks-FM; Brown-LE; Appel-L; Borhani-NO; Evans-D; Whelton-P
Hypertension. 1995 Dec; 26(6 Pt 1): 950-6

Variations in magnesium and zinc in hypertensive patients receiving different treatments

We studied the influence of captopril, atenolol, and verapamil on serum and intraerythrocyte concentrations of magnesium and zinc in 30 normotensive control subjects (12 men and 18 women, aged 30 to 65 years, mean +/- SD 45.76 +/- 12.15 years) and 30 patients with untreated mild or moderate essential hypertension (14 men and 16 women, aged 30 to 65 years, mean +/- SD 49.50 +/- 13.58 years). Ten each of the hypertensive patients were treated with captopril, atenolol, or verapamil. Physical examination and biochemical analyses (serum Mg and Zn) were done in all participants at baseline, and in patients after 3 and 6 months of treatment. The results were compared according to a nested design with Neumann-Keuls test. We found no significant differences between controls and patients in serum and intraerythrocyte concentrations of Zn at the start of the study, although there was a significant decrease in serum Zn in patients after 3 (P < .01) and 6 months (P < .001) of treatment, regardless of the drug used. This decrease was thought to be attributable to the zincuric effect of captopril or to dietary measures, or both. Intraerythrocyte Zn was not significantly affected by antihypertensive treatment. Serum and intraerythrocyte concentrations of Mg were significantly lower (P < .001) in hypertensive than in normotensive subjects, and serum Mg in patients treated with verapamil was significantly lower (P < .05) than after treatment with captopril or atenolol. Serum Mg concentration was related directly with serum concentrations of high density lipoprotein cholesterol (r = 0.4043, P < .05). We conclude that supplementation with Mg may benefit patients with hypertension.

Rubio-Luengo-MA; Maldonado-Martin-A; Gil-Extremera-B; Gonzalez-Gomez-L; Luna-del-Castillo-JD
Am-J-Hypertens. 1995 Jul; 8(7): 689-95

Functional platelet modifications induced by oral magnesium supplementation in normotensive and hypertensive pregnancy

Platelet functionality alterations have been correlated to the onset of hypertension in pregnancy and oral Mg++ supplementation has been clinically postulated to counteract such alterations. We, therefore tested the effect of 4 weeks oral Mg++ pyrrolidone carboxylate supplementation on platelet function. Forty-eight pregnant women were enrolled in the study at the beginning of the third trimester (30-32 weeks). Twenty women were preeclamptic, while 28 remained normotensive and served as controls. All the women received 360 mg/day magnesium pyrrolidone carboxylate for 4 weeks. DPH fluorescence, Na+/K(+)-ATPase and Ca(++)-ATPase activity, intracellular free Ca++ concentrations were determined prior and after the 4-weeks supplementation. Oral Mg++ supplementation significantly increased platelet DPH fluorescence in both normotensive and preeclamptic women. In normotensive pregnant women, it also significantly increased the activity of Na+/K(+)-ATPase, the activity of Ca(++)-ATPase and reduced the concentration of intraplatelet free Ca++. In hypertensive pregnant women, Mg supplementation increases Na+/K(+)-ATPase activity and decreases intracellular free Ca++; this, in turn, contributes to reducing the activity of Ca(++)-ATPase. Magnesium supplementation to preventing hypertension in pregnancy seems to have a consistent biochemical and clinical background.

Tranquilli-AL; Mazzanti-L; Staffolani-R; Salvolini-E; Garzetti-GG; Romanini-C
Boll-Soc-Ital-Biol-Sper. 1994 Oct-Nov; 70(10-11): 249-56

Hypertension and electrolyte therapy

Approximately 50 million Americans are at risk for cardiovascular and cerebrovascular disease as a result of hypertension (HTN). Education and treatment programs aimed at reducing HTN have been successful in decreasing morbidity and mortality from heart disease and strokes in recent years. In addition to pharmacologic means, prevention of HTN by lifestyle modifications has become a focus of public health education. One such modification, electrolyte therapy, has been associated with HTN control and is readily available through both dietary sources and supplementary tablets. This article presents an overview of electrolyte therapy as treatment for HTN, and reviews studies of the effects of sodium, potassium, and magnesium, and their combinations as treatment to reduce blood pressure. Strategies for nurses in educating the public on the effects of electrolytes and blood pressure are also discussed.

Prog-Cardiovasc-Nurs. 1994 Summer; 9(3): 32-7

Nutritional dose of magnesium in hypertensive patients on beta blockers lowers systolic blood pressure: a double-blind, cross-over study

OBJECTIVES. To evaluate if magnesium alters blood pressure in hypertensive patients treated with beta blockers and if such effect can be coupled to a change in potassium and magnesium levels in muscle, serum and urine.

DESIGN. A randomized double-blind, cross-over study with magnesium and placebo taken orally, each for 8 weeks.

SETTING. Outpatient clinic, University Hospital, Umea, Sweden.

SUBJECTS. Thirty-nine patients aged 26-69 years with moderate essential hypertension, treated before entry and during the study with continuous, unchanged beta blockers completed the study.

INTERVENTIONS. Random allocation to receive magnesium aspartate or placebo. Daily magnesium dose was 15 mmol (365 mg) distributed three times a day over 8 weeks.

MAIN OUTCOME MEASURES. Blood pressure, serum, urine and muscle magnesium and potassium. Measurements performed at the start, after 8 and 16 weeks.

RESULTS. Systolic supine and standing blood pressure significantly decreased when magnesium was supplemented following placebo but not when magnesium was given at start. When magnesium and placebo groups were independently compared there was no significant change in supine and standing systolic and diastolic pressure. Serum and urine magnesium and serum potassium were significantly higher after magnesium treatment, whilst no change was present in urine potassium or in muscle magnesium and potassium.

CONCLUSIONS. This study showed that 15 mmol magnesium day-1 given to mild to moderate hypertensive patients treated with beta blockers could be the cause of a significant decrease in supine and standing systolic blood pressure.

Wirell-MP; Wester-PO; Stegmayr-BG
J-Intern-Med. 1994 Aug; 236(2): 189-95

Reduction of blood pressure with oral magnesium supplementation in women with mild to moderate hypertension

In a double-blind controlled trial, 91 middle-aged and elderly women with mild to moderate hypertension who were not on antihypertensive medication were randomly assigned to treatment with magnesium aspartate-HCl (20 mmol Mg/d) or placebo for 6 mo. Magnesium aspartate-HCl in the given dose was well-tolerated and was not associated with an increased frequency of diarrhea compared with placebo. At the end of the study, systolic blood pressure had fallen by 2.7 mm Hg (95% CI -1.2, 6.7; P = 0.18) and diastolic blood pressure by 3.4 mm Hg (1.3, 5.6; P = 0.003) more in the magnesium group than in the placebo group. Blood pressure response was not associated with baseline magnesium status, as measured by dietary magnesium intake and urinary magnesium excretion. Urinary magnesium excretion in the magnesium group increased by 50% during the intervention period. No changes were seen in other biochemical indexes, including serum concentrations of total and high-density-lipoprotein cholesterol. The findings suggest that oral supplementation with magnesium aspartate-HCl may lower blood pressure in subjects with mild to moderate hypertension.

Witteman-JC; Grobbee-DE; Derkx-FH; Bouillon-R; de-Bruijn-AM; Hofman-A
Am-J-Clin-Nutr. 1994 Jul; 60(1): 129-35

Magnesium and diabetes: a review

OBJECTIVE: To discuss the potential link between diabetes mellitus (DM) and hypomagnesemia, the methods used to assess magnesium status, and the potential benefits of magnesium repletion in hypomagnesemic patients with DM.

DATA SOURCES: A MEDLINE search (key terms: magnesium and diabetes) was conducted to identify pertinent literature.

STUDY SELECTION: All major clinical trials and most published case reports were reviewed.

SYNTHESIS: Several studies have demonstrated a higher than expected frequency of magnesium deficiency in patients with DM. Hypomagnesemia may play a role in the development of retinopathy, altered glucose disposition, hypertension, abnormal platelet function, and other problems frequently observed in patients with DM. The lack of a widely available, accurate screening methodology is one of the main problems in assessing total body magnesium status. One study has suggested that hypomagnesemia in patients with DM may be related to enhanced urinary loss of magnesium. Several studies evaluating hypomagnesemia and glucose disposal have suggested a direct correlation between magnesium concentration and glucose disposal, with an improvement in glucose disposal with magnesium supplementation. It has been suggested that there is a relationship between hypomagnesemia and diabetic retinopathy; however, the effect of magnesium supplementation on the development of diabetic retinopathy has not been evaluated. Researchers evaluating the effect of magnesium on platelet aggregation have suggested that magnesium supplementation may reduce the incidence of vascular disease in hypomagnesemic patients with DM. Several studies have demonstrated a correlation between hypomagnesemia and hypertension.

CONCLUSIONS: Studies have suggested a link between hypomagnesemia and hyperglycemia, as well as an association between hypomagnesemia and the complications of DM. The American Diabetes Association has published a consensus statement suggesting that patients who have documented hypomagnesemia and DM receive magnesium supplementation.

White-JR Jr; Campbell-RK
Ann-Pharmacother. 1993 Jun; 27(6): 775-80

Magnesium supplementation prevents the development of alcohol-induced hypertension

The effect of chronic alcohol administration on blood pressure was investigated in 7-week-old Wistar rats. Tail-cuff blood pressure was significantly higher in rats who received 15% ethanol in drinking water than in control rats. Intracellular free calcium concentration of lymphocytes was increased, while magnesium concentration of erythrocyte, aorta, and skeletal muscle and erythrocyte ouabain-sensitive 22Na efflux rate constant (Kos) were decreased in alcohol-induced hypertensive rats but not in control rats. Extra cellular fluid volume was also increased in alcohol-administered rats. Oral magnesium supplementation (1% MgO in rat chow) attenuated the development of alcohol-induced hypertension accompanied by increased magnesium concentration of erythrocyte, aorta, skeletal muscle, and Kos and decreased intraerythrocyte sodium concentration. Norepinephrine half-life time of the heart and spleen was also increased in magnesium-supplemented rats. Blood pressure significantly correlated positively with intracellular calcium concentration and extra cellular fluid volume, negatively with magnesium concentration of erythrocyte, aorta, skeletal muscle, and Kos. These results suggest that increased intracellular calcium, which was partly due to magnesium depletion and suppressed sodium pump activity, and expanded body fluid volume had a possible role in the development of alcohol-induced hypertension. It is also suggested that oral magnesium supplementation had a hypotensive effect on alcohol-induced hypertension possibly through decreased intracellular sodium concentration caused by an activation of sodium pump and decreased sympathetic nervous activity.

Hsieh-ST; Sano-H; Saito-K; Kubota-Y; Yokoyama-M
Hypertension. 1992 Feb; 19(2): 175-82

Effects of dietary magnesium supplementation on diurnal variations of blood pressure and plasma Na+, K(+)-ATPase activity in essential hypertension

To evaluate the antihypertensive and hormonal effects of oral magnesium supplementation, 17 inpatients with untreated, uncomplicated mild-to-moderate essential hypertension (EH) and 8 age-matched normotensive controls (controls) were given MgO orally 3 times a day at a daily dose of 1.0 g (0.6 g per day as Mg) for a period of 2 weeks. Supplementation of MgO elicited a significant fall in averaged mean blood pressure calculated with a 24-h ambulatory blood pressure monitoring system (MBP) in EH from a baseline value of 104.3 +/- 12.2 to 99.5 +/- 11.6 mmHg (p < 0.05), while controls remained unaltered from a baseline value of 85.1 +/- 11.5 to 84.5 +/- 13.3 mmHg. The percentage reductions in systolic and diastolic blood pressures were similar during daytime and nighttime in EH. According to the extent of reduction in MBP with magnesium supplementation, EH patients were divided into 2 groups, responder and nonresponder. The level of plasma renin activity (PRA) in the responder group was significantly higher than that of the nonresponder group (p < 0.05). After 2 weeks of magnesium supplementation, the plasma level of Na+, K(+)-ATPase inhibitory activity (PATPI), defined as equivalency to ouabain, was reduced significantly from 0.75 +/- 0.54 to 0.40 +/- 0.30 mumol ouabain/ml (p < 0.05) in the responder group, while it remained unaltered in controls and the nonresponder group. PRA, plasma aldosterone concentration, urinary epinephrine and norepinephrine excretion, and urinary sodium excretion did not change significantly in either control subjects or EH (responder and nonresponder groups). A significant negative correlation existed between the pretreatment PRA and changes in MBP after magnesium supplementation in EH (r = -0.65, p < 0.01), and there was a significant positive correlation between changes in PATPI and changes in MBP as a whole (r = 0.41, p < 0.05). These results support the view that oral magnesium supplementation is a useful approach to treatment of patients with uncomplicated essential hypertension, especially those with high plasmas renin activity. It appears that magnesium suppresses circulating Na+,K(+)-ATPase inhibitory activity to attenuate vascular tone, and thereby reduces blood pressure in EH.

Jpn-Heart-J. 1992 Nov; 33(6): 785-800

Magnesium deficiency and diabetes mellitus. Causes and effects

A large body of evidence demonstrates the prevalence and adverse clinical consequences of magnesium deficiency in patients with diabetes mellitus. It would be prudent for physicians who treat these patients to consider magnesium deficiency as a contributing factor in many diabetic complications and in exacerbation of the disease itself. Repletion of the deficiency or prophylactic supplementation with oral magnesium may help avoid or ameliorate such complications as arrhythmias, hypertension, and sudden cardiac death and may even improve the course of the diabetic condition.

Postgrad-Med. 1992 Oct; 92(5): 217-9, 222-4

Treatment of preeclampsia and eclampsia

The characteristics and treatment of preeclampsia and eclampsia are reviewed. Risk factors for preeclampsia include (1) nulliparity, (2) a mother or sister(s) with a history of the disorder, (3) essential hypertension or renal disease, or (4) a twin or molar pregnancy. Preeclampsia is diagnosed when the systolic blood pressure (BP) increases by 30 mm Hg or the diastolic BP increases by 15 mm Hg after the 20th week of gestation and the BP rise is accompanied by edema, proteinuria, or both. Severe preeclampsia is diagnosed when the BP reaches or exceeds 160 mm Hg systolic or 110 mm Hg diastolic after bed rest. Eclampsia is the occurrence of seizures (in the preeclamptic patient) that cannot be attributed to other causes; it occurs in about 0.2% of preeclamptic patients. Magnesium sulfate (in the injectable, hydrated form) is the agent used most often for seizure prophylaxis in the preeclamptic patient in the United States. It is also used widely to control seizures once they develop. In the United States, diazepam is used to supplement magnesium sulfate if necessary to control seizures, but its use is not routine. Among antihypertensive agents, i.v. hydralazine is preferred in this country to control blood pressure in the severely preeclamptic or eclamptic patient. Several studies provide promising evidence that low-dose aspirin (60-150 mg daily beginning at 28-30 weeks of gestation) prevents preeclampsia in women who are at risk for its development. Until additional comparative studies are completed, magnesium sulfate and hydralazine will remain the standard of care for the treatment of preeclampsia in the United States.

Clin-Pharm. 1992 Mar; 11(3): 236-45

A comprehensive review of the salt and blood pressure relationship

Salt has played an important role in the human diet since earliest times. However, increases in the availability and consumption of dietary salt have raised concerns that excessive intakes may cause hypertension. Although recent research has linked salt intake to variations in blood pressure, definitive conclusions have been lacking. Uncertainties in this area are due to the complex effects of salt on the cardiovascular system and on blood pressure regulation. Nevertheless, many of these complexities are now well understood and have been summarized in this review. Among the topics we examine are the effects of salt on fluid and electrolyte homoeostasis; potential mechanisms of salt-induced hypertension; the epidemiology of salt intake and blood pressure; the effects of salt restriction and supplementation on blood pressure regulation; the potential roles of sodium and chloride ions, as well as interactions with dietary potassium, calcium, and magnesium; current theories of salt sensitivity; the clinical risks of dietary salt depletion; and the dietary sources of salt.

Muntzel-M; Drueke-T
Am-J-Hypertens. 1992 Apr; 5(4 Pt 1): 1S-42S

Magnesium supplementation as an adjuvant to synthetic calcium channel antagonists in the treatment of hypertension

Magnesium (Mg2+) has antagonistic properties to calcium (Ca2+) and has been termed the physiologic Ca2+ blocker. Synthetic Ca2+ channel blockers are extensively used as anti-hypertensive agents. It is hypothesised that when administered in combination synthetic Ca2+ channel blockers and Mg are synergistic in the treatment of hypertension.

Med-Hypotheses. 1991 Oct; 36(2): 140-1

The effect of magnesium on maternal blood pressure in pregnancy-induced hypertension. A randomized double-blind placebo-controlled trial

The effects of magnesium were compared with those of placebo in a randomized double-blind controlled study of 58 patients with pregnancy-induced hypertension, of whom 27 received magnesium and 31 placebo. Twenty patients in each group were nulliparas. The treatment comprised 48 h of either intravenous magnesium or placebo infusion followed by daily oral magnesium or placebo tablets until one day after delivery. Magnesium supplementation significantly reduced maternal mean arterial blood pressure (MAP). The gestational age at delivery was the same in both groups, whereas the relative fetal birth weight among nulliparas was reduced in the placebo group. Unbalanced analyses of variance suggested an influence of magnesium supplement on birth weight. The infants in the magnesium supplemented group spent fewer days in the neonatal intensive care unit. There were no perinatal deaths. Magnesium appeared to be beneficial in the management of pregnancy-induced hypertension. The better outcome associated with magnesium supplementation may not have been due to reduction of MAP and further studies are needed to clarify whether magnesium influences birth weight.

Rudnicki-M; Frolich-A; Rasmussen-WF; McNair-P
Acta-Obstet-Gynecol-Scand. 1991; 70(6): 445-50

Minerals and blood pressure

The mineral elements sodium, potassium, calcium and magnesium play a central role in the normal regulation of blood pressure. In particular, these mineral elements have important interrelationships in the control of arterial resistance. These elements, especially sodium and potassium, also regulate the fluid balance of the body and, hence, influence the cardiac output. Evidence shows that the present levels of intake of mineral elements are not optimum for maintaining normal blood pressure but predispose to the development of arterial hypertension. Research results suggest that without sodium chloride (common salt) and other sodium compounds being added to the diet arterial hypertension would be virtually non existent. Moreover, blood pressure would not rise with age. In communities with a high consumption of added sodium, a high intake of potassium and, possibly, magnesium seem to protect against the development of arterial hypertension and the rise of blood pressure with age. A marked reduction of sodium intake is effective in treating even severe hypertension. A moderate restriction of sodium intake or an increase in potassium intake exert remarkable antihypertensive effects, at least in some hypertensive patients. Magnesium and possibly also calcium supplements may be effective in reducing blood pressure in some hypertensives. In hypertensive patients treated with drugs sodium restriction and potassium and magnesium supplementation enhance the therapeutic effect, reduce the number and dosage, and lessen the adverse effects of prescribed antihypertensive drugs. Hence, a fall in sodium consumption and increases in potassium and magnesium consumption are useful in preventing and treating arterial hypertension.

Ann-Med. 1991 Aug; 23(3): 299-305

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