Mineral Studies – Calcium Magnesium Supplements

Calcium, vitamin D, dairy products, and risk of colorectal cancer in the cancer prevention study II nutrition cohort (United States).

McCullough ML, Robertson AS, Rodriguez C, Jacobs EJ, Chao A, Carolyn J, Calle EE, Willett WC, Thun MJ.

Epidemiology and Surveillance Research Department, American Cancer Society, 1599 Clifton Rd NE, Atlanta GA, 30309 USA.

OBJECTIVE: Calcium, vitamin D, and dairy product intake may reduce the risk of colorectal cancer. We therefore examined the association between these factors and risk of colorectal cancer in a large prospective cohort of United States men and women. METHODS: Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed questionnaire on diet, medical history, and lifestyle in 1992-93. After excluding participants with a history of cancer or incomplete dietary information, 60,866 men and 66,883 women remained for analysis. During follow-up through 31 August 1997 we documented 421 and 262 cases of incident colorectal cancers among men and women, respectively. Multivariate-adjusted rate ratios (RR) were calculated using Cox proportional hazards models. RESULTS: Total calcium intake (from diet and supplements) was associated with marginally lower colorectal cancer risk in men and women (RR = 0.87, 95% CI 0.67-1.12, highest vs lowest quintiles, p trend = 0.02). The association was strongest for calcium from supplements (RR = 0.69, 95% CI 0.49-0.96 for > or = 500 mg/day vs none). Total vitamin D intake (from diet and multivitamins) was also inversely associated with risk of colorectal cancer, particularly among men (RR = 0.71, 95% CI 0.51-0.98, p trend = 0.02). Dairy product intake was not related to overall risk. CONCLUSIONS: Our results support the hypothesis that calcium modestly reduces risk of colorectal cancer. Vitamin D was associated with reduced risk of colorectal cancer only in men.

J Womens Health (Larchmt). 2003 Mar;12(2):173-82.

Diet, body weight, and colorectal cancer: a summary of the epidemiologic evidence.

Giovannucci E.

Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts 02115, USA. edward.giovannucci@channing.harvard.edu

Colorectal cancer is the second leading cause of cancer death in the United States, and the number of new cases annually is approximately equal for men and women. Several nutritional factors are likely to have a major influence on risk of this cancer. Physical inactivity and excessive adiposity, especially if centrally distributed, clearly increase the risk of colon cancer. Hyperinsulinemia may be an important underlying risk factor. In conjunction with obesity and physical inactivity, which induce a state of insulin resistance, certain dietary patterns that stimulate insulin secretion, including high intakes of red and processed meats, saturated and trans-fats, and highly processed carbohydrates and sugars, may increase the risk of colon cancer. There is evidence suggesting that some component of red meat may independently increase the risk of colorectal cancer, and some micronutrients may be important as protective agents. Currently, the evidence is strongest for folate and calcium. Folate may be especially important in alcohol drinkers because alcohol appears to increase the risk, particularly when folate intake is low. This interaction may be related to the antifolate properties of alcohol. In contrast to earlier studies, more recent epidemiologic studies have generally not supported a strong influence of dietary fiber or fruits and vegetables, although these have other health benefits, and their consumption should be encouraged. The majority of colon cancers, as well as many other conditions, may be prevented by lifestyle alterations in the intake of these nutritional factors, in addition to other factors, such as smoking.

Early development of cancer chemoprevention clinical trials: studies of dietary calcium as a chemopreventive agent for human subjects.

Lipkin M.

Strang Cancer Prevention Center and Weill Medical College of Cornell University, New York, NY 10021, USA. lipkin@mail.rockefeller.edu

Early cancer chemoprevention clinical trials in human subjects had to be carried out with large numbers of subjects studied for long durations, measuring cancer as an end point. However new findings on abnormal epithelial cell growth and development during the multistage evolution of colonic tumors made it possible to carry out chemoprevention clinical trials in several stages, with fewer subjects studied for shorter durations, thus enabling investigators to analyze increasing numbers of chemopreventive agents and nutritional regimens in clinical trials. Supplemental dietary calcium was the first candidate chemopreventive agent studied in this multistage approach in human subjects, as a putative agent for colon cancer prevention. Early- and late-stage intermediate biomarker studies in humans have strongly suggested utility for supplemental dietary calcium to inhibit the development of benign and subsequent malignant colonic neoplasms. Preclinical experimental studies have further demonstrated the ability of increased dietary calcium to inhibit the evolution of colonic tumors when they were induced by targeted mutations, dietary factors, and particularly when given over a long duration of lifespan.

Dietary influences on survival after ovarian cancer.

Nagle CM, Purdie DM, Webb PM, Green A, Harvey PW, Bain CJ.

School of Population Health, University of Queensland, Brisbane, Australia.

We evaluated the effects of various food groups and micronutrients in the diet on survival among women who originally participated in a population-based case-control study of ovarian cancer conducted across 3 Australian states between 1990 and 1993. This analysis included 609 women with invasive epithelial ovarian cancer, primarily because there was negligible mortality in women with borderline tumors. The women’s usual diet was assessed using a validated food frequency questionnaire. Deaths in the cohort were identified using state-based cancer registries and the Australian National Death Index (NDI). Crude 5-year survival probabilities were estimated using the Kaplan-Meier technique, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from Cox regression models. After adjusting for important confounding factors, a survival advantage was observed for those who reported higher intake of vegetables in general (HR = 0.75, 95% CI = 0.57-0.99, p-value trend 0.01 for the highest third, compared to the lowest third), and cruciferous vegetables in particular (HR = 0.75, 95% CI = 0.57-0.98, p-value trend 0.03), and among women in the upper third of intake of vitamin E (HR = 0.76, 95% CI = 0.58-1.01, p-value trend 0.04). Inverse associations were also seen with protein (p-value trend 0.09), red meat (p-value trend 0.06) and white meat (p-value trend 0.07), and modest positive trends (maximum 30% excess) with lactose (p-value trend 0.04), calcium and dairy products. Although much remains to be learned about the influence of nutritional factors after a diagnosis of ovarian cancer, our study suggests the possibility that a diet high in vegetable intake may help improve survival.

Am J Clin Nutr. 2003 Jun;77(6):1448-52.

Calcium intake, body composition, and lipoprotein-lipid concentrations in adults.

Jacqmain M, Doucet E, Despres JP, Bouchard C, Tremblay A.

Division of Kinesiology (MJ and AT) and the Department of Food Science and Nutrition (J-PD), Laval University, Ste-Foy, Quebec.

BACKGROUND: Recent data suggest that variations in calcium intake may influence lipid metabolism and body composition. OBJECTIVE: The association between daily calcium intake and body composition and plasma lipoprotein-lipid concentrations was studied cross-sectionally in adults from phase 2 of the Quebec Family Study. DESIGN: Adults aged 20-65 y (235 men, 235 women) were studied. Subjects who consumed vitamin or mineral supplements were excluded. Subjects were divided into 3 groups on the basis of their daily calcium intake: groups A (< 600 mg), B (600-1000 mg), and C (> 1000 mg). RESULTS: Daily calcium intake was negatively correlated with plasma LDL cholesterol, total cholesterol, and total:HDL cholesterol in women and men after adjustment for variations in body fat mass and waist circumference (P < 0.05). In women, a significantly greater ratio of total to HDL cholesterol (P < 0.05) was observed in group A than in group C after correction for body fat mass and waist circumference. In women, body weight, percentage body fat, fat mass, body mass index, waist circumference, and total abdominal adipose tissue area measured by computed tomography were significantly greater (P < 0.05) in group A than in groups B and C, even after adjustments for confounding variables. Comparable trends were observed in men, but not after adjustment for the same covariates. CONCLUSION: A low daily calcium intake is associated with greater adiposity, particularly in women. In both sexes, a high calcium intake is associated with a plasma lipoprotein-lipid profile predictive of a lower risk of coronary heart disease risk compared with a low calcium intake.

Steroid induced osteoporosis: prevention and treatment

Roux C, Orcel P.

Institut de rhumatologie, hopital Cochin, centre d’evaluation des maladies osseuses, 27, rue du Faubourg-Saint-Jacques, 75014, Paris, France

Purpose. – Corticosteroid induced osteoporosis (CIO) is the most frequent complication of long-term corticosteroid therapy, and the most frequent cause of secondary osteoporosis. New data from biological, epidemiological and therapeutic studies provide basis for optimal management of this bone disease.Main points. – Corticosteroids are responsible for both quantitative and qualitative deleterious effects on bone, through their effect on bone cells, mainly on osteoblasts (with both a decrease in osteoblast activity and an increase in apoptosis). Epidemiological studies have shown an increased risk of fractures related to CIO, even for low doses, and during the first 6 months of treatment. Relative risk is 1.3 and 2.6 for peripheral and vertebral fractures respectively. Bone mineral density, measured by dual-energy X-ray absorptiometry, is decreased at spine and hip; the risk of fracture is higher in CIO as compared to post-menopausal osteoporosis, for a similar bone density. Prevention of CIO needs the use of the minimal efficacious dose, and treatment of calcium, vitamin D and gonadal hormones insufficiencies. Patients at risk of fracture, as post-menopausal women with prevalent fractures, should receive a bisphosphonate.Perspective. – It may be possible to reduce the fracture risk in patients on long-term corticosteroid therapy.

Joint Bone Spine. 2003 Jun;70(3):203-208.

Effects on bone mineral density of calcium and vitamin D supplementation in elderly women with vitamin D deficiency.

Grados F, Brazier M, Kamel S, Duver S, Heurtebize N, Maamer M, Mathieu M, Garabedian M, Sebert JL, Fardellone P.

Rheumatology Department, North Hospital Group, 80054 cedex 1, Amiens, France

Objectives. – Calcium and vitamin D deficiency is common in older individuals, particularly those who live in nursing homes, and increases the risk of osteoporosis and fractures.Methods. – We conducted a randomized double-blind placebo-controlled study of combined supplementation with 500 mg of elemental calcium, as carbonate, and 400 IU of vitamin D bid for 12 months in women older than 65 years of age with vitamin D deficiency, defined as serum 25(OH)D concentrations </=12 ng/ml.Results. – Mean patient age was 75 +/- 7 years, and median daily dietary intakes of calcium and vitamin D were 697 mg and 66.8 IU in the supplemented group (n = 95) and 671 mg and 61.8 IU in the placebo group (n = 97). The median serum 25(OH)D level was 7.0 ng/ml in both groups, and the medial intact parathyroid hormone (PTHi) levels were 49 and 48 pg/ml in the supplemented and placebo groups, respectively. The median increase in serum 25(OH)D was 22.0 ng/ml in the supplemented group and 4 ng/ml in the placebo group (P < 0.0001), and the median PTHi decrease was 17 and 5 pg/ml, respectively (P < 0.0001). The median bone mineral density increase was significantly greater in the supplemented group than in the placebo group: +2.98% vs. -0.21% at L2-L4 (P = 0.0009), +1.19% and -0.83% at the femoral neck (P = 0.015), +0.86% and -0.56% at the trochanter (P = 0.015), and +0.99% and +0.11% for the whole body (P = 0.01). Similarly, the median decrease in the main bone markers was significantly greater in the treated group than in the placebo group: -1.35 &mgr;g/l vs. +0.50 &mgr;g/l for bone alkaline phosphatase (P = 0.008), -16.6 nmol/mmol creatinine vs. -2.3 nmol/mmol creatinine for urinary type I amino-terminal telopeptide (P = 0.001), and -896 pmol/l vs. -201 pmol/l for serum type I carboxy-terminal telopeptide (P = 0.003). We found no significant differences between the two groups for serum calcium, although urinary calcium excretion changed more in the supplemented group than in the placebo group. In conclusion, bone mass in older women with vitamin D deficiency increases significantly at the lumbar spine, femur, trochanter, and whole body after calcium and vitamin D supplementation for 1 year, and concomitantly bone markers improved as vitamin D levels returned to normal.

BMC Public Health. 2003 Jun 18 [Epub ahead of print].

The influence of calcium and magnesium in drinking water and diet on cardiovascular risk factors in individuals living in hard and soft water areas with differences in cardiovascular mortality.

Nerbrand C, Agreus L, Lenner RA, Nyberg P, Svardsudd K.

:BackgroundThe role of water hardness as a risk factor for cardiovascular disease has been widely investigated and evaluated as regards regional differences in cardiovascular disease. This study was performed to evaluate the relation between calcium and magnesium in drinking water and diet and risk factors for cardiovascular disease in individuals living in hard and soft water areas with considerable differences in cardiovascular mortality.MethodsA random sample of 207 individuals living in two municipalities characterised by differences in cardiovascular mortality and water hardness was invited for an examination including a questionnaire about health, social and living conditions and diet. Intake of magnesium and calcium was calculated from the diet questionnaire with special consideration to the use of local water. Household water samples were delivered by each individual and were analysed for magnesium and calcium.ResultsIn the total sample, there were positive correlations between the calcium content in household water and systolic blood pressure (SBP) and negative correlations with s-cholesterol and s-LDL-cholesterol. No correlation was seen with magnesium content in household water to any of the risk factors.Calcium content in diet showed no correlation to cardiovascular risk factors. Magnesium in diet was positively correlated to diastolic blood pressure (DBP). In regression analyses controlled for age and sex 18.5% of the variation in SBP was explained by the variation in BMI, HbA1c and calcium content in water. Some 27.9% of the variation in s-cholesterol could be explained by the variation in s-triglycerides (TG), and calcium content in water.ConclusionsThis study of individuals living in soft and hard water areas showed significant correlations between the content of calcium in water and major cardiovascular risk factors. This was not found for magnesium in water or calcium or magnesium in diet. Regression analyses indicated that calcium content in water could be a factor in the complexity of relationships and importance of cardiovascular risk factors. From these results it is not possible to conclude any definite causal relation and further research is needed.

S Afr Med J. 2003 Mar;93(3):224-8.

Calcium supplementation to prevent pre-eclampsia–a systematic review.

Hofmeyr GJ, Roodt A, Atallah AN, Duley L.

Effective Care Research Unit, East London Hospital Complex, University of the Witwatersrand, Johannesburg/Fort Hare University, East London, E Cape.

BACKGROUND: Calcium supplementation during pregnancy may prevent high blood pressure and preterm labour. OBJECTIVE: To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child adverse outcomes. DESIGN: A systematic review of randomised trials that compared supplementation with at least 1 g calcium daily during pregnancy with placebo. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register (October 2001) and the Cochrane Controlled Trials Register (Issue 3, 2001) were searched and study authors were contacted. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed. Data were extracted and analysed. MAIN RESULTS: There was a modest reduction in the risk of pre-eclampsia with calcium supplementation (relative risk (RR) 0.68, 95% confidence interval (CI): 0.57-0.81). The effect was greatest for women at high risk of hypertension (RR 0.21, 95% CI: 0.11-0.39) and those with low baseline calcium intake (RR 0.32, 95% CI: 0.21-0.49). There was no overall effect on the risk of preterm delivery, although there was a reduction in risk among women at high risk of hypertension (RR 0.42, 95% CI: 0.23-0.78). There was no evidence of any effect of calcium supplementation on stillbirth or death before discharge from hospital. There were fewer babies with birthweight < 2,500 g (RR 0.83, 95% CI: 0.71-0.98). In one study, childhood systolic blood pressure > 95th percentile was reduced (RR 0.59, 95% CI: 0.39-0.91). CONCLUSIONS: Calcium supplementation appears to be beneficial for women at high risk of gestational hypertension and in communities with low dietary calcium intake. These benefits were confined to several rather small trials, and were not found in the largest trial to date, conducted in a low-risk population. Further research is required.

Adv Neurol. 2003;92:173-8.

Nutritional and metabolic aspects of stroke prevention.

Spence JD.

Department of Clinical Neurological Sciences, University of Western Ontario, Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, London, Ontario, Canada.

Epidemiologic evidence, animal studies, angiographic and ultrasound studies in humans, and a limited number of clinical trials suggest that vitamins C and E may be protective and that folate, B6, and B12, by lowering homocysteine levels, may reduce stroke. However, these hypotheses require testing before widespread use of supplementary vitamins can be generally recommended (62). Clinical trials under way will test those hypotheses. In the meantime, it should be understood that the role of diet is much more important than is widely recognized. A diet low in saturated fat and cholesterol, low in sodium, high in potassium and calcium, and containing a lot of fruits and vegetables reduces blood pressure as much as an antihypertensive drug and in coronary patients is twice as effective as statin drugs in reducing death and myocardial infarction. Such a diet can therefore be confidently recommended as a source not only of natural proportions of vitamins and antioxidants but also for benefits that we are only beginning to define.

Maturitas. 2003 Apr 25;44(4):299-305.

Calcium-vitamin D3 supplementation is cost-effective in hip fractures prevention.

Lilliu H, Pamphile R, Chapuy MC, Schulten J, Arlot M, Meunier PJ.

CLP-Sante, 9-11 rue du Mont Aigoual, F-75015 Paris, France. herve.lilliu@clp-sante.fr

OBJECTIVE: To assess the cost implications for a preventive treatment strategy for institutionalised elderly women with a combined 1200 mg/day calcium and 800 IU/day vitamin D(3) supplementation in seven European countries. DESIGN: Retrospective cost effectiveness analysis based on a prospective placebo-controlled randomised clinical trial. DATA SOURCES: Recently published cost studies in seven European countries. Clinical results from Decalyos, a 3-year placebo-controlled study in elderly institutionalised women. TRIALS: Decalyos study, with 36 months follow-up of 3270 mobile elderly women living in 180 nursing homes, allocated to two groups. One group received 1200 mg/day elemental calcium in the form of tricalcium phosphate together with 800 IU/day (20 microg) of cholecalciferol (vitamin D(3)), the other placebo. RESULTS: In the 36 months analysis of the Decalyos study, 138 hip fractures occurred in the group of 1176 women, receiving supplementation and 184 hip fractures in the placebo group of 1127 women. The mean duration of treatment was 625.4 days. Adjusted to 1000 women, 46 hip fractures were avoided by the calcium and vitamin D(3) supplementation. For all countries, the total costs in the placebo group were higher than in the group receiving supplementation, resulting in a net benefit of 79000-711000 per 1000 women. CONCLUSION: This analysis suggests that the supplementation strategy is cost saving. The results may underestimate the net benefits, as this treatment has also shown to be effective in decreasing the incidence of other non-vertebral fractures in elderly institutionalised women.

J Hum Nutr Diet. 2003 Apr;16(2):97-109.

Nutritional management of rheumatoid arthritis: a review of the evidence.

Rennie KL, Hughes J, Lang R, Jebb SA.

MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, UK; Independent Nutrition Consultant, 7 Holmesdale Park, Nutfield, Surrey, UK.

Rheumatoid arthritis (RA) is a debilitating disease and is associated with increased risk of cardiovascular disease and osteoporosis. Poor nutrient status in RA patients has been reported and some drug therapies, such as nonsteroidal anti-inflammatory drugs (NSAIDs), prescribed to alleviate RA symptoms, may increase the requirement for some nutrients and reduce their absorption. This paper reviews the scientific evidence for the role of diet and nutrient supplementation in the management of RA, by alleviating symptoms, decreasing progression of the disease or by reducing the reliance on, or combating the side-effects of, NSAIDs. Supplementation with long-chain n-3 polyunsaturated fatty acids (PUFA) consistently demonstrates an improvement in symptoms and a reduction in NSAID usage. Evidence relating to other fatty acids, antioxidants, zinc, iron, folate, other B vitamins, calcium, vitamin D and fluoride are also considered. The present evidence suggests that RA patients should consume a balanced diet rich in long-chain n-3 PUFA and antioxidants. More randomized long-term studies are needed to provide evidence for the benefits of specific nutritional supplementation and to determine optimum intake, particularly for n-3 PUFA and antioxidants.

Can Fam Physician. 2002 Nov;48:1789-97.

Premenstrual syndrome. Evidence-based treatment in family practice.

Douglas S.

Department of Family Medicine, Dalhousie University, Abbie Lane Bldg, QEII Hospital, 5909 Veterans Memorial Ln, Halifax, NS B3H 2E2. sue.douglas@dal.ca

OBJECTIVE: To evaluate the strength of evidence for treatments for premenstrual syndrome (PMS) and to derive a set of practical guidelines for managing PMS in family practice. QUALITY OF EVIDENCE: An advanced MEDLINE search was conducted from January 1990 to December 2001. The Cochrane Library and personal contacts were also used. Quality of evidence in studies ranged from level I to level III, depending on the intervention. MAIN MESSAGE: Good scientific evidence shows that calcium carbonate (1200 mg/d) and selective serotonin reuptake inhibitors are effective treatments for PMS. The most commonly used therapies (including vitamin B6, evening primrose oil, and oral contraceptives) are based on inconclusive evidence. Other treatments for which there is inconclusive evidence include aerobic exercise, stress reduction, cognitive therapy, spironolactone, magnesium, nonsteroidal anti-inflammatory drugs, various hormonal regimens, and a complex carbohydrate-rich diet. Although evidence for them is inconclusive, it is reasonable to recommend healthy lifestyle changes given their overall health benefits. Progesterone and bromocriptine, which are still widely used, are ineffective. CONCLUSION: Calcium carbonate should be recommended as first-line therapy for women with mild-to-moderate PMS. Selective serotonin reuptake inhibitors can be considered as first-line therapy for women with severe affective symptoms and for women with milder symptoms who have failed to respond to other therapies. Other therapies may be tried if these measures fail to provide adequate relief.

Panminerva Med. 2001 Sep;43(3):177-209.

Hypomagnesemia. A review of pathophysiological, clinical and therapeutical aspects.

Iannello S, Belfiore F.

Institute of Internal Medicine and Internal Specialties, Chair of Internal Medicine, University of Catania Medical School, Garibaldi Hospital, Catania, Italy. francesco.belfiore@iol.it

The aim of this paper is to discuss, on the basis of an extensive literature review, the role of magnesium (Mg) in health and disease. Mg is an essential cation playing a crucial role in many enzyme systems. Quantitative Mg body stores are regulated by metabolic and hormonal effects on gastrointestinal absorption and renal excretion. Mg is a smooth muscle relaxant, dilates coronary arteries and peripheral vessels, exerts antiarrhythmic effects, may have a permissive effect on catecholamine actions and can play a role in various thrombogenic conditions. Today, hypomagnesemia has become a recognized medical occurrence which may be associated with many different diseases, either genetic or acquired. Mg deficiency is one of the most frequent electrolyte abnormalities in clinical practice, but it is probably the most underdiagnosed one. Clinical manifestations of hypomagnesemia may begin insidiously or dramatically sudden. A large part of the population (especially aged subjects) may have an inadequate Mg intake and a chronic latent Mg deficiency. Routine inclusion of serum Mg analysis in the electrolyte panel represents a continued need to recognize hypomagnesemia and to treat Mg-depleted patients. New clinical studies on Mg deficiency are necessary to ascertain the usefulness and cost-effectiveness of Mg replacement therapy.

South Med J. 2001 Dec;94(12):1195-201.

Comment in:
• South Med J. 2003 Jan;96(1):104.

Magnesium: its proven and potential clinical significance.

Fox C, Ramsoomair D, Carter C.

Department of Family Medicine, State University of New York at Buffalo, 14215, USA.

Magnesium is the fourth most abundant cation in the body and is present in more than 300 enzymatic systems, where it is crucial for adenosine triphosphate (ATP) metabolism. Deficiency states result in increased insulin resistance, as well as increased smooth muscle and platelet reactivity. Magnesium deficiency has been shown to correlate with a number of chronic cardiovascular diseases, including hypertension, diabetes mellitus, and hyperlipidemia. Intravenous magnesium has been used therapeutically in critical situations such as status asthmaticus, torsades de pointes, and preeclampsia. Few controlled studies exist regarding the therapeutic uses of oral magnesium supplementation in chronic cardiovascular diseases. Randomized clinical trials are urgently needed to determine whether magnesium supplementation will alter the natural history of these disease states.

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

Magnesium deficiency and diabetes mellitus. Causes and effects.

Rude RK.

University of Southern California School of Medicine, Los Angeles 90033.

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.

J Cardiovasc Nurs. 1993 Oct;8(1):19-31.

Magnesium in congestive heart failure, acute myocardial infarction and dysrhythmias.

Hix CD.

Hackettstown Community Hospital, New Jersey.

Magnesium plays an important role in the functioning of the cardiovascular system. A decrease in magnesium has been linked with tachydysrhythmias, increased mortality in patients with congestive heart failure, and increased mortality after an acute myocardial infarction. The research shows that the use of magnesium supplements in these situations may be beneficial for treating and preventing life-threatening conditions. Magnesium supplements can be administered safely either orally or parenterally depending on the situation.

New Horiz. 1994 May;2(2):186-92.

Should we supplement magnesium in critically ill patients?

Olerich MA, Rude RK.

Department of Diabetes, Los Angeles County/University of Southern California Medical Center 90033.

Magnesium (Mg) deficiency is a common yet underdiagnosed problem in the ICU. Since only 1% of total body Mg is in the extracellular fluid, serum Mg concentrations may not adequately reflect Mg status. Utilizing techniques to measure intracellular Mg concentrations, Mg depletion has been shown to be present in about one half of all ICU patients. These patients have significantly higher morbidity and mortality rates than Mg-replete patients. Accurate identification of patients with Mg depletion requires a knowledge of the risk factors associated with Mg deficiency. These factors include poorly controlled diabetes mellitus, alcohol ingestion, severe diarrhea and steatorrhea, and the use of a number of pharmacologic agents that induce renal Mg wasting. Manifestations of Mg deficiency include hypokalemia, hypocalcemia, neuromuscular hyperexcitability, respiratory muscle weakness, and intractable arrhythmias. Mg deficiency may also play a role in the genesis of myocardial ischemia. In this article, we review the assessment, causes, and manifestations of Mg deficiency and suggest guidelines for adequate treatment.

Dis Mon. 1988 Apr;34(4):161-218.

Magnesium metabolism in health and disease.

Elin RJ.

Clinical Pathology Department, National Institutes of Health, Bethesda, Maryland.

Magnesium is an important element for health and disease. Magnesium, the second most abundant intracellular cation, has been identified as a cofactor in over 300 enzymatic reactions involving energy metabolism and protein and nucleic acid synthesis. Approximately half of the total magnesium in the body is present in soft tissue, and the other half in bone. Less than 1% of the total body magnesium is present in blood. Nonetheless, the majority of our experimental information comes from determination of magnesium in serum and red blood cells. At present, we have little information about equilibrium among and state of magnesium within body pools. Magnesium is absorbed uniformly from the small intestine and the serum concentration controlled by excretion from the kidney. The clinical laboratory evaluation of magnesium status is primarily limited to the serum magnesium concentration, 24-hour urinary excretion, and percent retention following parenteral magnesium. However, results for these tests do not necessarily correlate with intracellular magnesium. Thus, there is no readily available test to determine intracellular/total body magnesium status. Magnesium deficiency may cause weakness, tremors, seizures, cardiac arrhythmias, hypokalemia, and hypocalcemia. The causes of hypomagnesemia are reduced intake (poor nutrition or IV fluids without magnesium), reduced absorption (chronic diarrhea, malabsorption, or bypass/resection of bowel), redistribution (exchange transfusion or acute pancreatitis), and increased excretion (medication, alcoholism, diabetes mellitus, renal tubular disorders, hypercalcemia, hyperthyroidism, aldosteronism, stress, or excessive lactation). A large segment of the U.S. population may have an inadequate intake of magnesium and may have a chronic latent magnesium deficiency that has been linked to atherosclerosis, myocardial infarction, hypertension, cancer, kidney stones, premenstrual syndrome, and psychiatric disorders. Hypermagnesemia is primarily seen in acute and chronic renal failure, and is treated effectively by dialysis.

Am Heart J. 1992 Aug;124(2):544-9.

Magnesium deficiency and sudden death.

Eisenberg MJ.

A link between Mg deficiency and sudden death is suggested by a substantial number of studies published over the past three decades. Data come from epidemiologic, autopsy, clinical, and animal studies. They suggest that: (1) Sudden death is common in areas where community water supplies are Mg-deficient. (2) Myocardial Mg content is low in people who die of sudden death. (3) Cardiac arrhythmias and coronary artery vasospasm can be caused by Mg deficiency and (4) Intravenous Mg reduces the risk of arrhythmia and death immediately after acute myocardial infarction. Because of these data, Mg supplementation has been proposed as a possible method of reducing the risk of sudden death. Suggested ways of supplementing Mg include public education to change dietary habits, addition of Mg to community water supplies, fortification of foods, and oral supplementation. Despite the substantial number of studies linking Mg deficiency with sudden death, no prospective studies have yet investigated whether large-scale Mg supplementation is useful for the primary prevention of sudden death.

Ann Pharmacother. 1993 Jun;27(6):775-80.

Magnesium and diabetes: a review.

White JR Jr, Campbell RK.

College of Pharmacy, Washington State University, Spokane 99204.

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.

South Med J. 1999 Nov;92(11):1040-7.

Magnesium for the next millennium.

Swain R, Kaplan-Machlis B.

New Millennium Wellness and Sports Medicine, and the Department of Family Medicine, West Virginia University, Charleston, USA.

BACKGROUND: Magnesium is a trace mineral in several hundred chemical reactions in the body. It has therapeutic potential in many medical conditions. In this review, we attempted to clarify the current information on the role of magnesium as a therapeutic agent. METHODS: A MEDLINE search from 1966 through March 1999 was conducted, using PubMed and “Magnesium” and “Therapeutic Usage” as the two initial key headings. Important articles were also identified from the bibliographies of the initial articles. RESULTS: A total of 51 articles were included in this review. Articles were excluded if they were based on animal study or were in a language other than English. CONCLUSION: Magnesium has long been used as an ingredient in laxatives and antacids. It seems clear that intravenous magnesium also is effective for the suppression of ventricular ectopy in the hospital setting and is a first-line agent for torsades de pointes. It is less clear whether it is useful in patients with congestive heart failure or acute myocardial infarction (MI). Although effective for treatment of preeclampsia/eclampsia, its use in the termination of preterm labor has recently been questioned. In asthma and chronic lung disease, intravenous magnesium may be useful when conventional treatment has failed. Finally, magnesium may have a role in the prevention and treatment of vascular headaches.

Mol Aspects Med. 2003 Feb 6;24(1-3):137-46.

Low magnesium and atherosclerosis: an evidence-based link.

Maier JA.

Dipartimento di Scienze Precliniche-LITA Vialba, Universita di Milano, Via GB Grassi 74, 20157, Milano, Italy

Data indicates that magnesium deficiency caused by poor diet and/or errors in its metabolism may be a missing link between diverse cardiovascular risk factors and atherosclerosis. Experimentally induced low plasma levels of magnesium accelerate atherogenesis by increasing LDL concentrations and their oxidative modifications, and by promoting inflammation. In vitro studies have shown that low magnesium determines endothelial dysfunction, the initiating event leading to the formation of the plaque. Moreover, oral magnesium therapy has been shown to improve endothelial function in patients with coronary artery disease.Magnesium, which is an inexpensive, natural and rather safe element, could be useful in preventing atherosclerosis and as an adjuvant therapy in patients with clinical manifestations of the disease.

Mol Aspects Med. 2003 Feb 6;24(1-3):107-36.

Role of magnesium in the pathogenesis of hypertension.

Touyz RM.

Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, 110 Pine Avenue West, Que., H2W IR7, Montreal, Canada

Human essential hypertension is a complex, multifactorial, quantitative trait under polygenic control. Although the exact etiology is unknown, the fundamental hemodynamic abnormality in hypertension is increased peripheral resistance, due primarily to changes in vascular structure and function. These changes include arterial wall thickening, abnormal vascular tone and endothelial dysfunction and are due to alterations in the biology of the cellular and non-cellular components of the arterial wall. Many of these processes are influenced by magnesium. Small changes in magnesium levels may have significant effects on cardiac excitability and on vascular tone, contractility and reactivity. Accordingly magnesium may be important in the physiological regulation of blood pressure whereas perturbations in cellular magnesium homeostasis could play a role in pathophysiological processes underlying blood pressure elevation. For the most part, epidemiological and experimental studies demonstrate an inverse association between magnesium and blood pressure and support a role for magnesium in the pathogenesis of hypertension. However data from clinical studies have been less convincing and the therapeutic value of magnesium in the prevention and management of essential hypertension remains unclear. In view of the still ill-defined role of magnesium in clinical hypertension, magnesium supplementation is advised in those hypertensive patients who are receiving diuretics, who have resistant or secondary hypertension or who have frank magnesium deficiency. A magnesium-rich diet should be encouraged in the prevention of hypertension, particularly in predisposed communities because of the other advantages of such a diet in prevention. The clinical aspect that has demonstrated the greatest therapeutic potential for magnesium in hypertension, is in the treatment of pre-eclampsia and eclampsia. The present review discusses the role of magnesium in the regulation of vascular function and blood pressure and the implications in mechanisms underlying hypertension. Alterations in magnesium regulation in experimental and clinical hypertension and the potential antihypertensive therapeutic actions of magnesium will also be addressed.

Med Hypotheses. 2002 Jan;58(1):47-60.

The central role of magnesium deficiency in Tourette’s syndrome: causal relationships between magnesium deficiency, altered biochemical pathways and symptoms relating to Tourette’s syndrome and several reported comorbid conditions.

Grimaldi BL.

BonnieGr@aol.com

Prior studies have suggested a common etiology involved in Tourette’s syndrome and several comorbid conditions and symptomatology. Reportedly, current medications used in Tourette’s syndrome have intolerable side-effects or are ineffective for many patients. After thoroughly researching the literature, I hypothesize that magnesium deficiency may be the central precipitating event and common pathway for the subsequent biochemical effects on substance P, kynurenine, NMDA receptors, and vitamin B6 that may result in the symptomatology of Tourette’s syndrome and several reported comorbid conditions. These comorbid conditions and symptomatology include allergy, asthma, autism, attention deficit hyperactivity disorder, obsessive compulsive disorder, coprolalia, copropraxia, anxiety, depression, restless leg syndrome, migraine, self-injurious behavior, autoimmunity, rage, bruxism, seizure, heart arrhythmia, heightened sensitivity to sensory stimuli, and an exaggerated startle response. Common possible environmental and genetic factors are discussed, as well as biochemical mechanisms. Clinical studies to determine the medical efficacy for a comprehensive magnesium treatment option for Tourette’s syndrome need to be conducted to make this relatively safe, low side-effect treatment option available to doctors and their patients.

Headache. 2002 Apr;42(4):242-8.

Serum ionized magnesium levels and serum ionized calcium/ionized magnesium ratios in women with menstrual migraine.

Mauskop A, Altura BT, Altura BM.

New York Headache Center, SUNY Downstate Medical Center, Brooklyn 11203, USA.

OBJECTIVE: It has been suggested that magnesium deficiency may play an important role in menstrual migraine and that the serum ionized calcium (ICa2+)/ionized magnesium (IMg2+) ratio is important in migraine headache. Studies were designed to test these hypotheses. DESIGN: We prospectively evaluated 270 women seen at a headache clinic and in 61 women with menstrual migraine measured IMg2+, total magnesium, and ICa2+ levels so as to calculate the ICa2+/IMg2+ ratio. RESULTS: The incidences of IMg2+ deficiency were 45% during menstrual attacks, 15% during nonmenstrual attacks, 14% during menstruation without a migraine, and 15% between menstruations and between migraine attacks. The serum ICa2+ levels were within our reference range, but the ICa2+/IMg2+ ratio was elevated (P<.01) in menstrual migraine. CONCLUSIONS: The high incidence of IMg2+ deficiency and the elevated ICa2+/IMg2+ ratio during menstrual migraine confirm previous suggestions of a possible role for magnesium deficiency in the development of menstrual migraine.

Headache. 2002 Feb;42(2):114-9.

Oral magnesium load test in patients with migraine.

Trauninger A, Pfund Z, Koszegi T, Czopf J.

Department of Neurology, Medical Faculty, University of Pecs, Hungary.

OBJECTIVE: To determine whether migraineurs may have a systemic deficiency of magnesium. BACKGROUND: Magnesium deficiency has been shown to play a potential role in the pathogenesis of migraine, but there are no data on total body magnesium status in migraineurs. METHODS: An oral magnesium load test was performed by giving 3000 mg of magnesium lactate during a 24-hour interictal period to 20 patients with migraine (15 women and 5 men; mean age, 37.9 years) and 20 healthy volunteers (16 women and 4 men; mean age, 39.6 years). Baseline and postload magnesium concentrations were determined from serum and 24-hour urine specimens. RESULTS: There was no significant difference between the groups in the baseline serum and urine magnesium concentrations, although the latter tended to be lower (P = .064) in the migraine group. The postload magnesium concentrations were significantly higher within both the migraine (P < .0001 and P < .0001) and the control (P = .0009 and P < .0001) groups compared to the baseline values. After loading, the 24-hour urinary magnesium excretions were significantly lower (P = .0007) in the patients with migraine than in the controls, but serum values did not differ. CONCLUSIONS: Magnesium retention occurs in patients with migraine after oral loading, suggesting a systemic magnesium deficiency.

J Med Assoc Thai. 2001 Dec;84 Suppl 3:S645-9.

Serum magnesium in Thai coronary artery disease patients.

Wannasilp N, Poungvarin N, Pokum S, Leowattana W, Mahanonda N.

Department of Clinical Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Hypomagnesemia or magnesium (Mg) deficiency has been hypothesized to play a role in coronary artery disease (CAD). The authors aimed to evaluate serum Mg concentration in 100 CAD patients compared with 100 healthy controls. Mean values of serum Mg level in CAD and the control group were 2.14 +/- 0.39, 2.24 +/- 0.3 mg/dL respectively (P=0.052). The prevalence of Mg deficiency was 12 per cent in the CAD patients, and 5 per cent in the control group (odds ratio=2.59, 95% confident interval = 0.88-7.65, P=0.063). There was no significant difference in the serum Mg level between the 2 groups, although it tended to be lower in CAD patients. The prevalence of Mg deficiency did not differ significantly between the study group, however, it tended to be higher in CAD patients. These findings demonstrated that CAD patients may be associated with Mg deficiency, and contribute to the pathogenesis of CAD or acute thrombosis. Following this evidence, Mg treatment may be necessary in CAD patients with Mg deficiency or acute myocardial infarction (AMI).

Eur J Clin Nutr. 2002 May;56(5):409-14.

Dietary magnesium intake in type 2 diabetes.

Walti MK, Zimmermann MB, Spinas GA, Jacob S, Hurrell RF.

Laboratory for Human Nutrition, Institute of Food Science, Swiss Federal Institute of Technology (ETH) Zurich, Switzerland. monika.waelti@ilw.agrl.ethz.ch

BACKGROUND: Magnesium deficiency is common in type 2 diabetes and may have a negative impact on glucose homeostasis and insulin resistance, as well as on the evolution of complications such as retinopathy, thrombosis and hypertension. OBJECTIVE: To assess the dietary magnesium intake of patients with type 2 diabetes in Zurich, Switzerland and to compare the magnesium intake of diabetic and non-diabetic subjects. DESIGN: The magnesium intake of 97 randomly selected patients with type 2 diabetes and 100 healthy, non-diabetic controls matched for age and sex was estimated using a diet history method. During winter and summer periods, mean daily magnesium intakes were calculated from detailed information given by the test subjects about their eating habits over the previous 2 months. The calculations were performed using EBIS, a computer program based on a German nutrient data base (BLS 2.3), with food items specific to Switzerland added or directly analysed when necessary. RESULTS: The mean+/-s.d. daily magnesium intake of the male diabetic and male control subjects was 423.2+/-103.1 and 421.1+/-111.0 mg, respectively. The mean daily magnesium intake of the female diabetic and female control subjects was 419.1+/-109.7 and 383.5+/-109.7 mg, respectively. There were no significant differences in daily magnesium intake between the diabetic and the non-diabetic subjects and mean intakes in both groups exceeded Swiss recommended dietary intakes. CONCLUSIONS: Dietary intake of magnesium appears sufficient in Swiss adults with type 2 diabetes and is unlikely to contribute to the aetiology of magnesium deficiency. SPONSORSHIP: The Swiss Federal Institute of Technology, Zurich, Switzerland.

Crit Rev Oncol Hematol. 2002 Apr;42(1):79-91.

Magnesium-DNA interactions and the possible relation of magnesium to carcinogenesis. Irradiation and free radicals.

Anastassopoulou J, Theophanides T.

National Technical University of Athens, Chemical Engineering Department, Radiation Chemistry and Biospectroscopy, Zografou Campus, Zografou 15780, Athens, Greece. ianastas@central.ntua.gr

Magnesium deficiency causes renal complications. The appearance of several diseases is related to its depletion in the human body. In radiotherapy, as well as in chemotherapy, especially in treatment of cancers with cis-platinum, hypomagnesaemia is observed. The site effects of chemotherapy that are due to hypomagnesaemia are decreased using Mg supplements. The role of magnesium in DNA stabilization is concentration dependent. At high concentrations there is an accumulation of Mg binding, which induces conformational changes leading to Z-DNA, while at low concentration there is deficiency and destabilization of DNA. The biological and clinical consequences of abnormal concentrations are DNA cleavage leading to diseases and cancer. Carcinogenesis and cell growth are also magnesium-ion concentration dependent. Several reports point out that the interaction of magnesium in the presence of other metal ions showed that there is synergism with Li and Mn, but there is magnesium antagonism in DNA binding with the essential metal ions in the order: Zn>Mg>Ca. In the case of toxic metals such as Cd, Ga and Ni there is also antagonism for DNA binding. It was found from radiolysis of deaerated aqueous solutions of the nucleoside 5′-guanosine monophosphate (5′-GMP) in the presence as well as in the absence of magnesium ions that, although the addition of hydroxyl radicals (*OH) has been increased by 2-fold, the opening of the imidazole ring of the guanine base was prevented. This effect was due to the binding of Mg2+ ions to N7 site of the molecule by stabilizing the five-member ring imitating cis-platinum. It was also observed using Fourier Transform Infrared spectroscopy, Raman spectroscopy and Fast Atom Bombardment mass spectrometry that *OH radicals subtract H atoms from the C1′, C4′ and C5′ sites of the nucleotide. Irradiation of 5′-GMP in the presence of oxygen (2.5 x 10(-4) M) shows that magnesium is released from the complex. There is spectroscopic evidence that superoxide anions (O2-*) react with magnesium ions leading to magnesium release from the complex. From radiolysis data it was suggested that magnesium ions can act as radiosensitizers in the absence of oxygen, while in the presence of oxygen they act as protectors and stabilizers of DNA.

Med Hypotheses. 2001 Dec;57(6):705-13.

Tension headaches and muscle tension: is there a role for magnesium?

Altura BM, Altura BT.

Department of Physiology and Pharmacology, and The Center for Cardiovascular and Muscle Research, SUNY Health Science Center at Brooklyn, New York 11203, USA.

Although many theories and hypotheses have been offered for the etiology of tension-type headache (TH), no one previous hypothesis seems to adequately explain TH. This may, in large measure, account for why it is often difficult to effectively treat TH. Herein, we review current and old hypotheses of TH and offer a new hypothesis which is consistent with what is known about TH. We show that magnesium (Mg) metabolism may be pivotal in both the etiology and treatment of TH. Measurement of serum ionized Mg2+ (IMg2+) levels and brain intracellular free Mg2+ ([Mg2+]i) appear to offer excellent methods for establishing the validity of our hypothesis. Since approximately 70% of patients who have a TH exhibit muscular tightness and tenderness, it is distinctly possible that problems in Mg metabolism and dietary intake are the links to concomitant muscle tension and TH. The significance of release of pain mediators, muscle cramps, muscle strains (and damage) and muscle tension to TH, and its relationship to Mg metabolism, are reviewed. These are all associated with a Mg-deficient state. It seems clear from the available data that TH’s are more associated with muscle tension or scalp tension than any other headache type. From the data available, Mg supplementation appears to be of great benefit in many of these situations. We believe there is a great need for clinicians to examine Mg2+ metabolism, bioavailable Mg2+ in muscle tissues and blood, and the effectiveness of Mg salts (in a double-blinded, placebo-controlled manner) in subjects with TH and muscle tension.

Ned Tijdschr Tandheelkd. 1993 Sep;100(9):412, 413-4.

Prevention of osteoporosis and pathological calcifications

Driessens FC.

Based on physiological data about the influence of magnesium compounds on the degree of saturation of blood plasma with calcium phosphates, we have hypothesized in 1988 that magnesium deficiency is the real cause of osteoporosis and pathological calcifications. The incidence of these diseases is among the elderly as high as 40%. These diseases are the reason that there is such a discrepancy between the morbidity and mortality curve for the elderly as a function of age. Meanwhile it has been proven that a. in all osteoporotic patients the intracellular magnesium content of the erythrocytes is lower than in controls, b. this content can be restored to normal by oral magnesium supplementation without increasing the serum magnesium level, c. by this supplementation the bone density in perimenopausal women increases and d. this supplementation keeps the blood plasma and probably also the other extracellular fluids undersaturated with octocalcium phosphate so that it is impossible for pathological calcifications to occur or to progress. The possible benefits for dentistry are the following: a. perhaps mandibular resorption is retarded or inhibited by oral magnesium supplementation and b. this treatment may also help to inhibit or diminish dental calculus formation in heavy calculus formers. Since both aspects are accessible to experimental clinical investigation, we will soon have the answer to these questions.

J Nutr. 1979 Aug;109(8):1432-7.

Serum levels of selenium, calcium, copper magnesium, manganese and zinc in various human diseases.

Sullivan JF, Blotcky AJ, Jetton MM, Hahn HK, Burch RE.

Serum selenium as well as serum zinc, copper, magnesium, calcium and manganese were investigated in a control group of adult males and in 11 groups of patients in various disease states. Not only the change of each trace element but also the possible association between elements was studied in the various groups. All patients were fasting when sampled and studied only after the acute phase of the disease was corrected. Trace metal determinations were performed by atomic absorption spectrophometry (Mg, Ca, Cu, Zn) and by neutron activation analysis (Se, Mn). All patients showed low serum zinc when compared to controls. Cirrhotic patients had a low serum selenium level as well as low calcium, magnesium and zinc. Emphysemia and cancer patients had an elevated serum copper concentration while copper and manganese levels were elevated in congestive heart failure, infection and pschoses. To our knowledge this is the first time low serum selenium values have been demonstrated to be associated with the low serum zinc, calcium and magnesium levels found in cirrhotic patients.

Fed Proc. 1982 Sep;41(11):2807-12.

Trace minerals and atherosclerosis.

Mertz W.

Although there is no evidence for a direct cause-effect relationship between mineral and trace element status and atherosclerosis in humans, many elements exert a strong influence on individual risk factors for cardiovascular disease, such as disorders of blood lipids, blood pressure, coagulation, glucose tolerance, and circulating insulin. Studies in humans and animals have shown that optimal intakes of elements such as sodium, magnesium, calcium, chromium, copper, zinc, and iodine can reduce individual risk factors; some of these studies are consistent with the results of epidemiologic correlations. Influences of local geochemical environment and of dietary practices can result in mineral and trace element imbalances; deficiencies of chromium, iron, copper, zinc, selenium, and iodine are well defined. Detection and correction of such imbalances in populations, through diminishing individual risk factors, might ultimately reduce the incidence of atherosclerotic heart disease.

Anticancer Res. 1987 May-Jun;7(3 Pt A):259-69.

Dietary minerals and colon carcinogenesis (review).

Nelson RL.

Variations in dietary exposure to several minerals may alter the risk of acquiring colorectal cancer. These minerals include selenium, zinc, calcium, sodium, potassium, iron and fluoride. The mechanism by which each of these minerals alters cancer risk is not established. However, as both the epidemiologic and experimental evidence for major calorie sources, fat and protein, being the primary determinants of colorectal cancer risk is weakening, micronutrients may prove to be the primary determinants of risk in human colorectal cancer.

Biol Trace Elem Res. 1992 Jan-Mar;32:173-85.

Clinical implications of trace elements in endocrinology.

Neve J.

Department of Pharmaceutical Organic Chemistry, Free University of Brussels, Belgium.

The implications of essential trace elements in endocrinological processes, mainly thyroid function, growth, gonadal function, adrenal hormones, prolactin, glucose homeostasis, calcium-phosphorus metabolism, and thymulin activity, are reviewed. Most concerned elements in this field include iodine, zinc, selenium, copper, chromium, manganese and vanadium. The minerals are powerful modulators of several physiological functions that can be considerably perturbed in deficiency states. The resulting biochemical and clinical modifications can be prevented and/or corrected by adequate supplementation. Sometimes, however, they act like pharmacological agents when their beneficial effects are not the result of a correction of a nutritional deficiency state. Their potentialities as therapeutic agents are perfectly described in many cases, but some indications deserve further investigations.

J Nutr Elder. 1993;12(3):1-14.

Relationships between dietary minerals and plasma lipids and glucose among older adults.

Hermann J, Arquitt A, Hanson C.

This study evaluated the relationships between dietary minerals and plasma lipids and glucose of forty-three adults, age 60 and above. Subjects self-selected diets averaged 33% of calories from fat, and 205 mg of cholesterol per day. Plasma total cholesterol, HDL-cholesterol, triglycerides and glucose were determined enzymatically, and LDL-cholesterol was calculated. Plasma lipid values for subjects with dietary mineral intakes less than 2/3 of the RDA were compared to those with intakes greater than 2/3 of RDA. With lower copper intakes plasma triglycerides were elevated (p < or = 0.05). Both plasma total cholesterol and LDL-cholesterol were elevated with lower zinc intakes (p < or = 0.05). LDL-cholesterol was elevated with lower calcium intakes (p < or = 0.05) and with lower magnesium intakes fasting glucose was elevated (p < or = 0.05). No significant differences were observed in plasma lipids due to dietary fat, saturated fat or cholesterol intakes. In these older adults, dietary mineral intakes showed more relationships to plasma lipid parameters than did amount or composition of dietary fat or cholesterol.

J Am Coll Nutr. 1993 Aug;12(4):384-9.

The role of trace minerals in osteoporosis.

Saltman PD, Strause LG.

Dept. of Biology, University of California San Diego, La Jolla 92093.

Osteoporosis is a multifactorial disease with dimensions of genetics, endocrine function, exercise and nutritional considerations. Of particular considerations are calcium (Ca) status, Vitamin D, fluoride, magnesium and other trace elements. Several trace elements, particularly copper (Cu), manganese (Mn) and zinc (Zn), are essential in bone metabolism as cofactors for specific enzymes. Our investigations regarding the role of Cu, Mn and Zn in bone metabolism include data from studies with animals on Cu- and Mn-deficient diets. We have also demonstrated cellular deficiencies using bone powder implants, as well as fundamental changes in organic matrix constituents. In clinical studies we have demonstrated the efficacy of Ca, Cu, Mn and Zn supplementation on spinal bone mineral density in postmenopausal women. Each of these studies demonstrated the necessity of trace elements for optimal bone matrix development and bone density sustenance.

J Nutr. 1996 Sep;126(9 Suppl):2304S-2308S.

Intakes of minerals from diets and foods: is there a need for concern?

Pennington JA.

Division of Nutrition Research Coordination, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20892-6600, USA.

Continuous monitoring of the food supply through the Total Diet Studies allows for the identification of changes and trends in the mineral content of foods resulting from agricultural or manufacturing practices. The studies also allow for the estimation of average daily intakes of minerals and a comparison of these intakes with Recommended Dietary Allowances. The Total Diet Studies use a small number of foods (core foods) to represent the U.S. food supply. The core foods are purchased four times per year, prepared for consumption, and analyzed for 11 nutritional minerals. The food composition data are then merged with food consumption data from national surveys to provide estimates of daily intakes of minerals for selected age-sex groups. Results of the 1982-1991 Total Diet Studies indicated that average intakes of potassium, phosphorus, selenium, iodine and manganese were adequate. Sodium could not be adequately assessed because the studies did not include discretionary salt. Intakes of calcium, magnesium, iron, zinc and copper were below recommended intakes for some age-sex groups. Studies based on clinical and biochemical measurements confirm that calcium, iron and zinc are of concern for segments of the U.S. population. There are conflicting opinions about the need for concern for copper and magnesium.

J Am Coll Nutr. 1998 Apr;17(2):124-7.

The effect of a marathon run on plasma and urine mineral and metal concentrations.

Buchman AL, Keen C, Commisso J, Killip D, Ou CN, Rognerud CL, Dennis K, Dunn JK.

Division of Gastroenterology, Hepatology and Nutrition, University of Texas Houston Health Science Center, 77030, USA.

BACKGROUND: Little data exist on the requirements of trace metals and minerals for endurance athletes. Changes in body status of these elements must be examined before specific nutritional recommendations can be made. This study was designed to determine whether a marathon run was associated with changes in serum and urine metal and mineral concentrations. METHODS: Forty subjects who planned to complete the 1996 Houston-Tennaco marathon were recruited. Subjects had blood and urine samples collected 2 weeks prior to the race and immediately following the race. Blood and urine specimens were analyzed for copper, iron, magnesium and zinc concentrations. Blood was also analyzed for calcium concentration and ceruloplasmin activity. RESULTS: Twenty-six subjects (24 male, 2 female) completed the marathon. Finish times varied between 2 hours 43 minutes and 5 hours 28 minutes. There was no significant change in serum calcium, copper or zinc concentrations or ceruloplasmin activity. Serum and urine magnesium concentration decreased significantly (19.55+/-1.73 to 16.55+/-1.53 ppm, p=0.00001; 34.02+/-8.64 to 21.80+/-12.24 ppm, p=0.003, respectively). Serum iron concentration increased significantly (1.06+/-0.48 to 1.35+/-0.42 ppm, p=0.006), while urine copper and iron concentrations were below the limits of detection, zinc concentration did not change. CONCLUSIONS: Serum and urinary magnesium concentrations decrease during endurance running, consistent with the possibility of magnesium deficiency. This may be related to increased demand in skeletal muscle. Serum iron concentration increases, possibly related to tissue injury. The exact etiology for these observations, as well as their clinical significance, requires further investigation.

Biol Trace Elem Res. 2002 Mar;85(3):193-209.

Effects of elements in human blood pressure control.

Loyke HF.

St. Vincent Charity Hospital, Department of Medicine, Cleveland, OH 44115, USA.

This review enumerates and discusses the elements involved in the control of human blood pressure via a historical evolutionary form. The older and most recent element literature presentations were researched using MEDLINE and a manual review of documents cited. Independent data extraction and cross-referencing was performed. Of the 28 known elements that can influence blood pressure, 15 were found to be involved in human blood pressure regulation. The elements were divided into four groups: electrolyte, composed of sodium, potassium, calcium, and magnesium; metal, which included zinc, copper, and iron; toxic, made up of lead, mercury, cadmium, barium, thallium, arsenic; miscellaneous (lithium and selenium). Evolutionary historical data, possible mechanisms of actions, and interactions between elements that have been shown to influence blood pressure are discussed. Controversy exists over the therapeutic use of elements to alter blood pressure but is absent in the case of the toxic group where preventive control is a proven public health matter. The significance of these 15 elements in the regulation of human blood pressure has been established and ongoing studies will continue to reinforce their influence and importance.