Why A Common Mineral Deficiency Is Linked to Chronic Diseases
A critical mineral deficiency enhances inflammation, which is the foundation of the vast majority of diseases-from acute infections (including colds and the flu) to the chronic diseases-primarily caused by lifestyle (heart disease, cancer, diabetes, hypertension, Alzheimer’s, Parkinson’s, and strokes). While other conditions, including arthritis, skin rashes, sinusitis, allergies and asthma, are also triggered by inflammation.
Inflammation the immune’s protective and natural response to invading germs, injury in response to infection, irritation, or injury. It is characterized by redness, heat, swelling, and pain/
This important reaction attempts to limit the impact of the invading germs, toxic exposure and physical injury by localizing the impact, removing the toxin and repairing the surrounding tissue. Acutely, this process does exactly what it is supposed to do. However, ongoing, continuous inflammation, but this completely changes in chronic low-grade inflammatory states.
Chronic low-grade inflammation is one of the characteristics of the metabolic syndrome and interferes with insulin physiology. Ignorance has prevailed over the interrelationship between muscular lipid accumulation, chronic inflammation and insulin resistance because the central mediating factor is magnesium. It is magnesium that modulates cellular events involved in inflammation.
There are many factors that trigger inflammation. They are found in both our internal and external environments and include excessive levels of the hormone insulin (insulin resistance), emotional stress, environmental toxins (heavy metals), free-radical damage, viral, bacterial, fungal other pathogenic infections, obesity, overconsumption of hydrogenated oils, gum disease, radiation exposure, smoking, bacteria, viruses, fungi and certain pharmacological drugs.
Magnesium Deficiency & Chronic Inflammation.
Inflammation and systemic stress are critical to the development of chronic disease conditions. The chronic and continuous low-level stress that silent inflammation places on the body’s defense systems often results in an immune-system breakdown. Magnesium deficiency is a parallel silent insult happening at the core of our physiology. Magnesium deficiency enhances inflammation and pain.
Magnesium’s Critical Role
Magnesium, an abundant mineral in the body, is naturally present in many foods, added to other food products, available as a dietary supplement, and present in some medicines (such as antacids and laxatives). Magnesium is a cofactor in more than 300 enzyme systems that regulate diverse biochemical reactions in the body, including protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation. It contributes to the structural development of bone and is required for the synthesis of DNA, RNA, and the antioxidant glutathione. Magnesium also plays a role in the active transport of calcium and potassium ions across cell membranes, a process that is important to nerve impulse conduction, muscle contraction, and normal heart rhythm.
According to the National Institutes of Health, an adult body contains approximately 25 g magnesium, with 50% to 60% present in the bones and most of the rest in soft tissues. Magnesium levels are largely controlled by the kidney, which typically excretes about 120 mg magnesium into the urine each day. The amount removed by the kidneys is reduced when magnesium status is low.
It is difficult to assess magnesium status because most magnesium is inside cells or in bone. The most commonly used and readily available method for assessing magnesium status is measurement of serum magnesium concentration, even though serum levels have little correlation with total body magnesium levels or concentrations in specific organs. No single method is considered satisfactory. To comprehensively evaluate magnesium status, both laboratory tests and a clinical assessment might be required.
Are You Magnesium Deficient?
According to some estimates, more than 25% of the Americans are magnesium deficient. Symptomatic magnesium deficiency due to low dietary intake in otherwise-healthy people is uncommon because the kidneys limit urinary excretion of this mineral. However, habitually low intakes or excessive losses of magnesium due to certain health conditions, chronic alcoholism, and/or the use of certain medications can lead to magnesium deficiency.
Early signs of magnesium deficiency include loss of appetite, nausea, vomiting, fatigue, and weakness. As magnesium deficiency worsens, numbness, tingling, muscle contractions and cramps, seizures, personality changes, abnormal heart rhythms, and coronary spasms can occur. Severe magnesium deficiency can result in low serum calcium or potassium levels, because mineral functioning is disrupted.
Groups at Risk of Magnesium Inadequacy
Magnesium inadequacy can occur when intakes fall below the RDA but are above the amount required to prevent overt deficiency. The following groups are more likely than others to be at risk of magnesium inadequacy because they typically consume insufficient amounts or they have medical conditions (or take medications) that reduce magnesium absorption from the gut or increase losses from the body.
People with Gastrointestinal Diseases
The chronic diarrhea and fat malabsorption resulting from Crohn’s disease, gluten-sensitive enteropathy (celiac disease), and regional enteritis can lead to magnesium depletion over time. Resection or bypass of the small intestine, especially the ileum, typically leads to malabsorption and magnesium loss.
People with Type 2 Diabetes
Magnesium deficits and increased urinary magnesium excretion can occur in people with insulin resistance and/or type 2 diabetes. The magnesium loss appears to be secondary to higher concentrations of glucose in the kidney that increase urine output.
People with Alcohol Dependence
Magnesium deficiency is common in people with chronic alcoholism. In these individuals, poor dietary intake and nutritional status; gastrointestinal problems, including vomiting, diarrhea, and fatty stools resulting from pancreatitis; renal dysfunction with excess excretion of magnesium into the urine; phosphate depletion; vitamin D deficiency; acute alcoholic ketoacidosis; and hyperaldosteronism secondary to liver disease can all contribute to decreased magnesium status .
Seniors have lower dietary intakes of magnesium than younger adults. In addition, magnesium absorption from the gut decreases and renal magnesium excretion increases with age. Older adults are also more likely to have chronic diseases or take medications that alter magnesium status, which can increase their risk of magnesium depletion.
Magnesium and Health
Continuously low intakes of magnesium induce changes in biochemical pathways that can increase the risk of illness over time. This section focuses on four diseases and disorders in which magnesium might be involved: hypertension and cardiovascular disease, type 2 diabetes, osteoporosis, and migraine headaches.
Hypertension and Cardiovascular Disease
Hypertension is a major risk factor for heart disease and stroke. Studies to date, however, have found that magnesium supplementation lowers blood pressure, at best, to only a small extent. A meta-analysis of 12 clinical trials found that magnesium supplementation for 8–26 weeks in 545 hypertensive participants resulted in only a small reduction (2.2 mmHg) in diastolic blood pressure. The dose of magnesium ranged from approximately 243 to 973 mg/day. The authors of another meta-analysis of 22 studies with 1,173 normal blood pressure and hypertensive adults concluded that magnesium supplementation for 3–24 weeks decreased systolic blood pressure by 3–4 mmHg and diastolic blood pressure by 2–3 mmHg. The effects were somewhat larger when supplemental magnesium intakes of the participants in the nine crossover-design trials exceeded 370 mg/day. A diet containing more magnesium because of added fruits and vegetables, more low-fat or non-fat dairy products, and less fat overall was shown to lower systolic and diastolic blood pressure by an average of 5.5 and 3.0 mmHg, respectively. However, this Dietary Approaches to Stop Hypertension (DASH) diet also increases intakes of other nutrients, such as potassium and calcium, that are associated with reductions in blood pressure, so any independent contribution of magnesium cannot be determined.
Several prospective studies have examined associations between magnesium intakes and heart disease. The Atherosclerosis Risk in Communities study assessed heart disease risk factors and levels of serum magnesium in a cohort of 14,232 white and African-American men and women aged 45 to 64 years at baseline. Over an average of 12 years of follow-up, individuals in the highest quartile of the normal physiologic range of serum magnesium (at least 0.88 mmol/L) had a 38% reduced risk of sudden cardiac death compared with individuals in the lowest quartile (0.75 mmol/L or less). However, dietary magnesium intakes had no association with risk of sudden cardiac death. Another prospective study tracked 88,375 female nurses in the United States to determine whether serum magnesium levels measured early in the study and magnesium intakes from food and supplements assessed every 2 to 4 years were associated with sudden cardiac death over 26 years of follow-up. Women in the highest compared with the lowest quartile of ingested and plasma magnesium concentrations had a 34% and 77% lower risk of sudden cardiac death, respectively. Another prospective population study of 7,664 adults aged 20 to 75 years in the Netherlands who did not have cardiovascular disease found that low urinary magnesium excretion levels (a marker for low dietary magnesium intake) were associated with a higher risk of ischemic heart disease over a median follow-up period of 10.5 years. Plasma magnesium concentrations were not associated with risk of ischemic heart disease. A systematic review and meta-analysis of prospective studies found that higher serum levels of magnesium were significantly associated with a lower risk of cardiovascular disease, and higher dietary magnesium intakes (up to approximately 250 mg/day) were associated with a significantly lower risk of ischemic heart disease caused by a reduced blood supply to the heart muscle .
Higher magnesium intakes might reduce the risk of stroke. In a meta-analysis of 7 prospective trials with a total of 241,378 participants, an additional 100 mg/day magnesium in the diet was associated with an 8% decreased risk of total stroke, especially ischemic rather than hemorrhagic stroke. One limitation of such observational studies, however, is the possibility of confounding with other nutrients or dietary components that could also affect the risk of stroke.
A large, well-designed clinical trial is needed to better understand the contributions of magnesium from food and dietary supplements to heart health and the primary prevention of cardiovascular disease.
Type 2 Diabetes
Diets with higher amounts of magnesium are associated with a significantly lower risk of diabetes, possibly because of the important role of magnesium in glucose metabolism. Hypomagnesemia might worsen insulin resistance, a condition that often precedes diabetes, or it might be a consequence of insulin resistance. Diabetes leads to increased urinary losses of magnesium, and the subsequent magnesium inadequacy might impair insulin secretion and action, thereby worsening diabetes control.
Most investigations of magnesium intake and risk of type 2 diabetes have been prospective cohort studies. A meta-analysis of 7 of these studies, which included 286,668 patients and 10,912 cases of diabetes over 6 to 17 years of follow-up, found that a 100 mg/day increase in total magnesium intake decreased the risk of diabetes by a statistically significant 15%. Another meta-analysis of 8 prospective cohort studies that followed 271,869 men and women over 4 to 18 years found a significant inverse association between magnesium intake from food and risk of type 2 diabetes; the relative risk reduction was 23% when the highest to lowest intakes were compared.
A 2011 meta-analysis of prospective cohort studies of the association between magnesium intake and risk of type 2 diabetes included 13 studies with a total of 536,318 participants and 24,516 cases of diabetes. The mean length of follow-up ranged from 4 to 20 years. Investigators found an inverse association between magnesium intake and risk of type 2 diabetes in a dose-responsive fashion, but this association achieved statistical significance only in overweight (body mass index [BMI] 25 or higher) but not normal-weight individuals (BMI less than 25). Again, a limitation of these observational studies is the possibility of confounding with other dietary components or lifestyle or environmental variables that are correlated with magnesium intake.
Only a few small, short-term clinical trials have examined the potential effects of supplemental magnesium on control of type 2 diabetes and the results are conflicting. For example, 128 patients with poorly controlled diabetes in a Brazilian clinical trial received a placebo or a supplement containing either 500 mg/day or 1,000 mg/day magnesium oxide (providing 300 or 600 mg elemental magnesium, respectively). After 30 days of supplementation, plasma, cellular, and urine magnesium levels increased in participants receiving the larger dose of the supplement, and their glycemic control improved. In another small trial in Mexico, participants with type 2 diabetes and hypomagnesemia who received a liquid supplement of magnesium chloride (providing 300 mg/day elemental magnesium) for 16 weeks showed significant reductions in fasting glucose and glycosylated hemoglobin concentrations compared with participants receiving a placebo, and their serum magnesium levels became normal. In contrast, neither a supplement of magnesium aspartate (providing 369 mg/day elemental magnesium) nor a placebo taken for 3 months had any effect on glycemic control in 50 patients with type 2 diabetes who were taking insulin.
The American Diabetes Association states that there is insufficient evidence to support the routine use of magnesium to improve sugar control in people with diabetes. It further notes that there is no clear scientific evidence that vitamin and mineral supplementation benefits people with diabetes who do not have underlying nutritional deficiencies.
Magnesium is involved in bone formation and influences the activities of osteoblasts (bone cells) and osteoclasts. Magnesium also affects the concentrations of both parathyroid hormone and the active form of vitamin D, which are major regulators of bone homeostasis. Several population-based studies have found positive associations between magnesium intake and bone mineral density in both men and women. Other research has found that women with osteoporosis have lower serum magnesium levels than women with osteopenia and those who do not have osteoporosis or osteopenia. These and other findings indicate that magnesium deficiency might be a risk factor for osteoporosis.
Although limited in number, studies suggest that increasing magnesium intakes from food or supplements might increase bone mineral density in postmenopausal and elderly women. For example, one short-term study found that 290 mg/day elemental magnesium (as magnesium citrate) for 30 days in 20 postmenopausal women with osteoporosis suppressed bone turnover compared with placebo, suggesting that bone loss decreased.
Diets that provide recommended levels of magnesium enhance bone health, but further research is needed to elucidate the role of magnesium in the prevention and management of osteoporosis.
Magnesium deficiency is related to factors that promote headaches, including neurotransmitter release and vasoconstriction. People who experience migraine headaches have lower levels of serum and tissue magnesium than those who do not.
However, research on the use of magnesium supplements to prevent or reduce symptoms of migraine headaches is limited. Three of four small, short-term, placebo-controlled trials found modest reductions in the frequency of migraines in patients given up to 600 mg/day magnesium. The authors of a review on migraine prophylaxis suggested that taking 300 mg magnesium twice a day, either alone or in combination with medication, can prevent migraines.
Magnesium Interrupts and Prevents Inflammation
Magnesium is at the heart of the inflammatory process, it is the prime first cause when it is not present in sufficient quantities. Increases in extracellular magnesium concentration cause a decrease in the inflammatory response while reduction in the extracellular magnesium results in inflammation. Inflammation causes endothelial dysfunction and activated endothelium facilitates adhesion and migration of cancer cells.
This is probably the reason magnesium deficiency is a contributing factor to all of the major chronic diseases-heart disease, diabetes, hypertension, depression, and anxiety. Magnesium’s critical role in the inflammatory process, explains why its deficiency is linked to the development of many chronic diseases.
Dr. Andrzej Mazura and colleagues at Milan University in Italy confirmed magnesium’s key role it plays in inflammation. Their studies found experimental magnesium deficiency in the rat causes within a few days, measurable inflammation. While increasing magnesium interrupts the inflammatory response.
A 2006 issue of the Journal of the American College of Nutrition an article showing that as consumption of magnesium fell, the levels of C-reactive protein increased. C-reactive protein, or CRP, is an established marker of inflammation. It is produced in the liver and is a reliable predictor of clinical events of cardiovascular diseases, such as heart attacks and stroke, even in cases where cholesterol levels may be normal. For this reason, CRP assays may become a routine part of blood tests for determining heart disease risk. CRP levels in the blood are normally undetectable or very low; high levels are strongly associated with inflammation.
Dr. A. Mazur’s work has shown in experimentally induced magnesium deficiency in rats that after only a few days a clinical inflammatory syndrome develops and is characterized by leukocyte (white blood cell) and macrophage activation, release of inflammatory cytokines and excessive production of free radicals. “Magnesium deficiency induces a systemic stress response by activation of neuro endocrinological pathways,” writes Dr. Mazur. “Magnesium deficiency contributes to an exaggerated response to immune stress and oxidative stress is the consequence of the inflammatory response,” he continued.
Dietary surveys of people in the United States consistently show that intakes of magnesium are lower than recommended amounts. An analysis of data from the National Health and Nutrition Examination Survey (NHANES) of 2005–2006 found that a majority of Americans of all ages ingest less magnesium from food than their respective EARs; adult men aged 71 years and older and adolescent females are most likely to have low intakes. In a study using data from NHANES 2003–2006 to assess mineral intakes among adults, average intakes of magnesium from food alone were higher among users of dietary supplements (350 mg for men and 267 mg for women, equal to or slightly exceeding their respective EARs) than among nonusers (268 mg for men and 234 for women). When supplements were included, average total intakes of magnesium were 449 mg for men and 387 mg for women, well above EAR levels.
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