The Magnesium Hypothesis of Cardiovascular Disease
The Missing Mineral—Magnesium
(The Strong Link of Low Nutritional Magnesium and High Calcium-to-Magnesium Ratio in the Genesis of Cardiovascular Disease)
A Review of the Peer-Reviewed Science
by A. Rosanoff, PhD
Director of Research & Science Information Outreach Center for Magnesium Education & Research, Pahoa, HI
Mid-1950s, USA: Middle-aged people start dying of heart attacks. The new “epidemic” is so sudden and so forceful that doctors ask researchers for help: “How do we treat and prevent this onslaught of sudden death?” Many also wonder, “What is causing this phenomenon?” [See Fig. 1 and Appendix I]
Early Heart Disease Research Turns Away from Strong Evidence for Magnesium Hypothesis
Something in our lifestyle was allowing many otherwise healthy people to drop dead from heart attacks. The search was on for the cause. With no pathogen and no toxin, researchers began to look for things that “correlated” with heart attacks or strokes. Factors associated with an elevated risk of heart disease became the way to study this increasing problem. High blood pressure, smoking, obesity and high serum cholesterol came to be the best known of a growing list of cardiovascular risk factors—things to avoid or clinical measurements to correct.
However, populations from all over the world showed high rates of sudden cardiac death in areas with low soil and/or water magnesium levels; and animal research as early as 1936 implicated low nutritional magnesium in atherosclerosis—the hardening of arteries. By 1957 low magnesium was shown to be, strongly, convincingly, a cause of atherogenesis and the calcification of soft tissues. But this research was widely and immediately ignored as cholesterol and the high saturated-fat diet became the culprits to fight [see Appendices I and II].
Common Cardiovascular Disease (CVD) Risk Factors Are Linked to Low Mg Status
Ever since this early “wrong turn,” more and more peer-reviewed research has shown that low Mg is associated with all known cardiovascular risk factors, such as cholesterol and high blood pressure [see Appendix III].
Serum Magnesium Levels and Risk of CVD Death
A study as early as 1995 showed that serum Mg below 0.85 mmol/L was a risk factor for heart disease in a national study (NHANES) that ran from the first half of the 1970s through the early 1980s (see Gartside & Glueck, 1995). In 1999, Ford expanded this original 10-year NHANES study out to 19 years follow-up and found the same association: serum Mg below 0.8 mmol/L was associated with a higher risk of heart disease, both incidence and death. As with previous studies generating and supporting the Mg Hypothesis of CVD, these studies were pretty much ignored, and NHANES even stopped measuring urinary and serum Mg values, leaving researchers with only dietary Mg to study the world’s largest population with a high rate of CVD. Recent studies have confirmed this early work from NHANES data (see Appendix IV for list of studies validating this early NHANES work). Unfortunately, in the meantime (and presently in many areas) serum Mg levels of 0.75 mmol/L, nd even as low as 0.60 mmol/L, were seen as “normal” range for most clinical laboratories.Thus, when doctors test a patient with early signs of possible CVD for serum Mg, many values below the “safe” range—i.e., below 0.85 mmol/L—are deemed “normal” range Mg by the labs; so low Mg is often eliminated as a potential cause of the symptoms [see Appendix IV].
Importance of Calcium–Magnesium Balance and Danger of the Rising Ca:Mg Ratio
Calcium supplement recommendations have become common in medicine, however, without the necessary balancing with magnesium. As a result, recent studies are showing what the Magnesium Hypothesis of CVD long ago predicted: a rise in Ca intake from foods and/or supplements, without a concomitant balancing rise in Mg intake, can bring on heart disease. Why is this? The earliest animal studies of the Mg Hypothesis showed how low Mg status in animals caused calcification of soft tissues (see Appendix I). In the 1990s, Resnick and colleagues showed how high cellular Ca:Mg ratios manifest in tissues as the “fight or flight” response, bringing on clinical symptoms of CVD (see Fig. 4,Appendix V). After decades of rising dietary calcium intakes not balanced with rising dietary magnesium intakes (see Fig. 5a, 5b and Appendix V) and a population where a majority of US adults are not getting their daily Mg requirement, [See Below], dietary Ca:Mg ratios are on the rise [See Fig. 6 and Appendix V] and studies are showing that Ca supplements not balanced with magnesium increase the risk of heart disease (see Appendix V).
Why Is This Happening?
The modern processed food diet, so widespread for decades in the United States, is made from food commodities that are low in magnesium (and some other essential nutrients), mainly due to processing losses but also due to decreasing Mg levels in wheat [See Fig. 8 and Appendix VI], vegetables [See Fig. 9 and Appendix VI], and perhaps other food crops over the past 30+ years (see Appendix VI). Thus it is not surprising that most US adults are not getting their daily Mg requirement from the foods they eat (Fig. 7). Nuts and legumes, foods generally high in magnesium, are not a large part of the modern processed-food diet; trying to avoid calories and fats to prevent heart disease, people tend to avoid the fat in nuts even though it’s healthy fat, and in so doing they miss one of our highest food sources of Mg. Chocolate is quite high in magnesium but so often comes with sugar, a commodity that can tend to elevate the excretion of Mg in the urine. Leafy green vegetables are frequently seen as a good source of Mg; however, there is evidence that these sources may be providing less Mg than in the past (Appendix VI)—and certainly very few people in the general US population consume 7–9 fruit and vegetable servings every single day of their lives. Now that we are a few generations into this new, modern low-Mg diet, young mothers who are themselves low or deficient in Mg are having babies that start out life on a marginal Mg basis—a condition largely unrecognized by the medical community. At the same time, the stressful modern lifestyle, so widespread in the United States, can increase Mg need. Therefore, as a whole, our population certainly does not have the high body stores of Mg experienced by our ancestors or by peoples on traditional diets. As the modern processed-food diet and the stressful high-Mg-requiring lifestyle that goes with it expand throughout the world, more and more of the growing human population will experience the marginal Mg status our society has been living with for decades [Fig. 2& 3 and Appendix I], and we can expect (and we now see) increasing levels of CVD as a result. (See Appendices II andVI.)
What Can Medicine Do?
Given the facts that modern diets are low in Mg and rising in Ca and that the modern stressful lifestyle can raise Mg requirements, it can be expected that many will need to use Mg supplements regularly to prevent developing cardiovascular disease and its risk factors. When you as a physician see a patient with a CVD risk factor, measure the serum Mg. If it is below 0.85 mmol/L, start that patient on Mg therapy (see Appendix VII). If their serum Mg is at or above this level and they still have risk factors, consider doing a Mg retention test before eliminating “low Mg” as a possible causative factor. If CVD risk factors are not yet severe, consider doing this before prescribing statins, antihypertension medications and glucose-lowering medications. It is hoped that raising Mg status to a healthy, replete level will make it safe to gradually lower (and hopefully eliminate) the levels of medications (see Appendix VII).
How Much Mg? What Form of Mg? For How Long?
There are many forms of supplemental magnesium available for oral Mg therapy (see Appendix VII). It is common to prescribe 500 mg/day or more if it can be tolerated, less if not. Research subjects with low serum Mg have shown dips in serum Mg for the first 1–3 months of Mg therapy, followed by a rise in serum Mg to normal by 4–6 months (see Fig. 10a,10b and Appendix VII). If you monitor the Mg therapy by measuring urinary Mg, be aware that some research subjects low in Mg status show low urinary Mg during initial oral Mg therapy while their stores presumably replenish. It is a good idea to try oral Mg therapy as high as can be tolerated (given GI and bowel comfort) for 6 months at least. Powdered Mg supplements allow for easily altered Mg dose for personal tolerance, for daily Mg prescriptions to be easily broken into two or more doses, and for persons who don’t like pills to take their Mg supplement as a liquid.
When nutritional Mg is low, it is quite possible that other essential nutrients are either low or out of balance. Adequate and balanced intake of all essential nutrients is necessary for optimal health. (Seehttp://www.magnesiumeducation.com/essential-nutrients-for-humans)
Appendices & Associated References:
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