These days, most of us don’t face grave bodily harm. Instead, stressors are more likely to be psychological or emotional in nature, though various physical conditions (exposure to toxic chemicals or metals, nutrient-deprived food) can also put your body under strain. Worse still, stress tends to be long term, or chronic—you can kill or run away from a lion, but it’s much harder to cope with a bad relationship or a high-pressure job.
Whatever the source of the stress, your bodily response remains the same as that of your ancient ancestors: you release stress hormones. The longer you endure stress, the more stress hormones your body produces. And the more stress hormones your body produces, the more magnesium your body uses up. This is because magnesium regulates and controls hormone production; when your body is flooded with cortisol and other stress hormones, magnesium is quickly expended in an effort to bring levels down to normal. Without magnesium, your stress hormone levels will remain elevated for an extended period of time. The result of chronic stress, therefore, is chronic magnesium deficiency.
Magnesium Deficiency
Magnesium deficiency is a serious condition that can have many implications for your health—and your heart health in particular. As explained in Chapter 2, magnesium performs many roles in your body. It acts as a cofactor for various vitamins, minerals, enzymes, and other compounds, activating them and allowing them to carry out more than a thousand different chemical reactions that are necessary for your body to function properly. Without magnesium, your body simply cannot carry out the vital processes that allow you to conduct your daily activities.
Magnesium deficiency is particularly hard on your heart. Here are some of the heart-related functions that magnesium performs under optimal circumstances:
•Aids in detoxification and protects against the accumulation of environmental toxins and free radicals in the cells and tissues, thus protecting the arteries from potential sources of damage.
•Assists in the process by which DNA is copied and repaired, thus aiding in proper cell division, cell maintenance, and cell repair, allowing for proper generation and maintenance of heart muscle cells.
•Dilates blood vessels, making it easier for the heart to pump blood and more effectively transmit nutrients and oxygen to the body’s cells, tissues, and organs.
•Enhances immune function and helps protect against infection, which has been linked to an increased risk of heart disease.
•Helps regulate blood pressure and protects against spasms in the artery walls.
•Prevents the formation of dangerous blood clots that can obstruct the arteries.
More important, magnesium plays an essential role in both regulating the calcium in your body and producing the energy (Mg-ATP) your body needs to function. Without magnesium, these two vital processes cannot be maintained; the results of this failure can potentially be disastrous for your heart and cardiovascular system.
Electrolyte Imbalance. One of magnesium’s most critical jobs is to regulate calcium. As discussed in Chapter 3, magnesium and calcium are two electrolytes (charged molecules) that are forever engaged in a dynamic balancing act within your cells. Both electrolytes are important for good health, yet they act as biological antagonists to each other, the presence of one offsetting the presence of the other. When magnesium and calcium are not in balance—as in a state of magnesium deficiency—a wide range of health problems and chronic illnesses unfold, most notably heart disease.
At the cellular level, magnesium acts as a sort of gatekeeper, making sure that excess calcium doesn’t enter the interior of your cells. Magnesium acts as a natural calcium blocker; if magnesium isn’t available, calcium floods your cells, creating an electrolyte imbalance that can induce several serious heart conditions, including arrhythmia, angina, premature ventricular contraction, and hypertension.
Outside the cells, magnesium also helps regulate calcium by activating three hormones that control the level and location of calcium inside your body. Without an adequate supply of magnesium, these hormones are unable to properly perform their tasks. The result is that calcium accumulates and migrates to areas of the body where it does not belong—including your arteries, where deposits build up and contribute to atherosclerosis.
Worse still, excess calcium can activate your sympathetic nervous system (SNS). The SNS is the body system that controls your automatic, unconscious functioning; it is responsible for initiating both the “fight-or-flight” response and the inflammatory process. Without magnesium to check its presence, calcium overstimulates your SNS, triggering the inflammatory cascade that Peter Libby described in the chronic inflammation model. By stimulating the SNS, excess calcium also increases your already-high levels of stress hormones, creating a vicious circle: stress leads to magnesium deficiency, which leads to electrolyte imbalance balance, which leads to more stress!
Ideally, your body would attain a balanced ratio of magnesium to calcium, as discussed in Chapter 2. Unfortunately, even with an adequate intake of magnesium, it is very difficult to keep magnesium and calcium in equilibrium. Human biochemistry has evolved in such a way that the body is predisposed to hold onto as much calcium as possible, while simultaneously letting go of magnesium. Moreover, doctors frequently recommend that patients get more calcium in order to ward off osteoporosis and other ailments; as a result, the average American today tends to receive about ten times as much calcium as magnesium through diet and supplements. Factoring in magnesium depletion as a result of stress, it is hardly surprising that the vast majority of Americans suffer from heart-hurting electrolyte imbalances.
Decline in Energy Production. Another serious consequence of magnesium deficiency is a decline in energy production. Without magnesium, your heart also cannot make the energy it needs to work properly. Adenosine triphosphate (ATP) is the basic energy currency of your body’s cells; it enables most, if not all, of your body’s fundamental metabolic processes. But, as explained in Chapter 2, in order to carry out these vital processes, ATP first must be activated by magnesium. Under normal circumstances, free magnesium ions bind to an ATP molecule, forming a new compound called Mg-ATP that has a different shape and electrical charge, making it easier for the energy within to be accessed and used by your cells.
All of your heart’s 100 trillion cells need Mg-ATP in order to function, and your heart muscle cells are no exception. In fact, because your heart works harder than any other organ in the body, it needs the most Mg-ATP—and therefore the most magnesium. When your heart is deprived of magnesium, it cannot produce enough Mg-ATP. Without Mg-ATP, your heart muscle cells lack the energy to contract, and their ability to pump blood through your system is impaired.
Heart Cell Death and Artery Damage
As a result of both electrolyte imbalance and energy loss, your cardiovascular system begins to deteriorate. If your heart goes without Mg-ATP for prolonged periods of time, your heart cells begin to starve and die. This heart cell death (cardiac necrosis) can be one of the most devastating consequences of magnesium deficiency. But that’s not all. Research has shown that magnesium deficiency doesn’t just affect your heart cells; it also contributes to endothelial dysfunction, a condition in which the lining of your blood vessels is either injured or impaired. Without sufficient magnesium to regulate the levels of other electrolytes, calcium builds up in the interior of your cells, undermining their structural soundness and causing damage. In other words, magnesium deficiency compromises the integrity of your cardiovascular system from the cellular level on up.
Inflammation
With your heart cells dying and the lining of your blood vessels potentially damaged, inflammation sets in—if it hasn’t already in reaction to the electrolyte imbalance. As explained earlier, inflammation is essentially an immune response, designed to heal injured tissue. When your body senses a dead (necrotic) area or a wound in your arteries or heart, it sends remedial agents to repair and close the breach: blood cells, cholesterol, and different minerals, including calcium. These
agents accumulate in the wall of the heart or arteries, forming the composite substance known as vulnerable plaque. Sometimes, the whole area contracts and scars, leaving tough, fibrous tissue where healthy tissue once existed. And, without sufficient magnesium to regulate the levels of free calcium in your blood, deposits of this mineral also build up in your arteries and heart, leading to new obstructions and hardened tissue.
Heart Disease
As Fuster and Libby have shown, the end result of the inflammatory process is atherosclerosis and thrombosis, which in turn lead to the development of other heart diseases, including angina, heart attack, and stroke. Atherosclerosis arises when plaque builds up in your arteries, compromising the arteries’ ability to pump blood throughout your body, thus contributing to hypertension and angina. Thrombosis occurs when clots form in your blood vessels, preventing or limiting blood flow and potentially causing heart attack or stroke.
The important thing to remember here is that the entire sequence of events—from electrolyte imbalance to energy loss to cell death to inflammation to heart disease—is affected by magnesium deficiency. Furthermore, magnesium deficiency plays a role in every stage in the development of heart ailments, contributing to and often compounding the disease conditions.
The Evolution of the Starved Heart Model
The starved heart model is a relatively new theory developed by independent researcher Morley Robbins. The name of the theory comes from the Harvard scientist Joanne Ingwall, who in 1993 was the first to formally propose the idea that the heart is a metabolic powerhouse that depends on ATP for energy. Over the last two decades, Ingwall has devoted her research to showing that when deprived of this energy, the heart starves, a condition that leads to cell death and, eventually, disease.
But the theoretical origins of the starved heart model of heart disease go much further back, to Karl Ludwig Alfred Fiedler, an Austrian physician who was active in the early 1900s. Building on the work of Rudolf Virchow fifty years earlier, Fiedler hypothesized that heart disease follows three distinct phases: cardiac necrosis (heart cell death), inflammation, and then calcification. This idea was more thoroughly developed in the 1950s by Hans Selye, who is primarily known today as the first researcher to demonstrate the existence and effects of biological stress.
Selye’s work on stress extended to its effects on heart health. In 1958, Selye published his groundbreaking treatise The Chemical Prevention of Cardiac Necrosis. In it, he established that the true cause of heart disease was stress, which led to heart cell death, inflammation, and fibrosis/calcification. Only after a critical mass of cells die, Selye pointed out, does the process of heart disease truly begin.
In effect, Selye was saying that heart disease follows inflammation and atherosclerosis. For the first time in history, Selye was offering a viable model of heart disease that truly got at the cause of heart disease, not its effects. Perhaps even more significantly, Selye’s findings indicated that the effects of stress on your heart could be limited and even prevented by the use of magnesium supplements.
This idea was expanded upon by the pioneering researcher Mildred S. Seelig, a former president of the American College of Nutrition who spent more than fifty years researching the roles played by magnesium deficiencies in the development of disease. More than any other doctor or scientist, Seelig is responsible for drawing attention to magnesium as an important ingredient for good health, and for pointing out the connection between magnesium deficiency and cardiovascular disease. Seelig’s research also clearly established the direct link between stress and magnesium loss. Her findings demonstrated that ongoing exposure to stress and the resultant loss of magnesium leads to a vicious cycle that can significantly and rapidly deplete magnesium stores in the muscular tissue of the heart (myocardium), causing damage and allowing a dangerous influx of calcium into the interior of the heart cells, where it does not belong. Refining Selye’s work, Seelig showed that the end result of this magnesium depletion is heart cell death.
Increasingly, other scientists and doctors have begun to validate Seelig’s work. Burton and Bella Altura have done extensive work on the tendency of magnesium deficiency to cause vasospasms, or spasms in the blood vessels—a condition that has vast implications for a variety of heart conditions, including angina, hypertension, and heart attack. Significant research has also been conducted by cardiologist William Weglicki, former president of the North American division of the International Society for Heart Research. Since the 1990s, Weglicki has explored the ways by which heart disease is affected or caused by magnesium deficiency. Specifically, Weglicki has established the important link between low magnesium and inflammation, the precursor to many heart conditions and other health problems. Weglicki highlighted magnesium’s role as a regulator of calcium, and showed that an imbalanced ratio of calcium to magnesium triggers the inflammatory response that can be so damaging to the heart.
Together, these scientists have helped to create a firm foundation for the starved heart model, convincingly demonstrating that magnesium deficiency is a prime culprit in the electrolyte imbalance, energy depletion, cell death, and inflammation that leads to heart disease.
Evidence for the Starved Heart Model
In response to the work of Seelig, Weglicki, and the Alturas, the medical community has increasingly begun to give credence to the idea that magnesium deficiency is an important factor in the development of cardiovascular disease. Over the last two decades, compelling new research has begun to accumulate in support of the starved heart model. This section offers just a few examples from this growing body of work:
•A 1992 study published in the American Heart Journal reported that sudden death is common in areas where community water supplies are magnesium deficient; that people who die of sudden death caused by heart disease are more likely to have low magnesium levels in their heart cells; that cardiac arrhythmias and coronary artery spasms can be caused by magnesium deficiency; and that magnesium administered intravenously reduces the risk of arrhythmia and death immediately after heart attack.
•A 1992 study overseen by the Alturas and published in the journal Magnesium and Trace Elements found that blood levels of magnesium help determine the integrity and responsiveness of human blood vessels, and accordingly that low blood levels of magnesium result in a higher risk of ischemic heart disease, heart disease, atherosclerosis, and arterial spasms.
•A 1994 study published in the journal Magnesium Research reported that magnesium supplementation led to “an impressive decrease” in the frequency of angina attacks in patients who already suffered from this disease.
•A 1995 study published in the Journal of the American College of Nutrition reported that low magnesium levels are “significantly and inversely associated with coronary heart and vascular disease deaths and hospitalizations,” meaning that the risks for coronary heart disease and atherosclerosis increase as magnesium levels decrease.
•A comprehensive review published in 2012 by the American Journal for Clinical Nutrition examined previous studies involving more than 241,000 participants and found a “statistically significant inverse association between magnesium intake and risk of stroke.” In other words, the less magnesium in your body, the greater your risk for stroke.
•Also in 2012, Weglicki published an overview of animal and human studies in the journal Circulation, establishing a causative link between low magnesium levels and inflammation and showing that levels of C-reactive protein (the primary chemical marker used to evaluate inflammation) were consistently higher in adults who consumed less than half the DRI (Dietary Reference Intakes) of magnesium. Weglicki also asserted that low magnesium levels were associated with higher risk for arrhythmia, angina, and hypertension; and that low magnesium levels were frequently found in subjects suffering from obesity and/or metabolic syndrome (see Chapter 5).
•In 2013, a study published in the journal Hypertension, researchers found that each one-unit (1.0 mg/dL) increase in the blood concentra
tion of magnesium resulted in a 21 percent decrease in the risk of developing hypertension.
•In another 2013 study published in the American Journal of Clinical Nutrition, researchers periodically measured the magnesium levels of 7,664 test subjects with no prior history of heart disease over ten years. The researchers found that those with the lowest magnesium levels had a 60 percent greater risk of developing ischemic (oxygen-deprived) heart disease, and 70 percent greater likelihood of dying from it.
One of the most important studies to recognize magnesium’s relationship to heart disease is the Atherosclerosis Risk in Communities (ARIC) study, begun in 1987, with results and analyses published on a consistent basis in the American Heart Journal and elsewhere. This ongoing study follows over 14,000 test subjects between the ages of forty-five to sixty-four in order to assess dietary and other risk factors for different forms of heart disease. Analysis from this study shows magnesium deficiency is a significant risk factor for many serious heart conditions, including atherosclerosis, cardiac arrest, coronary heart disease, and coronary thrombosis—and is also an independent risk factor for several conditions that contribute to heart disease, including type 2 diabetes and metabolic syndrome.
Most recently, researchers from Harvard University’s School of Public Health published a review of sixteen earlier studies with a combined subject pool of over 300,000 people. The purpose of the review was to determine what role, if any, dietary magnesium plays in reducing the risk of cardiovascular disease. After analyzing the sixteen studies, the researchers found that the data overwhelmingly pointed to a significant link between magnesium and heart disease. In review, they found that increased dietary intake of magnesium reduces the overall risk of cardiovascular disease by as much as 30 percent, and reduces the risk of heart disease due specifically to oxygen loss by 22 percent.
Magnificent Magnesium Page 11