As scarce as truth is, the supply has always been in excess of the demand.

–Josh Billings

Articles in this Series:
Part 1 – Magnesium and the Mind/Body Connection in Disease
Part 2 – Magnesium – Nature's Calcium Blocker
Part 3 – The Calcium–To–Magnesium Ratio
Part 4 – Glutamate in Mood Disorders
Part 5 – Addiction
Part 6 – Glutamate and The Biology of Addiction in Overweight and Obesity

n the fall 1998, at the age of 77 and 36 years after becoming the first American astronaut to orbit the earth, former Marine Corp pilot and U.S. Senator John Glenn made aeronautics history again by becoming the oldest person ever to fly into space. The historic mission was widely lauded by the American media as a public relations boon for NASA, and as a testament to the heroic resiliency of the “greatest generation” in their golden years.

But (as with many other NASA endeavors) the true scientific value of the mission failed to garner more than a passing mention in most media reports. In actuality, NASA scientists had suspected for decades that valuable insight into the process of human aging and disease could be gained by observing the effect of spaceflight upon older individuals. Glenn’s willingness to render his services for the mission allowed for a truly unprecedented type of research into the biology of aging.

The physical stresses of spaceflight (including the exposure to low–gravity conditions and ultraviolet radiation) often manifest in a range of symptoms startlingly similar to those encountered in human aging. The fact that astronauts lose bone mass in space is well–known, but space travel is also associated with the notably rapid onset of cardiovascular disorders, blood–clotting abnormalities, insulin resistance, increased inflammation and oxidative stress, muscle wasting, immune suppression, insomnia, and even mood disorders such as anxiety and depression. In almost every biological respect we find that spaceflight acts as a potent accelerator of the aging process.

Exactly why these changes occur so rapidly in space is still somewhat of a mystery – though there are enough clues from the scientific literature to give some meaningful insight. It’s known that the weightless environment of space requires significantly less bone mass than the gravitational environment on earth; so, in keeping with the “use–it–or–lose–it” imperative of biology, rapid bone loss invariably occurs during space flight. As bone mass declines, the calcium from bone is released into the bloodstream. This is the reason why astronauts have been found to exhibit significantly elevated serum calcium levels (and increased urinary calcium excretion) as they lose bone during space missions.

See:

Study Link – Interventions to prevent bone loss in astronauts during space flight.

As we’ve seen in previous articles in this series, such an excess of calcium serves to exacerbate the stress response, which can cause all manner of age–related degenerative changes to the body. Of particularly pressing importance during space flight is the effect this exaggerated stress response can have on the heart and cardiovascular system. A serum calcium excess of the magnitude found during space travel can lead to dangerous increases in blood pressure, vasospasm, ischemia (lack of blood flow), thrombosis, and ultimately, heart failure.

Magnesium, as we’ve also seen, is needed to counter–act the stress–perpetuating effects of calcium. Yet the vicious cycle of the stress response, (as well as the large amount of physical exercise needed to slow the rate of bone loss in space) may deplete magnesium significantly, ultimately predisposing space travelers to permanent heart damage. Several researchers have noted that magnesium may be of life–saving importance if longer–duration interplanetary travel is ever to become a reality.

See:

Study Link – Interplanetary travel and permanent injury to normal heart.

In space flight, then, we see an extreme example of how an elevated calcium–to–magnesium ratio can exacerbate the stress response and rapidly accelerate the aging process. On earth, of course, the rate of age–related bone loss and serum calcium levels aren’t nearly as pronounced as they are in space, but conceptually, the same principles of calcium and magnesium interaction still apply. An adequate intake of both minerals, in proper ratio to one another, is essential in keeping calcium where it belongs (i.e., bones) while allowing magnesium to support youthful energy production. But currently, in the U.S., the average intake of calcium has been estimated to be at least four times higher than that of magnesium. From looking at the relevant research, we find reason to believe that this dietary imbalance may be a major factor in perpetuating the stress response and in accelerating the aging process on earth as well.

The Calcium–to–Magnesium
Ratio in the U.S.

In the U.S., the Recommended Daily Intake (RDI) of calcium is 1200 mg for both male and female adults. By contrast, the RDI for magnesium is between 310 and 420 mg per day depending upon age and gender. Based upon these numbers, it’s clear that consuming the “recommended” amounts of both minerals each day would result in a calcium–to–magnesium ratio of roughly between 3:1 and 4:1.

In actual practice, however, most Americans fail to consume the recommended amounts of both calcium and magnesium – but it seems that the average calcium–to–magnesium–intake ratio in the U.S. is still in the neighborhood of 3:1 to 4:1. Data from the 2005–2006 National Health And Nutrition Examination Survey (NHANES) indicates that the average US adult consumes approximately 1000 mg of calcium per day, and below 300 mg per day of magnesium (at this level of magnesium intake, it’s certain that magnesium deficiency is widespread; and, as we shall see, the harmful effects of calcium excess are even more pronounced in the presence of a magnesium deficiency).

See:

Report Link – What We Eat In America, NHANES 2005–2006.

Also of note, is that the above survey provides data on food intake alone. According to surveys of nutritional supplement usage, calcium supplements are among the most popular, being consumed by an estimated 43% of the population. The calcium ingested from such supplements is sure to skew the calcium–to–magnesium ratio even further towards an excess of calcium:

Study Link – Estimation of Total Usual Calcium and Vitamin D Intake in the United States.

Quote from the above study:

A total of 53% of the U.S. population reported using any dietary supplement (2003–2006), 43% used calcium (2003–2006), and 37% used vitamin D (2005–2006).

Note: some calcium supplements do contain small amounts of magnesium, but the magnesium they contain is usually poorly absorbed (e.g., magnesium oxide), while the calcium they contain is usually relatively well–absorbed. Ultimately, many calcium supplements may worsen calcium excess, even if they contain magnesium.

With these rough numbers forming a frame of reference, it seems likely that the overall calcium–to–magnesium ratio in the US diet may easily approach 4:1. For many people in the US – especially those consuming calcium supplements – it’s highly probable that this ratio could often even surpass 5:1. Knowing this, one wonders what the scientific and historical literature has to say about the health effects of such a ratio.

The Interaction of Calcium and Magnesium

Numerous human studies have shown that a high intake of calcium can inhibit magnesium absorption:

Study Link – The effect of a high intake of calcium on magnesium metabolism in normal subjects and patients with chronic renal failure.

Study Link – Increased need for magnesium with the use of combined oestrogen and calcium for osteoporosis treatment.

Quote from the above study:

High dietary Ca/Mg ratios interfere with Mg absorption, partially because Ca and Mg share a common intestinal absorption pathway… Vitamin D favours Ca over Mg absorption.

Some studies also show that when calcium intake is in significant excess of magnesium, magnesium is excreted from the body at an accelerated rate. The following study found that at the intake of approximately 1000 mg of calcium per day, 250–300 mg of magnesium was insufficient to maintain magnesium status:

Study Link – Frequency and Size of Meals and Serum Lipids, Nitrogen and Mineral Retention, Fat Digestibility, and Urinary Thiamine and Riboflavin in Young Women.

Quote from the above study:

Most of the individual and all of the mean magnesium retention values were negative, indicating that the magnesium content of the diet (250–300 mg/day) was not adequate for the subjects.

In previous newsletters in this series we’ve seen that the biological manifestations of emotional and physical stress underlie all types of mental and physical disorders. We’ve also seen how magnesium is essential for putting the brakes on the stress response, which explains why magnesium may play a much larger role in preventing the ravages of aging than is commonly recognized.

In this context, however, it’s important to recognize that excess calcium creates a de facto magnesium deficiency. In other words, an excess of calcium relative to magnesium is sufficient to trigger the stress response, even independent of other stressful stimuli. A high calcium–to–magnesium ratio can thus create all of the symptoms of outright magnesium deficiency, including cardiovascular damage, hypertension, arrhythmias, blood–clotting abnormalities, anxiety, depression, blood sugar disorders, immune suppression, sleep disorders, seizures, and even sudden cardiac death:

Study Link – Consequences of magnesium deficiency on the enhancement of stress reactions; preventive and therapeutic implications (a review).

Quote from the above study:

When magnesium (Mg) deficiency exists, stress paradoxically increases risk of cardiovascular damage including hypertension, cerebrovascular and coronary constriction and occlusion, arrhythmias and sudden cardiac death (SCD). In affluent societies, severe dietary Mg deficiency is uncommon, but dietary imbalances such as high intakes of fat and/or calcium (Ca) can intensify Mg inadequacy, especially under conditions of stress.

Clues To A Better Ratio

Researchers familiar with the biological interactions of calcium and magnesium commonly recommend that we consume twice as much calcium as magnesium each day (a 2:1 ratio). But, as we’ve seen, the average intake of calcium in the US is at least 4 or 5 times that of magnesium. It’s been noted in the scientific literature that women aiming to prevent or treat osteoporosis may be at risk for cardiovascular and blood–clotting disorders if this ratio isn’t balanced out with additional magnesium.

Study Link – Increased need for magnesium with the use of combined oestrogen and calcium for osteoporosis treatment.

Quote from the above study:

If the commonly recommended dietary Ca/Mg ratio of 2/1 is exceeded (and it can reach as much as 4/1 in countries with low to marginal Mg intakes), relative or absolute Mg deficiency may result, and this may increase the risk of intravascular coagulation, since blood clotting is enhanced by high Ca/Mg ratios.

Some evidence even suggests that the commonly–recommended 2:1 calcium–to–magnesium ratio may still be a bit higher–than–optimal. Historically, the relative level of minerals (including and especially calcium and magnesium) in groundwater from different geographical regions has been correlated with the incidence of certain diseases. People living in regions with mineral–rich hard water have repeatedly been shown to suffer less incidence of cardiovascular disease relative to those living in regions with mineral–poor soft water. Initially, it was thought that the presence of calcium was largely responsible, but subsequent research has shown that magnesium (i.e., a lower calcium–to–magnesium ratio) may be an even more important factor.

The following study from Finland found that the risk of heart attack (acute myocardial infarction, or AMI) was decreased by 4.9% for every 1 mg/L increase in the magnesium content of groundwater. But, as evidence of the dangers of excess calcium, for every 1 unit increase in the calcium–to–magnesium ratio of groundwater, heart attack risk increased by 3.1%:

Study Link – Calcium:Magnesium Ratio in Local Groundwater and Incidence of Acute Myocardial Infarction among Males in Rural Finland.

Quote from the above study:

Each 1 mg/L increment in Mg level decreased the AMI risk by 4.9%, whereas a one unit increment in the Ca:Mg ratio increased the risk by 3.1%. Ca and Cr did not show any statistically significant effect on the incidence and spatial variation of AMI. Results of this study with specific Bayesian statistical analysis support earlier findings of a protective role of Mg and low Ca:Mg ratio against coronary heart disease but do not support the earlier hypothesis of a protective role of Ca.

Several decades ago, when Finland had among the highest dietary calcium–to–magnesium ratio in the world (approximately 4:1 – similar to many people in the U.S. today) studies found that their incidence of coronary heart disease was notably higher than that of other cultures whose calcium–to–magnesium ratio was significantly lower. Japan – whose calcium–to–magnesium ratio at the time was barely above 1:1 – had a particularly low incidence of both cardiovascular disease and osteoporosis:

Study Link – Minerals, Coronary Heart Disease and Sudden Coronary Death.

Quote from the above study:

Under certain circumstances high intakes of calcium may increase rather than decrease the death rate from CHD [Coronary Heart Disease]. There is a highly significant positive correlation between death rates from CHD and estimated calcium to magnesium ratios of the average diets in OECD countries… Since the daily intake of calcium is higher in Finland than in most other countries the high death rate from CHD in this country cannot be attributed to a deficiency of calcium.

The graph below, adapted from the above study, seems to provide clear evidence of a direct relationship between heart disease and an excessive calcium–to–magnesium ratio in several countries. In this respect, it seems that a calcium–to–magnesium ratio of slightly above 1:1 (i.e., only slightly more calcium ingested each day relative to magnesium) is ideal.

Even animal research seems to confirm the harmful effects of an elevated calcium–to–magnesium ratio – especially when calcium is elevated in the context of a magnesium deficiency. In a particularly enlightening study, Japanese researchers recently investigated the effects of four different diets on 4 different groups of rats:

Group 1 – Fed the standard laboratory rodent diet

Group 2 – Fed the standard diet with the calcium level doubled

Group 3 – Fed the standard diet, but with the magnesium level lowered

Group 4 – Fed the standard diet, but with the magnesium level lowered and calcium doubled

The researchers found that structural and mitochondrial damage occurred in cells of the heart, liver, and kidney in groups 2 through 4.

In groups 3 and 4, magnesium was lower in serum and was lost from bone.

Levels of lipid peroxides were elevated in the livers of groups 3 and 4, and in the heart in group 4. Severe damage to heart cells was found in group 4.

Study Link – Effects of dietary magnesium deficiency in the rat: with special reference to ultrastructural examination.

Quote from the above study:

Epidemiologically, it has been suggested that dietary magnesium/calcium imbalance is associated with the risk of heart diseases. In the present study, the effects of magnesium deficiency and/or calcium over intake were investigated in rats…Our results thus suggest that dietary magnesium deficiency gives rise to retrogressive changes in some organs including the heart, and concurrent calcium overintake synergistically enhances the myocardial injury due to magnesium deficiency.

Calcium–To–Magnesium Ratio and Mood Disorders

As we’ve seen previously, the link between mood disorders like depression and anxiety, and cardiovascular disease is well–documented. If an elevated calcium–to–magnesium ratio exacerbates the stress response and predisposes to increased cardiovascular risk, it’s likely that this same ratio will play a role in mood disorders as well. Research is beginning to find that this is indeed the case.

Studies have found that women with the highest serum calcium–to–magnesium ratios have higher incidences of depression relative to those with lower ratios:

Study Link – Associations of serum Ca and Mg levels with mental health in adult women without psychiatric disorders.

Quote from the above study:

Women in the middle tertile of serum Ca/Mg ratio had significantly lower scores on depression and stress scales (p = 0.004 and p = 0.007, respectively) and a lower odds ratio (OR) for the risk of depressive mood disorder (OR = 0.31, CI(95%) 0.10–0.93) than those in the highest tertile. The OR for the risk of depressive mood disorder was higher in women in the lowest tertile of serum Mg than in those in the highest tertile (OR = 3.92, CI(95%) 1.11–13.83).

And while the serum level of minerals isn’t always indicative of overall mineral status, the level of minerals in cerebrospinal fluid (CSF) gives a direct indication of the amount and ratio of minerals acting on the brain and central nervous system. Depressed patients have been found to exhibit markedly elevated calcium–to–magnesium ratios in serum and cerebrospinal fluid:

Study Link – High serum and cerebrospinal fluid Ca/Mg ratio in recently hospitalized acutely depressed patients.

Quote from the above study:

Serum and CSF Ca/Mg ratios were found to be elevated in the depressed patients compared with the controls. A retrospective analysis of previous trials assessing serum/plasma or CSF Ca and Mg does not seem to refute the findings of this study.

Calcium excess and magnesium deficiency have both been linked with the onset of blood sugar disorders. Anxiety and depression are often precursors to diabetes, and interestingly, studies have found a link between low magnesium levels and depression in older diabetic subjects:

Study Link – Depressive Symptoms and Hypomagnesemia in Older Diabetic Subjects.

Quote from the above study:

Serum magnesium levels were significantly lower among depressive than control diabetic subjects (0.74 ± 0.25 vs. 0.86 ± 0.29 mmol/L, p = 0.02).

Hypercalcemia (i.e., excess calcium in the blood) is well–documented to be associated with depression:

Study Link – Recurrent Psychotic Depression Associated With Hypercalcemia And Parathyroid Adenoma.

And although hypercalcemia is often caused by tumors of the parathyroid gland, the excessive intake of calcium– and vitamin D–containing supplements has also been reported to cause hypercalcemia:

Study Link – Hypercalcemia Induced by Excessive Intake of Calcium Supplement, Presenting Similar Findings of Primary Hyperparathyroidism.

Quote from the above study:

Diagnostic interview revealed that she had been taking excessive calcium supplements of 3,000˜5,000 mg/day because she was worried about developing osteoporosis. Her hypercalcemia was cured after she stopped taking the supplements. The present case indicates that calcium supplementation of more than 2,500 mg/day elicits adverse effects on body mineral balance. Clear indications of the upper limits to supplements should be made known to the consumers.

The authors of the above study express concern regarding calcium supplementation of more than 2,500 mg/day. This amount may seem like a lot, but the inadvertent ingestion of such a high amount of calcium certainly isn’t beyond the realm of possibility for many people consuming nutritional supplements, medications, and fortified foods.

For example:

A popular over–the–counter chewable antacid contains 400 mg of calcium per tablet and advises users to “[c]hew 2–3 tablets as symptoms occur.  Repeat hourly if symptoms return, or as directed by a physician.” The label of this product advises (if the product is to be taken as a calcium supplement) that average daily consumption should not exceed 8 tablets – a full 3200 mg of elemental calcium (strangely, no such limit is advised if the product is taken as an antacid).

Also, calcium is often used as a component of the capsule fillers and tablet binders for nutritional supplements. When consuming multiple pills per day, this can often lead to an unexpectedly high calcium intake. Typical “drugstore” multivitamins usually contain at least four times as much calcium as magnesium, and a popular multi–vitamin supplement pack marketed towards bodybuilders, contains 2,000 mg of calcium and only 400 mg of magnesium (as magnesium oxide) when taken at the recommended dosage. Even worse, many other nutritional supplement products fail to list the calcium content of the pills when calcium is used as a filler or binder.

Or, consider that mere ¾ of a cup of a popular fortified breakfast cereal contains a full 1000 mg of calcium (and a paltry 24 mg of magnesium – a nearly 42:1 calcium–to–magnesium ratio). The list of such calcium–fortified foods and beverages is steadily increasing, and considering how easy it is to consume multiple servings of these foods at one sitting (e.g., fortified breakfast cereals, fortified fruit juice, etc.), it’s likely that such products may further disrupt the calcium–to–magnesium ratio in many people’s diets.

One wonders, in fact, if the rampant calcium fortification of foods – especially in the presence of declining magnesium intakes – has played a role in the modern epidemic of behavioral disorders affecting both children and adults. Hyperactivity is a well–documented effect of calcium excess, and combinations of magnesium and vitamin B6 (a magnesium co–factor) have shown promise in combating attention deficit hyperactivity disorder (ADHD) – a condition which is often characterized by low levels of intracellular magnesium:

Study Link – Improvement of neurobehavioral disorders in children supplemented with magnesium–vitamin B6. I. Attention deficit hyperactivity disorders.

Quote from the above study:

Children from the ADHD group showed significantly lower Erc–Mg values than control children (n = 36). In almost all cases of ADHD, Mg–B6 regimen for at least two months significantly modified the clinical symptoms of the disease: namely, hyperactivity and hyperemotivity/aggressiveness were reduced, school attention was improved. In parallel, the Mg–B6 regimen led to a significant increase in Erc–Mg values. When the Mg–B6 treatment was stopped, clinical symptoms of the disease reappeared in few weeks together with a decrease in Erc–Mg values.

Studies like this one remind us that the nutritional choices we make today affect not only our future risk of disease, but also our current mental state. By and large, young people may not be overly concerned about their future risk of diabetes or heart disease, but the mood disorders of youth, including: aggression, hyperactivity, anxiety, and depression, are often caused by many of the same factors which predispose to the degenerative effects of aging. The egregious imbalance between calcium and magnesium in the modern diet must certainly be counted among these factors.

Knowing that many such nutritional imbalances can have profound effects on behavior in the here–and–now, it’s interesting to wonder just what sort of effect some nutritional fine tuning could have on a person’s everyday life. Could proper nutrition and supplementation lead to less impetuous or compulsive behavior? Could it reduce aggressiveness and facilitate deeper interpersonal relationships? Could it improve a person’s “will power” in the face of addiction? In the next Integrated Supplements Newsletter, we'll examine such questions in the context of magnesium and related nutrients.

About Us: At Integrated Supplements, our goal is to bring you the wellness information and products you need to live your life to the fullest. We are dedicated to producing the highest–quality, all–natural nutritional supplements; and to educating the world on the health promoting power of proper nutrition. You can find out more by visiting: www.IntegratedSupplements.com

Articles in this Series:
Part 1 – Magnesium and the Mind/Body Connection in Disease
Part 2 – Magnesium – Nature's Calcium Blocker
Part 3 – The Calcium–To–Magnesium Ratio
Part 4 – Glutamate in Mood Disorders
Part 5 – Addiction
Part 6 – Glutamate and The Biology of Addiction in Overweight and Obesity

These statements have not been evaluated by the FDA. No Integrated Supplements product is intended to diagnose, treat, cure or prevent any disease.