The symposium proceedings on Oxidative Stress and Cardiovascular Injury of the Southern Society for Clinical Investigation presented during this year’s scientific session of the Southern Society for Clinical Investigation included an important paper on critical role of magnesium (Mg2+) deficiency in oxidative stress-induced cardiomyopathy.

“As emphasized by Weglicki and coworkers, Mg2+ deficiency is all too common and carries with it an increased risk of associated adverse cardiovascular events, including oxidative stress. Hypomagnesemia appears when dietary Mg2+ intake is restricted. It may also be the result of drug-induced Mg2+ wasting, such as occurs with loop diuretics and chemotherapeutics, or the neurohormonal activation that accompanies acute and chronic stressor states (ie, CHF, diabetes and the metabolic syndrome).”

The authors demonstrated that magnesium deficiency results in a rise in neurotransmitter substance P (SP) which in turn triggers a systemic inflammatory effect that includes cardiac and intestinal tissues. Elevations in substance P are sustained when the enzyme neutral endopeptidase (NEP) that is supposed to degrade it is impaired by reactive oxygen and nitrogen species. Importantly…

“An associated increase in intestinal permeability with evidence of mucosal invasion by inflammatory cells and accompanying fall in mucosal barrier function with endotoxemia are seen with Mg2+ deficiency. Endotoxin can stimulate the secretion of tumor necrosis factor-α from diverse cellular sources, including macrophages and cardiomyocytes, and can be attenuated by SP receptor blockade. Thus, this neurogenic signal-transduction pathway involving SP, endotoxemia and elevated tumor necrosis factor-α can contribute to the progressive nature of heart failure, including a decline in myocardial contractility.”

In other words, magnesium deficiency is a potent promoter of inflammatory damage to the heart (and the intestinal lining). This further explains why antagonizing magnesium with calcium supplementation can contribute to cardiovascular disease. Clinicians should bear in mind the concluding statement:

“The importance of careful monitoring of serum Mg2+ in the prevention and prompt correction of hypomagnesemia cannot be overemphasized.”

Readers may wish to read the previous posts on antacids and magnesium deficiency and increase in heart attack risk with calcium supplements.

A paper published only a couple months earlier in the journal Magnesium Research adds further emphasis. The authors state:

“Hypomagnesemia continues to cause difficult clinical problems, such as significant cardiac arrhythmias where intravenous magnesium therapy can be lifesaving. Nutritional deficiency of magnesium may present with some subtle symptoms such as leg cramps and occasional palpitation…We found that neuronal sources of the neuropeptide, substance P (SP), contributed to very early prooxidant/proinflammatory changes during Mg deficiency. This neurogenic inflammation is systemic in nature, affecting blood cells, cardiovascular, intestinal, and other tissues, leading to impaired cardiac contractility similar to that seen in patients with heart failure…Our findings emphasize the essential role of this cation in preventing cardiomyopathic changes and intestinal inflammation in a well-studied animal model, and also implicate the need for more appreciation of the potential clinical relevance of optimal magnesium nutrition and therapy.”

Clinical Pearl: serum and even erythrocyte membrane levels of magnesium reflect tissue levels poorly. Results of the intracellular x-ray fluorescence test (performed on cells scraped from the floor of the mouth) reliably correlate with heart, muscle and deep organ tissue mineral content.

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While insulin resistance and pre-diabetic but elevated glucose levels are widely recognized as  contributors to cardiovascular disease, it is less well-known that hypoglycemia also damages the cardiovascular system. A study just published in the journal Diabetic Medicine reports on one of the mechanisms:

“Intensive glycaemic control increases the incidence of hypoglycaemia. We sought to define the effects of hypoglycaemia on aldosterone, a hormone involved in cardiovascular injury and baroreflex impairment.”

The authors examined the effects of hypoglycaemia and normal blood sugar (euglycemia) on aldosterone and plasma renin activity through the use of the hypoglycaemic hyperinsulinaemic clamp protocol in which the glucose is dropped in a controlled fashion with insulin. What did the data show?

“In Study 1, aldosterone increased approximately 2.5-fold during hypoglycaemic hyperinsulinaemia but did not rise with euglycaemic hyperinsulinaemia. In Study 2, aldosterone increased significantly at glucose levels of 2.8 mmol/l; this increase was amplified with glucose of 2.2 mmol/l. Aldosterone increases paralleled those of ACTH.”

Parallel increases of ACTH (adrenacorticotropic hormone) show that the aldosterone increase is part of the hypothalamus-pituitary-adrenal  axis reaction to hypoglycemia. Regarding the signficance for cardiovascular disease, the authors state in conclusion:

“Hypoglycaemia increases aldosterone in a dose-dependent fashion…Because aldosterone activation of the mineralocorticoid receptor is implicated in the pathophysiology of cardiovascular injury, including vascular dysfunction, inflammation, baroreflex impairment and cardiac arrhythmias, these findings may be of relevance in individuals who experience hypoglycaemia.”

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Add sensory ganglionopathy, damage to the groupings of sensory neurons at the spinal level and in the cranium causing pain and other symptoms, to the list of depredations done to the nervous system by reactions to gluten according to a paper just published in the journal Neurology. The authors state:

“Gluten sensitivity can engender neurologic dysfunction, one of the two commonest presentations being peripheral neuropathy. The commonest type of neuropathy seen in the context of gluten sensitivity is sensorimotor axonal.”

They examined 409 patients with different kinds of damage to the peripheral nerves. Out of the 13% that had neurophysiologic evidence of sensory ganglionopathy, 32% had antibodies to gluten. (This is especially remarkable since there are factors which can cause the antibodies not the be expressed or detected resulting in a significant number of false negatives.) Another interesting fact was observed:

“The mean age of those with gluten sensitivity was 67 years and the mean age at onset was 58 years. Seven of those with serologic evidence of gluten sensitivity had enteropathy on biopsy…Autopsy tissue from 3 patients demonstrated inflammation in the dorsal root ganglia with degeneration of the posterior columns of the spinal cord.”

In other words, the damage can have started years before the person notices various possible symptoms including pains of various kinds, numbness, weird sensations (parasthesias), problems with walking, balance or coordination; cardiac arrhythmia, orthostatic hypotension (drop in blood pressure on standing with feelings of faintness), sudden hypertension, segmental loss of sweating, tremor, etc. Is there hope for improvement?

“Fifteen patients went on a gluten-free diet, resulting in stabilization of the neuropathy in 11. The remaining 4 had poor adherence to the diet and progressed, as did the 2 patients who did not opt for dietary treatment.“

The authors sum up their findings with this concluding statement:

“Sensory ganglionopathy can be a manifestation of gluten sensitivity and may respond to a strict gluten-free diet.”

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I’ve been seeing a lot of studies that document beneficial effects from drinking coffee, but I never expected this paper that was recently published in the journal Nutrition, Metabolism & Cardiovascular Diseases. Atrial fibrillation is the most common arrhythmia (irregular heart rhythm). The authors set out to investigate…

“the influence of coffee and caffeine consumption on atrial fibrillation (AF) in hypertensive patients…with regard to spontaneous conversion of arrhythmia.”

Spontaneous conversion is when the heart rhythm normalizes on its own. Along the way they made some interesting observations:

“Coffee consumption was higher in normotensive (normal blood pressure) patients. High coffee consumers were more frequent in normotensive patients compared with hypertensive patients. On the other hand, the intake of caffeine was similar in hypertensive and normotensive patients, owing to a higher intake in hypertensive patients from sources other than coffee. Within normotensive patients, we report that non-habitual and low coffee consumers showed the highest probability of spontaneous conversion, whereas, within hypertensive patients, moderate but not high coffee consumers had the lowest probability of spontaneous conversion.”

Interestingly, their data show that if you have high blood pressure, more coffee is better for normalizing atrial fibrillation. Their conclusion:

“Coffee and caffeine consumption influence spontaneous conversion of atrial fibrillation. Normotensive non-habitual coffee consumers are more likely to convert arrhythmia within 48h from the onset of symptoms. Hypertensive patients showed a U-shaped relationship between coffee consumption and spontaneous conversion of AF, moderate coffee consumers were less likely to show spontaneous conversion of arrhythmia.”

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