Magnesium represents one of the three key elements of the high-dose thiamine (vitamin B1) protocol for Parkinson’s disease. But why magnesium?
First, a substantial body of evidence has consistently shown in recent years that dietary magnesium intake is often inadequate to meet nutritional needs in a high percentage of the population in many countries. For example, data from the NHANES 2013-2016 have shown that half (48%) of the US population may take insufficient amounts of magnesium from dietary sources to meet their nutritional needs. Furthermore, micronutrient content of food over the past decades has markedly decreased, due to agriculture practices and food refining processes. Studies using serum total magnesium concentrations, despite the known limitations, have found that people having low-normal values of magnesium concentrations are at risk of developing subclinical, latent, chronic magnesium deficiency, which significantly impacts on health. As those levels which are close to the lower limit are reported by laboratories as being within the “normal” reference range, most physicians overlook them and magnesium deficiency goes undiagnosed and untreated.
Second, with aging, dietary magnesium intake decreases, absorption is reduced and urinary excretion increases, this leading to a negative balance. This aspect concerns also people with Parkinson’s disease (PwP) as most often Parkinson’s is diagnosed in persons 60 years old or older.
Third, vitamin D deficiency is another important risk factor for magnesium deficiency, as it causes a decrease in gastrointestinal absorption of magnesium. Vitamin D deficiency is highly frequent in PwP and is even more common in Parkinson’s than in the control population.
Fourth, there are many medicines which may reduce the absorption of magnesium. These medicines are used for common conditions. Examples include proton pump inhibitors (e.g. esomeprazole, omeprazole, pantoprazole), used to reduce gastric acid secretion, in peptic ulcer, gastro-oesophageal reflux, etc.; antibiotics; diuretics; antihypertensive medicines; and so on. Also in this case, given the common co-existence of medical conditions in Parkinson’s which often results in polypharmacy, PwP are exposed to this risk factor for magnesium deficiency.
Type I and type II diabetes mellitus, too, are often accompanied by magnesium deficiency, due to increased urinary excretion. Magnesium deficiency is associated with reduced insulin release and increased insulin resistance and, in non-diabetic patients, with increased risk of developing diabetes. This is very relevant to Parkinson’s, as PwP often have altered glucose metabolism, with reduced glucose tolerance and increased insulin resistance - exacerbated by levodopa, even in the presence of normal blood sugar. Furthermore, this alteration of glucose metabolism in Parkinson’s is associated with worsening symptoms and disease progression.
Finally, low concentrations of magnesium have been found in PwP brains.
All these considerations suggest that magnesium deficiency must be rather common in Parkinson’s. Even if PwP were not to be treated with high doses of thiamine (HDT), screening them for risk factors for magnesium deficiency would be advisable. This would mean: a) checking for age, alcohol intake, clinical and drug history, and b) performing some basic laboratory tests, to assess renal function (blood creatinine), diabetes or glucose intolerance (blood glucose), vitamin D3 deficiency (vitamin D3), serum and urinary magnesium and serum electrolytes – sodium, potassium, calcium, phosphate.
The consequences of magnesium deficiency can have a significant impact on the individual health. Over 300 enzymes require magnesium as co-factor for their action. Magnesium plays an essential role in reactions requiring ATP, energy metabolism, and synthesis of nucleic acids, fats and proteins. It is required for normal functioning of the nervous and cardiovascular system, blood glucose and blood pressure control, homeostasis of calcium and potassium metabolism and so on. The list of its roles is long and makes this so-long-neglected mineral a key player in many medical conditions.
But why including magnesium in high-dose thiamine protocol? In addition to the likelihood of magnesium deficiency in Parkinson’s, the interdependence between thiamine and magnesium provides the answer. Thiamine requires magnesium to be activated (into TPP) and to perform its function as a co-factor (“helper”) for many enzymes involved in key reactions in the cell, including energy production. It is then conceivable to assume that the substantial increase in thiamine intake with the amounts administered in HDT (vitamin B1) therapy, will significantly increase the demand for magnesium.
So, which form of magnesium should be taken? Many different forms of magnesium supplements are available in the market. Most provide the magnesium needed, while some have additional benefits. In general, organic forms are preferred as they have a better bioavailability. There are currently no guidelines on the dosage of magnesium to prevent or correct magnesium deficiency in Parkinson’s and to support HDT (vitamin B1) therapy at the same time. It seems safe, until such guidelines become available, to use doses below the magnesium UL (Tolerable Upper Intake Level) which, by definition, are unlikely to represent a risk of adverse reactions. The guidelines will have to take into account not only the individual’s magnesium status and the thiamine dose given but also the persistence of risk factors associated with a reduced intake and absorption or increased excretion of magnesium, which maintain a deficiency status (e.g., elderly, diabetes, medicines). Magnesium should not be taken if the renal function is impaired, unless prescribed by a physician.
Finally, magnesium deficiency clinically shares some of the signs found also in Parkinson’s, making in this way more challenging the search for the right dose of thiamine in high dose thiamine HDT (vitamin B1) therapy, unless it is corrected from the start.
It is highly desirable that further research be conducted to evaluate the role of magnesium and magnesium supplementation in Parkinson’s as well as in PwP who follow the high dose thiamine HDT (vitamin B1) protocol.
USDA, Agricultural Research Service, 2019. Usual Nutrient Intake from Food and Beverages, by Gender and Age, What We Eat in America, NHANES 2013-2016 Available www.ars.usda.gov/nea/bhnrc/fsrg