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Why deficiencies in vitamin D and magnesium are linked to asthma

This article for VitaminDWiki comes from a phone interview and follow ups with a primary care physician who tested the 25-OH Vitamin D level in each of his asthmatic patients, using a desired target range of 50-100ng/ml (typically 80 +/- 10 ng/ml was attained). He employs vitamin D in conjunction with enhanced magnesium intake (oral +/- transdermal) and oral vitamin C (ascorbate). Serum calcium levels were always paired with the Vitamin D assays.

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Asthma is a disorder with two components:

  1. inflammation, which research shows is due to abnormally high circulating pro-inflammatory cytokines
  2. airway muscle constriction (bronchial spasms) - which promote the wheezing

In the past several years, researchers have discovered that the level of cytokines is down regulated by vitamin D.

For many years, magnesium deficiency has been known for causing muscle spasms.
Intravenous magnesium, has been an emergency room mainstay as the final treatment for patients with life threatening status asthmaticus - where the wheezing otherwise just doesn't respond to the usual agents. Short of using IV magnesium, these patients would otherwise be intubated and put on artificial ventilation or would succumb to the asthma attack.

Both vitamin D and magnesium have been studied independently and found to be of some benefit in asthma.
But, in general there have been three problems with those studies:

  • First, the studies didn't use BOTH agents - so one component of asthma treatment was not being addressed.
  • Second, the dosing of vitamin D was low ( usually below 2,000 IU daily).
    Researchers usually have not approached vitamin D by targeting a blood level and instead have used fixed dosing. As a result, the vitamin D dosing given has been inadequate.
  • Third, magnesium comes in multiple forms which display markedly different characteristics of absorption.
    Often the studies used magnesium oxide orally, which is poorly and erratically absorbed. Diarrhea is often a side effect of magnesium oxide use and limits it's utility.

In unpublished clinical use, vitamin D3 was given to asthmatics with normal calcium status to achieve 25-(OH) vitamin D3 blood levels > 50 ng/ml and < 100 ng/ml (within the range of reference). Most patients attained 80 +/- 10 ng/ml. At these levels, there was substantial reduction in the frequency, intensity and duration of wheezing.
Then oral or trans-dermal magnesium was added and all but one patient became wheeze free (patient failed to attain target D3 level due to non compliance ).
Over time, prescription asthma medications were reduced incrementally and individually until patients were off of them, keeping an albuterol inhaler for rescue use.
These patients had access daily to medical care through the group's outpatient clinic.

To ensure uniformity of dose and to avoid confounding additives, the vitamin D3 recommended to patients was a brand that was in routine use by multiple researchers.
This was possible as the cost differential for high quality vitamin D3 is minimal.

Magnesium was more complex as the highly absorbable, sustained release magnesium supplements (ie- dimagnesium malate) garner a significant premium compared to unbranded magnesium oxide.
Magnesium oxide accounts for > 90% of the market share of individual magnesium supplements due to this price differential.

For patients with gastrointestinal intolerance (diarrhea) on oral magnesium, patients were advised to use magnesium transdermally by taking an epsom salt bath (magnesium sulphate) twice per week for 30 minutes. Patients could increase or decrease magnesium effect by adding or subtracting one bath per week (max: three baths per week). Epsom salt baths were effective in eliminating wheezing episodes in patients who had attained the desired target levels of vitamin D3. Patients using magnesium in any form had been screened to exclude reduced kidney function, slow heart rate and myasthenia gravis, as these conditions interact with magnesium in a complex fashion and can create undesired clinical outcomes. It was common to find that other potential drug : drug interactions could occur with magnesium. These were due to either magnesium binding to the drug (as with quinolone and tetracycline antibiotics) or use of proton pump inhibitors (ie - omeprazole / Prevacid) which significantly reduce the absorption of magnesium and increase gastrointestinal side effects. When oral drug:drug interactions were possible, patients were advised to choose the transdermal epsom salt baths to eliminate those possibilities. The only practical impediment limiting the effectiveness of the epsom salt bath was the availability of a bath tub in the home.

Combining magnesium with vitamin D3 addresses both of the known components involved in the genesis of asthma. Further, magnesium is necessary to complete the final activation of vitamin D3. When vitamin D is used without effectively addressing magnesium status, patients can experience aggravation of symptoms related to magnesium deficiency. This is due, in part, to the interplay between magnesium and calcium. When calcium dominates, muscle spasms are much more common. In essence, magnesium acts as one of nature's calcium channel manager.

The long standing and current approach to asthma management needs to be expanded to include the measurement and optimization of vitamin D3 blood levels into the upper quartile of the reference range. This target level allows a higher percentage of patients to experience vitamin D's regulatory benefit in reducing cytokines and mitigating the inflammatory response.

Although magnesium has long been an emergency room mainstay in preventing imminent death from a protracted asthmatic episode, the use of magnesium to avoid it's deficiency state has not become standard. The prevalence of insufficient magnesium intake is well documented by the National Health and Nutrition Examination Surveys (NHANES). Magnesium insufficiency is increasing in both genders and in all age ranges. The lack of a definitive blood assay to reflect magnesium status remains the central issue for clinicians. Interactions with other oral agents and medical conditions adds another layer of complexity to treatment. The cost of the most bioavailable forms of magnesium creates a financial barrier for many patients, particularly when multiple family members require supplementation.

Asthma has emerged as a condition due to under regulation of a gene(s) causing excess cytokine production and inflammatory action. Basic research has identified cholecalciferol (vitamin D3) as a potential target for manipulation to correct this defective regulation. The additional roles of magnesium in asthma are giving way to research efforts, yet several well understood obstacles remain for the experienced clinician to finesse.

People with asthma should talk with their health care provider about management of vitamin D and magnesium intakes.

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See also web

Guideline for the management of acute asthma in adults: 2013 update.
Magnesium concentration in acute asthmatic children. full text online
Comparison of salbutamol with normal saline and salbutamol with magnesium sulphate in the treatment of severe acute asthma.
Inhaled magnesium sulfate in the treatment of acute asthma.
High-dose magnesium sulfate infusion protocol for status asthmaticus: a safety and pharmacokinetics cohort study.
Magnesium use in asthma pharmacotherapy: a Pediatric Emergency Research Canada study. full text on-line
Asthma diagnosis and management.