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Meta-analysis of RCT: vitamin D lowers inflammatory markers but does not improve clinical condition in those with congestive heart failure

Posted on: October 20, 2015   by  John Cannell, MD


Congestive heart failure (CHF) is the result of years of heart damage via heart attacks, hypertension, calcification, inflammation, excessive alcohol use, infection, smoking and other factors. It can occur suddenly, such as after a severe heart attack, though usually develops gradually. CHF is simply pump failure, which occurs when the heart is unable to pump sufficiently to maintain blood flow in order to meet the body’s needs. Symptoms include tiredness, leg swelling, difficulty lying flat and frequent awakening.

In developed countries, around 2% of adults have CHF. In those over the age of 65, the prevalence of CHF increases to 6–10 %. Within a year after diagnosis, the risk of death is about 35%, after which it decreases to about 10% per year. This is not dissimilar to the risks with a number of types of cancers. CHF is the leading cause of hospitalization in people older than 65.

One of the causes of CHF is cardiomyopathy, which occurs when the heart muscle cells get weak, either for no apparent reason or due to a systemic disease. One form of cardiomyopathy is hypertrophic (thickened), and about 50% of hypertrophic cardiomyopathy is idiopathic, or from an unknown cause. It is increasingly recognized that vitamin D deficiency may be an all too common cause of “idiopathic” cardiomyopathy in infants. Recently, one English scientist argued that maintaining maternal and fetal vitamin D levels are as important as vaccinations.

Recently, scientists from China conducted a meta-analysis of seven randomized controlled trials of vitamin D used to treat CHF.

Jiang WL, Gu HB, Zhang YF, Xia QQ, Qi J, Chen JC. Vitamin D Supplementation in the Treatment of Chronic Heart Failure: A Meta-analysis of Randomized Controlled Trials. Clin Cardiol. 2015 Sep 28.

Six of the trials evaluated adults and one trial assessed infants. In 3 of the studies, patients were given between 2,000 to 4,000 IU/day of vitamin D. In the 3 remaining studies, patients received bolus, or stoss dosing, such as 100,000 IU/month. None of the trials focused solely on treating idiopathic cardiomyopathy with vitamin D and calcium.

The authors found no significant improvement in CHF in all six of the RCTs of adults. However, the infantile CHF study (60% idiopathic cardiomyopathy) was remarkable.

Nevertheless, for the usual reasons, this meta-analysis was not definitive. For instance, not all subjects were vitamin D deficient to begin with. Also, half of the studies used stoss dosing, which is not the way vitamin D is obtained naturally.

In the positive infantile CHF study, all the infants were vitamin D deficient and 60% had idiopathic cardiomyopathy. This study provided 1,000 IU/day to the infants. On a per pound basis, assuming the infants weighed 10 – 20 pounds, that is the equivalent of me taking 10,000 to 20,000 IU/day.

However, the authors did find a significant effect on cytokines, which are molecules that regulate inflammation as well as parathyroid hormone (PTH). Below are Forrest plots of vitamin D’s effect on cytokines, two pro-inflammatory [TNF-α: upper graph and CRP: middle graph) and one anti-inflammatory cytokine (IL-10), lower graph]:

cardiomyopathy figure

Figure: Forest plots for TNF-α (upper graph), CRP (middle graph), and IL-10 (lower graph). Abbreviations: CI, confidence interval; CRP, C-reactive protein; df, degrees of freedom; IL-10, interleukin-10; IV, inverse variance; SD, standard deviation; TNF-α, tumor necrosis factor-α.

The authors concluded,

“It has been well documented that inflammatory mediators are critically involved in the pathogenesis of ventricular remodeling and may serve as serum biomarkers reflecting the severity and prognosis of CHF. Recently, several studies suggested that circulating concentration of PTH was correlated with the severity of CHF and it could serve as a useful biomarker of the disease. In the present meta-analysis, our pooled results revealed that vitamin D supplementation was associated with a significant decrease in serum levels of TNF-α, CRP, and PTH. We can therefore infer that vitamin D may exert protective effects in patients with CHF by reducing inflammatory factors and PTH levels.”

However, what is needed is a RCT of 10,000 IU/day (plus calcium) solely on idiopathic cardiomyopathy in vitamin D deficient adults. I have written about this before.

I’m convinced that one cause of idiopathic cardiomyopathy in adults is vitamin D deficiency, just like in infants. If you have CHF or cardiomyopathy, keep your 25(OH)D in the upper range of normal, or about 80 ng/ml. This will usually require about 10,000 IU/day of vitamin D3. With CHF, it is crucial that you also take vitamin D’s cofactors, such as magnesium, zinc, boron and vitamin K2, which is why the Vitamin D Council recommends at least 3 capsules per day of D3Plus by Bio Tech Pharmacal.

2 Responses to Meta-analysis of RCT: vitamin D lowers inflammatory markers but does not improve clinical condition in those with congestive heart failure

  1. [email protected]

    Chronic Heart Failure not treated by Vitamin D, if dose size is ignored – meta-analysis Oct 2015
    Charts are marked showing which RCT had low doses of vitamin D, and should be ignored.

  2. allometric24

    It looks as if Ubiquinol (not ubiquinone) is a vital treatment for CHF. I know someone who has been taking it for some years. In spite of the fact that they have suffered long term from AF their ejection fraction is excellent.
    Those foolish enough to take statins would also be well advised to also take ubiquinol, around 100mg daily – to minimise muscular damage.

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