Chronic heart failure (CHF) due to left ventricular systolic dysfunction affects five million Americans and a similar number in Western Europe. The five year mortality rate for CHF is 50%. Approximately 90% of patients with CHF have vitamin D levels below 30 ng/ml. Several trials using vitamin D in CHF have shown equivocal results, but those studies are plagued with an inadequate trial design.
Now, Dr. Klaus Witte and 16 colleagues – of the Leeds Institute of Cardiovascular and Metabolic Medicine in England – published a randomized controlled trial (open access) in the prestigious Journal of the American College of Cardiology. They found that multiple echocardiogram measurements improved by supplementing with 4,000 IU/day of vitamin D3 for one year.
Witte KK, Byrom R, Gierula J, Paton MF, Jamil HA, Lowry JE, Gillott RG, Barnes SA, Chumun H, Kearney LC, Greenwood JP, Plein S, Law GR, Pavitt S, Barth JH, Cubbon RM, Kearney MT. Effects of Vitamin D on Cardiac Function in Patients With Chronic HF: The VINDICATE Study. J Am Coll Cardiol. 2016 Mar 24.
This study followed and cited trial guidelines Vasquez and I wrote about in 2005 (also open access):
Vasquez A, Cannell J. Calcium and vitamin D in preventing fractures: data are not sufficient to show inefficacy. BMJ. 2005 Jul 9;331(7508):108-9; author reply 109. No abstract available
In the design of the CHF trial, Witte et al used our suggestions:
- Only study vitamin D deficient (<20 ng/ml) subjects;
- Measure 25(OH)D before and after the trial;
- Obtain a final 25(OH)D level between 40 and 60 ng/ml;
- All the subjects must have the disease (CHF) being studied;
- Use daily, not weekly or monthly dosing;
- Assay the vitamin D preparation for potency;
- Use vitamin D3, not D2;
- Use physiological doses of vitamin D (4,000 IU/day);
- Study subjects for an adequate time (one year);
- Use objective measurements of function (sonograms); and
- Identify, but not treat, a vitamin D deficient placebo group.
Witte et al followed all of these suggestions and randomized 223 subjects with CHF already, all on optimal standard treatment, to placebo or 4,000 IU/day of vitamin D3. However, only 163 subjects completed the study. Mean 25(OH)D levels at baseline were about 10 ng/ml. That level increased to 46 ng/ml in the treatment group and remained at 10 ng/ml in the placebo arm.
The primary endpoint of the study, improvements in 6-minute walking distance, did not change with treatment, thought by the authors to be due to inadequate power. However, despite that, it showed that the amount of blood pumped by the left ventricle increased by about 6% in the treatment arm, but showed no change in the placebo group. There were also significant improvements in the size of the heart as measured by ultrasound, as well as significant improvements in PTH and in 1,25 di-hydroxy vitamin D.
The authors concluded:
“We have demonstrated that high-dose vitamin D3 supplementation is safe, well-tolerated, and associated with a clinically relevant improvement in cardiac function in chronic HF patients already taking current optimal therapies.”
Now, we just have to get other vitamin D researchers to properly design their studies.