Vitamin D status and cardiovascular disease risk factors

 

Reference: Zittermann A, Frisch S, Berthold HK, et al. Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Am J Clin Nutr. 2009;89:1321–7

Commentary by: John R. Endres, ND

Study Design: Randomized, double-blinded, placebo-controlled clinical trial.

Study subjects: Inclusion criteria: Healthy overweight (BMI >27) subjects (n=200) 18–70 years of age. Exclusion criteria: history of myocardial infarction, angina pectoris, heart valve disease, cholelithiasis, urolithiasis, insulin dependent diabetes mellitus, pacemaker implantation, pregnancy, lactation, vegetarianism, and vitamin D supplementation.

Participants were assigned to receive a placebo or 3,332 IU (83.3 µg) cholecalciferol as five drops of Vigantol (Merck)—an oily vitamin D preparation. The duration of the study was 12 months and compliance was assessed by measuring serum 25(OH)D concentrations. As a part of the weight reduction program, for the first six months the participants received weekly nutrition education as well as a phone consultation with a nutritionist. The body mass index and body fat composition were assessed at baseline and after 12 months. Energy and nutrient intake were assessed using a validated diet diary. Physical activity was assessed using a validated standardized questionnaire. The number of participants that completed the study was 165.

Outcome measures:

Primary: Weight loss, fat mass loss

Secondary: Blood pressure, blood lipids, pro-inflammatory cytokines, glucose metabolism, calciotropic hormones

Results: The authors report similar baseline physical characteristics for both the placebo and the treatment group and a similar decrease in energy and nutrient intake from 0 to 12 months for both groups. Weight-loss resulted in a decrease in waist circumference for both groups, however there were no statistically significant differences between the groups at the end of the study.

The authors report that while blood pressure and laboratory variables were comparable at baseline, significant effects were observed for the following secondary outcome measures over the 12 month study period including: 25(OH)D levels, calcitriol, parathyroid hormone (PTH), triglycerides, TNF, and blood pressure. The authors concluded that the data demonstrate that the treatment regimen is able to significantly improve several CVD risk factors in overweight subjects with inadequate vitamin D status participating in a weight-loss program.

Practice Implications and commentary: While the study was well conducted, the interpretation of the results is somewhat complicated by the fact that the data did not follow a normal distribution. While the results expressed a significant time effect for blood pressure, the authors admitted a limitation to interpretation of this result because blood pressure was only measured once at baseline and at the termination of the study.

As one would expect, 25(OH)D and calcitriol levels increased significantly in the treatment group with a corresponding decrease in PTH. This may be clinically significant as there is some evidence in the literature to support an inverse association between PTH levels as well as calcitriol and CVD. The pro-inflammatory cytokine, TNF, decreased 10.2% in the treatment group versus 3.2% in the placebo group. Since there appears to be some evidence, for the association of high TNF concentrations with atherosclerosis, congestive heart failure, and coronary heart disease mortality, this may also have clinical implications with respect to vitamin D supplementation. Lastly, the authors observed a statistically significant decrease in serum triglycerides in the treatment group compared with the control and state that this supports the findings from a previous publication in the Archives of Internal Medicine [Martins D, Wolf M, Pan D, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States. Arch Intern Med. 2007;167(11):1159–1165], which analyzed data from 15,088 subjects from the NHANES III. While Zittermann and colleagues made some clinically important observations in this study, their reference to the study by Martins’ group may have the most significant clinical application.

Martins, et al. found that the mean serum 25(OH)D levels were lower for those subjects with CVD risk factors and that serum 25(OH)D levels less than 30 ng/mL (<75 nmol/L) to be greater in women, ethnic minorities, and the elderly. In contrast to the study presented above, their analysis concluded an inverse relationship between serum 25(OH)D concentration and hypertension, obesity, and diabetes mellitus, which are well known risk factors for CVD.

The NHANES III data provides an excellent insight into the prevalence of many chronic diseases affecting the US population. Therefore, the implications for health benefits from CVD risk reduction with vitamin D supplementation to maintain optimal serum levels may be significant. Until recently, the optimal serum vitamin D concentration has been set at the minimum concentration necessary to prevent bone mineralization problems as evidenced by stimulation of PTH. That “optimal” level has long been considered to be 30 ng/mL (75 nmol/L). However, with the ubiquitous nature of the vitamin D receptor in humans, its myriad known and emerging functions, and the growing scientific evidence for its association with numerous diseases and disease risk factors (including those of CVD) suggest that previously considered “optimal” levels have been grossly underestimated.

Not until serum 25(OH)D levels reach approximately 40 ng/mL is it stored. At levels of 40 ng/mL or less, vitamin D is used as quickly as it is produced or ingested. For this reason the Vitamin D Council recommends taking 5,000 IU of vitamin D per day for three months and then testing for serum 25(OH)D levels and adjusting supplementation to maintain a level of 50–80 ng/mL (125–200 nmol/L) throughout the year. Laboratory testing is inexpensive and often covered by insurance. In conclusion, routine screening and periodic laboratory testing of patients combined with appropriate supplementation to maintain healthy vitamin D status may be wise for not only for CVD prevention but also for overall health maintenance.

About John R. Endres, ND
John R. Endres, ND, is Chief Scientific Officer for AIBMR Life Sciences located in Puyallup, Wash. Dr. Endres earned his degree in Naturopathic Medicine from Bastyr University. He is a member of the American Association of Naturopathic Physicians (AANP) and maintains his license to practice in Washington State. As Chief Scientific Officer for AIBMR Life Sciences, Dr. Endres manages a team of scientists, who collectively and collaboratively provide independent contract research and regulatory guidance services to the natural products and functional foods industries.

Copyright © 2009 by the Natural Medicine Journal All rights reserved. No part of this article may be reproduced in any form without the written permission of the publisher.