Sense and Nonsense of Dietary Supplements

Scientific evaluation of Cardiovascular health benefits of dietary supplements

vitamin-D

Vitamin D3

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Recent research investigated a wide range of health benefits that can be achieved by vitamin D supplementation. The best known are the muscular and the skeletal benefits to prevent Rickets. The internationally renowned medical institute, the Mayo Clinic, provides a very good overview of existing scientific evidence for the health benefits of vitamin D supplements .

The current International Osteoporosis Guidelines determine vitamin D insufficiency as vitamin D (25-OHD) blood levels <50 nmol/L and vitamin D deficiency if 25-OHD levels are <25 nmol/L. Based on these Guidelines the majority of people (aged >45 years) has insufficient or sub-optimal vitamin D levels ( 1-3 ). The summary below will focus on the benefits of vitamin D supplementation in cardiovascular disease prevention.


Cardiovascular disease

As reported on the website of the Mayo Clinic vitamin D deficiency or sub-optimal vitamin D levels are related with increased cardiovascular risk. Vitamin D deficiency has been linked with hypertension, immune function, myocardial infarction, stroke, and other cardiovascular-related diseases including atherosclerosis and endothelial dysfunction ( 4-8 ). A large prospective, case-controlled study of 18,000 men showed a significant correlation between low vitamin D levels and an increased risk for myocardial infarction ( 9 ). A Meta-analysis of 24 articles containing a total of 6123 cardiovascular disease cases in 65 994 participants also showed that lower vitamin D levels are linearly associated with increased cardiovascular risk and increased risk of cardiovascular disease-related mortality ( 10-14 ). A meta-analysis of 17 prospective cohort studies and randomized trials and found moderate to high doses of vitamin D supplementation may decrease the risk for cardiovascular disease. However, the amount of studies are limited and the available data is not very consistent ( 15 ). Only one study in the general population showed a very clear decrease in cardiovascular disease after vitamin D supplementation ( 16 ). In another trial of 148 women supplementation with vitamin D and calcium resulted in a significant increase in vitamin D blood levels by 72% and significant decreases in systolic blood pressure and heart rate compared with calcium supplementation alone ( 17 ). However, a different meta-analysis of 51 trials examining the effects of vitamin D supplements on cardiovascular outcomes found that although some trials showed benefits of vitamin D supplementation on risk factors, the overall trial data available could not demonstrate a consistent and statistically significant reduction in mortality or cardiovascular risk after vitamin D supplementation ( 18, 19 ). The authors do suggest a positive effect of vitamin D supplements as was seen in a different meta-analysis ( 14 ). They blame the fact that many of the included studies were not designed to evaluate cardiovascular outcomes.


Hypertension and left ventricular hypertrophy

Recent studies show low vitamin D levels are associated with hypertension and left ventricular hypertrophy. Supplementation with vitamin D provides relieve for left ventricular atrophy ( 20, 21 ). Two meta-analyses have looked at the effect of vitamin D on blood pressure levels. These meta-analyses did not demonstrate a significant effect of vitamin D on blood pressure, because the included trials were small and significant heterogeneity was observed ( 22, 23 ). A recent study in 112 patients with mild hypertension, showed that >80% had low vitamin D levels during winter and that supplementation with 75 µg of vitamin D3 on daily basis resulted in a significant reduction of systolic blood pressure by 4-7 mm Hg ( 24 ). However, better designed trials are needed to thoroughly investigate the benefits of vitamin D supplementation in lowering blood pressure. Other studies showed an association between low vitamin D levels and endothelial dysfunction and arterial stiffness ( 8 ). Supplementation of vitamin D in patients with low vitamin D levels showed significant improvement in arterial stiffness when compared with placebo. Furthermore studies have also shown an association between vitamin D supplementation and a decrease in pulse wave velocity and arterial stiffness ( 25, 26 ) and an inverse association between vitamin D levels and subclinical atherosclerosis as measured by carotid intimal-media thickness ( 27 ). These studies do suggest a beneficial effect of vitamin D supplementation on cardiovascular risk.

Conclusion

Traffic Light Green Studies show a chronic deficiency in vitamin D among people aged over 45, this is mostly acclaimed to the lack of exposure to sunlight and reduced vitamin D production. In addition, research shows that more and more age related disorders are associated to sub-optimal vitamin D levels. Although conclusive evidence of the health benefits of vitamin D supplements on cardiovascular disease risk is still lacking, many studies suggest positive effects. Despite the limited evidence for cardiovascular disease prevention, the recommendation of vitamin D supplements is justified by the wide spread insufficiency and the scientifically proven muscular and the skeletal health benefits. In conclusion, vitamin D supplements are recommended for people >45 years of age.

 

Accepted EFSA Claims

  • Vitamin D contributes to normal absorption/utilisation of calcium and phosphorus
  • Vitamin D contributes to normal blood calcium levels
  • Vitamin D contributes to the maintenance of normal bones
  • Vitamin D contributes to the maintenance of normal muscle function
  • Vitamin D contributes to the maintenance of normal teeth
  • Vitamin D contributes to the normal function of the immune system
  • Vitamin D has a role in the process of cell division
  • Calcium and vitamin D are needed for normal growth and development of bone in children
  • Vitamin D is needed for normal growth and development of bone in children.
Names: Vitamin D, cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2)
Diseases: Cardiovascular disease, hypercholesterolemia, diabetes

  

Reference List  

  1. van Dam RM et al. , Potentially modifiable determinants of vitamin D status in an older population in the Netherlands: the Hoorn Study. The American journal of clinical nutrition 85 , 755-61 (Mar, 2007).
  2. Passeri G et al. , Calcium metabolism and vitamin D in the extreme longevity. Experimental gerontology 43 , 79-87 (Feb, 2008).
  3. Hypponen E, C Power, Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. The American journal of clinical nutrition 85 , 860-8 (Mar, 2007).
  4. McGreevy C, D Williams, New insights about vitamin D and cardiovascular disease: a narrative review. Annals of internal medicine 155 , 820-6 (Dec 20, 2011).
  5. Forman JP et al. , Plasma 25-hydroxyvitamin D levels and risk of incident hypertension among young women. Hypertension 52 , 828-32 (Nov, 2008).
  6. Forman JP et al. , Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension 49 , 1063-9 (May, 2007).
  7. Burgaz A et al. , Confirmed hypertension and plasma 25(OH)D concentrations amongst elderly men. Journal of internal medicine 269 , 211-8 (Feb, 2011).
  8. Jorde R et al. , Serum 25-hydroxyvitamin D levels are strongly related to systolic blood pressure but do not predict future hypertension. Hypertension 55 , 792-8 (Mar, 2010).
  9. Giovannucci E et al. , 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Archives of internal medicine 168 , 1174-80 (Jun 9, 2008).
  10. Wang L et al. , Circulating 25-hydroxy-vitamin d and risk of cardiovascular disease: a meta-analysis of prospective studies. Circulation. Cardiovascular quality and outcomes 5 , 819-29 (Nov 1, 2012).
  11. Karakas M et al. , Low Levels of Serum 25-Hydroxyvitamin D Are Associated with Increased Risk of Myocardial Infarction, Especially in Women: Results from the MONICA/KORA Augsburg Case-Cohort Study. The Journal of clinical endocrinology and metabolism ,  (Nov 12, 2012).
  12. Lavie CJ et al. , Vitamin D status, left ventricular geometric abnormalities and cardiovascular disease. Journal of internal medicine ,  (Nov 2, 2012).
  13. Wang TJ et al. , Vitamin D deficiency and risk of cardiovascular disease. Circulation 117 , 503-11 (Jan 29, 2008).
  14. Grandi NC et al. , Vitamin D and cardiovascular disease: systematic review and meta-analysis of prospective studies. Preventive medicine 51 , 228-33 (Sep-Oct, 2010).
  15. Wang L et al. , Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Annals of internal medicine 152 , 315-23 (Mar 2, 2010).
  16. Bostick RM et al. , Relation of calcium, vitamin D, and dairy food intake to ischemic heart disease mortality among postmenopausal women. American journal of epidemiology 149 , 151-61 (Jan 15, 1999).
  17. Pfeifer M et al. , Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. The Journal of clinical endocrinology and metabolism 86 , 1633-7 (Apr, 2001).
  18. Sokol SI et al. , The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease. Vascular medicine 17 , 394-404 (Dec, 2012).
  19. Elamin MB et al. , Vitamin D and cardiovascular outcomes: a systematic review and meta-analysis. The Journal of clinical endocrinology and metabolism 96 , 1931-42 (Jul, 2011).
  20. Tamez H et al. , Vitamin D reduces left atrial volume in patients with left ventricular hypertrophy and chronic kidney disease. American heart journal 164 , 902-909 e2 (Dec, 2012).
  21. Fallo F et al. , Low serum 25-hydroxyvitamin D levels are associated with left ventricular hypertrophy in essential hypertension. Nutrition, metabolism, and cardiovascular diseases : NMCD 22 , 871-6 (Oct, 2012).
  22. Pittas AG et al. , Systematic review: Vitamin D and cardiometabolic outcomes. Annals of internal medicine 152 , 307-14 (Mar 2, 2010).
  23. Witham MD et al. , Effect of vitamin D on blood pressure: a systematic review and meta-analysis. Journal of hypertension 27 , 1948-54 (Oct, 2009).
  24. Larsen T et al. , Effect of cholecalciferol supplementation during winter months in patients with hypertension: a randomized, placebo-controlled trial. American journal of hypertension 25 , 1215-22 (Nov, 2012).
  25. Dong Y et al. , A 16-week randomized clinical trial of 2000 international units daily vitamin D3 supplementation in black youth: 25-hydroxyvitamin D, adiposity, and arterial stiffness. The Journal of clinical endocrinology and metabolism 95 , 4584-91 (Oct, 2010).
  26. Harris RA et al. , Vitamin D3 supplementation for 16 weeks improves flow-mediated dilation in overweight African-American adults. American journal of hypertension 24 , 557-62 (May, 2011).
  27. Carrelli AL et al. , Vitamin D deficiency is associated with subclinical carotid atherosclerosis: the Northern Manhattan study. Stroke; a journal of cerebral circulation 42 , 2240-5 (Aug, 2011).

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