The paper by the JBS3 Board dismisses the role of vitamin D in
reducing risk of cardiovascular disease (CVD) since large-scale randomized
controlled trials (RCTs) have not demonstrated the benefit [1]. However, a
more recent paper from the Women's Health Initiative calcium/vitamin D RCT
did report a beneficial effect in significantly lowering low-density
lipoprotein cholesterol and raising high-density lipoprotein cholesterol
[2]. This finding was made on the basis of 600 participants who had serum
25-hydroxyvitamin D [25(OH)D] and cholesterol levels measured at time of
enrollment and at the end of two years in the study. Serum 25(OH)D levels
were 38% higher in the active arm (mean 60.8 nmol/L) than in the placebo
arm after two years.
Evidence from observational studies strongly supports a role of
vitamin D in reducing risk of CVD. A meta-analysis of 19 observational
studies of CVD risk with respect to 25(OH)D levels found a relative risk
of 2.1 at 18 nmol/L, 1.6 at 30 nmol/L, 1.2 at 50 nmol/L, and 1.02 at 70
nmol/L [3]. The findings in Ref. 2 are in general agreement with the
findings in this meta-analysis.
The proper way to conduct vitamin D RCTs was outlined in a recent
paper. The guidelines include starting with a 25(OH)D-health outcome
relation, enrolling people with 25(OH)D levels near the low end of the
relation, supplementing with sufficient vitamin D to raise 25(OH)D levels
to the optimal level, then remeasuring 25(OH)D levels [4]. RCTs conducted
on groups with mean 25(OH)D levels above 50 nmol/L generally do not find
beneficial effects due to using too little vitamin D and having an
uncertainty larger than the expected benefit.
As to the suggestion that low 25(OH)D levels reflect or may be a
consequence of lifestyle factors rather than being a causal risk factor,
that is not correct. There will be two letters to the editor responding to
Ref. 154 (Autier et al.) published shortly in Lancet Diabetes &
Endocrinology pointing out that observational studies provide good
evidence and that all types of vitamin D studies should be considered and
evaluated using Hill's criteria for causality in a biological system.
References
1.JBS3 Board. Joint British Societies' consensus recommendations for the
prevention of cardiovascular disease (JBS3). Heart 2014;100:ii1-ii67
2. Schnatz PF, Jiang X, Vila-Wright S, et al. Calcium/vitamin D
supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol
profiles in the Women's Health Initiative calcium/vitamin D randomized
trial. Menopause. 2014 Mar 3. [Epub ahead of print]
3. Wang L, Song Y, Manson JE, et al. Circulating 25-hydroxy-vitamin D
and risk of cardiovascular disease: A meta-analysis of prospective
studies. Circ Cardiovasc Qual Outcomes. 2012;5:819-29.
4. Heaney RP. Guidelines for optimizing design and analysis of
clinical studies of nutrient effects. Nutr Rev. 2014;72:48-54.
Conflict of Interest:
I receive funding from Bio-Tech Pharmacal (Fayetteville, AR), the Sunlight Research Forum (Veldhoven) and the UV Foundation (McLean, VA).
The paper by the JBS3 Board dismisses the role of vitamin D in reducing risk of cardiovascular disease (CVD) since large-scale randomized controlled trials (RCTs) have not demonstrated the benefit [1]. However, a more recent paper from the Women's Health Initiative calcium/vitamin D RCT did report a beneficial effect in significantly lowering low-density lipoprotein cholesterol and raising high-density lipoprotein cholesterol [2]. This finding was made on the basis of 600 participants who had serum 25-hydroxyvitamin D [25(OH)D] and cholesterol levels measured at time of enrollment and at the end of two years in the study. Serum 25(OH)D levels were 38% higher in the active arm (mean 60.8 nmol/L) than in the placebo arm after two years.
Evidence from observational studies strongly supports a role of vitamin D in reducing risk of CVD. A meta-analysis of 19 observational studies of CVD risk with respect to 25(OH)D levels found a relative risk of 2.1 at 18 nmol/L, 1.6 at 30 nmol/L, 1.2 at 50 nmol/L, and 1.02 at 70 nmol/L [3]. The findings in Ref. 2 are in general agreement with the findings in this meta-analysis.
The proper way to conduct vitamin D RCTs was outlined in a recent paper. The guidelines include starting with a 25(OH)D-health outcome relation, enrolling people with 25(OH)D levels near the low end of the relation, supplementing with sufficient vitamin D to raise 25(OH)D levels to the optimal level, then remeasuring 25(OH)D levels [4]. RCTs conducted on groups with mean 25(OH)D levels above 50 nmol/L generally do not find beneficial effects due to using too little vitamin D and having an uncertainty larger than the expected benefit.
As to the suggestion that low 25(OH)D levels reflect or may be a consequence of lifestyle factors rather than being a causal risk factor, that is not correct. There will be two letters to the editor responding to Ref. 154 (Autier et al.) published shortly in Lancet Diabetes & Endocrinology pointing out that observational studies provide good evidence and that all types of vitamin D studies should be considered and evaluated using Hill's criteria for causality in a biological system.
References 1.JBS3 Board. Joint British Societies' consensus recommendations for the prevention of cardiovascular disease (JBS3). Heart 2014;100:ii1-ii67
2. Schnatz PF, Jiang X, Vila-Wright S, et al. Calcium/vitamin D supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol profiles in the Women's Health Initiative calcium/vitamin D randomized trial. Menopause. 2014 Mar 3. [Epub ahead of print]
3. Wang L, Song Y, Manson JE, et al. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: A meta-analysis of prospective studies. Circ Cardiovasc Qual Outcomes. 2012;5:819-29.
4. Heaney RP. Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr Rev. 2014;72:48-54.
Conflict of Interest:
I receive funding from Bio-Tech Pharmacal (Fayetteville, AR), the Sunlight Research Forum (Veldhoven) and the UV Foundation (McLean, VA).