Vitamin D Heart Controversy

January 13, 2012 Written by JP    [Font too small?]

A recent publication in the American Journal of Cardiology called into question the safety of high dose Vitamin D supplementation. In the paper, researchers from Johns Hopkins University School of Medicine investigated a proposed link between Vitamin D levels and an inflammatory protein (CRP) which is considered a risk factor for heart disease. Their conclusions report that levels of D below 21 ng/ml are associated with higher CRP or C-reactive protein. This determination came as no surprise. However, participants with Vitamin D concentrations significantly above 21 ng/ml also demonstrated elevated or undesirable CRP readings. The lead author of the piece, Dr. Muhammad Amer, stated that “Clearly vitamin D is important for your heart health, especially if you have low blood levels of vitamin D. It reduces cardiovascular inflammation and atherosclerosis, and may reduce mortality, but it appears that at some point it can be too much of a good thing.”

Regular readers of this site know that I frequently recommend Vitamin D testing and supplementation in order to reach 25(OH)D levels well in excess of 21 ng/ml. So, you may be wondering if this current controversy alters my point of view of Vitamin D therapy. The short answer is “no”. I’m not being stubborn, just basing my opinion on the best possible evidence.

In the past several months, at least four intervention studies have been carried out evaluating the impact of Vitamin D supplementation on systemic inflammation. Before I describe the results of these trials, please note that intervention trials possess greater scientific validity than population studies. In an intervention setting, direct measures of cause and effect are the primary end points. Population studies tend to rely on observation and uncontrolled data. It is for this reason that intervention trials are often called for to dispute or verify data initially presented in population studies. The Johns Hopkins’ piece is based on population data.

The latest evidence pertaining to Vitamin D supplementation and CRP levels indicates that Vitamin D lowers CRP in certain disease states such as in patients with colorectal cancer and kidney disease. On the other hand, D supplementation may not have much of an impact on relatively healthy adults of varying ages and weight. Please keep in mind that in none of these scenarios did Vitamin D therapy lead to higher CRP levels or other markers of systemic inflammation. All four of the previously mentioned trials have an interventional study design.

In closing, I want to share some underreported, but highly encouraging news about Vitamin D and cardiovascular health. Two current observational studies note that low levels of Vitamin D are correlated with a higher risk of all-cause mortality and heart attack incidence. In the mortality paper, the authors recommend Vitamin D levels of between 30 to 35 ng/ml – significantly higher than the Johns Hopkins’ publication. In addition, three intervention trials from late 2011 determined that Vitamin D supplementation is capable of improving blood pressure control, insulin sensitivity and lipid levels in at-risk populations including diabetics, hypertensives and seniors. All of this research and more points to a valuable role for Vitamin D in the promotion of heart health.

Note: Please check out the “Comments & Updates” section of this blog – at the bottom of the page. You can find the latest research about this topic there!

To learn more about the studies referenced in today’s column, please click on the following links:

Study 1 – Relation Between Serum 25-Hydroxyvitamin D and C-Reactive (link)

Study 2 – Effects of Supplemental Vitamin D and Calcium on Biomarkers of (link)

Study 3 – Impact of Cholecalciferol Treatment on Biomarkers of Inflammation(link)

Study 4 – Vitamin D Supplementation During Exercise Training Does Not Alter (link)

Study 5 – Maintenance of Wintertime Vitamin D Status with Cholecalciferol (link)

Study 6 – Association of 25-hydroxyvitamin D Deficiency with NT-Pro BNP Levels (link)

Study 7 – Vitamin D Deficiency and Mortality Risk in the General Population (link)

Study 8 – Regular Consumption of Vitamin D-Fortified Yogurt Drink (Doogh) (link)

Study 9 – Effect of Vitamin D on Insulin Sensitivity in Elderly Patients with (link)

Study 10 – Role of Vitamin D Supplementation in Hypertension (link)

High Blood Sugar/Insulin Resistance Promotes Arterial Stiffness

Source: Cardiovasc Diabetol. 2011 Apr 15;10:30. (link)

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Posted in Bone and Joint Health, Heart Health, Nutritional Supplements

9 Comments & Updates to “Vitamin D Heart Controversy”

  1. kristi Says:

    Interesting article. Have CRP/Vitamin D studies been done in people who regularly get plenty of sunshine – I’m thinking of those living closer to the equator?

  2. JP Says:

    Hi Kristi.

    There doesn’t appear to be much data on the topic of sun exposure/Vitamin D levels and CRP. Here are a few preliminary studies that examined this topic:

    Be well!


  3. Ted Hutchinson Says:

    Vitamin D Council’s response to same paper
    I would point to the fact that other researchers looking at the same NHANES data have produced these results.
    Serum 25-hydroxyvitamin D levels and all-cause and cardiovascular disease mortality among US adults with hypertension: the NHANES linked mortality study.Concentrations of 25(OH)D were inversely associated with all-cause and CVD mortality among adults with hypertension in the US. Enhancing vitamin D intake may contribute to a lower risk for premature death.

    another study looking at this same NHANES data set
    Association between vitamin D and diabetic neuropathy in a nationally representative sample: results from 2001-2004 NHANES.
    Conclusions  Vitamin D insufficiency is associated with self-reported peripheral neuropathy symptoms even after adjusting for demographic factors, obesity, co-morbidities, use of medications for neuropathy and diabetes duration and control.

    Vitamin D and Racial Disparity in Albuminuria: NHANES 2001–2006
    Suboptimal vitamin D status may contribute to racial disparity in albuminuria. Randomized controlled trials are needed to determine whether supplementation with vitamin analogues reduces risk for albuminuria or reduce racial disparity in this outcome.

    So all those opting for premature death or neuropathy should definitely keep their 25(OH)D levels 21 ng/mL.
    Those who prefer to live longer will try to keep 25(OH)D nearer the level naked human bodies living outdoors naturally attain and maintain and at which human milk is a complete food for human babies.

  4. JP Says:

    Thank you, Ted. The thoughtful information contained in the Vitamin D Council blog and your additional comments are much appreciated!

    Be well!


  5. JP Says:

    Update: A recent, scientific review about the safety of calcium supplementation in older women …

    The Effects of Calcium Supplementation on Verified Coronary Heart Disease Hospitalization and Death in Postmenopausal Women: A Collaborative Meta-Analysis of Randomized Controlled Trials

    Calcium supplementation, particularly with vitamin D, has been an approved public health intervention to reduce fracture risk. Enthusiasm for this intervention has been mitigated by meta-analyses suggesting that calcium supplementation with or without vitamin D increases myocardial infarction (MI) risk; however, concern has been raised over the design of these meta-analyses. We, therefore, undertook a meta-analysis of randomized controlled trials with placebo or no-treatment control groups to determine if these supplements increase all-cause mortality and coronary heart disease (CHD) risk including MI, angina pectoris and acute coronary syndrome, and chronic CHD verified by clinical review, hospital record, or death certificate in elderly women. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were searched from January 1, 1966, to May 24, 2013, for potentially eligible studies, reference lists were checked, and trial investigators were contacted where additional unpublished data were required. The search yielded 661 potentially eligible reports of which 18 met the inclusion criteria and contributed information on 63,563 participants with 3390 CHD events and 4157 deaths. Two authors extracted the data independently with trial data combined using random-effects meta-analysis to calculate the relative risk (RR). Five trials contributed CHD events with pooled relative RR of 1.02 (95% confidence interval [CI], 0.96–1.09; p = 0.51). Seventeen trials contributed all-cause mortality data with pooled RR of 0.96 (95% CI, 0.91–1.02; p = 0.18). Heterogeneity among the trials was low for both primary outcomes (I2 = 0%). For secondary outcomes, the RR for MI was 1.08 (95% CI, 0.92–1.26; p = 0.32), angina pectoris and acute coronary syndrome 1.09 (95% CI, 0.95–1.24; p = 0.22) and chronic CHD 0.92 (95% CI, 0.73–1.15; p = 0.46). In conclusion, current evidence does not support the hypothesis that calcium supplementation with or without vitamin D increases coronary heart disease or all-cause mortality risk in elderly women.

    More info:

    Be well!


  6. JP Says:

    Update: A powerful new study reports that Vitamin D dramatically lowers inflammation (a risk factor for cardiovascular disease) …

    Lupus. 2015 Apr;24(4-5):483-9.

    A randomized double-blind placebo-controlled study adding high dose vitamin D to analgesic regimens in patients with musculoskeletal pain.

    BACKGROUND: The current mode of therapy for many patients with musculoskeletal pain is unsatisfactory.

    PURPOSE: We aimed to assess the impact of adding 4000 IU of vitamin D on pain and serological parameters in patients with musculoskeletal pain.

    MATERIALS AND METHODS: This was a randomized, double-blinded and placebo-controlled study assessing the effect of 4000 IU of orally given vitamin D3 (cholecalciferol) (four gel capsules of 1000 IU, (SupHerb, Israel) vs. placebo on different parameters of pain. Eighty patients were enrolled and therapy was given for 3 months. Parameters were scored at three time points: prior to intervention, at week 6 and week 12. Visual analogue scale (VAS) scores of pain perception were recorded following 6 and 12 weeks. We also measured serum levels of leukotriene B4 (LTB4), interleukin 6 (IL-6), tumor necrosis factor alpha (TNFα) and prostaglandin E2 (PGE2) by ELISA.

    RESULTS: The group receiving vitamin D achieved a statistically significant larger decline of their VAS measurement throughout the study compared with the placebo group. The need for analgesic ‘rescue therapy’ was significantly lower among the vitamin D-treated group. TNFα levels decreased by 54.3% in the group treated with vitamin D and increased by 16.1% in the placebo group. PGE2 decreased by39.2% in the group treated with vitamin D and increased by 16% in the placebo group. LTB4 levels decreased in both groups by 24% (p < 0.05). CONCLUSION: Adding 4000 IU of vitamin D for patients with musculoskeletal pain may lead to a faster decline of consecutive VAS scores and to a decrease in the levels of inflammatory and pain-related cytokines. Be well! JP

  7. JP Says:

    Updated 06/15/16:

    Am Heart J. 2016 Jul;177:17-24.

    Sugar-sweetened carbonated beverage consumption and coronary artery calcification in asymptomatic men and women.

    BACKGROUND: Sugar-sweetened carbonated beverage consumption has been linked to obesity, metabolic syndrome, type 2 diabetes, and clinically manifest coronary heart disease, but its association with subclinical coronary heart disease remains unclear. We investigated the relationship between sugar-sweetened carbonated beverage consumption and coronary artery calcium (CAC) in a large study of asymptomatic men and women.

    METHODS: This was a cross-sectional study of 22,210 adult men and women who underwent a comprehensive health screening examination between 2011 and 2013 (median age 40 years). Sugar-sweetened carbonated beverage consumption was assessed using a validated food frequency questionnaire, and CAC was measured by cardiac computed tomography. Multivariable-adjusted CAC score ratios and 95% CIs were estimated from robust Tobit regression models for the natural logarithm (CAC score +1).

    RESULTS: The prevalence of detectable CAC (CAC score >0) was 11.7% (n = 2,604). After adjustment for age; sex; center; year of screening examination; education level; physical activity; smoking; alcohol intake; family history of cardiovascular disease; history of hypertension; history of hypercholesterolemia; and intake of total energy, fruits, vegetables, and red and processed meats, only the highest category of sugar-sweetened carbonated beverage consumption was associated with an increased CAC score compared with the lowest consumption category. The multivariable-adjusted CAC ratio comparing participants who consumed ≥5 sugar-sweetened carbonated beverages per week with nondrinkers was 1.70 (95% CI, 1.03-2.81). This association did not differ by clinical subgroup, including participants at low cardiovascular risk.

    CONCLUSION: Our findings suggest that high levels of sugar-sweetened carbonated beverage consumption are associated with a higher prevalence and degree of CAC in asymptomatic adults without a history of cardiovascular disease, cancer, or diabetes.

    Be well!


  8. JP Says:

    Updated 11/30/16:

    PLoS One. 2016 Nov 28;11(11):e0166869.

    High Vitamin D Consumption Is Inversely Associated with Cardiovascular Disease Risk in an Urban Mexican Population.

    BACKGROUND: Vitamin D deficiency is a major global public health problem. Recent epidemiological studies have assessed the relationship between vitamin D and multiple outcomes, including cardiovascular disease. However, this evidence is limited and inconclusive. Our purpose in this study was to evaluate the association between dietary vitamin D intake and cardiovascular disease risk in adult Mexican population.

    METHODS: We conducted a cross-sectional analysis with the baseline data from 6294 men and women aged 20-80 years participating in the Health Workers Cohort Study. Data on sociodemographic, lifestyle, and medical history factors were collected with a self-administered questionnaire. Dietary intake was evaluated by using a semi-quantitative food-frequency questionnaire. Cardiovascular disease risk was calculated using a recalibration of the Framingham heart disease prediction score. To evaluate the association between vitamin D intake and 10-year cardiovascular disease risk, odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using multiple logistic regression analysis.

    RESULTS: A total of 6294 subjects (1820 men and 4474 women) with a mean age of 42 years, were included. Of these, subjects in the highest quintile of vitamin D intake presented lower levels of triglycerides 14.6 mg/dL (P for trend = 0.001); 2.0 cm less in waist circumference (P for trend = 0.001) and 0.8 points less in the Framingham cardiovascular disease risk score (P for trend = 0.002) compared with the subjects in the lower quintile of vitamin D intake. Additionally, participants in the highest quintile of vitamin D consumption were less likely to develop elevated 10-year cardiovascular disease risk, compared with those in the lowest quintile (OR = 0.51; 95%CI: 0.33, 0.77; P for trend = 0.007).

    CONCLUSION: Our data suggest that higher consumption of vitamin D is associated with a reduced risk of cardiovascular disease in Mexican population.

    Be well!


  9. JP Says:

    Updated 03/07/18:

    Obesity (Silver Spring). 2018 Mar 4.

    Effect of Vitamin D Supplementation on Obesity-Induced Insulin Resistance: A Double-Blind, Randomized, Placebo-Controlled Trial.

    OBJECTIVE: The aim was to investigate whether vitamin D supplementation, combined with a hypocaloric diet, could have an independent effect on insulin sensitivity in subjects with both overweight and hypovitaminosis D. Changes from baseline in anthropometric parameters, body composition, glucose tolerance, and insulin secretion were considered as secondary outcomes.

    METHODS: Eighteen volunteers who were nondiabetic and vitamin D deficient and had BMI > 25 kg/m2 were randomized (1:1) in a double-blind manner to a hypocaloric diet + either oral cholecalciferol at 25,000 IU/wk or placebo for 3 months. Hyperinsulinemic-euglycemic clamp to measure insulin sensitivity was performed at baseline and after intervention.

    RESULTS: Body weight in both groups decreased significantly (-7.5% in the vitamin D group and -10% in the placebo group; P < 0.05 for both), with no between-group differences. Serum 25-hydroxyvitamin D levels in the vitamin D group increased considerably (from 36.7 ± 13.2 nmol/L to 74.8 ± 18.7 nmol/L; P < 0.001). Insulin sensitivity in the vitamin D group improved (from 4.6 ± 2.0 to 6.9 ± 3.3 mg·kg-1 ·min-1 ; P < 0.001), whereas no changes were observed in the placebo group (from 4.9 ± 1.1 to 5.1 ± 0.3 mg·kg-1 ·min-1 ; P = 0.84). CONCLUSIONS: Cholecalciferol supplementation, combined with a weight loss program, significantly improves insulin sensitivity in healthy subjects with obesity and might represent a personalized approach for insulin-resistant subjects with obesity. Be well! JP

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