How Much Vitamin D is Harmful?

Saturday, May 2, 2015 // Uncategorized

This article reviews some of the controversies surrounding Vitamin D.  First of all, it confirms what I tell my patients that it is difficult to take too much Vitamin D.  Secondly, while low levels of Vitamin D (if we really know what normal is) are associated with certain diseases, we don’t know whether screening for Vitamin D deficiency and supplementing with Vitamin D is of benefit.

tya Swift Yasgur MA, LMSW

April 07, 2015

The Vitamin D Debate: Conundrums and Complexities

The Vitamin D Debate: Conundrums and Complexities
The Vitamin D Debate: Conundrums and Complexities
But is Vitamin D deficiency as ubiquitous as it appears? According to a recent editorial, “clinical enthusiasm for supplemental vitamin D has outpaced available evidence on its effectiveness.”1 The authors cite the conclusions of the US Preventive Task Force’s (USPSTF) 2015 Task Force Recommendation Statement2 and the Institute of Medicine (IOM)’s 2011 Dietary Reference Intakes for Calcium and Vitamin D.3 Both sets of recommendations concluded that “data are insufficient to recommend vitamin D screening in routine clinical practice or to assess the effectiveness and overall balance of benefits and risks of supplemental vitamin D taken for the lowering of the risk of nonskeletal conditions.”1 Additionally, no national professional organization recommends population-wide screening for vitamin D deficiency, although individual researchers have disagreed with the conclusions of the USPSTF and the IOM recommendations.4

A summary of conclusions and recommendations of the USPSTF’s statement can be found in Table 1.

Recent Studies Investigating Vitamin D Supplementation for Nonskeletal Indications


Despite the cautionary approach of the USPSTF, research into vitamin D suggests noteworthy associations between vitamin D deficiency and risk of nonskeletal conditions, including CVD, stroke, obesity, cancer, asthma, preterm births, and all-cause mortality.

  • Researchers analyzed data of 2,148 subjects from the Cardiovascular Risk in Young Finns Study. The 25-hydroxyvitamin D [25-(OH)D] levels of subjects aged 3–18 years at baseline (in 1980) were measured from stored serum in 2010. Subjects were examined at age 30–45 years (in 2007). The main outcome measure was the carotid intima-media thickness (IMT), which is a surrogate measure of atherosclerosis. The researchers found that low 25-(OH)D levels in childhood were associated with increased carotid IMT in adulthood. They concluded that low 25-(OH)D levels in childhood “might have deleterious effects on vasculature.”5
  • Stroke patients with low vitamin D levels were found to be more likely than those with normal vitamin D levels to suffer severe strokes and have poor health outcomes following the stroke. Henninger et al analyzed data from 96 stroke patients over a one-year period and found that patients who had low vitamin D levels (defined as <30ng/mL) had twice the areas of dead tissue resulting from obstruction of blood supply, as compared to patients with normal vitamin D levels. For each 10ng/mL reduction in vitamin D level, the chance for healthy recovery in the three months following the stroke decreased by almost half, regardless of the patient’s age or initial stroke severity.6
  • Vitamin D deficiency has been associated with obesity and diabetes but the relationship is not clearly understood. Clemente-Postigo et al found that 25-(OH)D were diminished in prediabetic and diabetic patients, compared to normoglycemic subjects, independently of BMI and were closely related to glucose metabolism variables. They suggested that “vitamin D deficiency is associated more with carbohydrate metabolism than with obesity.”7
  • Recent Studies Investigating Vitamin D Supplementation for Nonskeletal Indications (cont.)

    • A prospective analysis of data from a phase III study of 1,043 patients newly diagnosed with metastatic colorectal cancer found that patients with higher vitamin D levels had better outcomes after treatment with chemotherapy and targeted therapy. The median overall survival for patients with the highest vitamin D levels was 32.6 months, as compared with 24.5 months for those with the lowest levels.8
    • Data from a cohort of 308,000 adults, aged 22–50 years old with at least one vitamin D measurement were analyzed for a possible association between vitamin D deficiency and asthma. The researchers found that among those with vitamin D deficiency , the odds of having an asthma exacerbation were 25% greater, compared to those with levels in the normal range – an association that remained significant, even after controlling for known confounders.9
    • The potential protective effects of vitamin D against preterm birth were examined in 2,327 pregnant women who gave birth to singleton, liveborn neonates, vs. 1,126 women who delivered preterm babies. The researchers found that the incidence of preterm birth at <37 weeks of gestation significantly decreased as levels of 25-(OH)D increased to approximately 90nmol/L from lower rates. The researchers concluded, “Our data support a protective association between maternal vitamin D sufficiency and preterm birth.”10
    • A Mendelian randomization analysis of 95,766 white participants of Danish descent from three cohorts, with median follow-up times of 19.1, 5.8, and 7.9 years were genotyped for genetic variants in DHCR7 and CYP2R1, affecting plasma 25-(OH)D concentrations. 35,334 also had plasma 25-(OH)D measurement. The researchers found that genetically low 25-(OH)D concentrations were associated with increased all-cause mortality, cancer mortality and other mortality, although not with increased cardiovascular mortality.11
    • Conclusion

      Manson and Bassuk1 point to complexities in the vitamin D story, including lack of consensus on the definition of optimal 25-(OH)D concentrations, the distinction between “bioavailable” and “free” 25-(OH)D, difference in references ranges used by various laboratories, and the absence of conclusive trials. They note that several large-scale general-population vitamin D supplementation trials in treating cancer, CVD, or all-cause mortality are underway. In the meantime, “physicians would be well advised to follow current USPSTF and IOM recommendations and avoid overscreening and overprescribing supplemental vitamin D.”

      Table 1: USPSTF Recommendations for Vitamin D Screening in Community-Dwelling, Nonpregnant, Asymptomatic adults (aged ≥18 years)

      Risk Assessment  

      Persons with low vitamin D intake, decreased vitamin D absorption, and little or no sun exposure may be at increased risk for vitamin D deficiency. Obesity and darker skin pigmentation may be associated with low levels of serum 25-hydroxyvitamin D [25-(OH)D] but it is unclear whether low levels in these populations reflect vitamin D deficiency or are associated with adverse clinical outcomes.

      Screening Tests  

      Testing methods to measure serum 25-(OH)D are available, but their accuracy is difficult to determine because of the lack of studies that use an internationally recognized reference standard and the lack of consensus on the laboratory values that define vitamin D deficiency.

      Treatment and Interventions  

      Oral vitamin D is the most common treatment for vitamin D deficiency, including vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). Other treatment options include increasing dietary vitamin D intake or sun exposure (which carries the risk of skin cancer).

      Balance of Benefits and Risks  

      The current evidence is insufficient to assess the balance of benefits and harms of screening for vitamin D deficiency in asymptomatic adults.

      Other Relevant USPSTF Recommendations  

      The USPSTF has recommendations regarding the use of vitamin D supplementation for the prevention of falls and fractures, and for the prevention of cardiovascular disease and cancer. These recommendations are available at the USPSTF website.


      1. Manson JE, Bassuk SS. Vitamin D research and clinical practice: at a crossroads. JAMA. 2015 Feb 19. [Epub ahead of print]
      2. LeFevre ML. U.S. Preventive Services Task Force. Summaries for Patients. Screening for vitamin D deficiency in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2015;162(2):133-140.
      3. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC; National Academies Press:2011.
      4. Heaney RP, Armas LA. Screening for vitamin D deficiency: is the goal disease prevention or full nutrient repletion? Ann Intern Med. 2015;162(2):144-145.
      5. Juonala M, Voipio A, Pahkala K, et al. Childhood 25-OH vitamin D levels and carotid intima-media thickness in adulthood: The Cardiovascular Risk in Young Finns Study. J Clin Endocrinol Metab. 2015 Feb 10:jc20143944. [Epub ahead of print]
      6. Hennnger N, Turetsky A, Goddeau RP. Vitamin D Status, Cerebral Ischemic Susceptibility, and Post-stroke Outcome. Poster presented at: The International Stroke Conference 2015. Abstract W MP62. February 11, 2015. Los Angeles, CA.
      7. Clemente-Postigo M, Muñoz-Garach A, Serrano M, et al. Serum 25-Hydroxyvitamin D and adipose tissue vitamin D receptor gene expression: relationship with obesity and type 2 diabetes. J Clin Endocrinol Metab. 2015 Feb 23:jc20143016. [Epub ahead of print]
      8. Ng K. Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance). Abstract 507. Poster presented at: The 2015 Gastrointestinal Cancers Society Annual Meeting. January 15, 2015. San Francisco, CA.
      9. Confino-Cohen R, Brufman I, Goldberg A, Feldman BS. Vitamin D, asthma prevalence and asthma exacerbations: a large adult population-based study. Allergy. 2014;69(12):1673-1680.
      10. Bodnar LM, Platt RW, Simhan HN. Early-pregnancy vitamin D deficiency and risk of preterm birth subtypes. Obstet Gynecol. 2015;125(2):439-447.
      11. Afzal S, Brøndum-Jacobsen P, Bojesen SE, Nordestgaard BG. Genetically low vitamin D concentrations and increased mortality: Mendelian randomization analysis in three large cohorts. BMJ. 2014 Nov 18;349:g6330.


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