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Vitamin D Science

Friday, January 11, 2019

Winter 2019 is here and many people will not get enough sun on their skin to maintain optimal vitamin D levels, therefore today's Friday Pearl will focus on vitamin D published science, popular beliefs, and the levels of vitamin D now considered optimal for health and disease prevention.

An evidence-based medicine review was published in the Journal of General Internal Medicine last year that examined the clinical evidence for many D beliefs.

Below are the four levels of evidence-based medicine, for readers who may not understand the concept.

Level one: Evidence obtained from at least one properly designed randomized controlled trial (RCT).

Level two: Evidence obtained from well-designed controlled trials without randomization.

Level three: Evidence obtained from multiple time-series designs with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidence.

Level four: Opinions of respected authorities, based on clinical experience, descriptive case studies, or reports of expert committees.

It would appear that the study investigators made their bottom-line recommendations based primarily on level one or two evidence-based medicine criteria appropriate for pharmaceutical drug study. Level two or three evidence-based study criteria is the most appropriate for nutrient studies, since it's impossible to exclude vitamins, minerals, and antioxidants from the normal diet.

Examining the evidence and the beliefs 

Disclaimer: Unfortunately, the FDA does not allow nutritional supplement companies to discuss nutrient effects on specific disease processes addressed in the Journal of Internal Medicine, so today's Pearl will address the article structure / function and general health and wellness issues associated with vitamin D levels only.

Tens of thousands of studies have now been conducted on vitamin D, with more than half of them being cohort or observational studies, demonstrating an association between deficits in vitamin D and a litany of health issues. These findings have fueled the hypothesis that vitamin D supplementation—a widely available, low-cost, and mostly harmless intervention—might help prevent illness, and help maintain health.

The beliefs discussed below originate from observational studies or theories drawing an association between low 25-hydroxy vitamin D test levels (25(OH)D), and increased risk of severity of medical concerns.

Belief: Vitamin D increases muscles mass and muscle strength 

The evidence seems to be growing that vitamin D plays a role of several tissues including skeletal muscle. Systematic review and meta-analysis study results suggest a small but significant positive effect of vitamin D supplementation on global muscle strength, particularly on those with low vitamin D levels, but no significant effect was found on muscle mass. 

Bottom line: Lower vitamin D concentrations continue to be prospectively associated with greater muscle loss in middle-aged and elderly men.

Belief: Vitamin D reduces falls 

Three studies have found an association between low vitamin D levels and falls among elderly patients in long-term care. Study investigators have postulated that vitamin D supplementation may reduce the risk of falling. Eight meta-analyses of vitamin D levels and falls have been conducted with conflicting results. 

Bottom line: Vitamin D supplementation may reduce the number of falls among the elderly. There is also likely an overall reduction in the number of fallers, although these results are less consistent.

Belief: Vitamin D reduces fractures

Meta-analyses of 17 observational studies found that 33 percent of hip fracture cases had lower vitamin D levels than controls.

Bottom line: The best available evidence shows an apparent reduction in fractures associated with vitamin D when given at moderate doses (more than 800 IU per day) together with calcium at low to moderate doses.

Belief: Vitamin D improves mental well-being  

A systematic review and meta-analysis assessed observational data on the relationship between vitamin D and depression. The findings suggest that patients with depression had lower vitamin D levels than did the healthy controls. Three cohort studies also included in the review showed a significantly increased risk of depression in patients with low vitamin D levels. However, further analysis of these cohort studies found poor randomization with large loss of follow-up. 

Bottom line: Vitamin D supplementation does not improve mental well-being scores in the general population without clear depression, even when 25(OH)D levels are low.

Belief: Vitamin D dose—more is better  

Two large RCTs provide concerning evidence that higher doses of vitamin D could increase the risk of falls and fractures. Given the present enthusiasm for vitamin D supplementation and the pervasive belief that more is better, these trials serve as a good reminder. Even in the two clinical areas of best evidence for vitamin D supplementation (falls and fracture prevention), massive doses can increase the very outcomes we are trying to prevent. 

Bottom line: High-dose vitamin D has been shown to increase the risk of falls and fractures. Single high-dose supplementation should not be recommended.

Vitamin D (25 (OH)D) levels should be tested routinely 

Some vitamin D study investigators do not recommend routine testing for vitamin D levels for several reasons: Vitamin D assays can vary by as much as 10 to 20 percent, even when repeating the test in the same person at the same time; enrollment in many vitamin D supplementation trials was not  based on 25(OH)D levels, and treatment of patients without screening 25(OH)D level was found to be beneficial. Finally, the $60 cost of routine screening / testing of 25(OH)D is an onerous and costly exercise.

Based on systematic review of studies on health outcomes associated with vitamin D, the Institute of Medicine recommends:

Deficiency: <30 ng/ml places a person at risk relative to bone health, and 30 to 50 ng /ml places some, but not all persons at risk for inadequacy.  

Sufficiency (adequate): >50 ng/ml meets the needs of 97.5 percent of the population. The IOM also states that levels >75 ng / m/l are not consistently associated with increased benefit.

Bottom line: Vitamin D supplementation in the general adult population is safe, and supplementation without testing is reasonable.

Vitamin D and mortality studies

Multiple observational studies have found a positive association between low vitamin D levels and an increase in all-cause mortality. The study investigators reviewed six of the systematic meta-analyses that examined the effect of vitamin D on mortality. 

Mortality was a secondary outcome on almost all of the trials included. Overall, the relative reduction in mortality ranged from 4 to 11 percent. Although low 25(OH)D levels have been associated with increased mortality in observational studies, it should be noted that emerging observational evidence indicates that high 25(OH)D levels (>120 ng /ml) are also associated with increased mortality. 

Bottom line: The effects of vitamin D on mortality are not consistently statistically significant.

Bottom line: Vitamin D may prove to be a good surrogate for general well-being. At the present time, evidence supports vitamin D supplementation to help prevent fractures (particularly if given with calcium) and possibly to prevent falls and slightly reduce mortality (particularly in patients >70 years of age). No other effects are proven. For many other conditions, the evidence for vitamin D supplementation is plagued by the use of small, poor-quality trials. Lastly, testing of 25(OH)D levels in the general population is not necessary, and very high doses should be avoided.

Ellen Troyer, with Spencer Thornton, MD, David Amess and the Biosyntrx staff

PEARL:  We found a new vitamin D blood level study conclusion published this month in the British Journal of Ophthalmology worth sharing, given that the risk of becoming nearsighted has been clinically proven over and over to be lower in those with higher vitamin D blood levels. These researchers found no nucleotide polymorphisms in the VDR gene to be associated with nearsightedness, which other studies have suggested as a possibility.

Bottom line: Vitamin D has an association with ocular function, in addition to its proven role as a biomarker for time spent outdoor. 

Given the unexplained increase in nearsightedness in young people, we recommend more outside in the sun time and less time in front of phones, tablets and monitors.  

The current Vitamin D Safe Upper Limit set by the US Institute of Medicine1,000 to 1,500 IU/day for infants, 2,500 to 3,000 IU/day for children 1-8 years, and 4,000 IU/day for children 9 years and older, adults, and pregnant and lactating teens and women. 

Vitamin D toxicity almost always occurs from overuse of 


A common sense aside: Sixty dollars for a vitamin D lab test seems a reasonable health expenditure, particularly for those developing nearsightedness, or those who have reached the age of possible vitamin D deficiency-related increased risk for falls and fractures, which are expected to exceed $40 billion in health care costs annually by 2020.