Doubt cast on vitamin D's role against disease

Vitamin controversy is not such a controversy if you ask the experts. #MSBlog #MSResearch

"Some of you may have seen the BBC news from last week that covered the meta-analysis below. The press release and article is worth reading. They both question the health benefits of vD supplements and clinical outcome for a host of diseases including MS."

"The difference between so called observational and intervention studies suggests that low vD levels are a marker of ill health, in our case MS. According this hypothesis inflammatory processes involved in pre-symptomatic MS and the clinical course of MS would reduce vD levels, which would then explain why low vD status is associated with MS. I have a problem with these conclusions regarding MS as they ignore the strong epidemiological data linking vD and/or sunshine to MS, for example latitude, migration studies, month of birth effect, parent-of-origin effects, difference in MS concordance rates between non-identical twins and siblings."

"As I am not a vD expert I asked Bruce Hollis, one of the world's preeminent vD experts for an opinion. This is what Bruce said: 

'Same old story, not enough vitamin D and wrong dosing schedules. Please read my recent paper in JCEM online as it discusses these issues. Happy Holidays all.'

The abstract from Bruce Hollis' review is below. He is simply making the point if you review a large number of studies that use the incorrect dose and dosing schedules of vD you get a result that suggest vD supplementation does not make a difference. In other words if you put crap in you get crap out. What Bruce and his colleagues are suggesting is that we need to properly designed vD intervention studies with adequate vD supplementation schedules that essentially keep your blood vD levels above 100 nmol/L all year round. Why this level? If you study populations that still live a hunter-gather existence in Africa, or people who work outdoor such as farmers and lifeguards, they all have blood levels above 100nmol/L."

"Therefore this meta-analysis does not change our advice regarding levels of vD supplementation. We still support the vD Council's recommendations of 5,000U of vD3 per day."

Conversion units of vD
  1. 40U = 1μg
  2. 400U = 10μg
  3. 600U = 15μg
  4. 2,000U = 50μg
  5. 5,000U = 125μg
  6. 10,000U = 250μg
This blogs recommendations for levels of vD supplementation:
  1. Children less than 2 yrs of age: 600U per day
  2. Children 2-10 years of age: 2,000U per day
  3. Children above 10 years of age: 5,000U per day
  4. Adults: 5,000U per day
  5. Pregnant woman: 10,000U per day
"Please note that this is an average recommendation and some people may need more than this and other less than this to maintain a blood level between 100 and 200 nmol/L. In an ideal world you would start vD supplementation at this level and after 6-8 weeks you would have your levels checked and adjusted accordingly. There are many factors that control blood levels in an individual apart from the dose of vD. It is also important to note that you should not be taking any calcium supplements with vD. Calcium supplements are only necessary for bone health or if you have thin bones."

News: Doubt cast on vitamin D's role against disease. BBC News 6 December 2013.

Autier et al. Vitamin D status and ill health: a systematic review. The Lancet Diabetes & Endocrinology 2014; 2(1):76 - 89. 

Background: Low serum concentrations of 25-hydroxyvitamin D (25[OH]D) have been associated with many non-skeletal disorders. However, whether low 25(OH)D is the cause or result of ill health is not known. 

Methods: We did a systematic search of prospective and intervention studies that assessed the effect of 25(OH)D concentrations on non-skeletal health outcomes in individuals aged 18 years or older. We identified 290 prospective cohort studies (279 on disease occurrence or mortality, and 11 on cancer characteristics or survival), and 172 randomised trials of major health outcomes and of physiological parameters related to disease risk or inflammatory status. Investigators of most prospective studies reported moderate to strong inverse associations between 25(OH)D concentrations and cardiovascular diseases, serum lipid concentrations, inflammation, glucose metabolism disorders, weight gain, infectious diseases, multiple sclerosis, mood disorders, declining cognitive function, impaired physical functioning, and all-cause mortality. 

Results: High 25(OH)D concentrations were not associated with a lower risk of cancer, except colorectal cancer. Results from intervention studies did not show an effect of vitamin D supplementation on disease occurrence, including colorectal cancer. In 34 intervention studies including 2805 individuals with mean 25(OH)D concentration lower than 50 nmol/L at baseline supplementation with 50 μg per day or more did not show better results. Supplementation in elderly people (mainly women) with 20 μg vitamin D per day seemed to slightly reduce all-cause mortality. 

Conclusions: The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status is reported in a wide range of disorders. In elderly people, restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival.

Hollis and Wagner. The role of the parent compound vitamin d with respect to metabolism and function: why clinical dose intervals can affect clinical outcomes. J Clin Endocrinol Metab. 2013 Dec;98(12):4619-28.

Context: There is no doubt that vitamin D must be activated to the hormonal form 1,25-dihydroxyvitamin D to achieve full biological activity or that many tissues participate in this activation process-be it endocrine or autocrine. We believe that not only is 25-hydroxyvitamin D important to tissue delivery for this activation process, but also that intact vitamin D has a pivotal role in this process. 

Objective: In this review, evidence on the vitamin D endocrine/autocrine system is presented and discussed in relation to vitamin D-binding protein affinity, circulating half-lives, and enzymatic transformations of vitamin D metabolites, and how these affect biological action in any given tissue. 

Conclusions: Circulating vitamin D, the parent compound, likely plays an important physiological role with respect to the vitamin D endocrine/autocrine system, as a substrate in many tissues, not originally thought to be important. Based on emerging data from the laboratory, clinical trials, and data on circulating 25-hydroxyvitamin D amassed during many decades, it is likely that for the optimal functioning of these systems, significant vitamin D should be available on a daily basis to ensure stable circulating concentrations, implying that variation in vitamin D dosing schedules could have profound effects on the outcomes of clinical trials because of the short circulating half-life of intact vitamin D.

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