Is low Vitamin D just a marker of disease - March 2023

Low vitamin D is a marker for poor health and increased risk for disease: But causality is still unclear in most cases – Oct 2022

Journal of Internal Medicine https://doi.org/10.1111/joim.13582C
Peter Bergman Editorial

It is almost 100 years since Adolf Windaus received the Nobel Prize in chemistry in 1928 for his studies’ on the constitution of sterols and their connection with vitamins’, including vitamin D and its role to prevent rickets [1]. The role of vitamin D to protect the bone has been well known since and has a central role in all medical textbooks. This part of vitamin D metabolism is generally known as the endocrine system, where the liver produces the storage form 25-hydroxyvitamin D (25OHD) and the kidney carries out the conversion into bioactive 1,25-dihydroxyvitamin D (1,25OHD), which mainly regulates calcium balance. In addition, the proform 25OHD can be activated locally in many different cell types, including monocytes, epithelial cells and even in neurons [2, 3]. Local production of the active form of vitamin D (1,25OHD) leads to activation of the vitamin D receptor and subsequent transcription of several hundreds of genes, depending on the cell type and physiological context [4]. This part of vitamin D metabolism is called the paracrine system and has been the focus of intense research during recent years [5]. In parallel with the molecular discoveries of vitamin D metabolism, there has been a rapid increase in observational studies that have found associations between low vitamin D levels and increased risk of many common diseases, including cancer, cardiovascular diseases, respiratory tract infections and Alzheimer's disease as well as all-cause mortality [6-9]. Combined, there has been a solid rationale to perform randomised controlled trials (RCTs) in many of these areas since there is a potential mechanism for beneficial effects and data from observational studies show an increased risk for disease with lower vitamin D levels in plasma. Randomised and placebo-controlled clinical trials of vitamin D supplementation in cancer, cardiovascular diseases and respiratory tract infections have shown both beneficial effects as well as null results [10, 11]. Interestingly, meta-analyses, where results from many RCTs are combined, have shown beneficial effects of vitamin D supplementation on cancer mortality and total mortality as well as reduced risk for respiratory tract infections [12-14]. In addition, Mendelian randomisation studies have shown an inverse association between genetically predicted 25OHD levels and all-cause mortality [15].

It is against this background that Sha et al. set out to obtain further information on the role of vitamin D in reduction of mortality from cancer and other causes, including cardiovascular and respiratory diseases [16]. They used data from the UK Biobank (n = 445,601 participants), including data on the use of vitamin D supplements (over-the-counter drugs or as part of a multivitamin product) and 25OHD levels defined as deficiency (<30 nmol/L) or insufficiency (30 to <50 nmol/L). The outcomes were all-cause and cause-specific mortality, with a focus on mortality due to cardiovascular disease, cancer and respiratory disease. Several covariates were also collected for the adjustment analyses, including demographic and socio-economic factors, which potentially could influence the outcome. The mean age of the cohort was 56.5 years, and a majority were overweight or obese. Interestingly, 21% of the cohort had vitamin D deficiency (<30 nmol/L) and 34.3% had insufficiency (<50 nmol/L). Only 4.3% reported a regular intake of vitamin D supplements, whereas 20.4% reported using multivitamin supplements on a regular basis. Consequently, users of vitamin D or multivitamin supplements had a higher level of 25OHD than nonusers.

Next, the authors analysed determinants associated with vitamin D deficiency. In general, worse health concomitant diseases, obesity, higher blood pressure, poor general health and the latitude of the test centre were factors associated with vitamin D deficiency or insufficiency, whereas the use of vitamin D or multivitamin supplements often had the reverse association, that is, healthier people had a higher tendency to take supplements.

The authors found that both vitamin D deficiency and insufficiency were associated with all-cause mortality and mortality due to cancer, cardiovascular disease (CVD) and respiratory diseases. Five different adjustment models were employed, and the hazard ratios were attenuated with increasing adjustment. The excess mortality was most prominent for CVD, followed by respiratory disease mortality and cancer mortality.

Finally, the association between self-reported vitamin D intake and the outcomes was analysed. Notably, no effect was observed, but after considering concomitant diseases and general health status in the broadest adjustment model, users of vitamin D supplements had 10% lower all-cause mortality and 11% lower cancer mortality, whereas mortality for CVD did not reach statistical significance. The strongest effect was found for respiratory diseases, where self-reported vitamin D intake was associated with 29% decreased mortality.

How should these results be interpreted in the light of available evidence? First, there have been many studies before this one with a similar message, that is, low vitamin D levels are associated with many different diseases, including those discussed here. For example, there is evidence from a large European consortium that low vitamin D levels are associated with increased mortality [17]. We also know that vitamin D has several important functions in the body, apart from regulating calcium homeostasis. A recent example is from the covid area, where vitamin D was found to suppress inflammation in T cells, with potential implications for prevention and treatment of SARS CoV-2 infection [18]. However, despite ample evidence from experimental and observational studies, solid data from RCTs showing beneficial effects against any indication are scarce, with a few exceptions. For example, vitamin D did not prevent CVD or cancer in a large and well-designed RCT [19]. In contrast, in the field of respiratory tract infections, the team around Adrian Martineau has performed two large meta-analyses, one of which is an individual patient data meta-analysis, which found small but statistically significant effects of vitamin D supplementation against respiratory tract infections (RTIs) [13, 14]. However, two recent RCTs could not find any evidence of vitamin D supplementation (or cod liver oil supplementation) against covid-19 [20-22]. Thus, there is still a discrepancy between experimental and observational data on one side and data from RCTs on the other. Why is that? There are three models to consider at this point. The first of these implies that low levels of 25OHD are directly causing the disease. Supplementation would then be the solution and lead to reduced risk of the disease. The other explanation could be a reverse association, that is, that the disease causes low vitamin D levels; for example, if a chronic disease leads to immobilisation indoors without exposure to the sun. The final model is that there is a spurious or ‘false’ association where a third factor leads to both low vitamin D levels and increased risk for the disease. In the paper by Sha et al., for example, subjects with self-reported poor health status had 77% higher odds to have vitamin D deficiency and 19% lower odds of taking vitamin D supplements. Thus, there is a significant risk of the healthy user effect, that is, that healthier people tend to take more supplements, spend more time outdoors and simply avoid diseases to a higher extent than poor, fragile and sick people do. Sha et al. apply an ambitious adjustment approach to avoid this risk, but as the authors point out themselves, it is impossible to adjust for so-called hidden or residual confounders. This means that there could still be additional factors that we cannot adjust for, which could influence the observed associations. Thus, despite the impressive size of the study by Sha et al., we still cannot draw firm conclusions on causality and whether vitamin D supplementation can reduce mortality from CVD, cancer or respiratory diseases.

But which advice should we give to the public, physicians and policy makers about vitamin D deficiency and risk for disease? A pragmatic approach could be to focus on groups at the highest risk for vitamin D deficiency and supplement those <50 nmol/L with 1000–2000 IU/day. This would support the bone, improve immunity and potentially also reduce the risk of respiratory tract infections. Perhaps this strategy could also reduce mortality from CVD, cancer and respiratory disease, as suggested by Sha et al., but solid evidence from bona fide randomised and placebo-controlled clinical trials is still warranted.
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Regarding: Feb 2023

Journal of Internal Medicine https://doi.org/10.1111/joim.13621
William B. Grant, Barbara J. Boucher First published: 22 February 2023
To the Editor,

In a recent editorial, Peter Bergman stated that whether associations between low 25-hydroxyvitamin D [25(OH)D] concentrations and poor health are causally linked was unclear in most cases [1]. His statement was based on the consideration of vitamin D randomized controlled trials (RCTs). However, as discussed at length in a recent review, most vitamin D RCTs have been poorly designed, conducted, and analyzed [2], having been based on guidelines for pharmaceutical drugs rather than on nutrients. Heaney outlined guidelines for trials of nutrients such as vitamin D in 2014 [3]. These guidelines include, for vitamin D, that serum 25(OH)D concentrations of the proposed participants must be measured, and only subjects with low values should be included, that vitamin D doses used must raise 25(OH)D concentrations to values associated with reduced risk in observational studies, and that, therefore, achieved concentrations must be measured. However, most vitamin D RCTs have included many participants with relatively high 25(OH)D concentrations, have used too low vitamin D doses, and did not base their analyses on individual participant 25(OH)D concentrations.

Also overlooked in the editorial is that Mendelian randomization (MR) studies have now demonstrated the causality of vitamin D in reducing risk of several types of disease. In MR studies, data for alleles of genes involved in the vitamin D pathway are used to estimate genetic variations in serum 25(OH)D (genome-wide association studies) using perhaps 100,000 participants and have then examined health outcomes with those gene variants in large study populations. The assumption is that, because individuals are randomized into study groups by the genetic variants they carry, bias due to confounding and reverse causation is avoided [4]. The Hyppönen group, using MR analyses of findings stratified by baseline 25(OH)D concentration (i.e., non-linear analyses), has shown many significant effects of vitamin D in participants with low 25(OH)D concentrations. This methodology has already demonstrated causality for several health outcomes in their hands, including cardiovascular disease, dementia, and all-cause mortality rates, using data from the UK Biobank [4] as well as for hypertension, multiple sclerosis, and type 2 diabetes mellitus by others that they cite [4].

RCTs and MR studies have not supported the causality of vitamin D in the reducing risk of cancers. However, the evidence from observational studies and geographical ecological studies, as well as an understanding of the mechanisms involved, provides sufficient evidence for causality when considered by Hill's criteria for causality in a biological system [5, 6]. It should also be noted that the Vitamin D and Omega-3 Trial (VITAL) [7] had serious shortcomings including that the mean 25(OH)D concentration for those in the vitamin D treatment arm with 25(OH)D data was 30 ng/mL, that the vitamin D dose was 2000 IU/d but that all participants were permitted to take up to 600–800 IU/d vitamin D and to receive solar UVB, and that outcomes were not analyzed in terms of achieved 25(OH)D concentrations. Nevertheless, secondary analyses did find significant reductions for cancer incidence for those with a BMI <25 kg/m2 and overall reductions in the cancer mortality rate whe n the earliest years of data were omitted.
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Authors reply: March 2023

Journal of Internal Medicine https://doi.org/10.1111/joim.13622
Peter Bergman
Dear Editor,

I have read the letter by Dr Grant with great interest [1]. The question whether vitamin D can prevent common diseases, such as hypertension, diabetes and cardiovascular diseases is often debated. The field is somewhat polarised between hard-line sceptics and more positive “believers”. Both teams use a long line of evidence to support their respective views. In my editorial, I tried to shed light on some of the different views in the field and pointed out that there is still a lack of solid results from large, randomised and placebo-controlled clinical trials (RCTs) for most indications. One exception could be the effects on respiratory tract infections, where two large meta-analyses on RCTs have shown a small but statistically significant effects of about 8%–10% [2, 3]. However, two recent RCTs on vitamin D supplementation against COVID-19 failed to show any beneficial effect [4, 5]. These are just a few examples, but it is clear that we lack evidence from bona fide RCTs on the beneficial effects of vitamin D supplementation for most indications.
However, I do agree with Dr Grant that there are many other pieces of evidence that point in favour of vitamin D for many human diseases. For example, there is mechanistic evidence that vitamin D can modulate inflammation in T-cells from patients infected with SARS CoV-2 [6], vitamin D can directly induce antimicrobial peptides in human macrophages and fight tuberculosis [7] and – as an example, the vitamin D receptor is expressed in beta cells in the pancreas [8]. On top of these mechanistic leads, there are many observational studies that show that low vitamin D levels are associated with an increased risk for disease. And, more recently, several studies based on Mendelian randomisation analysis suggest that vitamin D levels can be linked to human disease. Up to this point, I agree with Dr Grant.

Nevertheless, the bar for certainty is higher than a plausible mechanism, observational evidence and Mendelian randomisation analyses and needs to be based on solid RCTs. It is always possible to find problems with available RCTs in the field and claim that they were not performed in the correct way. However, to be able to change paradigms and guidelines, we need solid evidence from RCTs and that is currently lacking for most indications, as I pointed out in my editorial. For medical doctors, including myself, it is important to follow guidelines and regulations. Thus, any clinical decision to start vitamin D supplementation has to be based on solid evidence. Dr Grant has a slightly different platform in this discussion, because he represents a company that produce and sell vitamin D supplements to the public. This difference might not be decisive for his standpoints but is nevertheless important to keep in mind as there could be a conflict of interest here.

To end in a more positive note, there is still a lot to discover in the field of vitamin D and the optimal RCT, which consider all possible confounders, has not yet been performed. Thus, there is more to learn and perhaps we will reach a more solid evidence base in this field in the future. Until then, I recommend a pragmatic approach where vitamin D supplementation should be directed towards risk-groups for vitamin D deficiency, such as the obese, pregnant women, and those with darker skin. A cut-off level of 50 nmol/L will work for most individuals and supplementation with 1000–2000 IU/day will support the bone, improve immunity, and potentially also reduce the risk for respiratory tract infections.
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Vitamin D is not just association - examples of RCTs finding that adding D fights diseases

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100 most-recently updated RCTs in VitaminDWiki - (from 900+)

This list is automatically updated

Items found: 1016
Title Modified
Multiple Sclerosis treated by 50,000 IU Vitamin D bi-weekly plus Omega-3 – RCT July 2018 06 Jul, 2018
Seniors getting Vitamin D (but no exercise) for 3 months failed to increase muscle strength – RCT June 2018 03 Jul, 2018
1200 IU vs 400 IU of vitamin D did not improve bone health or immunity of children who were sufficient – RCT July 2018 03 Jul, 2018
Improved recovery from ischemic stroke with Vitamin D (300,000 IU injection) – RCT June 2018 29 Jun, 2018
Omega-3 reduced aggressive incidents in prisoners by 30 percent – RCT June 2018 19 Jun, 2018
Teen dancers had 3X fewer traumatic injuries after 120,000 IU Vitamin D over a week – RCT June 2018 13 Jun, 2018
Adding Vitamin D, Omega-3, etc to children’s milk improved memory (yet again) – RCT June 2018 09 Jun, 2018
Response to Vitamin D varies with Vitamin D Binding Protein gene – RCT May 2018 06 Jun, 2018
400 IU of Vitamin D provided no benefit to children (not a surprise) – RCT March 2018 30 May, 2018
Pregnancies helped a lot by Vitamin D (injection then 50,000 IU monthly) – RCT May 2018 28 May, 2018
9,000 dollar prize for RCT which found cognition improved after taking 4,000 IU of Vitamin D for 18 weeks – May 2018 26 May, 2018
Omega-3 reduced violence in children and violence between parents – RCT May 2018 26 May, 2018
Vitamin D every 25 days may be BETTER than daily – RCT May 2018 24 May, 2018
430 genes changed when 3,800 IU Vitamin D added in late second trimester – RCT May 2018 22 May, 2018
Cardiovascular risk markers not helped by 20,000 IU of vitamin D weekly – RCT May 2018 17 May, 2018
Treatment of malnourished children greatly augmented by Vitamin D – RCT May 2018 04 May, 2018
Omega-3 for just 3 months greatly reduced psychosis for 80 months – RCT Aug 2015 02 May, 2018
Severe acute pancreatitis treated in 11 ways by Omega-3 in just 7 days – RCT April 2018 01 May, 2018
Omega-3 reduced cost of Sepsis by 2900 dollars per patient (12 RCT) – April 2018 24 Apr, 2018
Knee pain and depression reduced by monthly 50,000 IU vitamin D – RCT April 2018 21 Apr, 2018
No genetic response to 4,000 IU of Vitamin D (other studies disagree) – RCT April 2018 15 Apr, 2018
Urinary sepsis – a single Vitamin D injection reduced hospital days by 40 percent – RCT April 2018 06 Apr, 2018
Ethical Quandary – give Vitamin D to all in RCT – March 2018 06 Apr, 2018
Far more Vitamin D in breast milk from a 150,000 IU dose than from daily 5,000 IU – RCT May 2018 21 Mar, 2018
IBS quality of life improved by vitamin D (50,000 IU every two weeks) – RCT May 2016 14 Mar, 2018
Open Heart Surgery associated with low vitamin D, but not if 150,000 IU before surgery – RCT March 2018 13 Mar, 2018
3 days of Omega-3 before cardiac surgery reduced risk of post-op bleeding by half – RCT March 2018 13 Mar, 2018
Nordic Walking and 4,000 IU of vitamin D lowered cholesterol, fat, weight, and lipids (senior women) – RCT Feb 2018 09 Mar, 2018
Depression – is it reduced by Vitamin D and or Omega-3 – RCT 2019 09 Mar, 2018
Biochemical rickets non-existent if breastfeeding mother got 600,000 IU of vitamin D (3 dollars) – RCT Dec 2017 03 Mar, 2018
People felt less aggression after just 6 weeks of Omega-3 – RCT Dec 2017 03 Mar, 2018
Pain not relieved by monthly 100,000 IU of vitamin D (need 50,000 IU weekly) – RCT Feb 2018 02 Mar, 2018
Zinc cut in half the rate of prediabetes progressing to diabetes (20 mg) – RCT Oct 2017 28 Feb, 2018
Zinc cut in half the rate of prediabetes progressing to diabetes (20 mg) – RCT Oct 2018 28 Feb, 2018
Omega-3 supplement better than farmed salmon at raising Omega-3 index – RCT Feb 2018 25 Feb, 2018
BMI reduced by Vitamin D (not much reduction – only got VitD to 26 ng) – RCT Feb 2018 24 Feb, 2018
ADHD reduced by just 3,000 IU of Vitamin D and methylphenidate for just 12 weeks – RCT Feb 2018 22 Feb, 2018
ADHD significantly reduced by just 3,000 IU of Vitamin D and methylphenidate for just 12 weeks – RCT Feb 2018 22 Feb, 2018
35,000 IU vitamin D weekly during 3rd quarter pregnancy – RCT March 2013 16 Feb, 2018
Elite Athletes do well with weekly 35,000 IU of Vitamin D – RCT Feb 2017 16 Feb, 2018
Bedwetting reduced 40 percent by 1,000 IU of vitamin D for 2 months – RCT Feb 2018 06 Feb, 2018
Skin whitening cream (RD) may cause blotchy skin, 5,000 Vitamin D can treat it – RCT Feb 2018 06 Feb, 2018
Powder-based Vitamin D may be gut-friendly (Cystic Fibrosis) – RCT Aug 2017 05 Feb, 2018
Atopic dermatitis treated by Vitamin D (in dogs too) - RCT Feb 2018 04 Feb, 2018
Sickle Cell clinical trial will inject 300,000 IU of vitamin D – RCT due 2020 31 Jan, 2018
Allergic rhinitis in children reduced somewhat during pollen season by just 1,000 IU of vitamin D – RCT Jan 2018 31 Jan, 2018
Prediabetes corrected in 3 months by 1,000 IU of vitamin D as pill or in yogurt – RCT Jan 2018 29 Jan, 2018
Monthly vitamin D dosing had higher response than 3 per month – RCT Jan 2018 28 Jan, 2018
Fish oil increased Vitamin D levels, krill oil decreased them – RCT Jan 2018 27 Jan, 2018
Low-dose statin plaque formation stopped by Omega-3 – RCT Dec 2017 24 Jan, 2018
Spinal Cord injury outcome was better if got Vitamin D and progesterone within 4 hours – RCT 2016 13 Jan, 2018
Influenza reduced by 1.7 with 1200 IU D3, also reduced related asthma by 6X – RCT May 2010 10 Jan, 2018
Amyotrophic Lateral Sclerosis patients helped by Omega-3 (behind publisher paywall) – RCT Sept 2017 04 Jan, 2018
Amyotrophic Lateral Sclerosis patients helped by Omega-3 – RCT Sept 2017 04 Jan, 2018
Gestational diabetes treated by Vitamin D plus Omega-3 – RCT Feb 2017 02 Jan, 2018
Less weight gain with high fat diet if add Vitamin D (in rats) – RCT Dec 2017 02 Jan, 2018
Less weight gain if add Vitamin D, even if have a high fat diet (in rats) – RCT Dec 2017 02 Jan, 2018
Vitamin D and RCTs (Randomized Controlled Trials) 31 Dec, 2017
Following breast cancer 100K IU Vitamin D doses twice a month helped a lot – RCT July 2016 31 Dec, 2017
Breathing by ever-smokers improved by monthly Vitamin D – RCT 2017 29 Dec, 2017
Breathing by ever-smokers improved by monthly Vitamin D (mailed) – RCT 2017 29 Dec, 2017
Brain Tumor surgery – will previous injection of 300,000 IU Vitamin D help – RCT 2018 29 Dec, 2017
Lupus reduced when half of participants got to 38 ng of Vitamin D (not statistically significant) – RCT Jan 2017 26 Dec, 2017
Clinically Isolated Syndrome progresses to Multiple Sclerosis, unless UVB treatments – RCT Dec 2017 17 Dec, 2017
Breastfed infant bones not helped by 800 IU of Vitamin D (not enough) – RCT Dec 2017 12 Dec, 2017
800 IU of vitamin D got most Danish children to only above 20 nanograms – RCT Oct 2016 12 Dec, 2017
Dementia risk reduced 29 percent by just 10 hours of computer brain plasticity training – RCT Dec 2017 08 Dec, 2017
Sleep disorders treated with 50,000 IU Vitamin D every 2 weeks – RCT May 2017 07 Dec, 2017
Ventilator-associated pneumonia death rate cut in half by Vitamin D injection (300,000 IU) – RCT July 2017 06 Dec, 2017
Vitamin D depression RCT canceled: too many were taking Vitamin D supplements, etc. Feb 2018 28 Nov, 2017
Prostate Cancer might be treated by 4,000 IU of vitamin D and aspirin – RCT 2021 28 Nov, 2017
Vitamin D changed microbiota in gut and airway, might reduce cystic fibrosis – RCT Nov 2017 27 Nov, 2017
Senior cognition improved somewhat by 4,000 IU of Vitamin D (if initially less than 30 ng) – RCT April 2017 20 Nov, 2017
Hypertension not controlled by 26 ng of Vitamin D (50,000 IU bi-weekly A-A) – RCT Nov 2017 18 Nov, 2017
Fluoride caused bone problems in 80 percent of Vitamin D deficient rats – RCT Nov 2017 13 Nov, 2017
Bone loss stopped by monthly 12,000 IU of vitamin D – RCT June 2016 07 Nov, 2017
Lymphoid cancer deaths cut in half with 400 IU of vitamin D and 1 gram of Calcium (WHI) – RCT Nov 2017 04 Nov, 2017
Heart Failure Quality of Life greatly improved by 10,000 IU of vitamin D – RCT Oct 2017 01 Nov, 2017
Blood pressure reduced by monthly 100,000 IU of vitamin D in those who were deficient – RCT Oct 2017 29 Oct, 2017
Multiple Sclerosis stem cell treatment (HSCT) probably not benefit from 200,000 IU of vitamin D – RCT 2020 25 Oct, 2017
Probably Fractures of the Tibia can be healed with 100,000 IU of vitamin D weekly – RCT 2023 23 Oct, 2017
Vitamin D taken daily (4,000 IU) vs weekly (50,000 IU) – RCT 2019 23 Oct, 2017
Delay onset of Multiple Sclerosis with 100,000 IU of vitamin D every two weeks – RCT 2020 23 Oct, 2017
Severe sepsis may be prevented by 400,000 IU of vitamin D – RCT 2023 23 Oct, 2017
Perhaps fewer bone non-unions with 100,000 IU weekly of vitamin D – RCT 2018 23 Oct, 2017
Preemies getting 800 IU of vitamin D were 3X less likely to have low bone density 4 weeks later – RCT Oct 2017 22 Oct, 2017
Vitamin D supplementation for newborns – 400 IU daily vs 50,000 IU dose – RCT Sept 2016 21 Oct, 2017
Transdermal Magnesium cream worked for non-athletes– RCT April 2017 20 Oct, 2017
Can burn pain be relieved by 4 g of Omega-3 and 2,000 IU of vitamin D – RCT due 2021 18 Oct, 2017
HIV patients helped by monthly 120,000 IU of Vitamin D – RCT Oct 2017 17 Oct, 2017
Falls and vitamin D – another poor study – RCT Oct 2017 04 Oct, 2017
2000 IU of vitamin D should improve toddlers health in winter – RCT almost completed Feb 2014 03 Oct, 2017
Children helped by 2,000 IU of vitamin D, but not RDA amount (600 IU) – RCT Sept 2017 03 Oct, 2017
More than 5X increase in activation of scores of genes for women with Vitamin D (20,000 IU weekly) RCT Oct 2017 01 Oct, 2017
Prostate Cancer treatment (Vitamin D, Omega-3, Tumeric) RCT ending Dec 2018 26 Sep, 2017
Monthly 120,000 IU Vitamin D plus daily Calcium was great during pregnancies – RCT Sept 2017 23 Sep, 2017
Early Rheumatoid Arthritis helped by 300,000 IU of vitamin D – RCT June 2017 23 Sep, 2017
Semi-activated vitamin D (HyD3) successfully being used in human trials – RCT Sept 2017 22 Sep, 2017
Mother got 100,000 IU of vitamin D monthly, breastfeeding infant got a little – RCT Aug 2016 13 Sep, 2017
Omega-3 reduced dry eye (computer related) by 3X - RCT June 2015 12 Sep, 2017

100 most-recently updated Meta-analyses in VitaminDWiki - (from 600+)

This list is automatically updated

Items found: 710
Title Modified
Low vitamin D is a risk factor for tuberculosis – meta-analysis Dec 2016 30 Dec, 2016
Colorectal cancer 60 percent less likely: high vs low Vitamin D level – meta-analysis Dec 2016 22 Dec, 2016
Vitamin D during pregnancy reduces risk of childhood asthma by 13 percent – meta-analysis Dec 2016 16 Dec, 2016
Birth weight and length increased with high levels of vitamin D – meta-analysis March 2015 15 Dec, 2016
Pregnancy with Vitamin D supplementation – meta-analysis Feb 2015 15 Dec, 2016
Low vitamin D increased probability of low birth weight by 60 percent – meta-analysis June 2012 13 Dec, 2016
Crohn’s disease associated with vitamin D and latitude – meta-analysis Dec 2015 11 Dec, 2016
Slipped upper femoral epiphysis (hip pain in teen) associated with vitamin D – meta-analysis May 2015 10 Dec, 2016
3000 IU of vitamin D minimum to reduce parathyroid hormone (PTH) – meta-analysis Sept 2015 10 Dec, 2016
Fatty Fish in diet increases vitamin D level a few nanograms – meta-analysis Sept 2015 10 Dec, 2016
Atrial fibrillation sometimes treated by Omega-3 – meta-analysis Sept 2015 10 Dec, 2016
Fracture risk reduced somewhat by 800 IU of vitamin D and Calcium – meta-analysis Oct 2015 10 Dec, 2016
Preterm birth extended by 2 weeks with Omega-3 – Meta-analysis Nov 2015 10 Dec, 2016
Asthma medicines not helped by vitamin D (if only a small amount of D is taken) – meta-analysis Dec 2015 10 Dec, 2016
Coronary Artery Disease without diabetes 5 times more likely if VDR gene problems – meta-analysis May 2016 10 Dec, 2016
Colorectal Cancer recurrence not prevented by 1,000 IU of vitamin D – meta-analysis Dec 2016 09 Dec, 2016
Bladder cancer modifiable risk factors include low vitamin D – meta-analysis March 2016 08 Dec, 2016
Bladder cancer 60 percent less likely if have high vitamin D – meta-analysis Dec 2015 08 Dec, 2016
Vitamin D Receptor genes bb and BB and Osteoporosis, esp. for blacks – meta-analysis Nov 2012 05 Dec, 2016
Rheumatoid arthritis is 40 percent more likely in Caucasians with a vitamin D receptor problem – meta-analysis Sept 2015 05 Dec, 2016
Rheumatoid Arthritis strongly associated with low vitamin D – meta-analysis April 2016 04 Dec, 2016
Eczema (Atopic Dermatitis) treated by 1600 IU of vitamin D – meta-analysis Dec 2016 03 Dec, 2016
Multiple Sclerosis: number needed to treat with vitamin D may be as low as 1.3 – Meta-analysis Oct 2013 19 Nov, 2016
Childhood asthma about 1.3 times more likely if poor Vitamin D Receptor – meta-analysis Aug 2016 12 Nov, 2016
Tuberculosis 1.3 times more likely if poor Vitamin D Receptor – meta-analysis Oct 2016 12 Nov, 2016
Vitamin D receptor polymorphisms are risk factors for various cancers – meta-analysis Jan 2014 12 Nov, 2016
Multiple Sclerosis 23 percent more likely if born in April vs. Oct – meta-analysis Nov 2012 05 Nov, 2016
Vitamin D supplementation improves muscle strength in healthy adults – meta-analysis of 6 RCT Aug 2014 31 Oct, 2016
2X more Parkinson's disease if modified vitamin D receptor genes – meta-analysis Aug 2014 26 Oct, 2016
800 IU Vitamin D does not help heart – meta-analysis Aug 2011 25 Oct, 2016
Cognitive Impairment 2.4X more likely if low vitamin D – meta-analysis July 2012 21 Oct, 2016
Anti-depression medication about as good as big increase in vitamin D – meta-analysis of flawless data April 2014 09 Oct, 2016
Chronic Pain reduced somewhat by Vitamin D supplementation – meta-analysis Sept 2016 01 Oct, 2016
Peripheral Arterial Disease patients have low vitamin D levels – meta-analysis Oct 2015 01 Oct, 2016
Atrial Fibrillation 1.3 times more likely if low vitamin D – meta-analysis Sept 2016 26 Sep, 2016
10 percent of colon cancer linked to Vitamin D Receptor – meta-analysis April 2012 23 Sep, 2016
10 percent of colon cancer linked to a type of vitamin D gene – meta-analysis April 2012 23 Sep, 2016
Parkinson's and Alzheimer's: associations with vitamin D receptor genes and race – meta-analysis July 2014 23 Sep, 2016
Acute Lower Respiratory Infections in Children - associated with low vitamin D – meta-analysis Dec 2014 16 Sep, 2016
Magnesium is associated with prevention and treatment of Diabetes – Meta-analysis Aug 2016 11 Sep, 2016
More vitamin D needed during pregnancy – meta-analysis Oct 2014 01 Sep, 2016
Vitamin D receptor gene associated with 50 percent more type 2 Diabetes – meta-analysis March 2013 22 Jul, 2016
Chronic Pancreatitis associated with painful bones (vitamin D) – meta-analysis July 2013 19 Jul, 2016
Vitiligo is associated with low vitamin D (nothing about treatment) – meta-analysis March 2016 12 Jul, 2016
Blood pressure is reduced by more than 800 IU of vitamin D – meta-analysis Aug 2016 08 Jul, 2016
ADHD 2 times more likely if poor Omega-6 to Omega-3 ratio – meta-analysis May 2016 07 Jun, 2016
Migraine headaches quickly reduced with Magnesium – Meta-analysis Jan 2016 02 Jun, 2016
Preterm birth 30 percent more likely if low vitamin D – meta-analysis May 2016 20 May, 2016
Lower respiratory tract infections in children associated with Low Vitamin D – meta-analysis May 2016 15 May, 2016
40 ng Vitamin D perhaps optimal for reduced mortality – Meta-analysis Jan 2012 13 May, 2016
3X variation in response to dose of vitamin D – meta-analysis June 2012 24 Apr, 2016
Omega-3 helps childhood cognition – meta-analysis April 2016 12 Apr, 2016
Late stage AMD 2.2 more likely if low vitamin D – meta-analysis April 2016 08 Apr, 2016
Poor cognition associated with low vitamin D in elderly (Asians now too) – meta-analysis March 2016 01 Apr, 2016
Kidney stones associated with higher vitamin D (but not agree how much 20-100 ng) – meta-analysis March 2016 01 Apr, 2016
Kidney cancer 22 percent less likely if high vitamin D – meta-analysis Nov 2015 30 Mar, 2016
Vitamin D3 levels decreased by consumption of UV mushrooms – meta-analysis Feb 2016 16 Feb, 2016
2X more preeclampsia when vitamin D less than 30 ng, etc. - meta-analysis March 2013 16 Jan, 2016
Rheumatoid Arthritis associated with lower vitamin D and higher latitude – meta-analysis Jan 2016 13 Jan, 2016
Bladder cancer 25 percent less likely if have high vitamin D – meta-analysis April 2015 24 Dec, 2015
Bladder cancer 25 percent less likely if have high vitamin D – meta-analysis Oct 2014 24 Dec, 2015
Alzheimer's Disease more likely with low vitamin D – meta-analysis Oct 2012 13 Dec, 2015
Chronic Widespread Pain – 40 percent more likely if vitamin D deficient – meta-analysis Sept 2015 12 Dec, 2015
Chronic Widespread Pain associated with Vitamin D under 10 ng – meta-analysis Oct 2015 12 Dec, 2015
Vitamin D response reduced if taken with Calcium – meta-analysis Oct 2015 01 Dec, 2015
COPD strongly associated with Vitamin D receptor problems – meta-analysis Aug 2015 01 Dec, 2015
Diabetics are 2.7 X more likely to get peripheral neuropathy if low vitamin D – meta-analysis Dec 2014 13 Nov, 2015
Obese are 3.4 X more likely to be Vitamin D deficient – meta-analysis Sept 2015 13 Nov, 2015
Gene makes COPD 2.6X more likely unless get more vitamin D – meta-analysis Dec 2014 04 Nov, 2015
Gut problems more likely if low vitamin D (IBD: 1.6, UC: 2.3) – meta-analysis Aug 2015 31 Oct, 2015
Autism is associated with low vitamin D – meta-analysis Oct 2015 30 Oct, 2015
Cognitive decline in elderly slowed by Omega-3 – meta-analysis May 2015 24 Oct, 2015
Chronic Heart Failure not treated by Vitamin D, if dose size is ignored – meta-analysis Oct 2015 20 Oct, 2015
1.5X increased infection, sepsis, and death if in ICU with low vitamin D - Meta-analysis Dec 2014 20 Oct, 2015
Cancer risk weakly associated wit vitamin D-binding protein – meta-analysis Sept 2015 15 Oct, 2015
Cancer risk weakly associated with vitamin D-binding protein – meta-analysis Sept 2015 15 Oct, 2015
Depression is associated with low Magnesium – meta-analysis April 2015 14 Oct, 2015
Atopic Dermatitis risk is 55 percent higher if low vitamin D – Meta-analysis Oct 2015 12 Oct, 2015
Acute fracture patients – 70 percent were vitamin D deficient – meta-analysis Sept 2015 05 Oct, 2015
Knee joint space narrowing (Osteoarthritis) 1.5X worse with low vitamin D – meta-analysis Sept 2015 03 Oct, 2015
Sports benefits from up to 50 ng of Vitamin – meta-analysis - Nov 2012 29 Sep, 2015
Low vitamin D - anemia 2.2X more likely (no surprise) – meta-analysis Aug 2015 28 Aug, 2015
COPD 2.6X more likely if poor vitamin D binding protein – meta-analysis Dec 2014 27 Aug, 2015
Infant wheezing 40 percent less likely if mother supplemented with vitamin D, vitamin E, or Zinc – meta-analysis Aug 2015 25 Aug, 2015
Colon cancer 30 percent more likely if low vitamin D – 12th meta-analysis Aug 2015 14 Aug, 2015
Migrants from Middle East are slightly more vitamin D deficient than those from Africa - meta-analysis Aug 2015 11 Aug, 2015
Low density lipoprotein cholesterol is predictable from vitamin D levels – meta-analysis March 2012 09 Aug, 2015
Alzheimer’s disease 21 percent more likely if low vitamin D – meta-analysis Aug 2015 07 Aug, 2015
Active form of vitamin D (calcitriol) cut in half the fractures following organ transplant – meta-analysis Aug 2011 26 Jul, 2015
Vitamin D associated with 50 percent less ischemic stroke – meta-analysis Aug 2012 12 Jul, 2015
Hypertension is associated with low vitamin D in some groups – meta-analysis April 2015 07 Jul, 2015
Obesity causes 20 percent of all cancer, low vitamin D may be the connection – meta-analysis - Sept 2014 31 May, 2015
Obese of all ages have lower levels of vitamin D – meta-analysis May 2015 10 May, 2015
Increased risk of some female cancers if low vitamin D (due to genes) – meta-analysis June 2015 03 May, 2015
Does vitamin D treat pain – still not absolutely, positively sure – meta-analysis April 2015 30 Apr, 2015
Pregnancy and Vitamin D – meta-analysis April 2015 20 Apr, 2015
Low vitamin D and depression - Study and meta-analysis, April 2013 19 Apr, 2015
Anorexia nervosa patients have low vitamin D levels, but respond well to supplementation – Meta-analysis Nov 2014 15 Apr, 2015
Vitamin D and Respiratory Tract Infections – meta-analysis with charts June 2013 24 Mar, 2015
Hip fractures reduced 30 percent with 800 IU of vitamin D – meta-analysis July 2012 16 Mar, 2015
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