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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.
 Download the PDF from VitaminDWiki


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: 978
Title Modified
Should not add rock Calcium to Vitamin D (after 20 year followup: 6% increase in heart problems – no surprise) – RCT May 2024 23 May, 2024
2X less risk of respiratory distress syndrome if 50,000 IU of Vitamin D just before premature birth – RCT May 2024 18 May, 2024
Children with ADHD again helped by 50,000 IU weekly Vitamin D – RCT June 2024 18 May, 2024
Sepsis (with mechanical ventilation) treated by 5days of 50,000 IU of Vitamin D – RCT May 2024 06 May, 2024
Military gave Vitamin D but only 40% got above 30 ng, no benefit was noticed for the entire group – RCT July 2024 02 May, 2024
Bone fractures not reduced with 400 IU of Vitamin D plus Calcium (no surprise) WHI – strange RCT May 2024 01 May, 2024
TB treatment helped by the addition of Vitamin D (100,000 IU bi-weekly) – RCT April 2024 09 Apr, 2024
Sucrosomia Vitamin D appears to be 2 X more bio-available– RCT Aug 2023 29 Mar, 2024
Following Digestive Cancer 2,000 IU of Vitamin D were given. Those whose Omega-3 levels rose had fewer Cancer problems – RCT March 2024 25 Mar, 2024
50,000 IU of Vitamin D weekly greatly decreased bone loss from prostate cancer therapy - RCT March 2024 24 Mar, 2024
100% not need COVID hospitalization with fluvoxamine plus one other drug – Thailand RCT April 2024 16 Mar, 2024
Atopic Dermatitis not helped by small weekly doses of Vitamin D (8K 2y-6y.16K 12y-18y) – RCT March 2024 14 Mar, 2024
Vertigo incidence reduced 40% by just 7,000 IU Vitamin D given weekly - RCT Feb 2024 22 Feb, 2024
2800 IU of Vitamin D in late pregnancy resulted in 3X fewer fractures, 4X fewer enamel defects in offspring – RCT Jan 2024 12 Feb, 2024
Little Vitamin D does not reduce risk of CVD – RCT meta-analysis Dec 2023 08 Feb, 2024
COVID deaths cut in half by a single dose of 600,000 IU of Vitamin D - RCT Jan 2024 31 Jan, 2024
Obese asthmatic children Vitamin D - 50,000 IU then 8,000 IU daily - RCT Jan 2024 24 Jan, 2024
PMS reduced by 50,000 IU every two weeks - RCT Jan 2024 15 Jan, 2024
COVID fought by Vitamin D: OBSERVATIONS: YES, RCTs: NO - Dec 2023 15 Jan, 2024
Gestational Diabetes best fought by Vitamin D plus probiotics – RCT review Dec 2023 11 Jan, 2024
Vitamin D response: 800 IU: 20 ng, 3200 IU: 45 ng – RCT March 2012 06 Jan, 2024
Vitamin D loading dose of 30,000 IU twice a week is safe and effective – RCT July 2023 22 Dec, 2023
1.77 nmol response to 100 IU of Vitamin D (46 RCTs) – meta-analysis Sept 2023 16 Dec, 2023
Individualized – RCT Nov 2023 25 Nov, 2023
Autistics have half of the response to Vitamin D – RCT Oct 2018 08 Nov, 2023
Cancers reduced after 2 years of 2000 IU Vitamin D daily (2nd RCT) – RCT Aug 03 Nov, 2023
Vitamin D 100,000 IU loading dose and stem cell transplants – RCT Oct 2023 31 Oct, 2023
4,000 IU of daily Vitamin D during pregnancy is good (Mongolia this time) – RCT Oct 2023 24 Oct, 2023
5000 IU Vitamin D daily resulted in lower health care costs - RCT Oct 2023 21 Oct, 2023
Parkinson’s disease: Review of low-dose vitamin D RCTs found small benefit – Sept 2023 07 Oct, 2023
Vitamin D given daily, weekly, or monthly has similar response (116 RCTs) – meta-analysis Aug 2023 02 Oct, 2023
Gingivitis (inflammation of the gums) substantially reduced by Vitamin D – RCT July 2023 19 Sep, 2023
Muscles improved in women with 50,000 IU vitamin D weekly (8 weeks) plus daily Magnesium – RCT Sept 2020 16 Sep, 2023
Venous ulcers healed 4X faster with weekly 50,000 IU vitamin D – RCT Oct 2012 08 Sep, 2023
Chronic Periodontitis reduced by Vitamin D (60,000 IU weekly for 8 weeks) – RCT July 2023 01 Sep, 2023
Vitamin D3 fortified bread better than 1,000 IU supplement – RCT April 2016 01 Sep, 2023
Muscle pain in obese women reduced by aerobic exercise plus 50,000 IU Vitamin D - RCT May 2021 27 Aug, 2023
Bone fractures of children not reduced if given little vitamin D, no Calcium etc. – RCT May 2023 27 Aug, 2023
Senior Cognition not improved by 2,000 IU Vitamin D avg.- RCT Aug 2023 26 Aug, 2023
NAFLD in children nicely treated by combination of Vitamin D and Omega-3 – RCT Dec 2016 21 Aug, 2023
Investigation of segregated patient groups may be more effective than classical vitamin D RCTs - Carlberg July 2023 15 Aug, 2023
Breast Cancer survival: 44% with just 10,000 IU of vitamin D per week, 33% with placebo – RCT Dec 2023 13 Aug, 2023
TB again not prevented by a small amount of Vitamin D – RCT Aug 2023 10 Aug, 2023
Schizophrenia severity reduced somewhat by daily 2,000 IU of Vitamin D – RCT Aug 2023 07 Aug, 2023
Sleep greatly improved by 50,000 IU of vitamin D once every two weeks – RCT Sept 2018 07 Aug, 2023
Smoking does not decrease response to monthly Vitamin D – RCT July 2020 03 Aug, 2023
1 % weight loss delays brain aging by nearly nine months - RCT April 2023 28 Jul, 2023
Pain not reduced by 60,000 IU monthly vitamin D (need 50,000 IU weekly) – RCT Aug 2023 22 Jul, 2023
Vitamin K2-7 decreases arterial stiffness (cleans arteries) – RCT Feb 2015 20 Jul, 2023
Raynaud's pain decreased with 600,000 IU monthly vitamin D – RCT May 2012 17 Jul, 2023
Respiratory infections reduced by 63 percent with 4000 IU vitamin D daily - RCT Dec 2012 17 Jul, 2023
Gestational Diabetes reduced with 50,000 IU of vitamin D every 3 weeks and daily Calcium – RCT June 2014 17 Jul, 2023
50,000 IU of Vitamin D every 2 weeks reduced gestational diabetes – RCT Feb 2015 12 Jul, 2023
Afib in Finland reduced 30% by Vitamin D (3200 IU) – RCT June 2023 09 Jul, 2023
COVID in hospital stopped by Vitamin D Receptor activators (curcumin, quercetin) – RCT June 2023 25 Jun, 2023
Multiple Sclerosis treated equally by UVB and weekly 50,000 IU of Vitamin D – RCT July 2023 18 Jun, 2023
Vitamin D-disease associations vary with the type of study – RCT, Observational, MR - July 2022 03 Jun, 2023
Little second-hand smoke problem in children if mother had added Vitamin D while pregnant - RCT Feb 2023 25 May, 2023
Tuberculosis not prevented by a tiny amount of vitamin D (equiv to 1,400 IU daily) – RCT May 2023 22 May, 2023
TB not treated by vitamin D given for only 2 months – RCT Sept 2017 22 May, 2023
Chronic tonsillitis virtually eliminated in children by Vitamin D (50,000 IU weekly) – RCT May 2023 20 May, 2023
Infants getting an additional 800 IU of vitamin D for 2 years had 60% fewer psychiatric symptoms at age 7 – RCT May 2023 19 May, 2023
Response to infant 2,000 IU Vitamin D daily was in 194 ng, monthly dosing was 20% less – RCT May 2023 17 May, 2023
4X reduction in prediabetes progressing to T2D if more than 50 ng of vitamin D – RCT March 2023 01 May, 2023
200 IU of Vitamin D does not prevent preeclampsia – RCT Aug 2012 01 May, 2023
Multiple Sclerosis is again not fought by 5,000 IU vitamin D daily (need at least 10X more) – RCT May 2023 01 May, 2023
Resulting childhood Asthma cut in half if 4,400 IU Vitamin D (5 ways to improve it) - RCT April 2023 20 Apr, 2023
10,000 IU of Vitamin D is too much if you also take Calcium supplements – RCT Sept 2018 12 Apr, 2023
Bone mineral density improvement by Vitamin D plus fluoride is augmented by laser acupuncture – RCT March 2023 22 Mar, 2023
COVID 3X less likely if Xyilotol nasal spray 3X per day – RCT Dec 2022 24 Feb, 2023
Urinary Incontinence reduced by 50,000 IU of vitamin D weekly (details behind paywall) – RCT Feb 2023 24 Feb, 2023
Half as many problems if take Vitamin D (300,000 IU) before thyroidectomy – RCT Jan 2021 24 Feb, 2023
COVID recovery 1.6X faster after 200,000 IU of Vitamin D RCT – Feb 2023 22 Feb, 2023
Fracture 4X less likely following kidney transplant if high-dose Vitamin D (100,000 every 2 weeks) – RCT Jan 2023 25 Jan, 2023
Lupus: 60,000 IU Vitamin D monthly got to only 34 ng, not enough to help – RCT Jan 2023 04 Jan, 2023
After Colorectal Cancer Surgery the immune system was maintained by Vitamin D (8,000 IU daily) – RCT Jan 2023 03 Jan, 2023
Anxiety and Depression decreased in senior prediabetics with weekly 25,000 IU of Vitamin D – RCT Sept 2022 22 Dec, 2022
Hyperparathyroidism resulting from CKD eliminated by 8,000 IU of vitamin D daily for 12 weeks– RCT 2018 13 Dec, 2022
ADHD significantly treated by daily Magnesium plus weekly Vitamin D – RCT April 2021 30 Nov, 2022
Long-COVID fatigue reduced by Vitamin C and l-Arginine in one month– RCT Nov 2022 24 Nov, 2022
Dark-skinned infants got minimal vitamin D from 4 minutes sunbathing daily – RCT Nov 2022 16 Nov, 2022
Vitamin D is needed before most surgeries – many studies and RCTs 13 Nov, 2022
Half as much AFIB after bypass if 600,000 IU of vitamin D before surgery – RCT April 2022 13 Nov, 2022
Depression decreased by Vitamin D (12th study in VitaminDWiki) – RCT Nov 2022 12 Nov, 2022
Grip strength of children not improved by 800 IU Vitamin D daily (not nearly enough) – RCT Feb 2018 31 Oct, 2022
Colorectal Cancer – vitamin D did not help (too small of a response) – RCT Oct 2022 29 Oct, 2022
Influenza infection 5X less likely if got vitamin D – small RCT Feb 2022 23 Oct, 2022
Fewer children died of pneumonia after 100,000 IU Vitamin D injection – RCT March 2021 23 Oct, 2022
Omega-3 supplementation reduced preterm birth rate by 4X – RCT July 2020 21 Oct, 2022
Immune systems of overweight black women improved by monthly 60,000 IU Vitamin D – RCT Oct 2022 14 Oct, 2022
Diabetic inflammation synergistically decreased by Vitamin D and exercise – RCT June 2022 09 Oct, 2022
Ultra-low UV LED added to office desk lamp would add 7 ng to winter Vitamin D levels – RCT Oct 2022 04 Oct, 2022
Vitamin D2 again decreased vitamin D3 levels – RCT Nov 2012 02 Oct, 2022
COVID in hospital fought by Vitamin D (25,000 IU daily for 4 days, then 25K weekly) - RCT – July 2022 02 Oct, 2022
Vitamin D does not help when most are not deficient (cataract surgery in this case) – RCT Sept 2022 30 Sep, 2022
3,200 IU of daily not help much in population already having 30 ng of Vitamin D – RCT Jan 2022 27 Sep, 2022
Small Vitamin D doses for a short time never help (not improve vaccination in this case) – RCT Sept 2022 24 Sep, 2022
The challenges of a Vitamin D RCT – too many already taking it, etc. – Martineau Sept 2022 13 Sep, 2022
One day of 12,000 IU of sublingual Vitamin D raised levels by 8.6 ng in 5 days – RCT July 2022 11 Sep, 2022
Risk of COVID not reduced by 3,200 IU of vitamin D during 6 months (no surprise) – RCT March 2022 09 Sep, 2022

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

This list is automatically updated

Items found: 674
Title Modified
Bladder cancer in muscles 2.7 times more-likely if vitamin D less than 20 ng -meta-analysis May 2024 23 May, 2024
Women have conception problems when vitamin D levels are less than 24 ng – meta-analysis May 2024 23 May, 2024
Adults with eating disorders consumed less than 400 IU of vitamin D – meta-analysis May 2024 22 May, 2024
COVID and Vitamin D: 2X more likely to die if low, 2X more likely to survive if supplement – umbrella meta-analysis April 2024 24 Apr, 2024
100,000 IU of Vitamin D monthly (27 ng) is not enough to reduce fractures and falls – meta-analysis April 2024 15 Apr, 2024
Non-Hodgkin Lymphoma 20 percent more likely if low UV – meta-analysis April 2019 01 Apr, 2024
COVID fought by Vitamin D: 2.3X less likely to die of COVID if supplemented, 1.9 X less likely to become infected – meta-analysis March 2024 31 Mar, 2024
COVID fought by Vitamin D: 2.3X less likely to die of COVID if supplemented, 1.9 X less likely to become infected – meta-analysis March 2024 31 Mar, 2024
Insulin resistance in overweight youths treated Vitamin D (such as 50K IU weekly) – meta-analysis April 2024 20 Mar, 2024
Celiac Disease 2.2X higher risk if low vitamin D, Gluten Free Diet slightly increases D – meta-analysis March 2024 17 Mar, 2024
1.5X more likely to die of Prostate Cancer if low vitamin D when initially diagnosed – meta-analysis March 2024 13 Mar, 2024
Vitamin D reduces: pre-eclampia 1.6 X, postpartum dep. 3.6 X, autism 1.5X etc. - meta-analysis March 2024 11 Mar, 2024
Vitamin D deficiency increases risk of Dementia by 1.4 X and Alzheimer’s by 1.5 X – Meta-analysis March 2024 11 Mar, 2024
Vitamin D supplementation decreased the risk of preeclampsia by 39% – meta-analysis Feb 2024 07 Mar, 2024
Muscle strength improved with Calfidediol (a form of vitamin D) - meta-analysis May 2022 29 Feb, 2024
Muscle Inflammation (idiopathic inflammatory myopathy) 3.2 X more likely if low Vitamin D – meta-analysis Feb 2024 29 Feb, 2024
5 X less COVID infection of health care workers who took lots of vitamin D – meta-analysis Feb 2024 28 Feb, 2024
Overactive bladder 4.4 X more likely if low vitamin D – meta-analysis Feb 2024 21 Feb, 2024
Little Vitamin D does not reduce risk of CVD – RCT meta-analysis Dec 2023 08 Feb, 2024
Early Childhood Caries 1.4 times more likely if 20-30 ng of Vitamin D – meta-analysis Jan 2024 03 Feb, 2024
Vitamin D is the best Vitamin to prevent a stroke - meta-analysis Jan 2024 31 Jan, 2024
Rickets risk reduced by mre than 11 ng of Vitamin D - meta-analysis Jan 2024 29 Jan, 2024
Cystic Fibrosis patients have low vitamin D (need different dosing) – meta-analysis Jan 2024 18 Jan, 2024
Bone loss reduced in women by vitamin D supplementation - Meta-analysis Jan 2024 15 Jan, 2024
Multiple Sclerosis treatment not helped by small doses of vitamin D (yet again) – meta-analysis Jan 2024 12 Jan, 2024
Vitamin D has successfully fortified milk products, bread, orange juice, etc. – meta-analysis Dec 2023 24 Dec, 2023
Omega-3 helped periodontal treatment (details behind paywall) - meta-analysis Dec 2023 21 Dec, 2023
Neuromyelitis optica spectrum disorder (a rare nerve inflammation) 24X more likely to be vitamin D deficient – meta-analysis Dec 2023 20 Dec, 2023
1.77 nmol response to 100 IU of Vitamin D (46 RCTs) – meta-analysis Sept 2023 16 Dec, 2023
Vitamin D3 is 40% better than D2 if normal weight, no difference if overweight –Meta-analysis October 2023 16 Dec, 2023
IBS - Vitamin D was the only micronutrient under DRV - meta-analysis Oct 2023 16 Dec, 2023
Morbid Obesity is associated with low Vitamin D around the globe - meta-analysis Dec 2023 08 Dec, 2023
An eye infection (non-infectious uveitis) 2X more likely if low vitamin D a year before – Meta-analysis Dec 2023 07 Dec, 2023
Small doses for a short time rarely help (Omega-3, post surgery this time) – meta-analysis Nov 2023 27 Nov, 2023
Chronic Kidney not helped much by little vitamin D (none got to a 75 nmol level) – meta-analysis Sept 2023 25 Nov, 2023
Bariatric Surgery in Adolescents: 41% vitamin D deficient - meta-analysis Nov 2023 22 Nov, 2023
Depression in seniors greatly reduced by Vitamin D (e.g. 50,000 IU) – meta-analysis June 2023 06 Nov, 2023
Dental caries 1.22 X more likely if Vitamin D Deficient – meta-analysis Oct 2023 20 Oct, 2023
Infections in children reduced a bit by 2,000 IU of vitamin D - meta-analysis July 2023 08 Oct, 2023
Vitamin D given daily, weekly, or monthly has similar response (116 RCTs) – meta-analysis Aug 2023 02 Oct, 2023
Sepsis 2X-3X more likely if poor Vitamin D Receptor – meta-analysis Sept 2023 27 Sep, 2023
High Selenium intake cuts risk of Osteoporosis in half - meta-analysis - July 2023 25 Sep, 2023
Pancreatic Cancer survival 2.3 X more likely if good level of Vitamin D – meta-analysis Sept 2023 15 Sep, 2023
Thyroid Cancer 1.4 X higher risk if low vitamin D– meta-analysis Feb 2018 29 Aug, 2023
Myocarditis, Pericarditis 2X more likely if had COVID vaccination in previous 30 days - meta-analysis June 2023 25 Aug, 2023
Indoor athletes have 4.5 ng less Vitamin D (Asia in this case) – meta-analysis April 2023 24 Aug, 2023
NAFLD weakly associated with low vitamin D – meta-analysis 2013 21 Aug, 2023
Knee Osteoarthritis treated by vitamin D if use more than 2,000 IU daily or non-daily high dose – meta-analysis Aug 2023 21 Aug, 2023
Type 2 Diabetes treated by Vitamin D (often 50,000 IU weekly) – meta-analysis July 2023 21 Aug, 2023
IBS reduced by 50,000 IU of Vitamin D (weekly or bi-weekly) – Meta-analysis July 2023 16 Aug, 2023
Osteoporotic bone fractures predicted by 12 risk factors - taking little Vitamin D is one of them – meta-analysis Aug 2023 06 Aug, 2023
Vitamin D response independent of dosing interval – meta-analysis July 2023 03 Aug, 2023
Psoriasis not treated by monthly Vitamin D -meta-analysis July 2023 02 Aug, 2023
Death of women from cancer 24% less likely if 20 ng more vitamin D – meta-analysis Sept 2013 31 Jul, 2023
ICU patients 30 % less likely to die if have enough vitamin D – meta-analysis Nov 2016 31 Jul, 2023
Prostate Cancer Survivors are 2.3 X more likely to have high levels of Vitamin D – meta-analysis Sept 2023 30 Jul, 2023
Asthma occurrence rate reduced 3X by Vitamin D – 8 study meta-analysis - Aug 2021 24 Jul, 2023
Alzheimer’s 1.6X more likely if vitamin D is less than 25 ng – meta-analysis July 2023 20 Jul, 2023
Rheumatoid Arthritis pain is reduced by Vitamin D, high doses also reduced inflammation (CRP) – Meta-analysis July 2023 13 Jul, 2023
77% of Asians have less than 30 ng of Vitamin D – meta-analysis June 2023 03 Jul, 2023
T1 Diabetes increased by 27% by second year of COVID – meta-analysis June 2023 01 Jul, 2023
Yet another reason to take Vitamin D while pregnant – fight COVID - meta-analysis May 2023 10 Jun, 2023
Low vitamin D while pregnant – a health emergency (Indonesia in this case) – meta-analysis May 2023 06 Jun, 2023
Malaria death 3X less likely in mice given vitamin D (looks good for humans too) – meta-analysis June 2023 06 Jun, 2023
Better Cognition needs at least 25 ng of Vitamin D (38 studies)– meta-analysis June 2023 03 Jun, 2023
Inflammation associated with Cancer reduced by Vitamin D – meta-analysis May 2023 28 May, 2023
Afib 40% less likely after heart by-pass if have enough Vitamin D – meta-analysis May 2023 27 May, 2023
16 factors increase the risk of early-onset colorectal cancer, only vitamin D decreases the risk – meta-analysis May 2023 22 May, 2023
Melanoma is 1.4X more-likely if low Vitamin D – meta-analysis May 2023 18 May, 2023
Breast Cancer not prevented by vitamin D when use small doses or for just a short time – Meta-analysis April 2023 11 May, 2023
Prostate Cancer death 40 percent less likely if 40 ng level of vitamin D – Meta-analysis Oct 2018 30 Apr, 2023
Vitamin D during pregnancy increased child’s bone mineral density – meta-analysis April 2023 27 Apr, 2023
COVID death 1.5 X less likely if high vitamin D, emergency D (50K to 100K) is great – meta-analysis March 2023 08 Apr, 2023
Backpain relief – low evidence that drugs or NSAIDS help – Meta-analysis March 2023 29 Mar, 2023
Breast Cancer risk - meta-analysis of 50 studies - Dec 2019 25 Mar, 2023
Ovarian Cancer 37 percent less likely if high vitamin D – meta-analysis March 2023 20 Mar, 2023
Vitamin D Deficiency in South America - meta-analysis March 2023 09 Mar, 2023
Fractures 1.5 X more-likely if low serum Magnesium – meta-analysis March 2023 08 Mar, 2023
Childhood BMI decreased when add a little Vitamin D – meta-analysis March 2023 03 Mar, 2023
Preeclampsia reduced by 33 percent if high vitamin D – meta-analysis Feb 2023 23 Feb, 2023
Sjögren's Disease ( dry eye, dry mouth, etc.) associated with low vitamin D - Meta-analysis Feb 2023 11 Feb, 2023
Recurrent Stroke 5X more-likely if very low vitamin D - meta-analysis Feb 2023 11 Feb, 2023
Infertile patients 1.7X more-likely to become pregnant if take Vitamin D – meta-analysis Feb 2023 06 Feb, 2023
Depression is especially reduced by large intermittent doses of vitamin D – meta-analysis – April 2023 01 Feb, 2023
COVID ICU 3X less-likely if take any amount and type of Vitamin D – meta-analysis Jan 2023 22 Jan, 2023
Childhood and youth obesity – more than 4,000 IU vitamin D average daily would help – meta-analysis Jan 2023 12 Jan, 2023
Colorectal Cancer 10 percent more likely if poor Vitamin D Receptor – meta-analysis Jan 2023 08 Jan, 2023
Depression reduced if take more than 5,000 IU of vitamin D daily – umbrella meta-analysis – Jan 2023 06 Jan, 2023
Risk of heart failure increased 1.4X if low vitamin D – meta-analysis Dec 2022 28 Dec, 2022
Hip fractures greatly reduced by sunshine, vitamin D, and vitamin K – meta-analysis Sept 2012 23 Dec, 2022
COVID and Vitamin D: any amount of D, at any time, for any duration reduced ICU - meta-analysis Dec 2022 14 Dec, 2022
ICU Vitamin D supplementation not help (study ignored level achieved) – meta-analysis 2022 07 Dec, 2022
Incidence Autism and ADHD reduced 18 percent per 10 ng of Vitamin D during pregnancy – meta-analysis Jan 2022 06 Dec, 2022
Low vitamin D in Malaysia (85 percent less than 30 ng) – meta-analysis Nov 2022 05 Dec, 2022
Vitamin D, by itself, does not decrease BMI – meta-analysis March 2018 04 Dec, 2022
Some measures of metabolic syndrome are decreased by Vitamin D (may need Mg) – meta-analysis Oct 2022 24 Oct, 2022
Small doses of Vitamin D do not reduce childhood breathing allergies – meta-analysis Oct 2022 18 Oct, 2022
Best psoriasis treatment was combo of Vitamin D, UVA, and Calcium – meta-analysis Jan 2022 08 Oct, 2022
Inflammation markers reduced by Vitamin D - umbrella meta-analysis Oct 2022 08 Oct, 2022
Many ear problems are strongly associated with low vitamin D – meta-analysis Feb 2022 08 Oct, 2022

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