Toggle Health Problems and D

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: 924
Title Modified
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
200 IU of Vitamin D does not prevent pre-eclampsia – RCT Aug 2012 23 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
Cod liver oil does not prevent Respiratory Infections (no surprise, only 400 IU of vitamin D) RCT – Sept 2022 08 Sep, 2022
Overweight needed more EPA (4 grams) to fight depression – RCT Aug 2022 30 Aug, 2022
1 pill a day is better than multiple (probably 1 per 2 weeks would be even better) - RCT Aug 2022 26 Aug, 2022
Half of infants had less than 20 ng of Vitamin D with 800 IU (need more) – RCT Sept 2022 25 Aug, 2022
60,000 IU of vitamin D monthly is healthy and safe – RCT Aug 2022 19 Aug, 2022
Early COVID treatments rarely work 7 days after symptoms, this trial gave Vitamin D on 7th day – RCT May 2022 26 Jul, 2022
Unethical to restrict Vitamin D to half of the asthmatic children in RCT – June 2018 25 Jul, 2022
COVID children helped by Vitamin D, trial terminated: unethical to not give Vitamin D to all: – RCT July 2022 25 Jul, 2022
Faster growth in infants getting 1200 IU of Vitamin D – RCT July 2022 16 Jul, 2022
Birth rates doubled with Vitamin D - 300,000 for infertile men – RCT Nov 2017 04 Jul, 2022
1289 genes changed with higher doses of Vitamin D - RCT Dec 2019 03 Jul, 2022
Hypertension (both systolic and diastolic) reduced with 2,000 IU of vitamin D – RCT June 2014 23 Jun, 2022
Breastfed Infants need more than an daily average of 800 IU of Vitamin D – RCT June 2022 21 Jun, 2022
Magnesium and Vitamin D - pre-colon cancer – RCT Dec 2018 13 Jun, 2022
Hypertension reduced by Magnesium plus 3,000 IU of vitamin D for 12 weeks – RCT July 2022 12 Jun, 2022
4X less likely to get COVID following 4,000 IU daily for a month – RCT April 2022 12 Jun, 2022
50,000 IU of Vitamin D weekly for 6 months after cardiac failure helps – RCT May 2022 11 Jun, 2022
Vitamin D treatment of Chronic Kidney Disease: monthly better than daily – RCT May 2022 10 Jun, 2022
Nutritional RCTs: types and concerns – June 2022 09 Jun, 2022
COVID hospital deaths reduced 2X by 8 days of UVB – pilot RCT May 2022 05 Jun, 2022
400,000 IU of vitamin D 3 days after COVID symptoms reduced 14 day mortality by 3X – Annweiler RCT May 2022 02 Jun, 2022
Urate (kidney stones, gout) reduced by Calcium – RCT June 2022 29 May, 2022
Patients hospitalized with COVID not helped by 500,000 IU of Vitamin D – RCT – May 2022 28 May, 2022
Loading dose of Vitamin D for patients hospitalized with COVID (140,000 IU) – RCT completed 2021 22 May, 2022
Short-term response to 1,000 IU of Vitamin D tripled in obese when Magnesium was added – RCT April 2022 17 May, 2022
2.5 X reduced risk of cancer in 70 year-olds by a small amount of Vitamin D, Omega-3 and exercise – RCT April 2022 25 Apr, 2022
HIV not helped by 2,000 IU of Vitamin D (no surprise) – RCT April 2022 25 Apr, 2022
21 fewer days in hospital with ARDS (COVID) if 10,000 IU of Vitamin D daily after enter hospital – RCT April, 2022 18 Apr, 2022
Pregnant women in HIV therapy adding Vitamin D had 3X fewer deaths - RCT April 2022 16 Apr, 2022
Breast Cancer not prevented by 1,000 IU of Vitamin D (no surprise) – RCT Aug 2021 14 Apr, 2022
Risk of Frailty reduced 4X by 4,000 IU of vitamin D – RCT April 2022 10 Apr, 2022
Atrial Fibrillation risk reduced by 0.84 in those raising Vitamin D levels above 30 ng – RCT April 2022 04 Apr, 2022
Influenza vaccine antibodies not change with Vitamin D – 21 ng or 44 ng – RCT Feb 2019 22 Mar, 2022
Response to Vitamin D varies with genes (3,000 IU, weight loss in this RCT) – March 2022 22 Mar, 2022
Handgrip strength increased 9 percent in college athletes with 8 weeks of Omega-3 – RCT Feb 2022 18 Mar, 2022
Monthly vitamin D helped hearts with low vitamin D a bit (need it more frequently) – RCT March 2022 11 Mar, 2022
Psoriasis reduced for those getting Vitamin D levels above 50 ng – RCT Feb 2018 11 Mar, 2022
10,000 IU of Vitamin D for 3 years found to help bone by two measurement methods – RCT Feb 2022 28 Feb, 2022
Teeth alignment completed faster if good levels of vitamin D – RCT Feb 2022 24 Feb, 2022
Tuberculosis treatment helped a bit by a bit of Vitamin D - RCT Feb 2022 24 Feb, 2022
HIIT reduced appetite of sedentary overweight men, adding a bit of vitamin D helped a bit – RCT Feb 2022 24 Feb, 2022
Preterm birth rate of pregnant smokers cut in half if take Omega-3 – RCT May 2017 20 Feb, 2022
100,000 IU of Vitamin D3 monthly for 4 months to diabetics (D2 bombed) – RCT Dec 2019 13 Feb, 2022
4,000 IU of Vitamin D is too small a dose to help Obese - RCT Feb 2022 09 Feb, 2022
Group achieving 30 ng (vs 26 ng) were 2X less likely to get COVID symptoms - RCT Jan 2022 31 Jan, 2022
In vitro fertilization NOT helped by 600,000 IU of vitamin D – RCT Sept 2021 30 Jan, 2022
Uterine Fibroids cut in half in group taking 1,000 IU of Vitamin D - RCT Jan 2022 30 Jan, 2022
Nutritional supplementation during COVID hospitalization helped - RCT - Jan 2022 30 Jan, 2022
NAFLD not reduced by 1680 IU of vitamin D plus Omega-3 (no surprise) – RCT Jan 2022 24 Jan, 2022
800 IU vitamin D resulted in 20 ng, 3200 IU resulted in 45 ng – RCT March 2012 19 Jan, 2022
Tested positive for COVID, taking probiotics stopped symptoms 5 days sooner - RCT Jan 2022 18 Jan, 2022
Monthly 120,000 IU of Vitamin D while breastfeeding was good – RCT Jan 2022 11 Jan, 2022
Resistance training can be aided by Vitamin D, 50,000 IU monthly is not often enough – RCT Dec 2021 11 Jan, 2022
Mortality reduction needs more than monthly 60,000 IU of Vitamin D - RCT Jan 2022 11 Jan, 2022
Off Topic: EDTA similar reduction in heart attack as Vitamin C, aspirin and Mg – RCT March 2013 04 Jan, 2022
Several smoking problems treated by Vitamin D (bi-weekly, 50,000 IU) - RCT Dec 2021 29 Dec, 2021
Omega-3 did not prevent depression (they failed to reduce Omega-6, which blocks Omega-3) – RCT Dec 2021 22 Dec, 2021
Sleep not helped when half got to 35 ng of Vitamin D (may need 60 ng) – RCT Dec 2021 10 Dec, 2021
Less cognitive decline in older blacks getting 2,000 IU of vitamin D daily for years (VITAL, etc. post analysis) – RCT Dec 2021 02 Dec, 2021
Nanoemulsion Vitamin D faster and better (paywall) – RCT Dec 2021 02 Dec, 2021
Most Diabetics getting 40,000 IU of vitamin D weekly did not get to 30 ng (needed gut-friendly form) - RCT June 2020 30 Nov, 2021
Sunburning reduced by 200,000 IU of Vitamin D – RCT April 2017 28 Nov, 2021
Nursing home vaccinated against Influenza, 800 IU of vitamin D daily cut infection rate in half – small RCT Oct 2021 04 Nov, 2021
Low vitamin D while pregnant increases risk of autism (a 2016 RCT reduced risk by adding Vitamin D) – Dec 2021 01 Nov, 2021
Sleeps disorders nicely treated by Vitamin D (50,000 IU twice a month) – RCT May 2017 27 Oct, 2021
Additional Vitamin D not help – infants previously had 35 ng of vitamin D – RCT Sept 2021 18 Oct, 2021
Stoss (loading) dose of vitamin D resulted in bigger response at 30 days (again) – RCT April 2021 14 Oct, 2021

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

This list is automatically updated

Items found: 610
Title Modified
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 Vitamin D (Note: less than half of the studies used more than 600 IU) – 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
Cancer incidence and mortality not changed by small Vitamin D doses – meta-analysis Oct 2022 08 Nov, 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
Thyroid Cancer 1.4 X higher risk if low vitamin D– meta-analysis Feb 2018 12 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
Maternal pregnancy problems if Vitamin D is less than 40 ng – meta-analysis Oct 2022 05 Oct, 2022
Vitamin D reduces BMI and waist circumference – umbrella meta-analysis – Sept 2022 27 Sep, 2022
Blood pressure reduced if take more than 4.5 grams of Omega-3 daily– umbrella meta-analysis Aug 2022 23 Sep, 2022
IBD treated in children by Vitamin D, especially if use more than 2,000 IU daily for 12 weeks – meta-analysis – Sept 2022 14 Sep, 2022
Worse COVID during 3Q pregnancy if 2.5 ng lower Vitamin D – meta-analysis Sept 2022 14 Sep, 2022
Glycemic control of type 2 diabetes – only Vitamin D had high quality studies – meta-analysis Sept 2022 14 Sep, 2022
Colorectal cancer 14 percent less likely if 10 ng more Vitamin D – 22nd meta-analysis – Sept 2022 13 Sep, 2022
Ignoring dose size etc, meta-analysis concludes that Vitamin D does not help (stroke risk in this case) – Aug 2022 05 Sep, 2022
CAD patients with low vitamin D were 1.6 X more likely to die – 27th meta-analysis Aug 2022 29 Aug, 2022
Cardiovascular death 1.5X more likely if less than 20 ng of Vitamin D – 22nd meta-analysis Nov 2019 29 Aug, 2022
Even after a Cancer diagnosis Vitamin D improves survival – meta-analysis Aug 2022 19 Aug, 2022
Depression reduced if use more than 2,800 IU of vitamin D – meta-analysis Aug 2022 18 Aug, 2022
Ulcerative Colitis treated 4X better when Vitamin D was added – Meta-Analysis – July 2022 01 Aug, 2022
Vitamin D fortification of food provides no bone benefit (typically a tiny amount of D) - meta-analysis July 2022 25 Jul, 2022
Shift work associated with lower Vitamin D in 12 of 13 studies – meta-analysis July 2022 22 Jul, 2022
meta-analysis admin test with 55 associations 19 Jul, 2022
Gestational diabetes risk reduced 1.5X by Vitamin D – meta-analysis March 2021 14 Jul, 2022
Asthma treated by Vitamin D - 13th Meta-analysis – July 2022 10 Jul, 2022
IBS helped by vitamin D (virtually ignoring dose size, type and duration) – meta-analysis June 2022 09 Jul, 2022
Severe COVID 2.6 X less likely if supplement with Vitamin D – 26th meta-analysis - July 2022 07 Jul, 2022
Asthma has been treated by 40 ng of vitamin D, but not this time – meta-analysis June 2022 05 Jul, 2022
2X increase risk of Asthma if a particular Vitamin D Receptor mutation – meta-analysis Feb 2022 04 Jul, 2022
Cancer mortality reduced 40 pcnt by 2000 IU Vitamin D daily if normal weight – Meta-analysis June 2022 03 Jul, 2022
Magnesium reduces inflammation (CRP) and increases nitric oxide – meta-analysis Feb 2022 27 Jun, 2022
Vitamin D and the Critically Ill - meta-analysis – April 2022 09 Jun, 2022
Miscarriage 1.6 X more likely if low vitamin D – meta-analysis May 2022 09 Jun, 2022
Recurrent Miscarriage 4X more likely if low vitamin D – meta-analysis June 2022 07 Jun, 2022
Magnesium helps bones a bit – meta-analysis Jan 2022 05 Jun, 2022
More hip fractures if low vitamin D (2.1X in case-controlled studies) – meta-analysis May 2022 01 Jun, 2022
Vitamin D reduces preeclampsia, gestational diabetes and hypertension - 38th meta-analysis Dec 2021 31 May, 2022
Omega-3 increases Vitamin D levels – Meta-analysis May 2022 20 May, 2022
Omega-3 improves pregnancies – Meta-analysis May 2022 12 May, 2022
COVID-19 treated by Vitamin D (reduce ICU by 3X) - 22nd meta-analysis - Dec 29, 2021 01 May, 2022
Magnesium fights diabetes (yet again)– meta-analysis Nov 2021 20 Apr, 2022
Need at least 6,000 IU of Vitamin D daily during pregnancy and breastfeeding (Wagner) – meta-analysis March 2022 15 Apr, 2022
High-dose Vitamin D safe for children (10,000 IU daily, 600,000 IU bolus) – meta-analysis April 2022 15 Apr, 2022
Alzheimer’s patients have less Magnesium – meta-analysis Jan 2022 08 Apr, 2022
BPH increased risk if poor Vitamin D Receptor in Asians – meta-analysis April 2022 06 Apr, 2022
Low Vitamin D associated with preeclampsia - meta-analysis Feb 2022 24 Mar, 2022
Pregnancy problems (LBW, PTB, SGA) associated with low vitamin D, 42nd meta-analysis – March 2022 24 Mar, 2022
COVID-19 mortality extrapolates to zero at 50 ng of vitamin D – 18th Meta-analysis Sept 2021 18 Mar, 2022
COPD treated by Vitamin D – meta-analysis March 2022 12 Mar, 2022
Delirium or cognitive problems after surgery 1.5X more likely if low vitamin D –meta-analysis Aug 2022 04 Mar, 2022
Arterial Stiffness and Vitamins – only Vitamin D was found to help – meta-analysis Feb 2022 27 Feb, 2022
Small doses of vitamin D do not reduce risk of Acute Respiratory Infection - meta-analysis Feb 2022 15 Feb, 2022
Small vitamin D doses while pregnant do not decrease infant allergies – meta-analysis Feb 2022 03 Feb, 2022
Latent Tuberculosis 44 percent less likely if Vitamin D more than 30 ng - 14th meta-analysis Jan 2022 01 Feb, 2022
COVID test positive is about half as likely if have Vitamin D – 24th meta-analysis - Jan 2022 01 Feb, 2022
White Matter Hyperintensities (brain) 1.8X more likely if 10 ng less vitamin D - meta-analysis Jan 2022 31 Jan, 2022
Small amounts of Vitamin D reduce Influenza risk by 22 percent (loading dose is far better) – meta-analysis Jan 2022 25 Jan, 2022
Poor Vitamin D receptor reduced vitamin D levels -meta-analysis Jan 2022 23 Jan, 2022
Vitamin D fights COVID (54 studies of 1,400,000 people) – 23rd meta-analysis - Dec 2021 10 Jan, 2022
Anemia 1.6 X more likely during pregnancy if low Vitamin D – meta-analysis Dec 2021 02 Jan, 2022
COVID-19 death increased 2X if low Vitamin D (less than 10 to less than 30 ng) – 21st meta-analysis Dec 2021 14 Dec, 2021
Pregnancies helped by Vitamin D (insulin and birth weight in this case) – meta-analysis Oct 2019 05 Dec, 2021
Vitamin D loading doses quickly and safely raise levels – meta-analysis Dec 2021 03 Dec, 2021
3.3 X more likely to die if infected with SARS-Cov-2 plus a second pathogen – meta-analysis May 2021 17 Nov, 2021
COVID-19 risk reduced by vitamin D supplementation – umbrella review of 7 meta-analysis – Oct 2021 06 Nov, 2021
Need at least 6,000 IU daily while breastfeeding to eliminate Vitamin D deficiency – meta-analysis Oct 2021 01 Nov, 2021
Colorectal cancer 40 percent less likely if 1000 IU more Vitamin D – 21st meta-analysis – Oct 2021 29 Oct, 2021
Those with TB were 3.2 X more likely to have low vitamin D – 13th meta-analysis Sept 2021 20 Oct, 2021
COVID-19 treated by Vitamin D (example: ICU reduced by 5X) – 20th meta-analysis Oct 13, 2021 19 Oct, 2021
Severe COVID-19 2.5 X more likely if low vitamin D (23 studies) – 19th meta-analysis Oct 2021 19 Oct, 2021
Recurrrent Cardiovascular deaths cut in half if 10 ng more Vitamin D – meta-analysis Sept 2021 18 Oct, 2021
Viral respiratory infections reduced by both Vitamin D and Zinc – meta-analysis -Oct 2021 11 Oct, 2021
Two thirds of South Asians have low Vitamin D (less than 20 ng) – meta-analysis Oct 2021 11 Oct, 2021
Low Vitamin D is associated with dying sooner (70 studies) – meta-analysis Jan 2019 07 Oct, 2021
Severe COVID-19 5X more likely if low vitamin D (23 studies) – 16th meta-analysis July 2021 05 Oct, 2021
COVID-19 death 1.6 X more likely if low vitamin D (24 studies) – 17th meta-analysis Aug 2021 05 Oct, 2021
Enveloped virus infection (RSV, coronavirus, HIV, etc.) 1.5X more likely if poor Vitamin D Receptor – meta-analysis Dec 2018 02 Oct, 2021
Dialysis patients 23 percent more likely to live if had just 10 ng more Vitamin D – meta-analysis Feb 2018 29 Sep, 2021
Is low Vitamin D just a marker of disease - March 2023        
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