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.
 Download the PDF from VitaminDWiki

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.
 Download the PDF from VitaminDWiki

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

Loading Dose

Pregnancy

Children

Diabetes

Virus

Obesity

Multiple Sclerosis

Autoimmune

Better than Daily

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

This list is automatically updated

Items found: 1016
Title Modified
2,000 IU of vitamin D during pregnancy got infants to just above 12 ng – RCT July 2015 21 Oct, 2015
Congestive heart failure in infants virtually cured by 1000 IU of vitamin D – RCT Feb 2012 20 Oct, 2015
Colon Cancer proven again to not be treated by just 1000 IU of vitamin D – RCT Oct 2015 20 Oct, 2015
5,000 IU Vitamin D was not enough to reduce preeclampsia but did help future infant – RCT April 2014 15 Oct, 2015
Colds not decreased if people already vitamin D sufficient – RCT Oct 2012 13 Oct, 2015
Respiratory diseases helped by vitamin D if initially have low level – RCT review Jan 2015 13 Oct, 2015
MRI (8 weeks) cut vitamin D levels of rats in half - RCT July 2015 04 Oct, 2015
MRI (perhaps 400 hours) cut vitamin D levels of rats in half - RCT July 2015 04 Oct, 2015
Chron’s disease helped when vitamin D level raised above 30 ng – RCT Feb 2015 03 Oct, 2015
Gestational diabetes reduced by just two 50,000 IU doses of vitamin D – RCT Nov 2014 02 Oct, 2015
Hypertension reduction sometimes needs more than 4,000 IU of vitamin D for 6 months – RCT Oct 2014 22 Sep, 2015
Post menopausal vaginal dryness treated with vitamin D vaginal suppositories – RCT March 2015 16 Sep, 2015
Monthly 100,000 IU vitamin D supplementation got virtually all vitamin D deficient subjects above 20 ng – RCT April 2014 15 Sep, 2015
Vitamin D given once every two months does not help – proven again – RCT Sept 2015 15 Sep, 2015
Rate of injuries from falls cut in half by just 800 IU of vitamin D and exercise – RCT May 2015 13 Sep, 2015
2000 IU of vitamin D reduced fatigue of advanced cancer – RCT May 2012 03 Sep, 2015
Hives treatment augmented by 60,000 IU Vitamin D weekly – RCT June 2015 22 Aug, 2015
2X fewer Senior falls in group getting 100,000 IU vitamin D monthly via Meals-on-Wheels – RCT Aug 2015 18 Aug, 2015
39% fewer falls with 2000 IU than 800 IU – RCT June 2010 17 Aug, 2015
Schizophrenia relapses reduced 3X by Omega-3 – RCT Mar 2015 17 Aug, 2015
Response to 1000 IU of vitamin D varies by about 4 percent due to gene variants – RCT July 2014 09 Aug, 2015
Will knee osteoarthritis be prevented with 1700 IU of vitamin D – proposed RCT 08 Aug, 2015
Crohn's disease treated by Vitamin D - RCT June 2015 07 Aug, 2015
Prediabetes reduced after restoring Magnesium levels – RCT April 2015 02 Aug, 2015
Volleyball players jump higher with Magnesium - RCT 2014 27 Jul, 2015
Vitamin D2 from cooked mushroom added virtually no vitamin D to bloodstream - RCT July 2015 25 Jul, 2015
Pain not reduced by vitamin D (only used 1,000 IU) - RCT Dec 2014 16 Jul, 2015
Cognitively impaired brain atrophy was slowed 40 percent by Omega-3 and B vitamins – RCT July 2015 14 Jul, 2015
Diabetes RCT we expect to fail just 50,000 IU monthly - July 2014 12 Jul, 2015
Monthly vitamin D (120,000 IU) got most overweight African Americans about 35 ng – RCT July 2015 05 Jul, 2015
1000 IU vitamin D not enough in winter to restore levels in children - RCT June 2015 24 Jun, 2015
No multiple sclerosis relapses during pregnancy if 50,000 IU of Vitamin D weekly – RCT April 2015 21 Jun, 2015
Near the end of pregnancy 50,000 IU vitamin D weekly was great – RCT April 2013 08 Jun, 2015
Postoperative adhesions reduced in rats supplemented with vitamin D – RCT May 2015 04 Jun, 2015
COPD reduced by vitamin D taken once every 60 days – RCT Dec 2014 03 Jun, 2015
CYP2R1 gene probably responsible for low vitamin D response – RCT April 2014 02 Jun, 2015
400 IU Vitamin D did not affect menopause (400 IU affects virtually nothing) - RCT May 2015 01 Jun, 2015
500,000 IU of vitamin D reduced time in hospital after lung failure – RCT 2015 27 May, 2015
Breast Cancer medicine pain reduced with 4300 IU vitamin D – RCT June 2012 24 May, 2015
Reduced depression with single 300,000 IU injection of vitamin D – RCT June 2013 22 May, 2015
If you must take statins and want to avoid hardening of arteries, take vitamin K2 – RCT May 2015 22 May, 2015
Diabetes decreased with 300 mg of Mg (Mg Sulfate) – RCT July 2014 18 May, 2015
Off topic: Large dose of Vitamin A increased allergic reaction in girls by 1.8X – RCT May 2015 02 May, 2015
Atopic Dermatitis (Eczema) in Mongolian children reduced with 1,000 IU of vitamin D – RCT Oct 2014 02 May, 2015
Age-related cognitive decline in rats mitigated by Vitamin D intervention – RCT Oct 2012 01 May, 2015
Respiratory infections (RTI) cut in half by 20,000 IU weekly vitamin D if initially deficient – RCT March 2015 18 Apr, 2015
Breast Cancer is prevented by vitamin D – but more RCT are needed to understand why – April 2015 15 Apr, 2015
Asthma not reduced by taking vitamin D every 60 days (no surprise) – RCT Feb 2015 13 Apr, 2015
Tuberculosis not treated by 7,000 IU Vitamin D daily average for 6 weeks – RCT April 2015 13 Apr, 2015
Probability of getting TB reduced 60 percent with just 800 IU of vitamin D – RCT Aug 2012 13 Apr, 2015
Hemodialysis not helped by weekly vitamin D2 – RCT April 2015 08 Apr, 2015
Prostate cancer reduced when 4000 IU vitamin D was added– Hollis RCT April 2015 02 Apr, 2015
Peripheral Neuropathy in type II Diabetes reduced a bit by 50,000 IU weekly of vitamin D – RCT Feb 2015 28 Mar, 2015
Following primary hyperparathyroidism surgery 1600 IU vitamin D was not enough to help - RCT Feb 2015 25 Mar, 2015
Lupus not treated by monthly 50,000 IU vitamin D (no surprise) – RCT April 2015 23 Mar, 2015
Heart failure markers reduced by 400 IU of vitamin D and Calcium (surprise) – RCT Jan 2015 18 Mar, 2015
Death due to cystic fibrosis reduced about 4X due to 250000 IU of vitamin D – RCT June 2012 17 Mar, 2015
Cystic fibrosis helped with single dose of 250,000 IU of vitamin D – RCT July 2012 17 Mar, 2015
3000 IU reduced hypertension for the vitamin D insufficient – RCT Aug 2012 16 Mar, 2015
MS helped by average daily 2800 IU vitamin D – RCT Aug 2012 16 Mar, 2015
1600 IU vitamin D was enough to get all (white, non-obese) elderly to 20 ng – RCT Dec 2012 16 Mar, 2015
Many preemies need at least 800 IU of vitamin D – RCT May 2013 16 Mar, 2015
More blood was pumped by those getting 800,000 IU of vitamin D after heart failure – RCT Oct 2013 16 Mar, 2015
Calcium and Vitamin D Supplementation in Postmenopausal Women – RCT Nov 2013 16 Mar, 2015
4000 IU vitamin D daily for just 5 days reduced inflammation after heart attack – RCT Jan 2013 16 Mar, 2015
Hypertension reduced 6.8 mmHg with 3,000 IU of vitamin D daily – RCT May 2012 16 Mar, 2015
Infants getting 1400 IU vitamin D weekly grew better – RCT May 2011 16 Mar, 2015
Women taking 4,000 IU reduced pregnancy risks in half RCT May 2010 16 Mar, 2015
TB treatment helped with Vitamin D – RCT Sept 2012 16 Mar, 2015
Pregnancy helped by single dose of 60,000 IU of Vitamin D – RCT March 2015 15 Mar, 2015
Vitamin D2 DECREASED blood levels of Vitamin D3 by 12 ng – RCT July 2012 14 Mar, 2015
Vaginosis not reduced by average of 2800 IU vitamin D daily – RCT Nov 2014 07 Mar, 2015
Diabetic hypertension reduced with Vitamin D and Calcium – RCT March 2015 05 Mar, 2015
Gestational Diabetes reduced 40 percent by 5,000 IU of vitamin D – RCT April 2014 02 Mar, 2015
24 ng lower response to Vitamin D due to obesity, low initial Vitamin D, and genetics – RCT Feb 2015 24 Feb, 2015
Adding 4,000 IU of vitamin D daily at 20 weeks pregnancy not help much – RCT March 2014 18 Feb, 2015
Is 4000 IU the best Vitamin D dose for seniors – RCT underway – Feb 2015 08 Feb, 2015
Weight loss includes muscle loss unless add vitamin D, whey and leucine – RCT Feb 2015 07 Feb, 2015
Farmed fish not have enough vitamin D to increase levels – RCT Feb 2014 27 Jan, 2015
Muscle increased 17 percent in vitamin D insufficient elderly getting 4,000 IU for 4 months – RCT Oct 2013 27 Jan, 2015
7000 IU of vitamin D restored most HIV youths to above 32 ng - RCT March 2014 22 Jan, 2015
VITdAL-ICU - AMA RCT Sept 2014 21 Jan, 2015
100000 IU vitamin D monthly helps COPD patients – 3 RCT 20 Jan, 2015
50,000 IU Vitamin D one time after birth helped – RCT Jan 2015 14 Jan, 2015
T2 Diabetes helped by aerobic exercise, adding 1200 IU vitamin D helped even more – RCT Sept 2014 10 Jan, 2015
Atopic dermatitis dramatically reduced in Iran with 1600 IU of vitamin D – RCT March 2012 07 Jan, 2015
Newborn Apgar score slightly higher if deficient mother had daily 4,000 IU vitamin D – RCT March 2014 06 Jan, 2015
Arterial stiffness reduced by a single dose of 100,000 IU of vitamin D – RCT Dec 2014 06 Jan, 2015
Vitamin D aided progesterone in reducing traumatic brain injury – RCT Dec 2012 03 Jan, 2015
Calcium in blood did not increase when increase vitamin D to 40 ng – RCT Oct 2013 28 Dec, 2014
Calcium in blood (tightly regulated) did not increase when increase vitamin D to 40 ng – RCT Oct 2013 28 Dec, 2014
50,000 IU monthly safe to take without any vitamin D testing – RCT Dec 2013 22 Dec, 2014
People with old burns improved muscle strength with 2200 IU average vitamin D – RCT Sept 2014 20 Dec, 2014
Probiotic (L. reuteri NCIMB 30242 ) greately increased vitamin D levels for many – RCT July 2013 14 Dec, 2014
Increasing vitamin D level in blood failed to decrease Fatty Liver inflammation – RCT Aug 2014 10 Dec, 2014
Recent Diabetics treated by supplementation which achieved 60 ng of vitamin D – RCT Sept 2014 03 Dec, 2014
Vitamin D supplementation helps– now proven in Germany as well – RCT Dec 2013 02 Dec, 2014
Vitamin D intervention increased by 20 percent the survival of critically ill patients- RCT June 2014 29 Nov, 2014
1600 IU daily Vitamin D raised adult blood levels above 20 ng – RCT Nov 2011 29 Nov, 2014
Fibromyalgia pain with trazodone reduced by 50 percent with weekly 50,000 IU of vitamin D – RCT Nov 2014 22 Nov, 2014

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

This list is automatically updated

Items found: 710
17794 visitors, last modified 06 Mar, 2023,
Printer Friendly Follow this page for updates