DOI

DOI: 10.1159/000499187
Randomized Controlled Trial Am J Nephrol 2019;49(4):284-293. Epub 2019 Mar 15. Rationale for Raising Current Clinical Practice Guideline Target for Serum 25-Hydroxyvitamin D in Chronic Kidney Disease Stephen A Strugnell, Stuart M Sprague, Akhtar Ashfaq, Martin Petkovich, Charles W Bishop

PMID: 30878999 DOI: 10.1159/000499187 https://pubmed.ncbi.nlm.nih.gov/30878999/

Results: Progressive increases in serum 1,25-dihydroxyvitamin D and reductions in plasma iPTH and serum bone turnover markers were observed as mean posttreatment serum 25-hydroxyvitamin D rose from 13.9 ng/mL (in Quintile 1) to 92.5 ng/mL (in Quintile 5), irrespective of CKD stage. Mean serum calcium, phosphorus and FGF23, eGFR, and urine Ca:Cr ratio (collectively "safety parameters") did not significantly change from Quintile 1. Suppression of iPTH and bone turnover markers was not observed until serum 25-hydroxyvitamin D rose to at least 50.8 ng/mL (Quintile 3).

Conclusion: '''ERC therapy produced exposure-dependent reductions in plasma iPTH and bone turnover markers only when mean serum total 25-hydroxyvitamin D reached at least 50.8 ng/mL, indicating that current targets for vitamin D repletion therapy in CKD are too low. Gradual elevation of mean serum 25-hydroxyvitamin D to 92.5 ng/mL was not associated with significant adverse changes in safety parameters.'''

DOI: 10.3945/jn.110.134742
J Nutr 2011 Apr 1;141(4):692-7. Response to vitamin D supplementation during Antarctic winter is related to BMI, and supplementation can mitigate Epstein-Barr Virus Reactivation Sara R Zwart, Satish K Mehta, Robert Ploutz-Snyder, YaVonne Bourbeau, James P Locke, Duane L Pierson, Scott M Smith

PMID: 21539011 DOI: 10.3945/jn.110.134742 https://pubmed.ncbi.nlm.nih.gov/21539011/

Abstract: Maintaining vitamin D status without sunlight exposure is difficult without supplementation. This study was designed to better understand interrelationships between periodic vitamin D supplementation and immune function in Antarctic workers. The effect of 2 oral dosing regimens of vitamin D supplementation on vitamin D status and markers of immune function was evaluated in people in Antarctica with no UV light exposure for 6 mo. Participants were given a 2000-IU (50 μg) daily (n = 15) or 10,000-IU (250 μg) weekly (n = 14) vitamin D supplement for 6 mo during a winter in Antarctica. Biological samples were collected at baseline and at 3 and 6 mo. Vitamin D intake, markers of vitamin D and bone metabolism, and latent virus reactivation were determined. After 6 mo, the serum 25-hydroxyvitamin D concentration (mean ± SD) increased from 56 ± 17 to 79 ± 16 nmol/L and from 52 ± 10 to 69 ± 9 nmol/L in the 2000-IU/d and 10,000-IU/wk groups, respectively (main effect over time, P < 0.001). Participants with a greater BMI (participant BMI range = 19–43 g/m2) had a smaller increase in 25-hydroxyvitamin D after 6-mo supplementation (P < 0.05). Participants with high serum cortisol and higher serum 25-hydroxyvitamin D were less likely to shed Epstein-Barr virus in saliva (P < 0.05). The doses given raised vitamin D status in participants not exposed to sunlight for 6 mo, and the efficacy was influenced by baseline vitamin D status and BMI. The data also provide evidence that vitamin D, interacting with stress, can reduce risk of latent virus reactivation during the winter in Antarctica.

DOI: 10.1016/j.jsbmb.2010.02.021
J Steroid Biochem Mol Biol 2010 Jul;121(1-2):297-300. Epub 2010 Mar 1. Worldwide status of vitamin D nutrition P Lips

PMID: 20197091 DOI: 10.1016/j.jsbmb.2010.02.021 https://pubmed.ncbi.nlm.nih.gov/20197091/

Abstract: The vitamin D status depends on the production of vitamin D3 in the skin under the influence of ultraviolet radiation and vitamin D intake through the diet or vitamin D supplements. The serum 25-hydroxyvitamin D (25(OH)D) concentration is the parameter of choice for the assessment of vitamin D status. Low serum levels of calcium and phosphate and an elevated level of alkaline phosphatase can also point to vitamin D deficiency. Usually, between 50% and 90% of vitamin D in the body is coming from the production in the skin and the remainder is from the diet. The production of vitamin D3 in the skin depends on sunshine exposure, latitude, skin-covering clothes, the use of sun block and skin pigmentation. In general, serum 25(OH)D is lower with higher latitudes and with darker skin types, but there are exceptions. Vitamin D deficiency (serum 25(OH)D<25 nmol/l) is highly prevalent in India and China while vitamin D status is better in Japan and South-East Asia. Vitamin D deficiency is very common in the Middle-East and there is a relationship with skin covering clothes and staying outside of the sun. A poor to moderate vitamin D status is also common in Africa, probably caused by the dark skin types and cultural habits of staying outside of the sunshine. Vitamin D status is much better in North America where vitamin D deficiency is uncommon but vitamin D insufficiency (serum 25(OH)D between 25 and 50 nmol/l) is still common. In the United States and Canada milk is usually supplemented with vitamin D and the use of vitamin supplements is relatively common. Vitamin D status in Latin America usually is reasonable but there are exceptions and vitamin D insufficiency still occurs quite often. In Australia and New Zealand a poor vitamin D status was seen in the elderly who were often vitamin D deficient and also in immigrants from Asia. Vitamin D deficiency also occurred in children when the mother was vitamin D deficient. Within Europe, vitamin D status usually is better in the Nordic countries than around the Mediterranean. This may be due to a lighter skin and sun seeking behaviour and a high consumption of cod liver oil in the Northern countries while in Southern Europe people stay out of the sunshine and have a somewhat darker skin. '''A very poor vitamin D status was observed in non-western immigrants, especially in pregnant women. In conclusion, vitamin D deficiency and insufficiency are globally still very common especially in risk groups such as young children, pregnant women, elderly and immigrants.'''

DOI: 10.1093/jn/nxaa233
J Nutr 2020 Oct 12;150(10):2624-2627.. Vitamin D and COVID-19: Lessons from Spaceflight Analogs Sara R Zwart, Scott M Smith

PMID: 32710111 PMCID: PMC7454737 DOI: 10.1093/jn/nxaa233 https://pubmed.ncbi.nlm.nih.gov/32710111/

'''How could vitamin D deficiency or insufficiency possibly affect SARS-CoV-2 severity and mortality? The answer may be related to the paracrine and autocrine actions of vitamin D. All cells of the immune system express, or have the ability to express, vitamin D receptors, and all are sensitive to 1,25(OH)2D (12). Vitamin D can influence the immune system in a number of ways, including inhibition of B-cell proliferation and differentiation as well as inhibition of T-cell proliferation (11). Vitamin D also facilitates an induction of T-regulatory cells, resulting in decreased production of inflammatory cytokines and an increase in anti-inflammatory cytokine production (11).''' SARS-CoV-2 infection results in an aggressive inflammatory response (20), and it is possible that adequate vitamin D status may blunt the production of inflammatory cytokines during infection. Vitamin D is also a negative regulator of the RAS, and this regulation is independent of calcium metabolism (21). 1,25(OH)2D can increase ACE2 expression and attenuate the angiotensin II–induced inflammatory response that includes generation of reactive oxygen species and vasoconstriction (22), which is the pathway that is stimulated during SARS-CoV-2 infection (7). 1,25(OH)2D can alleviate lipopolysaccharide-induced acute lung injury through this mechanism (23).

...

As others have mentioned, it is unlikely that one silver bullet will end the COVID-19 pandemic; however, evidence-based recommendations can be made that may reduce the risk of a severe response to SARS-CoV-2 infection or viral reactivation. Simpson and Katsanis (43) have reported the benefits of exercising during the COVID-19 pandemic that was based on the evidence they found in their spaceflight research. We recommend that people maintain optimal vitamin D status to support immune function and lower their risk of viral reactivation, a recommendation that also comes from our National Aeronautics and Space Administration (NASA)–funded research. We are not advocating for ultra-high doses of vitamin D supplementation because of possible side effects, but rather a level of supplementation that will prevent vitamin D deficiency and maintain serum concentrations >30 ng/mL. We determined from our Antarctic research that doses of 1000–2000 IU/d, which are within IOM guidelines (24), are likely sufficient. Modifiable measures such as these may have the potential to safely and easily offer some protection and reduce risk.

DOI: 10.1002/rmv.2032
Rev Med Virol 2019 Mar;29(2):e2032. Epub 2019 Jan 6. The interplay between vitamin D and viral infections Majid Teymoori-Rad, Fazel Shokri, Vahid Salimi, Sayed Mahdi Marashi

PMID: 30614127 DOI: 10.1002/rmv.2032 https://pubmed.ncbi.nlm.nih.gov/30614127/

Abstract: The pleiotropic role of vitamin D has been explored over the past decades and there is compelling evidence for an epidemiological association between poor vitamin D status and a variety of diseases. While the potential anti-viral effect of vitamin D has recently been described, the underlying mechanisms by which vitamin D deficiency could contribute to viral disease development remain poorly understood. The possible interactions between viral infections and vitamin D appear to be more complex than previously thought. Recent findings indicate a complex interplay between viral infections and vitamin D, including the induction of anti-viral state, functional immunoregulatory features, interaction with cellular and viral factors, induction of autophagy and apoptosis, and genetic and epigenetic alterations. While crosstalk between vitamin D and intracellular signalling pathways may provide an essential modulatory effect on viral gene transcription, the immunomodulatory effect of vitamin D on viral infections appears to be transient. The interplay between viral infections and vitamin D remains an intriguing concept, and the global imprint that vitamin D can have on the immune signature in the context of viral infections is an area of growing interest.

DOI: 10.1038/s41467-021-22036-z
ARTICLE NATURE COMMUNICATIONS (2021) 12:1724 www.nature.com/naturecommunications

Exposure to SARS-CoV-2 generates T-cell memoryin the absence of a detectable viral infection Zhongfang Wang, Xiaoyun Yang, Jiaying Zhong, Yumin Zhou, Zhiqiang Tang, Haibo Zhou, Jun He, Xinyue Mei, Yonghong Tang, Bijia Lin, Zhenjun Chen, James McCluskey, Ji Yang, Alexandra J. Corbett, Pixin Ran

DOI: 10.1038/s41467-021-22036-z https://doi.org/10.1038/s41467-021-22036-z

T-cell immunity is important for recovery from COVID-19 and provides heightened immunity for re-infection. However, little is known about the SARS-CoV-2-specific T-cell immunity in virus-exposed individuals. Here we report virus-specific CD4+and CD8+T-cell memory in recovered COVID-19 patients and close contacts. We also demonstrate the size and quality of the memory T-cell pool of COVID-19 patients are larger and better than those of close contacts. However, the proliferation capacity, size and quality of T-cell responses in close contacts are readily distinguishable from healthy donors, suggesting close contacts are able to gain T-cell immunity against SARS-CoV-2 despite lacking a detectable infection. Additionally, asymptomatic and symptomatic COVID-19 patients contain similar levels of SARS-CoV-2-specific T-cell memory. Overall, this study demonstrates the versatility and potential of memory T cells from COVID-19 patients and close contacts, which may be important for host protection.

DOI: 10.3390/nu12092663
Nutrients 2020 Aug 31;12(9):2663. Geomapping Vitamin D Status in a Large City and Surrounding Population-Exploring the Impact of Location and Demographics Helena Scully, Eamon Laird, Martin Healy, James Bernard Walsh, Vivion Crowley, Kevin McCarroll

PMID: 32878330 PMCID: PMC7551618 DOI: 10.3390/nu12092663 https://pubmed.ncbi.nlm.nih.gov/32878330/

Abstract: Vitamin D status was assessed in a large urban area to compare differences in deficiency and to geomap the results. In total, 36,466 participants from 28 geographical areas were identified in this cross-sectional, retrospective analysis of general practitioner (GP)-requested 25(OH)D tests at St James's Hospital, Dublin between 2014 and 2018. The population were community-dwelling adults, median age 50.7 (18-109 years) with 15% of participants deficient (<30 nmol/L), rising to 23% in the winter. '''Deficiency was greatest in younger (18-39 years) and oldest (80+ years) adults, and in males versus females (18% vs. 11%, p < 0.001). Season was the biggest predictor of deficiency (OR 4.44, winter versus summer, p < 0.001), followed by location (west Dublin OR 2.17, north Dublin 1.54, south Dublin 1.42 versus rest of Ireland, p < 0.001) where several urban areas with an increased prevalence of deficiency were identified.''' There was no improvement in 25(OH)D over the 5-year period despite increased levels of testing. One in four adults were vitamin D deficient in the winter, with significant variations across locations and demographics. Overall this study identifies key groups at risk of 25(OH)D deficiency and insufficiency, thus providing important public health information for the targeting of interventions to optimise 25(OH)D. Mandatory fortification may be necessary to address this widespread inadequacy.

DOI: 10.1038/s41598-021-81419-w
Sci Rep 2021 Jan 21;11(1):1981. Autumn COVID-19 surge dates in Europe correlated to latitudes, not to temperature-humidity, pointing to vitamin D as contributing factor Stephan Walrand

PMID: 33479261 PMCID: PMC7820009 DOI: 10.1038/s41598-021-81419-w https://pubmed.ncbi.nlm.nih.gov/33479261/

To determine the factor triggering the sudden surge of daily new COVID-19 cases arising in most European countries during the autumn of 2020. The dates of the surge were determined using a fitting of the two last months of reported daily new cases in 18 European countries with latitude ranging from 39° to 62°. '''The study proves no correlation between the country surge date and the 2 weeks preceding temperature or humidity but shows an impressive linear correlation with latitude. The country surge date corresponds to the time when its sun UV daily dose drops below ≈ 34% of that of 0° latitude.''' Introducing reported seasonal blood 25-hydroxyvitamin D (25(OH)D) concentration variation into the reported link between acute respiratory tract infection risk and 25(OH)D concentration quantitatively explains the surge dynamics. Several studies have already substantiated a 25(OH)D concentration impact on COVID-19 severity. However, by comparing different patient populations, discriminating whether a low 25(OH)D concentration is a real factor underlying COVID-19 severity or only a marker of another weakness that is the primary severity factor can be challenging. The date of the surge is an intrapopulation observation and has the benefit of being triggered only by a parameter globally affecting the population, i.e. decreases in the sun UV daily dose. The results indicate that a low 25(OH)D concentration is a contributing factor to COVID-19 severity, which, combined with previous studies, provides a convincing set of evidence.

DOI: 10.3109/03009747309097085
Scandinavian Journal of Rheumatology Volume 2, 1973 - Issue 4 Effects of Large Doses of Calciferol on Patients with Rheumatoid Arthritis: A Double-Blind Clinical Trial Johan Brohult & Bertil Jonson

Pages 173-176 | Received 18 Jan 1973, Published online: 12 Jul 2009

https://doi.org/10.3109/03009747309097085 https://www.tandfonline.com/doi/abs/10.3109/03009747309097085

Abstract

In a double-blind clinical trial on 49 patients with rheumatoid arthritis, calciferol was given in a dose of 100 000 IU per day for 1 year to 24 patients, while the remaining 25 received placebo. Objective and subjective improvement was noted in 67% of the calciferol group and in 36% of the control group, while objective and subjective deterioration was noted in 4% of the calciferol group and in 32% of the control group. The mean values for sedimentation rate and a2-globulin decreased and the mean hemoglobin level increased in the calciferol group. The consumption of analgesics and antiinflammatory medicines decreased significantly in the calciferol group and after 1 year morning stiffness had eased and hand strength had increased in this group.

The assumption that 100ug (4000IU) of Vitamin-D is the safe upper limit is arbitrary from a health standpoint. It stems from a number of errors, assumptions, ignorance and conservatism from years back. The Institute of Medicine in America (IoM) was tasked with establishing guidelines for safe food based intake of Vitamins and Minerals to protect from the usual nutrient deficiency diseases. At that time Rickets was the only thing that was accepted to be affected by Vitamin-D. So after many years of treating all sorts of diseases more or less successfully with Cod-Liver-Oil, irradiated mushrooms and milk and UV radiation it was found that too much could be a bad thing. Some of the effects were due to gross over doses even at the time. Others are likely to have been due to manufacturing side products that were not adequately removed by purification. Still others were almost certainly from Vitamin-A overdose when providing massive Cod-liver-Oil doses to gain substantial Vitamin-D effects. So even though generous doses had been used the lack of knowledge and measurement tools and production control led to negative incidents. This was back in the 1930s to 1960s. So an attempt was to find a safe amount to ingest to fix Rickets but not cause harm. The IoM looked at some of the recent papers and they showed that under 250ug (10'000IU) daily resulted in no harm. They also had a (erroneous) paper to show that 15ug (600IU) was enough to prevent Rickets if someone was getting some sunlight and oily sea fish. So they decided that 7.5ug (300IU) would be a good amount for people to take and 50ug should be the danger limit because it was 20% of the safe limit (without any justification). Some years later due to pressure and the fact that the supplement need had been miscalculated to protect 5% instead of 95% of the population they changed the amounts to around double. A whole generation of doctors who have read research and treated patients know that these limits and recommendations are total rubbish and should not be used to correct deficiency or to expect maintenance. Many disorders are routinely treated with a wide variety of expensive patent Vitamin-D analogues and compounds in doses that will make the head spin. Even children are offered 2500ug (100'000IU) single bolus doses and many trials have used 1250ug (50'000IU) monthly doses without notable harm. In the early days it was thought more was better but it was the wild west and some things were more than necessary. Daily mega doses of 7500-12500ug (300'000-500'000IU) back in the 1930's were in use, some got sick from it even though it did treat their autoimmune condition. Fast forward to 1973 and we have a modest Swedish trial where a supra-physiological dose of 2500ug (100'000IU) daily is given for 12 months to those with an autoimmune disease (rheumatoid arthritis) in the old more is better style to see if doing it carefully would be ok. Sure enough there is benefit to be seen and with careful monitoring no danger, the authors suggest that THIS is probably the upper limit of safety as doses of double that have shown danger. Take note that this is 100 times the IoM danger limit of today. And 400 times the suggested dose for a pregnant mother, and 1000 times more than is suggested as a minimum daily top up for preventing Rickets (which is not quite enough). Who are you going to blindly follow, those that have proven the safety of something and used in therapeuticly to control autoimmune diseases or those who only plan to control Rickets with outdated erroneous information? Simply put if someone tells you that Vitamin-D is dangerous in physiological natural doses they are ignorant or lying, there is no middle ground. (Any dose size, even sun exposure is dangerous for a very small fraction of those with rare genetic diseases, not talking about those here) I leave you a link to the 1973 paper and will place the 2021 paper I posted earlier that treats another autoimmune disease (multiple sclerosis) successfully and safely with doses up to 2500ug (100'000IU) daily in a comment. If your doctor fails to consider this information they are not your friend. "Trials with large doses of calciferol for the treatment of rheumatoid arthritis have been made in the past. Clinical improvement was reported by Dreyer & Reed in 1935 with doses of about 300000 to 500000 IU calciferol per day and several similar observations were published during the next few years."

DOI: 10.1136/ard.2007.069831
Vitamin D and autoimmunity: new aetiological and therapeutic considerations Yoav Arnson1, Howard Amital1, Yehuda Shoenfeld2

DOI: 10.1136/ard.2007.069831 https://ard.bmj.com/content/66/9/1137 http://dx.doi.org/10.1136/ard.2007.069831

Abstract

Vitamin D is frequently prescribed by rheumatologists to prevent and treat osteoporosis. Several observations have shown that vitamin D inhibits proinflammatory processes by suppressing the enhanced activity of immune cells that take part in the autoimmune reaction. Moreover, recent evidence strongly suggests that vitamin D supplementation may be therapeutically beneficial, particularly for Th1-mediated autoimmune disorders. Some reports imply that vitamin D may even be preventive in certain disorders such as multiple sclerosis and diabetes type 1. It seems that vitamin D has crossed the boundaries of calcium metabolism and has become a significant factor in a number of physiological functions, specifically as a biological inhibitor of inflammatory hyperactivity.

DOI: 10.1155/2015/913804
Biomed Res Int. 2015; 2015: 913804. Published online 2015 May 4.

Association between Serum 25-Hydroxyvitamin D Level and Rheumatoid Arthritis Xiaomin Cen, Yuan Liu, Geng Yin, Min Yang, and Qibing Xie

doi: 10.1155/2015/913804 PMCID: PMC4434189 PMID: 26064964 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434189/

Abstract

The objective of this study is to examine and evaluate whether serum 25(OH)D is associated with disease activity in patients with rheumatoid arthritis (RA). Our results suggested that serum 25(OH)D in RA groups has significant lower level (35.99 ± 12.59 nmol/L) than that in the normal groups (54.35 ± 8.20 nmol/L, P < 0.05). Based on the DAS28, patients with RA were divided into four subgroups, and no differences were found in the four groups (P > 0.05). The 25(OH)D levels in complete remission, low disease activity, middle disease activity, and high disease activity group were 32.86 ± 12.26, 33.97 ± 13.28, 38.41 ± 10.64, and 38.94 ± 13.35 nmol/L, respectively. Based on the serum 25(OH)D levels, patients with RA were divided into inadequate group and normal group, and there were no significant differences in baseline characteristics and disease activity in the two groups. Our results showed that serum 25(OH)D levels in the inadequate group are significantly lower than those in the normal group. However, no correlations were found between 25(OH)D levels and disease activity among 116 patients with RA. The present findings will help to understand the association between 25(OH)D and disease activity of RA.

DOI: 10.1210/jc.2013-2653
J Clin Endocrinol Metab. 2013 Dec; 98(12): 4619–4628. Published online 2013 Oct 8.

The Role of the Parent Compound Vitamin D with Respect to Metabolism and Function: Why Clinical Dose Intervals Can Affect Clinical Outcomes Bruce W. Hollis, Carol L. Wagner

doi: 10.1210/jc.2013-2653 PMCID: PMC3849670 PMID: 24106283 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849670/

Indeed, any high-dose, long-interval dosing schedule can be considered pharmacological rather than physiological.

'''Circulating vitamin D, the parent compound for tissue vitamin D activation, likely has an important direct physiological role beyond what was originally anticipated through the local tissue autocrine system. Based on emerging data from the laboratory and from clinical trials and on available knowledge of vitamin D axis metabolism, it appears likely that for the optimal benefits of vitamin D supplementation, enough vitamin D should be provided on a daily basis to ensure that stable circulating concentrations are maintained over time. This view implies that schedules for vitamin D dosing could have profound effects on the outcomes of clinical trials, due to the short circulating half-life of vitamin D'''

DOI: 10.1111/febs.15495
FEBS J. 2020 Jul 23 Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: an Israeli population‐based study Eugene Merzon, Dmitry Tworowski, Alessandro Gorohovski, Shlomo Vinker, Avivit Golan Cohen, Ilan Green, Milana Frenkel Morgenstern

doi: 10.1111/febs.15495 [Epub ahead of print] PMCID: PMC7404739 PMID: 32700398 https://pubmed.ncbi.nlm.nih.gov/32700398/

Of 7,807 individuals, 782 (10.1%) were COVID‐19‐positive, and 7,025 (89.9%) COVID‐19‐negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID‐19 [19.00 ng/mL (95% confidence interval [CI] 18.41‐19.59) vs. 20.55 (95% CI 20.32‐20.78)]. Univariate analysis demonstrated an association between low plasma 25(OH)D level and increased likelihood of COVID‐19 infection [crude odds ratio (OR) of 1.58 (95% CI 1.24‐2.01, p<0.001)], and of hospitalization due to the SARS‐CoV‐2 virus [crude OR of 2.09 (95% CI 1.01‐ 4.30, p<0.05)]. In multivariate analyses that controlled for demographic variables, and psychiatric and somatic disorders, the adjusted OR of COVID‐19 infection [1.45 (95% CI 1.08‐1.95, p<0.001)], and of hospitalization due to the SARS‐CoV‐2 virus [1.95 (95% CI 0.98‐4.845, p=0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low‐medium socioeconomic status were also positively associated with the risk of COVID‐19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID‐19.

Conclusion Low plasma 25(OH)D level appears to be an independent risk factor for COVID‐19 infection and hospitalization.

DOI: 10.1007/s00508-021-01833-y
Wien Klin Wochenschr 2021 Mar 15;1-3.

Strong correlation between prevalence of severe vitamin D deficiency and population mortality rate from COVID-19 in Europe Isaac Z Pugach, Sofya Pugach

PMID: 33721102 PMCID: PMC7957444 DOI: 10.1007/s00508-021-01833-y

Results: There were data sets from 10 countries that fitted the criteria and were analyzed. Severe vitamin D deficiency was defined as 25(OH)D less than 25 nmol/L (10 ng/dL). '''Pearson correlation analysis between death rate per million of population from coronavirus disease 2019 (COVID-19) and prevalence of severe vitamin D deficiency showed a strong correlation with r = 0.79, p = 0.007. Over time, correlation strengthened, and r coefficient asymptotically increased.''' After adjusting for countries' age structure and per capita health expenditures, multiple linear regression analysis showed that higher prevalence of severe vitamin D deficiency is associated with increased mortality. Each 1% increase in prevalence increased deaths by 55 per million (95% confidence interval, CI 8-102), p = 0.03.

Conclusion: The authors recommend universal screening for vitamin D deficiency, and further investigation of Vitamin D supplementation in randomized control studies, which may lead to possible treatment or prevention of COVID-19.

DOI: 10.1016/j.nut.2020.111106
Nutrition Volume 84, April 2021, 111106 Applied nutritional investigation Increased risk for COVID-19 in patients with vitamin D deficiency

https://doi.org/10.1016/j.nut.2020.111106 DOI: 10.1016/j.nut.2020.111106 https://www.sciencedirect.com/science/article/pii/S0899900720303890

Vitamin D deficiency is strongly associated with increased risk for coronavirus disease 2019 (COVID-19). The odds ratio for COVID-19 increases with vitamin deficiency in black individuals. Diabetes, obesity, and periodontal disease are associated with an increased risk for both COVID-19 and vitamin D deficiency.

DOI: 10.1101/2021.01.28.21250673
Is vitamin D deficiency associated with the COVID-19 epidemic in Europe? Dimitra Rafailia Bakaloudi, Michail Chourdakis

doi: https://doi.org/10.1101/2021.01.28.21250673 https://www.medrxiv.org/content/10.1101/2021.01.28.21250673v2

Abstract The authors have withdrawn this manuscript because, following comments received during the review process, they have updated the number of countries included in their study (and also changed from 5 to 10 years the limit for Vit-D information studies that they included), which led to non-significant correlations between mortality and infections and Vit D deficiency prevalence. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

DOI: 10.1186/s12967-021-02838-x
J Transl Med 2021 Apr 26;19(1):166 Vitamin D status of Arab Gulf residents screened for SARS-CoV-2 and its association with COVID-19 infection: a multi-centre case-control study Nasser M Al-Daghri, Osama E Amer, Naif H Alotaibi, Dara A Aldisi, Mushira A Enani, Eman Sheshah, Naji J Aljohani, Naemah Alshingetti, Suliman Y Alomar, Hanan Alfawaz, Syed D Hussain, Abdullah M Alnaami, Shaun Sabico

PMID: 33902635 PMCID: PMC8072076 DOI: 10.1186/s12967-021-02838-x https://pubmed.ncbi.nlm.nih.gov/33902635/

Results: Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 positive group compared to the negative group after adjustment for age and BMI (52.8 nmol/l ± 11.0 versus 64.5 nmol/l ± 11.1; p = 0.009). Being elderly (> 60 years) [Odds ratio 6 (95% Confidence Interval, CI 2-18; p = 0.001) as well as having type 2 diabetes (T2D) [OR 6 (95% CI 3-14); p < 0.001)] and low HDL cholesterol (HDL-c) [OR 6 (95% CI 3-14); p < 0.001)] were significant risk factors for COVID-19 infection independent of age, sex and obesity.

Conclusions: Among Arab Gulf residents screened for SARS-CoV-2, serum 25(OH) D levels were observed to be lower in those who tested positive than negative individuals, but it was the presence of old age, diabetes mellitus and low-HDL-c that were significantly associated with risk of COVID-19 infection. Large population-based randomized controlled trials should be conducted to assess the protective effects of vitamin D supplementation against COVID-19.

DOI: 10.1016/j.dsx.2021.03.006
Diabetes Metab Syndr 2021 Mar 13;15(3):757-764. Impact of the vitamin D deficiency on COVID-19 infection and mortality in Asian countries Ranil Jayawardena, Dhanushya T Jeyakumar, Tormalli V Francis, Anoop Misra

PMID: 33823331 PMCID: PMC7955807 DOI: 10.1016/j.dsx.2021.03.006 https://pubmed.ncbi.nlm.nih.gov/33823331/

Results: Positive correlations were observed for prevalence of vitamin D deficiency with COVID-19 infections (r = 0.55; p = 0.01; R2 = 0.31) and mortalities (r = 0.50; p = 0.01; R2 = 0.25). Moreover, the associations for the COVID-19 infections and mortalities improved to r = 0.76 (p = 0.002; R2 = 0.58) and r = 0.65 (p = 0.03; R2 = 0.42), respectively, after predicting with confounding factors. Similarly, mean vitamin D level had a significant negative correlation with COVID-19 infections (r = -0.77; p = 0.04; R2 = 0.59) and mortalities (r = -0.80; p = 0.03; R2 = 0.63) when combining with confounders.

Conclusion: Prevalence of vitamin D deficiency is significantly positively associated whereas the mean vitamin D level is significantly negatively associated with both infection and mortality rate of COVID-19 among Asian countries upon predicting with all confounders.

DOI: 10.1080/13543784.2021.1901883
Expert Opin Investig Drugs 2021 Apr 23;1-14. The time to offer treatments for COVID-19 Binh T Ngo, Paul Marik, Pierre Kory, Leland Shapiro, Raphael Thomadsen, Jose Iglesias, Stephen Ditmore, Marc Rendell, Joseph Varon, Michael Dubé, Neha Nanda, Gino In, Daniel Arkfeld, Preet Chaudhary, Vito M Campese, Diana L Hanna, David E Sawcer, Glenn Ehresmann, David Peng, Miroslaw Smogorewski, April Armstrong, Rajkumar Dasgupta, Fred Sattler, Denise Brennan-Rieder, Cristina Mussini, Oriol Mitja, Vicente Soriano, Nicolas Peschanski, Gilles Hayem, Marco Confalonieri, Maria Carmela Piccirillo, Antonio Lobo-Ferreira, Iraldo Bello Rivero, Mika Turkia, Eivind H Vinjevoll, Daniel Griffin, Ivan Fn Hung

PMID: 33721548 PMCID: PMC8074648 DOI: 10.1080/13543784.2021.1901883 https://pubmed.ncbi.nlm.nih.gov/33721548/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074648/

COVID-19 has characteristic phases, beginning as a viral influenza like illness which may then deteriorate to an inflammatory phase with a subsequent hyperinflammatory reaction characterized by cytokine release; Acute respiratory distress syndrome and a coagulopathy are responsible for mortality.

The focus of treatment of COVID-19 has been on very ill hospitalized patients. Outpatients who do not require hospitalization are told to home quarantine with no effective treatment.

The public health authorities have pursued universal immunization to prevent the disease, and several vaccines are now being administered to the population of the entire world. However, vaccination alone may not be sufficient to stop the disease as the virus continues to propagate with newly developing variants.

We reviewed treatments now available to use in parallel with vaccination to fight COVID-19. '''We found a number of agents, some already approved and in use in a number of countries.

We recommend that agents with known safety profile and preliminary evidence of possible benefit be used together with universal vaccination, while long-term studies proceed in parallel to prove efficacy.'''

DOI: 10.3390/nu13020411
Nutrients 2021 Jan 28;13(2):411. Vitamin D Supplementation to Prevent COVID-19 Infections and Deaths-Accumulating Evidence from Epidemiological and Intervention Studies Calls for Immediate Action Hermann Brenner

PMID: 33525447 PMCID: PMC7911431 DOI: 10.3390/nu13020411 https://pubmed.ncbi.nlm.nih.gov/33525447/

Abstract: The COVID-19 pandemic poses an unprecedented threat to human health, health care systems, public life, and economy around the globe. The repertoire of effective therapies for severe courses of the disease has remained limited. '''A large proportion of the world population suffers from vitamin D insufficiency or deficiency, with prevalence being particularly high among the COVID-19 high-risk populations. Vitamin D supplementation has been suggested as a potential option to prevent COVID-19 infections, severe courses, and deaths from the disease, but is not widely practiced. This article provides an up-to-date summary of recent epidemiological and intervention studies on a possible role of vitamin D supplementation for preventing severe COVID-19 cases and deaths. Despite limitations and remaining uncertainties, accumulating evidence strongly supports widespread vitamin D supplementation, in particular of high-risk populations, as well as high-dose supplementation of those infected.''' Given the dynamics of the COVID-19 pandemic, the benefit-risk ratio of such supplementation calls for immediate action even before results of ongoing large-scale randomized trials become available.

DOI: 10.1002/1878-0261.12924
Molecular Oncology 04 February 2021 Research Article Vitamin D supplementation to the older adult population in Germany has the cost‐saving potential of preventing almost 30 000 cancer deaths per year Tobias Niedermaier, Thomas Gredner, Sabine Kuznia, Ben Schöttker, Ute Mons, Hermann Brenner

https://doi.org/10.1002/1878-0261.12924 https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.12924

Recent meta‐analyses of randomized controlled trials (RCTs) have demonstrated significant reduction in cancer mortality by vitamin D supplementation. We estimated costs and savings for preventing cancer deaths by vitamin D supplementation of the population aged 50+ years in Germany. Our analysis is based on national data on cancer mortality in 2016. The number of preventable cancer deaths was estimated by multiplying cancer deaths above age 50 with the estimated proportionate reduction in cancer mortality derived by vitamin D supplementation according to meta‐analyses of RCTs (13%). Saved costs were estimated by multiplying this number by estimated end‐of‐life cancer care costs (€40 000). Annual costs of vitamin D supplementation were estimated at 25€ per person above age 50. Comprehensive sensitivity analyses were conducted. In the main analysis, vitamin D supplementation was estimated to prevent almost 30 000 cancer deaths per year at approximate costs of €900 million and savings of €1.154 billion, suggesting net savings of €254 million. Our results support promotion of supplementation of vitamin D among older adults as a cost‐saving approach to substantially reduce cancer mortality.

Important to note that the active Vitamin-D3 ingredient Cholecalciferol cost for adult supplementation is under EUR1.00 per adult per year. On a not-for-profit national scale compounding or food fortification program the cost would be further reduced substantially from a competitive retail price of closer to EUR15 for a generous dose of 200ug per day.

DOI: 10.1016/S2213-8587(21)00051-6
The Lancet Diabetes and Endocrinology Articles| Volume 9, ISSUE 5, P276-292, May 01, 2021, March 30, 2021 Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials David A Jolliffe, PhD, Prof Carlos A Camargo Jr, MD, John D Sluyter, PhD, Mary Aglipay, MSc, Prof John F Aloia, MD, Davaasambuu Ganmaa, PhD, et al.

DOI:https://doi.org/10.1016/S2213-8587(21)00051-6 https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00051-6/fulltext

Interpretation Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400–1000 IU for up to 12 months, and age at enrolment of 1·00–15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation.

DOI: 10.1101/2020.11.27.20239087
BMJ Nutrition Dietary supplements during the COVID-19 pandemic: insights from 1.4M users of the COVID Symptom Study app - a longitudinal app-based community survey Panayiotis Louca, Benjamin Murray, Kerstin Klaser, Mark S Graham, Mohsen Mazidi, Emily R Leeming, Ellen Thompson, Ruth Bowyer, David A Drew, Long H Nguyen, Jordi Merino, Maria Gomez, Olatz Mompeo, Ricardo Costeira, Carole H Sudre, Rachel Gibson, Claire J Steves, Jonathan Wolf, Paul W Franks, Sebastien Ourselin, Andrew T Chan, Sarah E Berry, Ana M Valdes, Philip C Calder, Tim D Spector, Cristina Menni

doi: https://doi.org/10.1101/2020.11.27.20239087 https://www.medrxiv.org/content/10.1101/2020.11.27.20239087v1

Conclusion We observed a modest but significant association between use of probiotics, omega-3 fatty acid, multivitamin or vitamin D supplements and lower risk of testing positive for SARS-CoV-2 in women. No clear benefits for men were observed nor any effect of vitamin C, garlic or zinc for men or women. Randomised controlled trials of selected supplements would be required to confirm these observational findings before any therapeutic recommendations can be made.

DOI: 10.4103/jfmpc.jfmpc_78_18
Journal ListJ Family Med Prim Carev.7(2); Mar-Apr 2018 J Family Med Prim Care. 2018 Mar-Apr; 7(2): 324–330. Vitamin D deficiency in India P Aparna, S Muthathal, Baridalyne Nongkynrih, and Sanjeev Kumar Gupta

doi: 10.4103/jfmpc.jfmpc_78_18 PMCID: PMC6060930 PMID: 30090772 https://pubmed.ncbi.nlm.nih.gov/30090772/

Abstract Vitamin D is a fat-soluble vitamin playing a vital role in human physiology. Vitamin D deficiency is prevalent worldwide. This deficiency has many consequences which are still being explored, apart from the well-known skeletal complications. With this review, we aim to summarize the existing literature on Vitamin D status in India and understand the enormity of the problem. The prevalence of Vitamin D deficiency ranged from 40% to 99%, with most of the studies reporting a prevalence of 80%–90%. It was prevalent in all the age groups and high-risk groups alike. With the consequences of Vitamin D deficiency, namely, autoimmune diseases, cardiovascular diseases, cancer, and tuberculosis being explored, we can imagine the burden it would cause in our country. We need to create awareness among the public and healthcare providers about the importance of Vitamin D and the consequences of deficiency. Our Indian diet generally fails to satisfy the daily requirement of Vitamin D for a normal adult. This stresses on the need for fortifying various food with Vitamin D, through the national programs. This silent epidemic should be addressed appropriately with concrete public health action.

DOI: 10.1186/s12931-020-01554-2
Respir Res 2020 Nov 9;21(1):294. The association between serum vitamin D and obstructive sleep apnea: an updated meta-analysis Xiaoyan Li, Jie He, Jie Yun

PMID: 33167989 PMCID: PMC7653837 DOI: 10.1186/s12931-020-01554-2 https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-020-01554-2

Results: Twenty-nine eligible studies compromising 6717 participants met the inclusion criteria of the meta-analysis. The results revealed that the serum 25(OH)D level was significantly lower in OSA patients than the controls. According to the severity of the disease, subgroup analysis was performed; the results demonstrated that the serum 25(OH)D level was not decreased in mild OSA patients compared with the controls, while the serum 25(OH)D level in moderate and severe OSA patients was lower than that in the controls. Furthermore, based on ethnicity, BMI, PSG type, study quality and latitude, the subjects were divided into different subgroups for meta-analysis. The results revealed that the serum 25(OH)D level in all OSA subgroups was decreased compared with that in the control group.

DOI: 10.1136/bmjresp-2020-000845
BMJ Open Respir Res 2021 Jan;8(1):e000845. Sleep apnoea is a risk factor for severe COVID-19 Satu Strausz, Tuomo Kiiskinen, Martin Broberg, Sanni Ruotsalainen, Jukka Koskela, Adel Bachour, Aarno Palotie, Tuula Palotie, Samuli Ripatti, Hanna M Ollila

PMID: 33436406 PMCID: PMC7804843 DOI: 10.1136/bmjresp-2020-000845 https://pubmed.ncbi.nlm.nih.gov/33436406/

Results: We identified 445 individuals with COVID-19, and 38 (8.5%) of them with OSA of whom 19 out of 91 (20.9%) were hospitalised. OSA associated with COVID-19 hospitalisation independent from age, sex, BMI and comorbidities (p-unadjusted=5.13×10-5, OR-adjusted=2.93 (95% CI 1.02 to 8.39), p-adjusted=0.045). OSA was not associated with the risk of contracting COVID-19 (p=0.25). A meta-analysis of OSA and severe COVID-19 showed association across 15 835 COVID-19 positive controls, and n=1294 patients with OSA with severe COVID-19 (OR=2.37 (95% 1.14 to 4.95), p=0.021).

Conclusion: Risk for contracting COVID-19 was the same for patients with OSA and those without OSA. In contrast, among COVID-19 positive patients, OSA was associated with higher risk for hospitalisation. Our findings are in line with earlier works and suggest OSA as an independent risk factor for severe COVID-19.

DOI: 10.1016/B978-0-12-386960-9.00002-2
Vitam Horm 2011;86:23-62. Vitamin D and innate and adaptive immunity Martin Hewison

PMID: 21419266 DOI: 10.1016/B978-0-12-386960-9.00002-2 https://pubmed.ncbi.nlm.nih.gov/21419266/

Abstract In the last 5 years there has been renewed interest in the health benefits of vitamin D. A central feature of this revival has been new information concerning the nonclassical effects of vitamin D. In particular, studies of the interaction between vitamin D and the immune system have highlighted the importance of localized conversion of precursor 25-hydroxyvitamin D (25OHD) to active 1,25-dihydroxyvitamin D (1,25(OH)(2)D) as a mechanism for maintaining antibacterial activity in humans. The clinical relevance of this has been endorsed by increasing evidence of suboptimal 25OHD status in populations across the globe. Collectively these observations support the hypothesis that vitamin D insufficiency may lead to dysregulation of human immune responses and may therefore be an underlying cause of infectious disease and immune disorders. The current review describes the key mechanisms associated with vitamin D metabolism and signaling for both innate immune (antimicrobial activity and antigen presentation) and adaptive immune (T and B lymphocyte function) responses. These include coordinated actions of the vitamin D-activating enzyme, 1α-hydroxylase (CYP27B1), and the vitamin D receptor (VDR) in mediating intracrine and paracrine actions of vitamin D. Finally, the review will consider the role of immunomodulatory vitamin D in human health, with specific emphasis on infectious and autoimmune disease.

DOI: 10.1080/19381980.2017.1300213
Dermatoendocrinol 2017 Apr 13;9(1):e1300213. eCollection 2017. Evaluation of vitamin D3 intakes up to 15,000 international units/day and serum 25-hydroxyvitamin D concentrations up to 300 nmol/L on calcium metabolism in a community setting S M Kimball, N Mirhosseini, M F Holick

PMID: 28458767 PMCID: PMC5402701 DOI: 10.1080/19381980.2017.1300213 https://pubmed.ncbi.nlm.nih.gov/28458767/

Abstract: Supplementation by the general public with vitamin D at doses above the Tolerable Upper Level of Intake (UL) is becoming quite common. The objective of the current analysis was to characterize the effect of vitamin D supplementation at doses up to 15,000 IU/d in a community-based program on vitamin D status, calcium homeostasis as well as on kidney, liver and immune function. We evaluated data collected for 3,882 participants in a community program for whom there were blood measurements at program entry and at follow-up within 6-18 months between 2013 and 2015. '''Participants were supplemented with a wide range of vitamin D doses (1,000 - 15,000 IU/d) aimed at achieving serum 25-hydroxyvitamin D [25(OH)D] levels of at least 100 nmol/L. Serum 25(OH)D concentrations up to 300 nmol/L were achieved without perturbation of calcium homeostasis or incidence of toxicity. Hypercalcemia and hypercalciuria were not related to an increase in 25(OH)D concentrations nor vitamin D dose. To achieve serum 25(OH)D levels >100 nmol/L on average, required vitamin D intakes of 6,000 IU/d for normal Body Mass Index (BMI), 7,000 IU/d for overweight and 8,000 IU/d for obese.''' Doses of vitamin D in excess of 6,000 IU/d were required to achieve serum 25(OH)D concentrations above 100 nmol/L, especially in individuals who were overweight or obese without any evidence of toxicity. Serum 25(OH)D concentrations up to 300 nmol/L were found to be safe.

DOI: 10.1007/s11154-017-9424-1
Rev Endocr Metab Disord 2017 Jun;18(2):153-165. The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention Michael F Holick

PMID: 28516265 DOI: 10.1007/s11154-017-9424-1 https://pubmed.ncbi.nlm.nih.gov/28516265/

Abstract Vitamin D deficiency and insufficiency is a global health issue that afflicts more than one billion children and adults worldwide. '''The consequences of vitamin D deficiency cannot be under estimated. There has been an association of vitamin D deficiency with a myriad of acute and chronic illnesses including preeclampsia, childhood dental caries, periodontitis, autoimmune disorders, infectious diseases, cardiovascular disease, deadly cancers, type 2 diabetes and neurological disorders.''' This review is to put into perspective the controversy surrounding the definition for vitamin D deficiency and insufficiency as well as providing guidance for how to treat and prevent vitamin D deficiency.

DOI: 10.1002/iid3.367
Immun Inflamm Dis 2021 Mar;9(1):128-133. Epub 2020 Dec 15. Evidence and implications of pre-existing humoral cross-reactive immunity to SARS-CoV-2 Amandine Mveang Nzoghe, Paulin N Essone, Marielle Leboueny, Anicet Christel Maloupazoa Siawaya, Eliode Cyrien Bongho, Ofilia Mvoundza Ndjindji, Rotimi Myrabelle Avome Houechenou, Selidji Todagbe Agnandji, Joel Fleury Djoba Siawaya

PMID: 33320447 PMCID: PMC7860591 DOI: 10.1002/iid3.367 https://pubmed.ncbi.nlm.nih.gov/33320447/

Results: Sera from 32 subjects (out of 135 [23.7%]) were reactive to SARS-CoV-2 N-antigen, suggesting the presence of anti-SARS-CoV-2 N-antigen antibodies.' Conclusion: Although the clinical relevance of the observed reactivity can only be speculated and needs to be investigated, the implication of this finding for coronavirus disease 2019 seroepidemiological survey and vaccines' clinical trials is critical.

DOI: 10.1542/peds.2015-1669
Pediatrics 2015 Oct;136(4):625-34. Maternal Versus Infant Vitamin D Supplementation During Lactation: A Randomized Controlled Trial Bruce W Hollis, Carol L Wagner, Cynthia R Howard, Myla Ebeling, Judy R Shary, Pamela G Smith, Sarah N Taylor, Kristen Morella, Ruth A Lawrence, Thomas C Hulsey

PMID: 26416936 PMCID: PMC4586731 DOI: 10.1542/peds.2015-1669 https://pubmed.ncbi.nlm.nih.gov/26416936/

Results: Of the 334 mother-infant pairs in 400 IU and 6400 IU groups at enrollment, 216 (64.7%) were still breastfeeding at visit 1; 148 (44.3%) continued full breastfeeding to 4 months and 95 (28.4%) to 7 months. Vitamin D deficiency in breastfeeding infants was greatly affected by race. Compared with 400 IU vitamin D3 per day, 6400 IU/day safely and significantly increased maternal vitamin D and 25(OH)D from baseline (P < .0001). Compared with breastfeeding infant 25(OH)D in the 400 IU group receiving supplement, infants in the 6400 IU group whose mothers only received supplement did not differ.

Conclusions: Maternal vitamin D supplementation with 6400 IU/day safely supplies breast milk with adequate vitamin D to satisfy her nursing infant's requirement and offers an alternate strategy to direct infant supplementation.

In a similar study they showed that Vitamin-D2 was not adequate at the same dose levels.

DOI: 10.1017/S0007114511007161
Br J Nutr 2012 Nov 14;108(9):1557-61. Epub 2012 Jan 23. Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l Martine F Luxwolda, Remko S Kuipers, Ido P Kema, D A Janneke Dijck-Brouwer, Frits A J Muskiet

PMID: 22264449 DOI: 10.1017/S0007114511007161 https://pubmed.ncbi.nlm.nih.gov/22264449/

Abstract: Cutaneous synthesis of vitamin D by exposure to UVB is the principal source of vitamin D in the human body. Our current clothing habits and reduced time spent outdoors put us at risk of many insufficiency-related diseases that are associated with calcaemic and non-calcaemic functions of vitamin D. Populations with traditional lifestyles having lifelong, year-round exposure to tropical sunlight might provide us with information on optimal vitamin D status from an evolutionary perspective. We measured the sum of serum 25-hydroxyvitamin D₂ and D₃ (25(OH)D) concentrations of thirty-five pastoral Maasai (34 (SD 10) years, 43 % male) and twenty-five Hadzabe hunter-gatherers (35 (SD 12) years, 84 % male) living in Tanzania. They have skin type VI, have a moderate degree of clothing, spend the major part of the day outdoors, but avoid direct exposure to sunlight when possible. Their 25(OH)D concentrations were measured by liquid chromatography-MS/MS. The mean serum 25(OH)D concentrations of Maasai and Hadzabe were 119 (range 58-167) and 109 (range 71-171) nmol/l, respectively. These concentrations were not related to age, sex or BMI. People with traditional lifestyles, living in the cradle of mankind, have a mean circulating 25(OH)D concentration of 115 nmol/l. Whether this concentration is optimal under the conditions of the current Western lifestyle is uncertain, and should as a possible target be investigated with concomitant appreciation of other important factors in Ca homeostasis that we have changed since the agricultural revolution.

DOI: 10.1098/rspb.2014.3085
Proc Biol Sci 2015 Dec 22;282(1821):20143085. Evolution of the immune system in humans from infancy to old age A Katharina Simon, Georg A Hollander, Andrew McMichael

PMID: 26702035 PMCID: PMC4707740 DOI: 10.1098/rspb.2014.3085 https://pubmed.ncbi.nlm.nih.gov/26702035/

Abstract This article reviews the development of the immune response through neonatal, infant and adult life, including pregnancy, ending with the decline in old age. A picture emerges of a child born with an immature, innate and adaptive immune system, which matures and acquires memory as he or she grows. It then goes into decline in old age. These changes are considered alongside the risks of different types of infection, autoimmune disease and malignancy.

Nice picture