Editing Vitamin D

'''Vitamin D''' is a fat-soluble steroid [[hormone]] responsible for the intestinal absorption of [[calcium]], [[iron]], [[magnesium]], [[Phosphorus|phosphate]] and [[zinc]]. In humans, dietary Vitamin D is negligible; most comes from exposure of skin to sunlight or from supplementation. 

==Function ==
Vitamin D is fat-soluble, regulates calcium levels, helps modulate the immune system, and is vital to good bone health.<ref name="vdr" /><ref name="Paul2011" />

=== Vitamin D2 ===
Vitamin D2, known as ergocalciferol, is a vitamin D found in plants, mushrooms, and yeasts, and sometimes in foods fortified with vitamin D.<ref name="lpi">{{Cite web|url=https://lpi.oregonstate.edu/mic/vitamins/vitamin-D|title=Vitamin D | date = 2014-04-22 | website = Linus Pauling Institute|language=en|access-date=2018-12-23}}</ref> 

=== Vitamin D3 ===
Vitamin D3, known as cholecalciferol, is synthesized in the human skin from the UVB radiation in sunlight. D3 can also be obtained from [[:Category:Supplements|supplements]].<ref name="lpi" />

==VDR gene ==
The VDR gene, also known as nuclear receptor subfamily 1 group I member 1, provides instructions for making vitamin D receptor, which controls the body's response to vitamin D.<ref name="vdr">https://medlineplus.gov/genetics/gene/vdr/</ref> Vitamin D-dependent rickets, alopecia areata (an autoimmune disease), intervertebral disc disease, kidney stones and leprosy have all been linked to the VDR gene.<ref name="vdr" />

== Immune function ==

Vitamin D improves [[regulatory T cell]] function in healthy adults<ref name="bock2011">{{Cite journal | doi = 10.1002/dmrr.1276| issn = 1520-7560| volume = 27 | issue = 8| pages = 942–945| last1 = Bock | first1 = Gerlies | last2 = Prietl | first2 = Barbara | last3 = Mader | first3 = Julia K. | last4 = Höller | first4 = Evelyne | last5 = Wolf | first5 = Michael | last6 = Pilz | first6 = Stefan | last7 = Graninger | first7 = Winfried B. | last8 = Obermayer-Pietsch | first8 = Barbara M. | last9 = Pieber | first9 = Thomas R.| title = The effect of vitamin D supplementation on peripheral regulatory T cells and β cell function in healthy humans: a randomized controlled trial| journal = Diabetes/Metabolism Research and Reviews| date = Nov 2011 | pmid = 22069289 | url = https://pubmed.ncbi.nlm.nih.gov/22069289 }}</ref>
<ref name="smolders2009">{{Cite journal | doi = 10.1371/journal.pone.0006635| issn = 1932-6203| volume = 4 | issue = 8| pages = 6635| last1 = Smolders | first1 = Joost | last2 = Thewissen | first2 = Mariëlle | last3 = Peelen | first3 = Evelyn | last4 = Menheere | first4 = Paul | last5 = Tervaert | first5 = Jan Willem Cohen | last6 = Damoiseaux | first6 = Jan | last7 = Hupperts | first7 = Raymond| title = Vitamin D Status Is Positively Correlated with Regulatory T Cell Function in Patients with Multiple Sclerosis| journal = PLOS ONE| access-date = 2016-11-10| date = 2009-08-13| url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0006635}}</ref> and in patients with relapsing remitting [[multiple sclerosis]],<ref name="smolders2009" /> suggesting that it may play a role in both preventing and ameliorating [[autoimmune disease]]. Experimental studies have shown that vitamin D helps protect against a proliferation of [[CD4+ T cell]]s, and reduces the number of [[Th1]] and [[interleukin 17|IL-17]] cytokines.<ref name="Paul2011">https://www.atsjournals.org/doi/full/10.1164/rccm.201108-1502CI</ref> 

== Infectious disease ==

Vitamin D deficiency increases the risk of viral infections.{{Citation needed}}

===Epstein-Barr virus===

An [[Epstein-Barr virus]] protein [[EBNA]]-3 has an affinity for the [[Vitamin D receptor]] and may actually block the activation of VDR-dependent genes by Vitamin D.<ref name="hellman2010">{{Cite journal| doi = 10.1007/s00018-010-0441-4| issn = 1420-9071| volume = 67 | issue = 24| pages = 4249–4256| last1 = Yenamandra | first1 = Surya Pavan | last2 = Hellman | first2 = Ulf | last3 = Kempkes | first3 = Bettina | last4 = Darekar | first4 = Suhas Deoram | last5 = Petermann | first5 = Sabine | last6 = Sculley | first6 = Tom | last7 = Klein | first7 = George | last8 = Kashuba | first8 = Elena | title = Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes| journal = Cellular and molecular life sciences: CMLS| date = Dec 2010 | pmid = 20593215 | url = https://doi.org/10.1007%2Fs00018-010-0441-4 }}</ref>

==Deficiency ==
Vitamin D deficiency can cause complex medical problems, and because vitamin D cannot be absorbed from sunlight shining through windows, people who are [[severe and very severe ME|mostly or totally housebound]] are particularly at risk of Vitamin D deficiency.{{citation needed | date = 2022}}

{{See also|Vitamin D deficiency}}

==Supplementation==

===Recommended level===

The recommended blood level of Vitamin D varies considerably by government body and health society. 

The US [[Institute of Medicine]] suggests levels between 20 ng/ml and 50ng/ml.<ref name="mayovitd">{{cite web | last = Theimer | first= Sharon | date = 2015-03-15 | title =  Vitamin D Toxicity Rare in People Who Take Supplements, Mayo Clinic Study Finds|url= http://newsnetwork.mayoclinic.org/discussion/vitamin-d-toxicity-rare-in-people-who-take-supplements-mayo-clinic-study-finds/| publisher= Mayo Clinic News Network|access-date= 2016-11-10}}</ref>

The Vitamin D Council suggests a level of 50 ng/ml or 125 nmol/l as ideal.<ref name="VitDcouncil">[https://www.vitamindcouncil.org/about-vitamin-d/testing-for-vitamin-d/ Vitamin D Council - Testing for vitamin D]</ref><ref name="Why50nmgl">[https://www.vitamindcouncil.org/blog/why-should-you-keep-your-vitamin-d-level-around-50-ngml/ Vitamin D Council - Why should you keep your vitamin D level around 50 ng/ml?]</ref>

In the [[United States]], 41.6% have serum levels below 20 ng/ml, the threshold for deficiency or 82.1% of African-Americans and 69.2% of Hispanics.<ref name="forrest2011">{{Cite journal| doi = 10.1016/j.nutres.2010.12.001| issn = 1879-0739| volume = 31 | issue = 1| pages = 48–54| last1 = Forrest | first1 = Kimberly Y. Z. | last2 = Stuhldreher | first2 = Wendy L.| title = Prevalence and correlates of vitamin D deficiency in US adults| journal = Nutrition Research (New York, N.Y.)| date = Jan 2011 | pmid = 21310306 | url = https://tahomaclinic.com/Private/Articles4/WellMan/Forrest%202011%20-%20Prevalence%20and%20correlates%20of%20vitamin%20D%20deficiency%20in%20US%20adults.pdf }}</ref>

===Toxicity===

Taking very high Vitamin D levels long term can cause [[hypercalcemia]], which causes serious health problems, although more serious effects like kidney stones are relatively rare. Taking very high amounts of [[calcium]] (1,000mg daily) combined with moderate levels of vitamin D can also be harmful. The NHS and the US Office of Dietary Supplements both recommend a maximum daily limit of 100mcg (4,000IU).<ref name="mayovitd" />

== ME/CFS ==

A retrospective study found patients with CFS have lower levels of Vitamin D than the general population. However, it was uncertain whether this is correlated with the amount of time CFS patients spend indoors or with some other factor.<ref name="berkovitz2013">{{Cite journal | doi = 10.1024/0300-9831.79.4.250| issn = 0300-9831| volume = 79 | issue = 4| pages = 250–254| last1 = Berkovitz | first1 = Saul | authorlink = Saul Berkovitz | last2 = Ambler | first2 = Gareth | last3 = Jenkins | first3 = Michael | last4 = Thurgood | first4 = Sue| title = Serum 25-hydroxy Vitamin D Levels in Chronic Fatigue Syndrome: a Retrospective Survey| journal = International Journal for Vitamin and Nutrition Research| date = 2009-07-01| url = http://econtent.hogrefe.com/doi/abs/10.1024/0300-9831.79.4.250}}</ref><ref name="abokrysha2012">{{Cite journal | doi = 10.1111/j.1526-4637.2011.01304.x| issn = 1526-4637| volume = 13 | issue = 3| pages = 452–458| last = Abokrysha | first = Noha T.| title = Vitamin D deficiency in women with fibromyalgia in Saudi Arabia| journal = Pain Medicine (Malden, Mass.)| date = March 2012 | pmid = 22221390 | url = https://academic.oup.com/painmedicine/article/13/3/452/1852088}}</ref>

Raising Vitamin D levels has reportedly resulted in remission for some CFS patients.<ref name="IACFSME">[https://iacfsme.org/PDFS/Attachment-E-Annedore-Hoeck,-Vitamin-D.aspx IACFS/ME - Vitamin D deficiency results in chronic fatigue and multi-system symptoms]</ref>

Recent research has found no toxicity at 10,000 IU per day and levels as high as 15,000 IU/day are probably tolerated.{{citation needed | date = 2022}}  At this dosage it will take 75-90 before symptom improvement is expected to be seen.  Some people have seen some symptoms improved within days, but those are likely a small minority.{{Citation needed}}

In 2015, Witham et al. found that high-dose oral vitamin D3 did not improve markers of vascular health or fatigue in patients with [[chronic fatigue syndrome]]. The study consisted of patients meeting the the [[Fukuda criteria]] (1994) for CFS and the [[Canadian Consensus Criteria|Canadian (2003) ME/CFS criteria]] who were either given 100,000 units oral vitamin D3 or a matching placebo every 2 months for 6 months.<ref name="Witham2015" />

In 2017, a study by Earl et al. concluded that low serum concentrations of total 25(OH)D do not appear to be a contributing factor to the level of fatigue of CFS/ME.<ref name="Earl2017">[https://doi.org/10.11136/bmjopen-2016-015296 Earl KE, Sakellariou GK, Sinclair M, et al. Vitamin D status in chronic fatigue syndrome/myalgic encephalomyelitis: a cohort study from the North-West of England. BMJ Open. 2017;7(11):e015296. doi:10.1136/bmjopen-2016-015296]</ref> 

== Fibromyalgia ==

A cohort of Saudi women with [[fibromyalgia]] was found to be Vitamin D deficient. Vitamin D status was inversely correlated with [[pain]]. High dose Vitamin D supplementation resulted in improvement or resolution of symptoms.<ref name="abokrysha2012" /> A second study also found improvement of symptoms with Vitamin D supplementation.<ref name="matthana2011">{{Cite journal | issn = 0379-5284| volume = 32 | issue = 9| pages = 925–929| last = Matthana | first = Mona H.| title = The relation between vitamin D deficiency and fibromyalgia syndrome in women| journal = Saudi Medical Journal| date = Sep 2011 | pmid = 21894355 | url = https://pubmed.ncbi.nlm.nih.gov/21894355/ }}</ref>

== Autoimmune disease ==

Low vitamin D is a possible or known risk factor for [[systemic lupus erythematosus]],<ref name="kamen2006">{{Cite journal | doi = 10.1016/j.autrev.2005.05.009| issn = 1568-9972| volume = 5 | issue = 2| pages = 114–117| last1 = Kamen | first1 = Diane L. | last2 = Cooper | first2 = Glinda S. | last3 = Bouali | first3 = Henda | last4 = Shaftman | first4 = Stephanie R. | last5 = Hollis | first5 = Bruce W. | last6 = Gilkeson | first6 = Gary S.| title = Vitamin D deficiency in systemic lupus erythematosus| journal = Autoimmunity Reviews| series = Special Issue on CIS Spring School of Autoimmune Diseases| access-date = 2016-11-10| date = February 2006| url = http://www.sciencedirect.com/science/article/pii/S1568997205000935}}</ref> [[multiple sclerosis]], [[rheumatoid arthritis]], type 1 diabetes,<ref name="Paul2011" /> [[inflammatory bowel disease]],<ref name="cantorna2004">{{Cite journal | issn = 1535-3702| volume = 229 | issue = 11| pages = 1136–1142| last1 = Cantorna | first1 = Margherita T. | last2 = Mahon | first2 = Brett D. | title = Mounting Evidence for Vitamin D as an Environmental Factor Affecting Autoimmune Disease Prevalence| journal = Experimental Biology and Medicine | date = 2004-12-01| url = http://ebm.sagepub.com/content/229/11/1136 | pmid = 15564440}}</ref> alopecia areata (an autoimmune disease causing hair to fall out),<ref name="vdr" /> and the autoimmune thyroid disease [[Hashimoto's thyroiditis (hypothyroidism)]].<ref name="bizzaro2015">{{Cite journal | doi = 10.1007/s12026-014-8579-z| issn = 1559-0755| volume = 61 | issue = 1-2| pages = 46–52| last1 = Bizzaro | first1 = Giorgia | last2 = Shoenfeld | first2 = Yehuda | title = Vitamin D and autoimmune thyroid diseases: facts and unresolved questions| journal = Immunologic Research| date = February 2015 | pmid = 25407646 | url = https://pubmed.ncbi.nlm.nih.gov/25407646/}}</ref> Active [[Crohn's disease]] has also been found to be associated with lower Vitamin D levels.<ref name="hvas2013">{{Cite journal| doi = 10.1016/j.crohns.2013.01.012| issn = 1876-4479| volume = 7 | issue = 10| pages = 407-413| last1 = Jørgensen | first1 = Søren Peter | last2 = Hvas | first2 = Christian Lodberg | last3 = Agnholt | first3 = Jørgen | last4 = Christensen | first4 = Lisbet Ambrosius | last5 = Heickendorff | first5 = Lene | last6 = Dahlerup | first6 = Jens Frederik| title = Active Crohn's disease is associated with low vitamin D levels| journal = Journal of Crohn's & Colitis| date = November 2013 | pmid = 23403039 | url = https://academic.oup.com/ecco-jcc/article/7/10/e407/379813}}</ref>

===Multiple sclerosis===

Among people with early stage [[multiple sclerosis]] (MS), those with higher vitamin D levels had better outcomes five years after follow up.<ref name="NIHvitd">{{Citation | last = Torgan | first =  Carol | date = 2014-02-03 | title =  Vitamin D Levels Predict Multiple Sclerosis Progression|url= http://www.nih.gov/news-events/nih-research-matters/vitamin-d-levels-predict-multiple-sclerosis-progression|newspaper= NIH Research Matters|access-date= 2016-11-10}}</ref><ref name="ms-trust-vitaminD" />

It is theorized that there may be a link between low Vitamin D, [[Epstein-Barr virus]] and MS.<ref name="holmoy2008">{{Cite journal| doi = 10.1016/j.mehy.2007.04.030| issn = 0306-9877| volume = 70 | issue = 1| pages = 66–69| last = Holmøy | first = Trygve| title = Vitamin D status modulates the immune response to Epstein Barr virus: Synergistic effect of risk factors in multiple sclerosis| journal = Medical Hypotheses| access-date = 2016-11-10| date = 2008| url = http://www.sciencedirect.com/science/article/pii/S0306987707003167}}</ref>
<ref name="ms-trust-vitaminD">{{Cite web|url=https://mstrust.org.uk/life-ms/diet/vitamin-d|title=Vitamin D|website=MS Trust|language=en|access-date=2021-03-11}}</ref><ref name="ms-trust-ebv">{{Cite web|url=https://mstrust.org.uk/a-z/epstein-barr-virus|title=Epstein Barr virus|website=MS Trust|language=en|access-date=2021-03-11}}</ref>

There are high levels of both vitamin D deficiency among Scotland's 15,000 MS sufferers;<ref name="ms-scotland">{{Cite web|url=https://www.mssociety.org.uk/contact-us/scotland|title=Scotland | last = | first =  | author-link =| date = |website=Multiple Sclerosis Society UK|language=en|archive-url=|archive-date=|url-status=|access-date=2021-03-11}}</ref> Scotland has the highest prevalence of MS anywhere in the world at over 200 per 100,000 of the population, with over 400 per 100,000 in Orkney, and Scottish ancestry is a recognized risk factor.<ref name="Tarlington2019">{{Cite journal | last = Tarlinton | first = Rachael Eugenie|author-link = | last2 = Khaibullin | first2=Timur | author-link2 = | last3 = Granatov | first3 = Evgenii | author-link3 = | last4 = Martynova | first4 = Ekaterina | authorlink4 = | last5 = Rizvanov | first5 = Albert | authorlink5 = |last6 = Khaiboullina | first6 = Svetlana | authorlink6 =  | date = Jan 2019 | title = The Interaction between Viral and Environmental Risk Factors in the Pathogenesis of Multiple Sclerosis|url=https://www.mdpi.com/1422-0067/20/2/303|journal=International Journal of Molecular Sciences|language=en|volume=20|issue=2|pages=303|doi=10.3390/ijms20020303|pmc=|pmid=|access-date=|quote=|via=}}</ref><ref name="ms-trust">{{Cite web|url=https://mstrust.org.uk/a-z/prevalence-and-incidence-multiple-sclerosis|title=Prevalence and incidence of multiple sclerosis|website=MS Trust|language=en|access-date=2021-03-11}}</ref>

==Notable studies==
*2014, Association between vitamin D status and markers of vascular health in patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)<ref name="Witham2014">{{Cite journal | last1 = Witham | first1 = Miles  | authorlink1 = | last2 = Kennedy | first2 = Gwen | authorlink2 = | last3 = Belch | first3 = Jill | authorlink3 = | last4 = Hill | first4 = Alexander | authorlink4 = | last5 = Khan | first5 = Faisel | authorlink5 = Faisel Khan | title   = Association between vitamin D status and markers of vascular health in patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) | journal = International Journal of Cardiology  | volume = 174 | issue = 1   | page = 139 - 140 | date = 2014 | pmid = 25455721 | url = https://www.researchgate.net/profile/Jill-Belch/publication/261292125_Association_between_vitamin_D_status_and_markers_of_vascular_health_in_patients_with_chronic_fatigue_syndromemyalgic_encephalomyelitis_CFSME/links/5e1ddc32a6fdcc28e9c70319/Association-between-vitamin-D-status-and-markers-of-vascular-health-in-patients-with-chronic-fatigue-syndrome-myalgic-encephalomyelitis-CFS-ME.pdf
 | doi = 10.1016/j.ijcard.2014.03.145}}</ref> 
*2015, Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome – A randomised controlled trial<ref name="Witham2015">{{Cite journal | last1 = Witham | first1 = MD | authorlink1 = | last2 = Adams | first2 = F  | authorlink2 = | last3 = McSwiggan | first3 = S  | authorlink3 = | last4 = Kennedy | first4 = G | authorlink4 = | last5 = Kabir | first5 = G | authorlink5 = | last6 = Belch | first6 = JJ | authorlink6 = | last7 = Khan | first7 = F | authorlink7 = Faisel Khan | title = Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome – A randomised controlled trial | journal = Nutrition, Metabolism and Cardiovascular Diseases | volume = 25 | issue = 3 | page = 287-294 | date = 2015 | url = https://www.nmcd-journal.com/article/S0939-4753(14)00315-9/fulltext | pmid = 25455721  | doi =10.1016/j.numecd.2014.10.007}}</ref>
*2017, Vitamin D status in chronic fatigue syndrome/myalgic encephalomyelitis: a cohort study from the North-West of England <ref name="Earl2017" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695299/ (Full Text)] 
*2018, Exogenous VD3 alleviates chronic fatigue syndrome by activating MEKs/ERKs-SIRT1 signaling pathway in skeletal muscle<ref name="Wu2018">{{Cite journal | last =Wu | first = Fangnan | last2 = Huder | first2=Chaolu | last3 = Tian | first3=Zhenjun | date = 2018-10-04 | title = PO-132 Exogenous VD3 alleviates chronic fatigue syndrome by activating MEKs/ERKs-SIRT1 signaling pathway in skeletal muscle|url=https://ojs.uclouvain.be/index.php/EBR/article/view/10353|journal=Exercise Biochemistry Review|language=en|volume=1|issue=4|doi=10.14428/ebr.v1i4.10353|issn=2593-7588}}</ref> [https://ojs.uclouvain.be/index.php/EBR/article/view/10353 (Abstract)]

==See also==
*[[Vitamin D deficiency]]
*[[Photophobia]] (light sensitivity)
*[[Severe and very severe ME]]
*[[Dr Lapp's supplement recommendations]]
*[[Malnutrition]]

==Learn more==
*[http://lpi.oregonstate.edu/mic/vitamins/vitamin-D Linus Pauling Institute Micronutrient Information Center - Vitamin D]
*[https://www.drugs.com/vitamin-d.html Vitamin D] - drugs.com
*[https://medlineplus.gov/ency/article/002405.htm Vitamin D] - MedlinePlus Encyclopedia

==References ==
{{reflist}}
[[Category:Potential treatments]]
[[Category:Supplements]]
[[Category:Vitamins]]
[[Category:Nutrients]]