Vitamin D: Difference between revisions

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=== Vitamin D2 ===
=== 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 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 ===
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== Immune function ==
== 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>
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>  
<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 ==
== Infectious disease ==
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===Epstein-Barr virus===
===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>
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 ==
==Deficiency ==
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The recommended blood level of Vitamin D varies considerably by government body and health society.  
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 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>
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>
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===
===Toxicity===
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== ME/CFS ==
== 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 | author-link=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>
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>
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>
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== Fibromyalgia ==
== 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>
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 ==
== 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>
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===
===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" />
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>
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>
<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=|authorlink= | 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>
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==
==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
*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>  
  | 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>
*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)]  
*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)]
*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==
==See also==

Latest revision as of 22:21, May 18, 2023

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

Function[edit | edit source]

Vitamin D is fat-soluble, regulates calcium levels, helps modulate the immune system, and is vital to good bone health.[1][2]

Vitamin D2[edit | edit source]

Vitamin D2, known as ergocalciferol, is a vitamin D found in plants, mushrooms, and yeasts, and sometimes in foods fortified with vitamin D.[3]

Vitamin D3[edit | edit source]

Vitamin D3, known as cholecalciferol, is synthesized in the human skin from the UVB radiation in sunlight. D3 can also be obtained from supplements.[3]

VDR gene[edit | edit source]

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.[1] Vitamin D-dependent rickets, alopecia areata (an autoimmune disease), intervertebral disc disease, kidney stones and leprosy have all been linked to the VDR gene.[1]

Immune function[edit | edit source]

Vitamin D improves regulatory T cell function in healthy adults[4] [5] and in patients with relapsing remitting multiple sclerosis,[5] 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 cells, and reduces the number of Th1 and IL-17 cytokines.[2]

Infectious disease[edit | edit source]

Vitamin D deficiency increases the risk of viral infections.[citation needed]

Epstein-Barr virus[edit | edit source]

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.[6]

Deficiency[edit | edit source]

Vitamin D deficiency can cause complex medical problems, and because vitamin D cannot be absorbed from sunlight shining through windows, people who are mostly or totally housebound are particularly at risk of Vitamin D deficiency.[citation needed]

Supplementation[edit | edit source]

Recommended level[edit | edit source]

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.[7]

The Vitamin D Council suggests a level of 50 ng/ml or 125 nmol/l as ideal.[8][9]

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.[10]

Toxicity[edit | edit source]

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).[7]

ME/CFS[edit | edit source]

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.[11][12]

Raising Vitamin D levels has reportedly resulted in remission for some CFS patients.[13]

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] 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 (2003) ME/CFS criteria who were either given 100,000 units oral vitamin D3 or a matching placebo every 2 months for 6 months.[14]

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.[15]

Fibromyalgia[edit | edit source]

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.[12] A second study also found improvement of symptoms with Vitamin D supplementation.[16]

Autoimmune disease[edit | edit source]

Low vitamin D is a possible or known risk factor for systemic lupus erythematosus,[17] multiple sclerosis, rheumatoid arthritis, type 1 diabetes,[2] inflammatory bowel disease,[18] alopecia areata (an autoimmune disease causing hair to fall out),[1] and the autoimmune thyroid disease Hashimoto's thyroiditis (hypothyroidism).[19] Active Crohn's disease has also been found to be associated with lower Vitamin D levels.[20]

Multiple sclerosis[edit | edit source]

Among people with early stage multiple sclerosis (MS), those with higher vitamin D levels had better outcomes five years after follow up.[21][22]

It is theorized that there may be a link between low Vitamin D, Epstein-Barr virus and MS.[23] [22][24]

There are high levels of both vitamin D deficiency among Scotland's 15,000 MS sufferers;[25] 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.[26][27]

Notable studies[edit | edit source]

  • 2014, Association between vitamin D status and markers of vascular health in patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)[28]
  • 2015, Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome – A randomised controlled trial[14]
  • 2017, Vitamin D status in chronic fatigue syndrome/myalgic encephalomyelitis: a cohort study from the North-West of England [15] (Full Text)
  • 2018, Exogenous VD3 alleviates chronic fatigue syndrome by activating MEKs/ERKs-SIRT1 signaling pathway in skeletal muscle[29] (Abstract)

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. 1.0 1.1 1.2 1.3 https://medlineplus.gov/genetics/gene/vdr/
  2. 2.0 2.1 2.2 https://www.atsjournals.org/doi/full/10.1164/rccm.201108-1502CI
  3. 3.0 3.1 "Vitamin D". Linus Pauling Institute. April 22, 2014. Retrieved December 23, 2018.
  4. Bock, Gerlies; Prietl, Barbara; Mader, Julia K.; Höller, Evelyne; Wolf, Michael; Pilz, Stefan; Graninger, Winfried B.; Obermayer-Pietsch, Barbara M.; Pieber, Thomas R. (November 2011). "The effect of vitamin D supplementation on peripheral regulatory T cells and β cell function in healthy humans: a randomized controlled trial". Diabetes/Metabolism Research and Reviews. 27 (8): 942–945. doi:10.1002/dmrr.1276. ISSN 1520-7560. PMID 22069289.
  5. 5.0 5.1 Smolders, Joost; Thewissen, Mariëlle; Peelen, Evelyn; Menheere, Paul; Tervaert, Jan Willem Cohen; Damoiseaux, Jan; Hupperts, Raymond (August 13, 2009). "Vitamin D Status Is Positively Correlated with Regulatory T Cell Function in Patients with Multiple Sclerosis". PLOS ONE. 4 (8): 6635. doi:10.1371/journal.pone.0006635. ISSN 1932-6203. Retrieved November 10, 2016.
  6. Yenamandra, Surya Pavan; Hellman, Ulf; Kempkes, Bettina; Darekar, Suhas Deoram; Petermann, Sabine; Sculley, Tom; Klein, George; Kashuba, Elena (December 2010). "Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes". Cellular and molecular life sciences: CMLS. 67 (24): 4249–4256. doi:10.1007/s00018-010-0441-4. ISSN 1420-9071. PMID 20593215.
  7. 7.0 7.1 Theimer, Sharon (March 15, 2015). "Vitamin D Toxicity Rare in People Who Take Supplements, Mayo Clinic Study Finds". Mayo Clinic News Network. Retrieved November 10, 2016.
  8. Vitamin D Council - Testing for vitamin D
  9. Vitamin D Council - Why should you keep your vitamin D level around 50 ng/ml?
  10. Forrest, Kimberly Y. Z.; Stuhldreher, Wendy L. (January 2011). "Prevalence and correlates of vitamin D deficiency in US adults" (PDF). Nutrition Research (New York, N.Y.). 31 (1): 48–54. doi:10.1016/j.nutres.2010.12.001. ISSN 1879-0739. PMID 21310306.
  11. Berkovitz, Saul; Ambler, Gareth; Jenkins, Michael; Thurgood, Sue (July 1, 2009). "Serum 25-hydroxy Vitamin D Levels in Chronic Fatigue Syndrome: a Retrospective Survey". International Journal for Vitamin and Nutrition Research. 79 (4): 250–254. doi:10.1024/0300-9831.79.4.250. ISSN 0300-9831.
  12. 12.0 12.1 Abokrysha, Noha T. (March 2012). "Vitamin D deficiency in women with fibromyalgia in Saudi Arabia". Pain Medicine (Malden, Mass.). 13 (3): 452–458. doi:10.1111/j.1526-4637.2011.01304.x. ISSN 1526-4637. PMID 22221390.
  13. IACFS/ME - Vitamin D deficiency results in chronic fatigue and multi-system symptoms
  14. 14.0 14.1 Witham, MD; Adams, F; McSwiggan, S; Kennedy, G; Kabir, G; Belch, JJ; Khan, F (2015). "Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome – A randomised controlled trial". Nutrition, Metabolism and Cardiovascular Diseases. 25 (3): 287-294. doi:10.1016/j.numecd.2014.10.007. PMID 25455721.
  15. 15.0 15.1 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
  16. Matthana, Mona H. (September 2011). "The relation between vitamin D deficiency and fibromyalgia syndrome in women". Saudi Medical Journal. 32 (9): 925–929. ISSN 0379-5284. PMID 21894355.
  17. Kamen, Diane L.; Cooper, Glinda S.; Bouali, Henda; Shaftman, Stephanie R.; Hollis, Bruce W.; Gilkeson, Gary S. (February 2006). "Vitamin D deficiency in systemic lupus erythematosus". Autoimmunity Reviews. Special Issue on CIS Spring School of Autoimmune Diseases. 5 (2): 114–117. doi:10.1016/j.autrev.2005.05.009. ISSN 1568-9972. Retrieved November 10, 2016.
  18. Cantorna, Margherita T.; Mahon, Brett D. (December 1, 2004). "Mounting Evidence for Vitamin D as an Environmental Factor Affecting Autoimmune Disease Prevalence". Experimental Biology and Medicine. 229 (11): 1136–1142. ISSN 1535-3702. PMID 15564440.
  19. Bizzaro, Giorgia; Shoenfeld, Yehuda (February 2015). "Vitamin D and autoimmune thyroid diseases: facts and unresolved questions". Immunologic Research. 61 (1–2): 46–52. doi:10.1007/s12026-014-8579-z. ISSN 1559-0755. PMID 25407646.
  20. Jørgensen, Søren Peter; Hvas, Christian Lodberg; Agnholt, Jørgen; Christensen, Lisbet Ambrosius; Heickendorff, Lene; Dahlerup, Jens Frederik (November 2013). "Active Crohn's disease is associated with low vitamin D levels". Journal of Crohn's & Colitis. 7 (10): 407–413. doi:10.1016/j.crohns.2013.01.012. ISSN 1876-4479. PMID 23403039.
  21. Torgan, Carol (February 3, 2014), "Vitamin D Levels Predict Multiple Sclerosis Progression", NIH Research Matters, retrieved November 10, 2016
  22. 22.0 22.1 "Vitamin D". MS Trust. Retrieved March 11, 2021.
  23. Holmøy, Trygve (2008). "Vitamin D status modulates the immune response to Epstein Barr virus: Synergistic effect of risk factors in multiple sclerosis". Medical Hypotheses. 70 (1): 66–69. doi:10.1016/j.mehy.2007.04.030. ISSN 0306-9877. Retrieved November 10, 2016.
  24. "Epstein Barr virus". MS Trust. Retrieved March 11, 2021.
  25. "Scotland". Multiple Sclerosis Society UK. Retrieved March 11, 2021.
  26. Tarlinton, Rachael Eugenie; Khaibullin, Timur; Granatov, Evgenii; Martynova, Ekaterina; Rizvanov, Albert; Khaiboullina, Svetlana (January 2019). "The Interaction between Viral and Environmental Risk Factors in the Pathogenesis of Multiple Sclerosis". International Journal of Molecular Sciences. 20 (2): 303. doi:10.3390/ijms20020303.
  27. "Prevalence and incidence of multiple sclerosis". MS Trust. Retrieved March 11, 2021.
  28. Witham, Miles; Kennedy, Gwen; Belch, Jill; Hill, Alexander; Khan, Faisel (2014). "Association between vitamin D status and markers of vascular health in patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)" (PDF). International Journal of Cardiology. 174 (1): 139 - 140. doi:10.1016/j.ijcard.2014.03.145. PMID 25455721.
  29. Wu, Fangnan; Huder, Chaolu; Tian, Zhenjun (October 4, 2018). "PO-132 Exogenous VD3 alleviates chronic fatigue syndrome by activating MEKs/ERKs-SIRT1 signaling pathway in skeletal muscle". Exercise Biochemistry Review. 1 (4). doi:10.14428/ebr.v1i4.10353. ISSN 2593-7588.