Advanced vitamin D topics - some people need much more D3 than normal, to suppress rheumatoid arthritis, multiple sclerosis, psoriasis etc.; newly discovered vitamin D compounds

This page is not at all complete.   I intend to add discussion of the articles listed below, and others, probably in September.

Before reading this page, please familiarise yourself with the research articles I link to and discuss at:
What every MD should know about vitamin D and the immune system
https://vitamindstopscovid.info/05-mds/

This page assumes a strong interest in biology and treatment arrangements which go not only beyond many MD's limited knowledge of vitamin D, but also beyond a properly informed knowledge of the needs for most people for D3 supplementation to enable the immune system to work well, as described in the above-mentioned page.

If you have this strong interest, a reasonable knowledge of biology and the ability to make your own decisions, even tentatively so, about your own and your family's health, then you might like to join the Nutrition for Immune System Health (NISH) email discussion list: https://NISH.groups.io .  This is a high-signal-to-noise ratio discussion group with MDs and nurses (only one so far), leading vitamin D researchers (many of whom are MDs), nutritionists, as well as autodidacts such as myself with no formal qualifications.


../ To the main page of this site.

Robin Whittle rw@firstpr.com.au  23 July 2021    Twitter: https://twitter.com/RobinWhittle3
(First established 2021-07-16.)

Disclaimer:

You are reading the best efforts of an electronic technician and computer programmer.   What I write will hopefully help you understand the research, but should not be mistaken for medical advice.  Medical advice is what you get after a doctor has examined you.  Even if I was a doctor, I haven't examined you!

Don't take my word for anything.  Please read the research articles I cite - or at least their abstracts and my summaries.  If you don't understand them, please ask your doctor or other healthcare professional to read them and advise you. 


Quick intro and some articles of interest

The articles linked to from the  ../05-mds/ page are broadly sufficient to understand everyone's need for circulating 25-hydroxyvitamin D levels of 50ng/ml 125nmol/L or more, in order that the immune system can work properly.  This is normally best achieved with supplemental vitamin D3, though in emergencies, a single, small, oral dose of calcifediol repletes these levels in about 4 hours.  Calcifediol is the name most commonly used for 25-hydroxyvitamin D as a pharmaceutical.

This applies directly to humans, but much the same is true of companion and agricultural non-human animals - who, without proper supplementation - may not be getting the D3 they need to be healthy.

After completing this page, I plan to write another page linking to and discussing research articles on vitamin D toxicity. 

This page concerns:
I can't write about all this yet, since I need to carefully read the articles first!

Regarding higher than normal D3 intakes to suppress autoimmune overly-inflammatory conditions:

The Coimbra Protocol

This was developed by Dr Cicero Coimbra in Brazil to suppress MS (Multiple Sclerosis) and potentially other autoimmune diseases.   I know two people who have used this approach to successfully suppress extremely debilitating rheumatoid arthritis.

https://www.coimbraprotocol.com/the-protocol-1

https://www.grassrootshealth.net/blog/dr-coimbras-protocol-multiple-sclerosis/


Patrick McCullough and colleagues in Ohio

Dr McCullough takes 1.25mg 50,000IU D3 a day to suppress psoriasis.  He and his colleagues research healthy D3 intakes for most people, and the much higher intakes which (with suitable medical supervision) suppress a variety of auto-immune diseases.

Daily oral dosing of vitamin D3 using 5000 TO 50,000 international units a day in long-term hospitalized patients: Insights from a seven year experience
Patrick J McCullough, Douglas S Lehrer and Jeffrey Amend.
Journal of Steroid Biochemistry and Molecular Biology 2019-01-04
https://www.sciencedirect.com/science/article/abs/pii/S0960076018306228 (Paywalled.)
https://sci-hub.se/10.1016/j.jsbmb.2018.12.010


Oral and Topical Vitamin D, Sunshine, and UVB Phototherapy Safely Control Psoriasis in Patients with Normal Pretreatment Serum 25-hydroxyvitamin D Concentrations: A Literature Review and Discussion of Health Implications
Patrick J McCullough, William McCullough, Douglas Lehrer, Jeffrey Travers and Steven Repas.
Nutrients 2021-04-27
https://www.mdpi.com/2072-6643/13/5/1511

Pete Batcheller - cluster headaches and migraine

The above two MDs are world leaders in clinical research regarding higher than normal D3 intakes to suppress MS, rheumatoid arthritis, psoriasis etc. - all of which are well known to be caused by excessive inflammation.

Pete Batcheller (Washington State, USA) is another such pioneer, though he has no medical qualifications.  He has a chemistry degree and is a retired US Navy fighter pilot and commander.  His research and outreach was prompted by his own debilitating cluster headaches.  

He has helped several thousand cluster headache and migraine sufferers suppress their symptoms with a protocol which resembles that of Dr Coimbra - with whom he later corresponded.  The link between excessive inflammation and his own cluster headaches was made clear in after he cleared the windscreen of his pickup truck of a layer of pollen which had settled there.  His D3, boron and other nutrients protocol had kept the CHs in abeyance for years, but they returned with a vengeance within hours of this gross pollen insult to his immune system.

Pete Batcheller's success in largely suppressing these awful conditions, with the help of people who he communicates with via his website, shows that there are significant human health problems which are not yet solved by MDs and professional researchers, but which are amenable solution to imaginative, highly motivated people who lack formal qualifications.

http://www.clusterheadaches.com


Here are some of the new articles I want to read and discuss on this page.

Helminths downmodulate inflammatory responses

Lack of helminthic down-modulation of overly inflammatory immune responses, evolved to counter such down-modulation, is a likely component of the etiology of these diseases:

Helminths-based bi-functional molecule, tuftsin-phosphorylcholine (TPC), ameliorates an established murine arthritis
Miri Blank, Tomer Bashi, Jordan Lachnish, Dana Ben-Ami-Shor, Ora Shovman, Mati Fridkin, Miriam Eisenstein, Alexander Volkov, Iris Barshack and Yehuda Shoenfeld.
PLoS One 2018-08-08
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0200615

Some people find relief by the introduction of helminths: https://helminthictherapywiki.org  and:

Trichuris suis therapy in Crohn’s disease
R W Summers, D E Elliott, J F Urban Jr, R Thompson and J V Weinstock  Gut 2005
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774382/


Mechanisms by which higher than normal D3 intakes might help suppress auto-immune hyper-inflammatory diseases

Vitamin D Resistance as a Possible Cause of Autoimmune Diseases: A Hypothesis Confirmed by a Therapeutic High-Dose Vitamin D Protocol
Dirk Lemke, Rainer Johannes Klement, Felix Schweiger, Beatrix Schweiger and Jörg Spitz
Frontiers in Immunology 2021-04-07
https://www.frontiersin.org/articles/10.3389/fimmu.2021.655739/=

An older Crohn's disease article.  I want to find some more recent ones too. See the articles which cite this one:

Therapeutic Effect of Vitamin D Supplementation in a Pilot Study of Crohn's Patients
Linlin Yang; Veronika Weaver; Jill, Smith; Sandra, Bingaman; Terry, Hartman and Margherita Cantorna
Clinical and Translational Gastroenterology 2013-01-13
https://journals.lww.com/ctg/...Therapeutic_Effect....aspx

176 Google citations.

Recently discovered - or at least little known to MDs - but potentially significant vitamin D compounds

Add a hydroxyl group to the 20th carbon in D3 and . . .

20S-Hydroxyvitamin D3, a Secosteroid Produced in Humans, Is Anti-Inflammatory and Inhibits Murine Autoimmune Arthritis
Arnold E. Postlethwaite, Robert C. Tuckey, Tae-Kang Kim, Wei Li, Syamal K. Bhattacharya, Linda K. Myers, David D. Brand, and Andrzej T. Slominski
Frontiers in Immunology 2021-06-30
https://www.frontiersin.org/articles/10.3389/fimmu.2021.678487/

Sulphated 25-hydroxyvitamin D is prevalent in the circulation:

The serum vitamin D metabolome: What we know and what is still to discover
Robert C. Tuckey, Chloe Y.S. Cheng, Andrzej T.Slominski
Journal of Steroid Biochemistry and Molecular Biology  2018-09-04
https://www.sciencedirect.com/science/article/abs/pii/S0960076018302206 (Paywalled.)
https://sci-hub.se/10.1016/j.jsbmb.2018.09.003
60 Google citations.

Regulation of circulating 25-hydroxyvitamin D levels by enzymes which degrade it, at rates approximately proportional to its concentration, forming a negative feedback system which makes it harder to raise higher levels than lower levels

I have a general idea that this works, but would like to know a lot more about the mechanisms and to what extent they are affected by and affect D3 levels - and more broadly conversion of D3 to 25OHD in cells outside the liver.

See the above-mentioned article: The serum vitamin D metabolome . . . .


#ra

Connections between Rheumatoid Arthritis (RA), psoriasis and potentially other conditions - and some cell-biology hypotheses of contributing causes

Perhaps there is a way of connecting tenuous knowledge of:
These are all deep and developing fields.  I expect my rabbit-hole alarm to go off frequently.  Hopefully I will find something interesting without being lost interminably in the warrens.

Citrullination [WP] involves an enzyme modifying an arginine amino acid when it is part of a protein.  An NH ketamine group is replaced with an O ketone group, both doubly bonded to the molecule.  This changes the arginine into citrulline, which is not a protein building amino acid.  The behaviour of the whole protein changes in several ways, and this can trigger the production of antibodies and then those antibodies attaching to said proteins, triggering a cell-destroying (inflammatory) response.

The articles below also concern some aspects of the HLA-DR [WP]  which may be involved in both RA and worse outcomes in COVID-19.  (I am yet to read these articles, except the last: Martin et al. 2021.)

How citrullination invaded rheumatoid arthritis research
Walther J van Venrooij & Ger JM Pruijn
Arthritis Research & Therapy 2014-01-29
https://arthritis-research.biomedcentral.com/articles/10.1186/ar4458


Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted α-Enolase T Cell Epitope in Rheumatoid Arthritis
Christina Gerstner, Anatoly Dubnovitsky, Charlotta Sandin, Genadiy Kozhukh, Hannes Uchtenhagen, Eddie A. James, Johan Rönnelid, Anders Jimmy Ytterberg, Jennifer Pieper, Evan Reed, Karolina Tandre, Mary Rieck, Roman A. Zubarev, Lars Rönnblom, Tatyana Sandalova, Jane H. Buckner, Adnane Achour and Vivianne Malmström
Frontiers in Immunology 2016-11-14 
https://www.frontiersin.org/articles/10.3389/fimmu.2016.00494


Progression on Citrullination of Proteins in Gastrointestinal Cancers
Shuzheng Song and Yingyan Yu
Frontiers in Oncology 2019-01-23
https://www.frontiersin.org/articles/10.3389/fonc.2019.00015


The influence of HLA genotype on the severity of COVID-19 infection
David J. Langton, Stephen C. Bourke, Benedicte A. Lie, Gabrielle Reiff, Shonali Natu, Rebecca Darlay, John Burn and Carlos Echevarria
HLA Immune Response Genetics 2021-04-19
https://onlinelibrary.wiley.com/doi/10.1111/tan.14284


Association between psoriasis and rheumatoid arthritis in a nationally representative population in the United States
Amylee Martin, Akshitha Thatiparthi, Jeffrey Liu, Jashin J. Wu.
Journal of the American Academy of Dermatology  Letter 2021-07-15
https://www.jaad.org/article/S0190-9622(21)01945-9/ (Paywalled.)

(Dr Wu has kindly sent me a copy of this article.)

A carefully conducted survey found that 8.1% of people with psoriasis reported a history of RA, while such a history was reported by only 4.0% of people without  psoriasis.  The OR for these findings varied from 2.82 for subjects aged 20 to 49 and 1.64 for subjects aged 50 and above.  The authors write:

This association may be attributed to a similar pathophysiology, with
tumor necrosis factor-alpha and interleukin 17 implicated in both the disorders.  Interestingly, tumor necrosis factor-alpha inhibitors have been reported to paradoxically induce and/or worsen psoriasis, most commonly, in individuals with RA or Crohn disease.


© 2021 Robin Whittle   Daylesford, Victoria, Australia