Advanced vitamin D topics - some people need much more D3 than
normal, to suppress rheumatoid arthritis, multiple sclerosis, psoriasis, cluster headaches, migraines
etc.; Newly discovered vitamin D compounds; The impact of lack of helminths on inflammatory responses, including severe COVID-19This page is a work in progress..
../ To the main page of this site.
Robin Whittle email@example.com 02 October 2021 Twitter: https://twitter.com/RobinWhittle3
(First established 2021-07-16.)
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
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.
Before reading this page, please familiarise yourself with the research articles I link to and discuss at:
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
On 2021-10-02 I added mention of new research on helminths
(intestinal worms) including how active helminth infections in Ethiopia
are associated with a 77% reduction of incidence of severe COVID-19.
This is really interesting and makes good sense once the evolutionary
history of helminth infections and the immune system is understood.
||Higher than normal 25-hydroxyvitamin D levels to suppress chronic inflammatory disorders.
of intestinal worm infections leads to self-destructively strong immune
responses, including auto-immune disorders and much greater risk of
||Other mechanisms related to rheumatoid arthritis and other autoimmune disorders.
||Compounds beyond D3, 25OHD and 1,25(OH)2D which are in the early stages of being researched.
||Regulation of 25-hydroxyvitamin D levels.
00 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
is the name most commonly used for 25-hydroxyvitamin D as a
pharmaceutical: https://vitamindstopscovid.info/04-calcifediol/ .
These discussions apply directly to humans - and generally to companion
and agricultural non-human animals, who - without proper
supplementation - may not be getting the D3 they need to be healthy.
This page concerns:
- D3 supplementation interventions to suppress
auto-immune inflammatory conditions, including those mentioned in the
title of this page.
- Cell-biology and molecular biology research and hypotheses
regarding the mechanisms by which higher than normal D3 supplemental
intakes might give rise to such suppression.
- The genetic and evolutionary background for the genetically
variable proclivity of humans (and other mammals) to have
self-destructively overly-inflammatory immune responses when we are not
infested by helminths (intestinal worms). Please see this section
for links to some relevant research articles: https://aminotheory.com/cv19/#helminthsgone and the use of deliberately introduced helminths to suppress these conditions (helminthic therapy).
- Intriguing new research concerning other aspects of vitamin D
biology which are beyond the three compounds I refer to as "vitamin D":
D3 cholecalciferol, 25-hydroxyvitamin D 25OHD calcifediol and 1,25-dihydroxyvitamin D calcitriol. (There are another three
matching compounds starting with vitamin D2, but D3 is the natural and
more effective base compound.)
This includes sulphates of 25-hydroxyvitamin D and a derivative of D3 -
20S-hydroxyvitamin D - which is the subject of current research.
I can't write about all this yet, since I need to carefully read the articles first!
01 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
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
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
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.
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 (
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 used oxygen as an abortant (to stop the CH
attack within minutes or tens of minutes) and after some years noticed
that he had little trouble with CHs in summer - the time of peak
vitamin D, since he spent a great deal of summer outdoors.
By experimentation, very extensive reading of prior research
literature, and work with now thousands of sufferers, Pete
Batcheller has developed a detailed, reliable, protocol which greatly
reduces and for some people eliminates the occurrence of these
frightening, exceedingly painful, cluster headaches.
He has helped over 5000 cluster headache and migraine sufferers
(personal conversation, 2021-08-22) suppress their symptoms with a protocol which resembles that of Dr
Coimbra - with whom he has 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. Illness can reduce circulating 25-hydroxyvitamin D
levels and so cause CHs to occur again - so extra D3 and/or first
generation antihistamines (which cross the blood-brain barrier) can be
used to counter this.
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
medical qualifications. His website is:
His Protocol is available as a PDF (
Download the CH Preventative Treatment Protocol . . .) at:
Preventative Treatment Protocol for Neurologists, Pain Specialists, and
Primary Care Physicians using the Anti-Inflammatory Regimen to Treat
Patients with Cluster Headache
Pete Batcheller, CDR USN (Ret.) January 15, 2017
This guidance for primary care physicians and neurologists
has been used successfully and without adverse outcomes by over 5000
cluster headache (and migraine) sufferers in the past 4
years. It includes suggested testing frequency for
25-hydroxyvitamin D levels, and for total calcium
and parathyroid hormone
levels, the latter two which should be monitored every 6 or 12 months to ensure they remain within their reference ranges.
Although directed at the needs of cluster headache sufferers, and to
the similar needs of those suffering from migraine, I think this
document is an excellent reference for people who are suffering from
other systemic hyper-inflammatory disorders, including all those
mentioned in the title of this page.
It is not an RCT or a peer-reviewed journal article. It is the
product of years of research and working with hundreds of people by the
time it was written. The subsequent thousands of successful
interventions (according to self-reported survey responses) and the
absence of reports of problems - to the researcher / sufferer who is
unusually well connected with thousands of sufferers - indicate that
this Protocol contains valuable guidance.
The mean 25OHD of CH sufferers before commencing the protocol was 22.8ng/ml
Typical daily D3 intakes were of the order of 0.25mg 10,000IU - along
with omega 3 fatty acids, particular forms of vitamin K2, boron, zinc,
magnesium and B vitamins as well as other vitamins and minerals.
The optimum pain-free 25-hydroxyvitamin D serum concentration was 83.4ng/mL
A handful of CHers under physician’s supervision, have reported sustained
serum 25(OH)D concentrations above 100 ng/mL, (250 nmol/L) some as high as 198 ng/mL.
They also reported total calcium serum concentrations were within
normal reference ranges and PTH concentrations at the low end of the
reporting range with no other symptoms other than a cessation of their
Mechanisms by which higher than normal D3 intakes might help suppress auto-immune hyper-inflammatory diseases:
D Resistance as a Possible Cause of Autoimmune Diseases: A Hypothesis
Confirmed by a Therapeutic High-Dose Vitamin D Protocol
, Rainer Johannes Klement, Felix Schweiger, Beatrix Schweiger and Jörg Spitz
Frontiers in Immunology 2021-04-07
02 Helminths downmodulate inflammatory responses
Please also see: https://aminotheory.com/cv19/#helminthsgone
As best we know, our ancestors, going
back tens of millions of years, were ubiquitously infected with
helminths (intestinal worms) which evolved to exude compounds which
down-modulate the inflammatory immune responses which mammals evolved
to destroy multicellular parasites. Antibodies and macrophages
(adaptive responses) and the innate responses which work well against
viruses, bacteria and fungi are no use against multicellular
Inflammatory immune responses involve
large-scale, indiscriminate, destruction of multiple cells - ideally
those of the parasite but also, unavoidably, our own. There
are several mechanisms, but one example is regulatory lymphocytes
secreting pro-inflammatory cytokines (immune system signaling
molecules) into the area where the parasite is located, which
attracts eosinophils [WP]
to the site. Eosinophils are the suicide bombers of the immune
system. Once activated (by appropriate cytokines) the eosinophil
disintegrates, releasing a variety of compounds from its
vacuoles. These destroy proteins, DNA, RNA and disrupt cells in
other ways, such as with reactive oxygen species. They also
release cytokines which affect the behaviour of other immune
Inflammatory responses can also play a role in fighting some viral infections. See McGregor et al. 2020 https://aminotheory.com/cv19/icu/#2020-McGregor
for Th1 regulatory lymphocytes responding to SARS-CoV-2 infection in
the lungs by emitting a pro-inflammatory mix of two-cytokines in their
startup program (a lot of a pro-inflammatory cytokine and a little of
an anti-inflammatory cytokine). After some time (hours, I
guess) the Th1 lymphocyte detects changes in other parts of the immune
system in its vicinity (a high level of a complement protein [WP])
which causes it to switch to an anti-inflammatory shutdown program, by
producing a little of the pro-inflammatory cytokine and more of the
anti-inflammatory cytokine. This is presumably a healthy response
to this infection. However, if the TH1 lymphocyte does not have enough 25-hydroxyvitamin D, then it cannot make this transition, and remains stuck indefinitely in its pro-inflammatory program.
McGregor et al. observed this failure to
transition to the anti-inflammatory shutdown program in Th1 cells from
the lungs of severe COVID-19 patients. It is reasonable to assume
that the lack of 25-hydroxyvitamin D caused
these Th1 cells to produce the (pro-inflammatory) cytokine storm which
causes widespread destruction of endothelial cells, especially in the
lungs, leading to hypoxia and tissue damage which cause microembolisms
and larger clots in the lungs, brain, heart and all other organs:
harmful and possibly deadly severe COVID-19.
It is also reasonable to assume similar
processes are at work in other acute hyper-inflammatory immune
dysregulation disorders which are to a large extent caused by
inadequate levels of 25-hydroxyvitamin D: sepsis (GS), Kawasaki disease (Stagi et al. 2015), Multisystem Inflammatory Syndrome (Fekatea et al. 2020) and pre-eclampsia [GS] .
However, for most people in many or most countries since (very
approximately) the early 20th century, an additional problem drives
excessive inflammatory responses: due to not having helminth
infections, our inflammatory immune responses are far stronger than
what would be healthy, because the genetic instructions which create
the immune system evolved over tens of millions of years in which the
base level responses had to be stronger than whatever strength is most
healthy, to compensate for the weakening effects of the
immunomodulatory compounds (we assume there are more than one) exuded
by likely several species of helminths.
The combination of nearly ubiquitous lack of helminths (leading to
overly strong inflammatory responses, differing from one individual to
the next according to genetic variation) AND the very widespread lack
of sufficient (such as 50ng/ml) 25-hydroxyvitamin D, is the setting
which gives rise to vast amounts of auto-immune disorders AND to the
acute hyper-inflammatory dysregulated immune responses which drive
sepsis, severe COVID-19 etc.
As we see from the previous section, for some or many people who
experience auto-immune problems with common (lower than 50ng/ml)
25-hydroxyvitamin D levels, and with 50ng/ml, it is frequently possible
to suppress the pathologically hyper-inflammatory immune responses
which cause their conditions by higher than normal (well above 50ng/ml)
25-hydroxyvitamin D levels. As far as I know, there is no
detailed research on the mechanisms which cause this.
In this context, I was not surprised to find this important new research:
Ethiopian COVID-19 patients with active helminth infections were found to have a 77% lower chance of severe COVID-19 compared to those without such infections. (p < 0.0001)
11 of the 257 patients without helminth infections died. None of the 284 patients with helminth infections died. (p = 0.009).
These two highly significant results are strong arguments for the causality being from
helminth infections to
protection from hyper-inflammatory immune responses. However, two other mechanisms come to mind, which I guess
are of limited or no significance:
- it is possible that a secondary cause might be people with poorer
sanitation and so living conditions (who are more prone to helminth
infections) may spend more time outdoors and so have higher
25-hydroxyvitamin D levels. Unfortunately these levels were not
- Assuming there is significant variation in the strength of the
immune response (in the absence of helminths) between individuals, as
is surely the case, then perhaps those with the stronger inflammatory
immune responses are less likely to be infected with helminths - and
these same people are more likely to develop severe COVID-19
because of that stronger inflammatory response.
The researchers attribute their observations to the patients having a
"different, more activated" immune response as a result of helminth
infection. However, there's no reason to believe that helminth
infections lead to better immune responses. For this to occur, they
would either have to produce anti-viral compounds which the human
immune system had not evolved, or somehow stimulate a greater antiviral
response than the human immune system would generate on its own.
These mechanisms can't be ruled out, but a more likely explanation for
most or all of the observed differences in outcome is as just
mentioned, especially in the context of the research by Miri Blank and
colleagues mentioned below.
Helminth infections cannot reasonably be introduced to fight severe
COVID-19, because they would take too long to develop. However,
these observations are most informative when trying to understand all
the factors which affect COVID-19 disease progression.
Ideally, I think, we would have one or more of the immunomodulatory
compounds exuded by helminths (at least one is currently known)
available as pharmaceutical treatments to suppress autoimmune disorders
AND sepsis, severe COVID-19 etc.
This little known field is fascinating and potentially as important for
the health of humans and our companion and agricultural animals as
As best I can tell, the helminth researchers and vitamin D researchers
have little or no contact or knowledge of each other's
work. They should compare notes more!
Here is one of the research articles concerning a helminthic compound
which down-modulates inflammatory immune responses. Ideally I
would have time to research this field more thoroughly. This page
is an early work in progress.
bi-functional molecule, tuftsin-phosphorylcholine (TPC),
ameliorates an established murine arthritis
Miri Blank, Tomer Bashi, Jordan Lachnish, Dana Ben-Ami-Shor,
Shovman, Mati Fridkin, Miriam Eisenstein, Alexander Volkov,
Barshack and Yehuda Shoenfeld.
PLoS One 2018-08-08
Some people find relief from autoimmune disorders by the introduction of helminths: https://helminthictherapywiki.org . This is a highly significant research article:
An older Crohn's disease article. I want to find some more recent ones too. See the articles which cite this one:
Here are two other articles concerning helminths and COVID-19:
There are other articles of interest in these citation lists.
03 Connections between Rheumatoid Arthritis (RA), psoriasis and
potentially other conditions - and some cell-biology hypotheses of
Regarding RA, please also see my earlier material on boron: https://aminotheory.com/cv19/#08-boron
Perhaps there is a way of connecting tenuous knowledge of:
- Helminthic down-modulation of inflammatory immune responses.
- High levels of supplemental D3 - with consequent high levels of
25-hydroxyvitamin D and potentially other less well known compounds.
- Research on citrullination and resultant antibodies and inflammatory immune responses.
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.
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
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
Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted α-Enolase T Cell Epitope in Rheumatoid Arthritis
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
Frontiers in Immunology 2016-11-14
Progression on Citrullination of Proteins in Gastrointestinal Cancers
and Yingyan Yu
Frontiers in Oncology 2019-01-23
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
Association between psoriasis and
rheumatoid arthritis in a nationally representative
population in the United States
, Akshitha Thatiparthi, Jeffrey Liu, Jashin J. Wu.
Journal of the American Academy of Dermatology Letter
(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.
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.
Frontiers in Immunology 2021-06-30
Sulphated 25-hydroxyvitamin D is prevalent in the circulation:
05 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 . . . .
© 2021 Robin Whittle Daylesford, Victoria, Australia