Medical Hypotheses, https://doi.Org/10.1016/j.mehy.2019.109256
Grupo de Farmacología, Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain icarlostutor at gmail.com
For years the successful use of high-dose Vitamin D for Multiple Sclerosis and Autoimmune diseases has been ignored by medical professionals. Perhaps because it requires adjusting the doses for each individual, rather the conventional one-size-dose fits all of Randomized Controlled Trials. Or, perhaps, because too many doctors still falsely believe that >2,000 IU can be toxic (still in medical textbooks a few years ago)
- Multiple Sclerosis treated when use high doses of vitamin D – meta-analysis May 2018
- Video by Dr. Coimbra – 95 percent of auto-immune cured with vitamin D in high doses - April 2014
- Multiple Sclerosis - Coimbra Protocol (high-dose Vitamin D) - by one of the 120 doctors of 20,000 patients - Dec 2018
- Vitamin D has treated Multiple Sclerosis and autoimmune diseases for 16 years – Coimbra April 2018
It is not clear when poor VDR ==> Disease vs when Disease ==> poor VDR
Items in both categories Autoimmune and Vitamin D Receptor are listed here:
- Autoimmune disease treated by Vitamin D, Zinc (and other activators of Vitamin D Receptor) – Oct 2019
- Vitamin D Receptor is associated in over 40 autoimmune studies
- Temporary hair loss (Telogen Effluvium) is 15X more likely if poor Vitamin D Receptor – Oct 2019
- Autoimmunity problems often associated with poor Vitamin D Receptors – March 2019
- Many autoimmune diseases associated with low vitamin D or poor Vit D genes – July 2019
- Adaptive and innate immune system, vitamin D genes, and Rheumatoid Arthritis – June 2019
- Resveratrol Role in Autoimmune Disease-A Mini-Review. – Dec 2016
- Immunological effects of vitamin D and their relations to autoimmunity – March 2019
- Resveratrol improves health (Vitamin D receptor, etc.)
- Vitiligo (spotty skin coloring) is 4 X more likely if poor Vitamin D Receptor – meta-analysis July 2018
- Vitamin D Receptor and autoimmune diseases – Jan 2017
- Inflammation and immune responses to Vitamin D (perhaps need to measure active vitamin D) – July 2017
- Many autoimmune diseases associated with latitude and vitamin D receptor – March 2016
- Vitamin D Receptor role in Autoimmune Diseases and or cancers – Nov 2013
- Endometriosis treated, and perhaps prevented, by vitamin D and Omega-3 - updated Fall 2019
Items in both categories Multiple Sclerosis and Vitamin D Receptor are listed here:
- Risk of Multiple Sclerosis varies with the Vitamin D Receptor – meta-analysis Dec 2019
- Multiple Sclerosis and Vitamin D Receptor super enhancers – March 2019
- Vitamin D genes increase MS relapses in children by 2X – May 2019
- Immunological effects of vitamin D and their relations to autoimmunity – March 2019
- Inflammation and immune responses to Vitamin D (perhaps need to measure active vitamin D) – July 2017
- Multiple Sclerosis risk increased due to genes - 22nd study – Aug 2017
- Multiple sclerosis (relapsing-remitting) increases activation of Vitamin D Receptor by 6.6 X – March 2017
- Multiple Sclerosis is more likely if poor Vitamin D Receptor (4X Mexico, 3X Iran)– Feb 2017
- Multiple Sclerosis much more likely if poor Vitamin D Receptor – several studies
- Multiple Sclerosis and the Vitamin D Receptor – meta-analysis July 2014
Overview MS and vitamin D contains the following summary
Clinical interventions have shown that Vitamin D can prevent, treat, and even cure Multiple Sclerosis, at a tiny fraction of the cost of the drugs now used to treat it, and without side effects.
- Fact: Low Vitamin D results in higher risk of getting MS
Increase latitude leads to decreased Vitamin D, which leads to increased risk of MS
Dark skinned people are far more likely to get MS (dark skin people typically have low vitamin D)
Elderly (who typically have low vitamin D) are more likely to get MS
Is there increased risk in people who already have diseases associated with low vitamin D - TB, for example ? ? ?
Women typically have 3X increased MS risk then men (note: women typically have 20% lower levels of vitamin D than men)
Exception: women in very sunny climates and dark-skinned women have the same MS risk as men
Obese are 60% more likely to get MS
Smokers - smokers have lower level of vitamin D and have higher incidence of MS (also, smokers are difficult to cure of MS in Brazil)
MS recurrence is much higher in spring - the lowest time of the year for vitamin D
increase in clouds/rainfall (which reduces available Vitamin D) is associated with increased risk of MS (Scotland, Western Washington)
MS incidence has increased 70% in a decade while the incidence of vitamin D deficiency doubled
Less MS in those with outdoor occupations PDF file, not a web page
- Fact: MS uses up Vitamin D
- Fact: Lower vitamin D (due to MS using up Vitamin D while fighting the disease) results in many other health problems (such as broken bones), so depleted vitamin D levels must be restored.
- Fact: Vitamin D looks so promising for preventing and treating MS that there were 25 INTERVENTION clinical trials as of Feb 2014
- Fact: Vitamin D reduced the MS relapse rate far better than Fingolimod which is now used for that purpose.
- Note: Fingolimod costs $25,000/year while vitamin D, which works better and has no site effects is 1000 times less expensive.
- Fact: 98% of the genes affected by Interferon are also affected by Vitamin D
- Note: 1 week of Interferon = $4,700, 1 week of vitamin D 10,000X lower cost
- Fact: MS Doctors in Brazil recommending 40-100 ng/mL of Vitamin D
- Fact: Many MS forums are recommending vitamin D to treat MS, with some taking 5,000 to 10,000 IU daily
Observation: Risk of going from pre-MS to MS reduced 68 percent with 7100 IU vitamin D – RCT Dec 2012
- This is an observation instead of a fact - it has not yet been confirmed.
- Fact: VERY LARGE doses of vitamin D have CURED 2,000 people of MS in Brazil
- Controversy: UVB fron sunlight or UVB bulb may be BETTER than Vitamin D for reducing the risk of getting MS
- Hypothesis: In addition to Vitamin D there are many other photoproducts produced by UVB that may promote health.
Summary: lack of consensus on how much to prevent, treat, or cure MS.
- How much Vitamin D to prevent many diseases - such as MS
- How much Vitamin D is needed to treat MS? There is currently no agreement
The recommendations range from 40 to 100 ng - which can result of a dose ranging from 3,000 to 20,000 IU/day
- How Vitamin D is needed to Cure MS?: It appears that 20,000-140,000 IU daily may be needed to CURE the disease
You must be under the supervision of a doctor who knows what to watch for in your individual situation.
High doses of Vitamin D cannot be used as a monotherapy.
You will need to adjust the cofactors: Typically increasing Magnesium and Vitamin K2, and reducing Calcium intake.
Your doctor will monitor these and might increase your intake of Vitamins B2, C, as well as Omega-3
Multiple Sclerosis and (lots of) Vitamin D - book by patient on Coimbra protocol - Feb 2016 contains protocol description
Vitamin D Protocol used by Dr. Coimbra for Multiple Sclerosis etc.
Snips as of April 2016 http://www.vitamindprotocol.com/dr.-coimbra-s-ms-protocol.html
- 1,000 IU's vitamin D per kilogram as a first approximation
(apparently increased/decreased depending of resulting vitamin D blood level)
- Vitamin B2, magnesium glycinate, boron, chromium picolinate, Omega 3 DHA, Zinc, Methylcobalamin form of B12, Choline, etc.
- Lack of B12 may affect 10%–15% of the general population and may be the most prevalent genetic risk factor for several human diseases
- Discontinue eating or drinking dairy products or calcium enriched foods or beverages, also no Ca supplements
- Drink as least 2.5 liters [85 ounces] of fluids, preferably water
- Required Tests: Vitamin D, Parathyroid, Blood calcium, urinary calcium
Comparing High-dose vitamin D therapies starts with
To the Editor
In a recently published article by Berezowska et al (1), they conclude that vitamin D supplementation may be a promising treatment for multiple sclerosis (MS), and represents a reliable background for further exploration of potential benefit regarding clinical improvements. Likewise, they add that a high dose vitamin D supplement intervention may contribute to bettering of physiological mechanisms, especially if baseline plasma levels are at the lower end of normal (1). Häusler and Weber (2) review the vitamin D potentially immune modulating mechanisms, followed by a summary of current and ongoing clinical trials, intended to assess whether vitamin D supplementation positively influences the outcome of central nervous system (CNS) demyelinating disease. However, in this article, it is underscored the fact that high doses of vitamin D could have negative effects in CNS demyelinating disease via T cell-stimulating effect of secondary hypercalcemia (2). Similar precautionary conclusions have been pointed out by other authors (1, 3-6). Although it has been described that following oral vitamin D supplementation, patients with MS have a lesser average increase in serum levels of 25-hydroxy-vitamin D (25-OH-D) than healthy individuals having similar starting concentrations (7), in MS patients vitamin D is usually administered in modest daily doses on the order of 1,000-3,000 IU in association with different disease-modifying therapies. This vitamin D supplementation is increasingly used, providing an added beneficial effect to patients (8).
Frequently, the vitamin D undesirable effects found by Fragoso et al. (9) in some MS patients treated with 8,000-150,000 lU/day (median 100,000 Ul/day) are highlighted; nevertheless, these authors do not indicate what dosing procedure and clinical follow-up had been done in the patients included in this study, and what preventive measures had been taken to avoid the possible side effects of high doses of vitamin D. Other comments about the data and conclusions provided by Fragoso et al (9) can be seen in the paper of Kimball et al (10). Very possibly, the fear to a considered inevitable development of toxic effects, may explain the little attention awakened by some early studies, any published more tan eighty years ago (11, 12), on the possible treatment of autoimmune disorders, concretely rheumatoid arthritis, with massive doses of vitamin D.
Vitamin D is a powerful regulator of the immune system activity and, in accordance with the neurologist CG Coimbra from the University of Sao Paulo in Brazil, most patients with autoinmune diseases have an increased resistance to the immunomodulatory effects of vitamin D, mainly due to genetic polymorphisms, which requires the administration of massive doses of this prohormone to be clinically effective. It may be interesting to note here, that Henderson et al (13) have recently described the case of a woman with absence of circulating vitamin D-binding protein (VDBP), presenting a severe deficiency of vitamin D that did not respond to supplementation. This congenital deficiency of VDBP resulted in normocalcemia and mild disruption of bone metabolism, however, it was accompanied by a severe autoimmune disease (debilitating ankylosing spondylitis).
From years ago, the so-called "Coimbra protocol" with very high daily doses of vitamin D3 (initial dosage=1,000 lU/kg of weight) has been used in America and Europe for the treatment of MS (more than 30,000 patients) and other autoimmune diseases. The clinical results seem to be good, and the patients themselves treated by Coimbra in Sao Paulo, or by one of the doctors accredited to follow this protocol all over the world (14), recommend this therapeutic protocol with insistence and enthusiasm in their facebook groups (15) and in the books telling his own clinical history (16, 17). According to these patients, with MS and other autoinmune disorders, "we constituted the best clinical trial for the Coimbra protocol validation". Currently some articles on this subject have been published (18, 19), and a recent study conducted in Brazil, shows that MS patients have a high degree of satisfaction with the vitamin D treatment, whether exclusive or complementary (20).
The Coimbra's protocol for autoimmune diseases treatment has not just been recognized, but neither evaluated, in the academic media. It is argued that are necessary more studies to determine the suitable vitamin D dosage, and perform protocolized clinical follow-up, to avoid undesirable toxic effects as the hypercalcemia with all its possible physiopathological complications. Nevertheless, these issues seem to have been resolved by Coimbra itself. Briefly it may be noted that the daily doses of vitamin D are established and adjusted through the serum parathormone (PTH) levels, and not those of 25-OH-D. Likewise, the patients must follow a diet with calcium restriction, magnesium supplementation, and a daily intake of at least 2.5 liters of water, to maintain a urinary calcium concentration below 250 mg/L, for kidney stones and nephrocalcinosis prevention. Another factor of great importance for a good clinical evolution of the patients, is the maintenance of an adequate emotional control, which, depending on the degree of affectation, could be achieved in approximately 90-95% of cases. Periodically analytical controls of, at least, serum calcium, phosphorus, urea, creatinine, PTH, and 25-OH-D, and also calcium in 24-hour urine samples, are performed. The biochemical and clinical monitoring of patients treated with this protocol for years, shows that, although they present very high levels of serum 25-OH-D (frequently greater than 1,000 ng/mL), with very low PTH values around to the inferior reference limit, do not develop hypercalcemia, hypercalciuria, or other toxic effects due to the massive doses administered of vitamin D. More details on this protocol are available in one of the most prestigious online information sources about vitamin D (21).
Although some studies, such as that of Martinsen and Burian (22), are already underway in different European countries, from here, I invite all those involved in the research and/or treatment of MS and other autoimmune diseases, that, free from prejudices, find out about the true therapeutic possibilities of the Coimbra protocol. Then, we can answer to the question raised by Hawkes et al. (23), if for MS patients, vitamin D is "caviar or a dog's dinner".
Disclosure statement. The autor reports no conflicts of interest
- Berezowska M, Coe S, Dawes H. Effectiveness of vitamin D supplementation in the management of multiple sclerosis: A systematic review. Int J Molec Sci. 2019; 20: 1301  - Download the PDF from VitaminDWiki
- Haüsler D, Weber MS. Vitamin D supplementation in central nervous system demyelinating disease- Enough is enough. Int J Molec Sci. 2019; 20: 218
- Goischke HK. Vitamin D supplementation as add-on therapy in multiple sclerosis-Balance between benefit and risk?: A comentary on Vitamin D supplementation in central nervous system demyelinating disease-Enough is enough. Int J Molec Sci 2019; 20: 1553.  - Download the PDF from VitaminDWiki
- Mclaughlin L, Clarke L, Khalilidehkordi E, Butzkueven H, Taylor B, Broadley SA. Vitamin D in the treatment of multiple sclerosis: A meta-analysis. J. Neurol. 2018; 265: 2893-2905.
- Pierrot-Deseilligny C, Souberbielle JC. Vitamin D and multiple sclerosis: An update. Mult Scler Disord. 2017; 14: 35-45.
- Zahoor I, Haq E. Vitamin D and multiple sclerosis: An update. In: Multiple Sclerosis: Perspe ctives in Treatment and Pathogenesis . Zagon IS, McLaughlin PJ (editors), Codon Publications, Brisbane. 2017: 71-85.
- Bargava P, Steele SU, Waubant E, Revijaran NR, Marcus J, Dembele M, et al. Multiple sclerosis patiens have a diminished serologic response to vitamin D supplementation compared to healthy controls. Mult Scler 2016; 22: 753-60.
- Linden J, Granasen G, Salzer J, Svenningsson A, Sundström P. Inflammatory activity and vitamin D levels in a MS population treated with rituximab. Mult Scler J Exp Transl Clin. 2019; 5: 1-10.
- Fragoso YD, Adoni T, Damasceno A, de Albuquerque-Damasceno CA, Brito-Ferreira ML, Finkelzsteijn A, et al. Unfavorable outcomes during treatment of multiple sclerosis with high doses of vitamin D. J Neurol Sci. 2014; 346: 341-342.
- Kimball S, Hanwell HE, Burton JM, Heaney RP, Holick MF, Hollis B, et al. Vitamin D supplementation in multiple sclerosis: Making a case for clarity. J Neurol Sci 2014; 347: 391-392.
- Dreyer I, Reed CI. The treatment of arthritis with massive doses of vitamin D. Arch Phys Therap. 1935; 16: 537-40.
- Brohult J, Jonson B. Effects of large doses of calciferol on patients with rheumatoid arthritis. Scand. J. Rheumatol. 1973; 2: 173-176.
- Henderson CM, Fink SL, Bassyouni H, Argiropoulus B, Brown L, Laha TJ et al. Vitamin D-binding protein deficiency and homozygous deletion of the GC gene. New Engl J Med 2019; 380: 1150-57.
- Coimbra Protocol Doctors (accessed March, 25, 2019): https://www.google.com/maps/d/u/0/viewer?ll=42.16108947061385%2C13.05220517481689&z=5&fbclid=IwAR0R3GFly-tU90-WEeL5PiUI1vxSZId9zPVzTobYduilES7AFjHhgn6vTo&mid=1fATZJUEhOsYYJdBY41h48FBkLaQ
- Coimbra Protocol Facebook Groups (accessed March, 25, 2019): https://mfacebook.com/notes/o-tratamento-com-vitamina-d-do-dr-c%C3%ADcero-coimbra-portugal/grupos-e-p%C3%A1ginas-relacionados-com-o-protocolo-do-dr-c%C3%ADcero-coimbra/1722518301305431/
- Domene AC. Multiple Sclerosis and (lots) Vitamin D: My eight-year treatment with the Coimbra protocol for autoinmune diseases. CreateSpace Independent Publishing Plattform, 2016.
- Butler J. Stop Multiple Sclerosis & Autoimmune Disease with High Dose Vitamin D: The first US patient treated by the first US Coimbra protocol doctor tells her story. Independently Published, 2017.
- Finamor DC, Sinigaglia-Coimbra R, Neves LCM, Gutierrez M, Silva JJ, Torres LD et al. A pilot study assessing the effect of prolonged administration of highly doses of vitamin D on the clinical course of vitiligo and psoriasis. Dermato-Endocrinol. 2013; 5: 222-234.
- Cadegiani FA. Remission of severe miastenia gravis after massive-dose of vitamin D. Am J Case Rep. –2016; 17: 51-54.
- Alves-Reis CF, Pereira-Guimaraes F. Multiple sclerosis patients perception about the use of vitamin D in clinical therapy. Rev Bras Cienc da Vida. 2017; 5 (1): 1-19.
- GrassrootsHealth (accessed March, 25, 2019)
- Martinsen I, Burian N. Adherence to the Coimbra Protocol in Adults with Autoimmune Disease. Bachelor Thesis, University College Copenhagen. 2019 (accesed March, 25, 2019): https://docs.google.com/document/d/1e4RWNdGJfM8bgBpU9ua9RydSxA1QZxGTwzZX8N5lc/fbclid=IwAR0QAE3mNEszfA0GcF3YOGsHFBTXaKZxzAX2k5gqw3CB9pqS1uMCATrU2OE
- Hawkes C, Giovannoni G, Lechner-Scott J, Levy M, Waubant E. Multiple sclerosis and vitamin Caviar or a dog's dinner?. Mult Scler Relat