Using 1000 IU/day per kg Body Weight to Force MS Into Remission
Cicero G. Coimbra, MD, PhD
Department of Neurology and Neurosurgery
Federal University of Sao Paulo, UNIFESP
President, Autoimmunity Investigation and Research Institute
About Dr. Cicero Coimbra
Dr. Coimbra received his medical degree from the Universidade Federal do Rio Grande do Sul in 1979. He did two years of internal medical residency and two years of adult neurology residency at the Hospital de Cl�nicas de Porto Alegre, Brazil; followed by a year of fellowship training in pediatric neurology at Jackson Memorial Hospital, Miami. Coimbra earned his PhD in clinical neurology from the Federal University of S�o Paulo in 1990. He has also completed post PhD training in experimental brain ischemia at the Laboratory for Brain Research, University of Lund, Sweden. He is currently Associate Professor in the Department of Neurology and Neurosurgery, Federal University of Sao Paulo, UNIFESP.
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The making of a new protocol
Dr. Coimbra wanted to change lives, to treat neurological disorders. After his fellowship, Coimbra started doing experimental research by inducing ischemic brain damage in rats (in S�o Paulo, Brazil and Lund, Sweden) and testing different treatments to see what worked. Moderate hypothermia (body temperature reduced to 33 degrees Celsius) provided robust protection to the rat brain. Conversely, postischemic hyperthermia was detrimental, and could trigger a chronic neurodegenerative process. Administration of choline - a natural component of neuronal membranes - provided a moderate protection, suggesting that restricted availability of choline after transient brain ischemia was critical for cell membrane repair and consequent neuronal survival.
"Seeing MS patients getting back to a normal life, young people no longer at risk of going blind or paraplegic - such experience gives great satisfaction to the doctor who has them under his/her care. It has been very gratifying." - Dr. Coimbra
Following a general rule for research work, Coimbra needed to be as up to date as possible on the latest findings related to his field of interest (clinical neuroscience). He realized that much of the therapeutic progresses achieved from clinical and experimental research had not been moved to clinical practice. In spite of their immediate clinical applicability, these practices were not being taught in medical schools - even after several confirmatory reports. At a certain point Coimbra was convinced vitamin D would be a fundamental therapeutic resource, as it stimulates the production of several neuroregenerative substances in the brain.
Coimbra began administering vitamin D in physiological doses (10,000 IU/day) to Parkinson's patients around the year 2001. He noticed that an extensive depigmented area on the forehead of one of his Parkinson's patients (who had also vitiligo - an autoimmune disorder) had virtually disappeared after 3 months on that daily dose. Searching the medical literature for the effects of vitamin D on the immune system revealed a significant number of published papers supporting a fundamental immunoregulatory role of that steroid, that vitamin D is actually a precursor of a powerful hormone that targets receptors in virtually all human cells to control a wide range of biological functions. Since MS is the most common neurological autoimmune disease and a major cause of incapacitating disabilities (like blindness, paraplegia) in young people, he decided to start treating MS patients in 2002 initially using similar doses of vitamin D.
What is a physiological dose of vitamin D?
Coimbra believes that 10,000 IU/day of vitamin D is a physiological dose. This is the amount of vitamin D a young person makes if they are light skinned, wearing shorts and a t-shirt for about 20-30 minutes of mid-day sun. This daily dose is totally safe. No precautions are necessary. It is worth noting that the IOM indicated that 10,000 IU/day was considered the "NOAEL"--the 'no observed adverse effect level'.
Coimbra calls the RDA a "paltry dose, although still officially recommended."
Why does vitamin D work?
The active form of vitamin D is the main regulator of the immune system. It empowers the innate immunity against microorganisms and suppresses autoimmunity (which is dependent on an abnormal "program" of immune activities known as "Th17", and is powerfully counteracted by vitamin D). Vitamin D also induces the proliferation of regulatory immune cells called "regulatory T lymphocytes." There is a vitamin D receptor (VDR) in every cell of the immune system. Vitamin D modifies the function of approximately 10% of human genes.
What does Dr. Coimbra's protocol entail?
Coimbra has been able to successfully suppress disease activity in about 95% of MS cases with variable (individually tailored) high daily doses of vitamin D. The doses are set according to the results of laboratory tests in order to compensate for that individual's degree of genetic vitamin D resistance. This resistance seems to underlie the predisposition to (and maintenance of) autoimmune aggression through the Th17 program of activities. As the protocol aims at regulating the immune system, it has been similarly effective in treating several other autoimmune diseases.
He and his team of 5 doctors have treated more than 4,000 patients at his clinic in San Paulo City using the protocol. He has trained 27 physicians who have launched their own clinics in other cities of Brazil and other countries such as Argentina (2), Peru (1), Portugal (1), Spain (1), Italy (3), Croatia (1) and Canada (1). An ophthalmologist in Naples, FL has been recently trained and is preparing to start a research project using the same protocol to treat autoimmune diseases like uveitis - a major cause of blindness in the general population.
The average initial dose for patients in this treatment protocol is about 1000 IU/day per kg of body weight. In addition to vitamin D, he also prescribes vitamin B2; a diet excluding calcium; and extra fluids (minimum 2.5L/day). After 2-3 months, the daily dose of vitamin D is adjusted in response to changes in laboratory test results. After one year the daily dose is further adjusted to compensate for adaptive changes of vitamin D metabolism (not unusual in patients receiving high doses), until a stable level of laboratory parameters is reached for that individual patient, the point at which vitamin D has reached its maximum immunological effect. This is usually achieved at the third or fourth medical appointment, after 2 years on vitamin D therapy.
The blood work that Coimbra is most interested in is the parathyroid hormone (PTH). PTH production is inhibited by vitamin D and his research has shown that vitamin D immune benefit is maximized when circulating PTH has reached the lower limit of its normal (reference) range. Achieving that level of PTH requires variable daily doses of vitamin D because biological resistance to vitamin D is different for each person. PTH values are also used as a safety gauge, as vitamin D intoxication cannot occur if PTH is not fully suppressed. He carefully monitors blood and urinary calcium, to avoid kidney stones. A calcium restricted diet and minimal daily hydration of 2.5 L are imperative precautions to avoid those potential side-effects. He also administers high doses of vitamin B2 (riboflavin). A significant part of the world population (10-15%) are not able to absorb enough vitamin B2 from normal daily doses to enable the chemical reactions within the body that convert D3 into the working form of vitamin D for immune function - 1,25HydroxyD.
After his patients have been at the correct blood level of PTH for 2-3 months, most if not all of the symptoms are gone, depending on whether permanent disabilities were already established before the beginning of vitamin D therapy. They are considered to be in remission as they no longer have relapses, nor new lesions in their MRI images. They no longer expect to be blind or paraplegic, or to become disabled. They have their life back!
After the third or fourth appointment, Coimbra recommends his patients return in 2 years and again in 5 years for a review appointment and to make sure that no further adjustment of their vitamin D dosage is necessary. Right now most patients are still on very high doses of vitamin D (in some cases levels up to or even higher than 4,000 ng/mL are required to maintain PTH around its lowest normal level and suppressed disease activity due to their very high degree of resistance to both beneficial and toxic effects of vitamin D; in most patients the circulating levels are within the range of 250-1,000 ng/mL). He has not been practicing long enough to determine how long high circulating levels of vitamin D have to be maintained to keep MS in remission.
Do you think it was the chicken or the egg?
Does low vitamin D cause MS? Or does MS cause low vitamin D?
Coimbra feels low vitamin D associated with genetically inherited vitamin D resistance and stressful life events trigger MS and other autoimmune disorders. Vitamin D is a natural, powerful inhibitor of autoimmune reactions. He cites latitude charts of MS incidence (the farther you are from the equator - the more prevalent the disease) as the initial epidemiological data which triggered intensive research and cumulative evidence - enabling development of his protocol.
Physicians interested in knowing the Coimbra vitamin D3 for MS protocol can write to: [email protected]