The Coimbra Protocol: How Supervised Vitamin D Therapy Works and What the Research Shows

What is the thinking behind the Coimbra Protocol?

The Coimbra Protocol rests on a hypothesis under study, which Lemke and colleagues in Frontiers in Immunology in 2021 call acquired vitamin D resistance: that some people with autoimmune disease respond weakly to vitamin D, so the amount is judged for the individual rather than from a chart, with parathyroid hormone proposed as the guide [3].

Research supports the idea that vitamin D response varies: people differ markedly in how strongly they respond to vitamin D, sorting into high, mid and low responders in studies of adults without autoimmune disease, and in one open-label study people with multiple sclerosis had a smaller rise in blood level than healthy controls on the same amount, a measure of blood level rather than of how cells respond [6][7][8][9][10].

An acquired resistance calling for very large amounts of vitamin D has not been shown: the responder studies were in adults without autoimmune disease at far lower amounts, no validated test for such a resistance exists, and no study has measured it during treatment and linked it to patient outcomes [3][11][2]. Its proposers share that caution: Lemke and colleagues, in Frontiers in Immunology in 2021, write of “A hallmark of acquired vitamin D resistance, if it exists” [3].

Parathyroid hormone is the proposed guide, and proposed is accurate: the 2013 pilot study asks for research into whether its fall is a useful marker [1] and the 2021 paper calls it the key information for finding the dose [3]. Whether dosing guided this way works better, or is safer, has not been tested.

Why is vitamin D called a hormone and not a vitamin?

Vitamin D is called a hormone because the body makes it, switches it on in two deliberate steps, and then uses the switched-on form to turn genes up and down, which is what a hormone does. A vitamin, strictly, is something the body cannot make and has to take in. According to a 2020 review by Charoenngam and Holick, “It is also known as an immunomodulatory hormone” [12].

The chemistry agrees. Skin holds 7-dehydrocholesterol, a relative of cholesterol built on the four linked rings that define a steroid, and ultraviolet B light breaks one of those rings open [13][14]. That is why vitamin D is classed as a secosteroid, a steroid with a cut ring. What leaves the skin, like what arrives in food, is fat soluble and biologically inert [15], and two enzymes change that, an enzyme being a protein that speeds up one reaction: the liver adds one oxygen and hydrogen group to make 25-hydroxyvitamin D, written 25(OH)D, and the kidney adds a second to make 1,25-dihydroxyvitamin D, also called calcitriol, the active form [16][17].

The active form behaves like a steroid hormone. It binds the vitamin D receptor, that receptor pairs with a partner called the retinoid X receptor, and the pair settles on short stretches of DNA called vitamin D response elements beside the genes it controls [18]. Mapping that binding across the genome of one human cell line found 2,776 positions where the receptor sat on DNA and 229 genes whose activity changed [19]; reviews put the number of directly controlled genes in the hundreds, at thousands of binding sites across many cell types, with a list that is not the same everywhere, because vitamin D target genes are largely tissue specific [20][21]. A molecule that arrives inert, is switched on deliberately in two places, and is read by a receptor on DNA in most tissues is a signalling molecule, not a nutrient in the ordinary sense.

How does the body absorb vitamin D?

The body absorbs vitamin D in the small intestine, dissolved in fat. According to a 2015 review by Reboul, vitamin D does not dissolve in water, so it is first packaged into micelles, tiny droplets built from fat, bile acids from the liver and enzymes from the pancreas [22]. Uptake into the gut lining is then partly protein-handled rather than passive: putting three cholesterol transporters into cells that normally lack them raised vitamin D uptake, and specific inhibitors of each lowered it again [23].

Bile flow is therefore part of the step, and a human tracer study shows it directly: in severe bile obstruction, absorption of plain cholecalciferol was minimal, while absorption of the already 25-hydroxylated form was relatively preserved [24]. A 2023 review of coeliac disease, inflammatory bowel disease and bariatric surgery concluded that all of the malabsorptive conditions it examined severely impair vitamin D status [25].

Almost all of what is absorbed travels bound to one protein, vitamin D binding protein, which carries every form on a single binding site [26]; in mice bred without it, 25(OH)D disappears from blood far faster [27]. Only the small unbound fraction is thought to enter cells, and Bouillon and colleagues write in their 2019 review that, for most situations, “the free hormone model is physiologically and clinically relevant” [26].

Body size changes the arithmetic. Whole-body ultraviolet exposure raised blood vitamin D3 by 57 per cent less in adults with obesity than in matched lean adults [28], and modelling in 686 unsupplemented adults read that as dilution through a larger fat mass rather than trapping in fat [29].

What has to happen before vitamin D can work?

Four things must happen before vitamin D can work: the liver adds a first oxygen and hydrogen group, the kidney or an immune cell adds a second, proteins carrying flavins made from riboflavin deliver electrons to both enzymes, and magnesium is present both to build those flavins and to run the parathyroid hormone signal that tells the kidney to act.

The liver step. One enzyme does most of this work in people. CYP2R1 was identified as the microsomal 25-hydroxylase, with catalytic efficiency measured 26-fold higher than the older candidate CYP27A1 [30][31], and human genetics settles it: people who inherit faulty copies cannot raise blood 25(OH)D normally even when given vitamin D [32][33][34]. Mice without the gene lose more than half of their blood level but not all of it, so another enzyme contributes in that species [35].

What is established and what is not should be said plainly. The flavin dependence of both electron delivery chains, the building of those flavins from riboflavin, the magnesium requirement of both flavin-building enzymes and the zinc in the receptor are established chemistry, measured on purified human or mammalian proteins, and the magnesium requirement for parathyroid hormone secretion is established in people. Never tested in people is the link between the two ends: no human study has measured riboflavin status, or given riboflavin, and then measured vitamin D status or 25-hydroxylation [55]. No study documents a magnesium requirement of the receptor itself, so none is claimed here [56].

What does vitamin D do once it is switched on?

Once switched on, vitamin D’s established job is mineral control: the active form raises calcium and phosphate absorption from the gut and keeps the skeleton mineralised, and Charoenngam and Holick wrote in 2020 that vitamin D plays “an essential undisputed role in the maintenance of calcium, phosphate, and bone metabolism” [12].

That job is governed by a loop rather than left running. Parathyroid hormone, calcium, phosphate and a bone hormone called FGF23 set how much active form the kidney makes [17][57]. Giving FGF23 to animals reduced kidney messenger RNA for the activating enzyme and increased it for the breakdown enzyme, starting within one hour [58], and FGF23 can deliver that message only because the kidney also carries klotho, a protein that turns an ordinary growth factor receptor into an FGF23 receptor [59].

The off switch is a single enzyme, CYP24A1, which dismantles both 25(OH)D and the active form, in people by two routes, one ending in a ring-closed product called the C23 lactone that the rat enzyme barely makes, so rat breakdown data do not transfer [42]. What happens when that switch fails is documented in children: sequencing in familial idiopathic infantile hypercalcaemia found recessive CYP24A1 mutations in six affected children, and the authors note that symptomatic high blood calcium may be triggered by ordinary vitamin D prophylaxis [60]. The two forms also last very different times, which is why only one is measured: the active form has a half-life of roughly 15 hours, 25(OH)D about two weeks [61].

How does vitamin D act on the immune system?

Vitamin D acts on the immune system in two directions, shown mostly in laboratory work on human cells: it switches on germ-killing defences in macrophages, and it lowers inflammatory signals from T cells and the generation of antibody-producing plasma cells [62][63][64]. What has been measured in people is narrower: two small trials in healthy adults found more regulatory T cells in blood after about three months, and neither measured a disease outcome [65][66].

Immune cells also make the active form themselves, without waiting for the kidney. Monocytes, macrophages and dendritic cells carry the activating enzyme CYP27B1 themselves, take 25(OH)D from the blood and make the active form inside themselves [67][68][69]. Cantorna and colleagues state in their 2015 paper that “All cells of the immune system have been shown to express the VDR” [70], so all of them can read the signal as well.

Control of this local activation differs from the kidney. In the kidney the enzyme answers to calcium and hormones; in a monocyte the same gene is driven by immune signalling, needing cross-talk between the JAK-STAT, NF-kappaB and p38 MAPK pathways and direct binding of a transcription factor called C/EBP beta to its promoter [71]. Cytokines and bacterial products switch it on [72], and the Th1 cytokine interferon gamma raises it further when a bacterial sensor is triggered [73]. The macrophage version also does not switch on its own brake: macrophages cultured from patients with sarcoidosis activated vitamin D with no matching 24-hydroxylating activity, even when loaded with substrate [74]. The kidney feedback loop therefore does not restrain this reaction, and reviews describe immune cells converting 25(OH)D in an unregulated way, dependent on how much the blood carries [12][75].

In immune cells the active form of vitamin D acts in two directions. On the first line of defence it switches germ killing on: when a toll-like receptor on a human macrophage detects bacteria, the cell raises both the receptor and the activating enzyme, makes a small antimicrobial peptide called cathelicidin, and kills tuberculosis bacteria inside itself [62]. The cathelicidin and beta defensin genes carry vitamin D response elements in their promoters, so the active form turns them on directly [76][77]. One caution decides how far that evidence reaches: the cathelicidin element sits in a short repeated stretch of DNA present in primates and absent from the mouse, rat and dog genomes, and reviews note that many mechanisms of vitamin D signalling in innate immunity appear species specific [77][78]. On the learned second line it does the opposite, and the mechanism is written into the receptor’s own behaviour: Carlberg, reviewing the field in 2022, writes that “VDR antagonizes pro-inflammatory transcription factors, such as NFAT, AP1 and NFkB, in immune cells” [21].

Two small double-blind, placebo-controlled trials gave vitamin D monthly to 59 and to 60 healthy adults for about three months; both found a higher frequency of regulatory T cells in blood, while the function of those cells and the numbers of other immune cell types did not change, and no clinically relevant safety concern was reported [65][66]. Those are blood markers in healthy volunteers over weeks, not disease outcomes.

Why does the same dose not work the same in everyone?

The same vitamin D dose does not work the same in everyone because the molecular response to the same intake differs between people, and because rare inherited faults in two enzymes, CYP2R1 and CYP24A1, can block its activation or its breakdown outright.

According to reviews by Carlberg, studies that read gene activity and chemical marks on DNA in blood immune cells before and after supplementation sorted volunteers into high, mid and low responders on those readings [8], and across two such studies, VitDmet and VitDbol, about 25 per cent were low responders [81]. The reason is open: Carlberg writes in 2019 that “it is not yet known which genomic and epigenomic variations determine the index” [81]. This is laboratory measurement in research volunteers, and no clinic test for it exists.

Two rare genetic faults differ from that variation, because a person who has either is genuinely stuck, and both are documented in people. Loss of function in CYP2R1 means blood 25(OH)D will not rise normally however much vitamin D is given, because the first switch itself is faulty [32][33][34]. Loss of function in CYP24A1 means the active form cannot be switched off, and blood calcium can rise severely [60]. Both are rare genetic faults in an enzyme, not shortages of a cofactor. Other inherited differences shift the numbers without blocking anything: common variants change how much carrier protein a person makes, although how large the resulting differences between population groups are depends on the laboratory method used [82][83], and a larger fat mass dilutes the same amount [29].

Which nutrients does vitamin D actually depend on?

Vitamin D depends on four nutrients at a chemically identified step: riboflavin (vitamin B2), magnesium, zinc and vitamin A. Vitamin K2 acts further along, on the proteins that direct where calcium goes. For all five, the chemistry is better established than the human evidence.

Iron is named only because the ferredoxin carrying electrons to the mitochondrial enzymes holds a two iron, two sulphur cluster [39]; no study was found testing iron status against vitamin D activation. The gaps are specific. No human study has measured riboflavin status and then measured vitamin D status; the one trial that gave both gave them inside a single combined supplement, so it cannot separate them [55]. No trial has tested elemental magnesium, or vitamin K2, as a safeguard for a higher vitamin D intake [85][94]. Boron and selenium are frequently listed as vitamin D cofactors, and no step in vitamin D absorption, activation, receptor action or breakdown is known to depend on either: the review arguing for boron’s biological roles states that the responsible mechanisms are poorly understood [97], and selenium’s documented work is in selenoproteins, thyroid hormone activation and antioxidant defence, where the relationship with intake is U-shaped [98].

What has been published on the protocol itself?

Three papers describe the Coimbra Protocol: a 2013 pilot study by Finamor and colleagues in Dermato-Endocrinology, a 2022 safety series by Amon and colleagues in Nutrients, and a 2021 hypothesis paper by Lemke and colleagues in Frontiers in Immunology. Together they are encouraging and preliminary, and none is a randomised controlled trial.

The pilot study of 2013 was open-label work in Sao Paulo, where 9 people with psoriasis and 16 with vitiligo took vitamin D3 35,000 IU once daily for six months with a low-calcium diet and at least 2.5 litres of fluid a day [1]. The psoriasis severity score improved in all nine, and of the 16 people with vitiligo, 14 had some repigmentation, none above 75%. The authors conclude that “High-dose vitamin D3 therapy may be effective and safe for vitiligo and psoriasis patients” [1]. The limits of the 2013 pilot study belong beside that: 25 patients, no control group, any standard treatments left unchanged during the study, and a corresponding author who developed the protocol.

The safety series of 2022, by Amon and colleagues, is the largest published body of monitoring data on the Coimbra Protocol: routine laboratory results from 319 self-selected patients at one German dermatology centre, reporting laboratory values only, with no disease outcomes, no control group and the treating physicians as authors [2].

The hypothesis paper of 2021 sets out the resistance idea and adds uncontrolled practice data on 41 people with relapsing-remitting multiple sclerosis; two authors declare that they practise the protocol and one owns the practice applying it [3].

Beyond those three, we found no published randomised controlled trial of the Coimbra Protocol: as of October 2026 none appears in PubMed under the Randomized Controlled Trial publication type or in ClinicalTrials.gov, although the German and WHO registries could not be searched, and Amon and colleagues state in Nutrients in 2022 that “randomized clinical trials are missing” [2].

What do vitamin D trials in autoimmune disease show?

Vitamin D trials in autoimmune disease show a mixed picture with some positive signals, and none of them tested the Coimbra Protocol. The 2025 D-Lay MS trial in JAMA found less disease activity after a first episode suggesting multiple sclerosis, with no significant difference in relapse; the VITAL trial (BMJ 2022) found fewer new autoimmune diagnoses, an effect that did not last in its follow-up; meta-analyses from 2026 found no overall reduction in relapse but a benefit in high-dose subgroups; and pooled trials in thyroid and bowel disease point in a favourable direction. Other meta-analyses, including Cochrane 2018 and one in rheumatoid arthritis, found no benefit.

Five further multiple sclerosis trials (VIDAMS, SOLAR, CHOLINE, PrevANZ and EVIDIMS) missed their primary outcomes [119][120][121][122][123]. As far as their abstracts report, none of these trials, favourable or null, set the dose by parathyroid hormone or body weight or used the calcium-restricted diet; a 2020 review by Feige and colleagues notes that amounts of up to 40,000 IU a day have been tested [124]. These trials therefore neither support nor refute the Coimbra Protocol directly.

What does the research show about vitamin D and cancer?

Vitamin D is not a cancer treatment, and Cure4Pain makes no claim that it prevents cancer. The published research differs by kind of study: observational studies link low levels with colorectal cancer but not breast cancer, genetic studies come out neutral, randomised trials have not reduced how many people develop cancer, and some analyses link higher levels with more prostate and pancreatic cancer.

Low levels travel with some cancers in observational studies. A 2019 analysis by McCullough and colleagues in the Journal of the National Cancer Institute pooled 17 groups of people followed over time, with 5,706 colorectal cancers. Risk was about 31% higher in those with the lowest vitamin D levels than in those in the middle of the range, and 19 to 27% lower in the 75 to 100 nmol/L band, with no further fall above it [125]. For breast cancer, Visvanathan and colleagues in the European Journal of Epidemiology in 2023 pooled 17 groups with 10,484 cases and found no association at any level, including the highest measured [126].

An association is not the same as a cause. Two ordinary explanations compete with cause and effect here. People with higher vitamin D levels also tend to be leaner, more active and outdoors more often, so something else may be doing the work. And illness itself lowers vitamin D, so a low reading in an unwell person can be a result of the illness rather than its cause. Autier and colleagues, who went through 290 observational studies and 172 trials in Lancet Diabetes and Endocrinology in 2014, concluded that low vitamin D looks like “a marker of ill health” [127][128].

Genetic studies test cause and effect for vitamin D and cancer, and come out neutral. Mendelian randomisation uses inherited gene variants, which are settled at conception and not shaped by lifestyle or illness, as a natural comparison. In the BMJ in 2017, Dimitrakopoulou and colleagues studied seven cancers, including breast and colorectal, in 70,563 cases and found “little evidence for a linear causal association” with vitamin D level [129]. He and colleagues in 2018 found no association for colorectal cancer in 10,725 cases, with 18,967 more in summary data [130]. A 2019 analysis with 122,977 breast cancer cases agreed, and its authors add that they can still not exclude “a modest or non-linear effect of vitamin D” [131].

Supplement trials have not reduced how many people develop cancer. In the VITAL trial, 25,871 adults took 2,000 IU a day or placebo for a median of 5.3 years, with no difference in cancer incidence [132]. In the D-Health trial, 21,308 adults took 60,000 IU monthly for five years, again with no difference, and no effect on prostate, breast, colorectal, lung cancer or melanoma individually [133]. Pooled analyses of randomised trials reach the same result [134].

Two trial findings concern what happens after a cancer appears rather than whether it appears. In a 2023 meta-analysis of 14 trials and 104,727 people, Kuznia and colleagues found a 6% fall in cancer deaths that was not statistically significant overall (risk ratio 0.94, 95% CI 0.86 to 1.02); deaths were 12% lower in the 10 trials that gave vitamin D daily, with no reduction in the 4 trials using large occasional doses [135][134]. In a secondary analysis of the VITAL trial, advanced cancer, meaning cancer that had spread or proved fatal, was less common in the vitamin D group (1.7% versus 2.1%, hazard ratio 0.83, 95% CI 0.69 to 0.99), a difference seen in people of normal weight but not in those with overweight or obesity [136]. Neither shows that vitamin D treats cancer: in 455 people with previously untreated metastatic colorectal cancer, a 2026 phase 3 trial found that adding high-dose vitamin D3 to chemotherapy did not improve progression-free survival [137].

Higher is not automatically better. In a 2014 meta-analysis by Xu and colleagues across 11,941 cases, higher vitamin D levels were associated with 17% higher risk of prostate cancer [138]. In a 2010 pooled analysis of eight groups by Stolzenberg-Solomon and colleagues, the risk of pancreatic cancer was about twice as high at levels of 100 nmol/L and above, and the authors wrote that advice to raise levels in healthy people for cancer prevention should be carefully considered [139]. In the D-Health trial, whose supplemented group reached a mean of 115 nmol/L, deaths from cancer were numerically higher (hazard ratio 1.15, 95% CI 0.96 to 1.39, not statistically significant), and its authors advised caution about that regimen in people who already had enough [140].

What Cure4Pain takes from the vitamin D and cancer research. Finding and correcting a documented vitamin D deficiency is worth doing on its own merits. Where vitamin D is given, daily dosing has better support than large occasional doses. We do not aim at any blood level for cancer, we do not treat cancer, and nothing in this research is a reason to take high doses on your own. The Institute of Medicine concluded in 2011 that for outcomes beyond bone, including cancer, the evidence was “inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirements” [141], and the 2024 Endocrine Society guideline suggests against supplementing above the dietary reference intake to lower disease risk in healthy adults younger than 75 [142]. This remains an active research question, and we will keep this section current as trials report.

What is known about the risks, and what do they teach us?

The known risks of very high vitamin D doses, including within the Coimbra Protocol, are raised calcium in the blood, raised calcium in the urine and kidney injury, which a 2020 critical review by neurologists describes as potentially life-threatening [124]. In most published cases these improved once found, though not always fully [4][5][143]. Because of those risks, the therapy is carried out under a trained physician, with tests, a calcium-restricted diet, high fluid intake and the dose set by results, never alone.

The largest safety paper on the Coimbra Protocol, by Amon and colleagues in Nutrients in 2022, reports the reassuring end: across more than 6,100 laboratory parameters in 319 patients, average calcium and kidney results stayed within normal ranges and no symptoms suggestive of raised calcium were reported [2]. It also reports what averages hide: vitamin D3 was stopped temporarily in 27 situations when urinary calcium excretion passed its threshold, and stopped altogether in 16 cases, among them no clinical effect, worsening symptoms, the diet, pregnancy, familial hypocalciuric hypercalcaemia and a significant rise in bone markers. With one centre, no control group, values its authors say were sometimes missing and no count of individual abnormal results, the rate of raised calcium under the protocol is not known.

For scale, the official upper intake level for adults is 4,000 IU a day, according to the Institute of Medicine in 2011 and, as 100 micrograms, the European Food Safety Authority in 2023 [141][144]; the doses reported under this protocol are far above it. One randomised trial, which also gave calcium where dietary intake was low, shows the risk of raised calcium moving with the dose, well below protocol amounts: according to Billington and colleagues in 2020, in 373 healthy adults on 400, 4,000 or 10,000 IU a day for three years, mild hypercalcaemia occurred in 4% overall, rising from 0% to 9% across the groups and resolving on repeat testing, and raised urinary calcium in 23%, from 17% to 31% [145]. A 2016 meta-analysis of long-term supplementation also found raised risks, but not related to dose [146]. In the same trial as Billington’s, radial bone density at three years was lower on 4,000 or 10,000 IU a day than on 400 IU, with no significant difference in bone strength [147]. No controlled bone data exist for this protocol, which also restricts calcium.

In October 2023 the Arzneimittelkommission der deutschen Aerzteschaft, the German drug commission, reported a 65-year-old man with multiple sclerosis, taking candesartan, who had taken 60,000 IU a day over six months and was found with a blood calcium of 3.2 mmol/L and reduced kidney function; he recovered fully. Its notice names this protocol, describes it as a therapeutic approach that is not scientifically proven, and advises against the treatment [4]. Whether a physician, the diet, the fluids and monitoring were in place is not reported.

Two case reports name the protocol. A 2021 report describes a 56-year-old woman with multiple sclerosis on a mean of 130,000 IU a day for 20 months, with a blood calcium of 3.23 mmol/L, whose kidney function took about six months to return to normal; repeated tests were on record, and the authors note that parathyroid hormone fell progressively and that values near the lower limit of normal may potentially alert to the risk [5]. A 2020 Swiss report, known to us only through the 2021 hypothesis paper, describes a 39-year-old with multiple sclerosis and an inherited endocrine gene change on 100,000 IU a day for seven months, with a blood calcium of 3.0 mmol/L and kidney impairment; the parathyroid hormone level had been raised before treatment, the kind of finding baseline testing is meant to catch [148]. Lemke and colleagues, the authors of the 2021 hypothesis paper, accept that toxicity is possible within the Coimbra Protocol and consider it rare, without giving a denominator [3].

Further cases at very high doses, not named as this protocol in the records we could read: 21 people in Brazil on a mean of 87,000 IU a day for about a year, with severe hypercalcaemia, kidney failure, stones, nephrocalcinosis and seizures, known to us only through a 2020 review [149]; a person with primary progressive multiple sclerosis after uncontrolled intake of over 50,000 IU a day, whose kidney function improved only partly [143]; and hospital admissions reported in 2023 and 2025 on high doses, one of them self-started and one in a person who also had sarcoidosis [150][151].

Professional bodies have stated their positions. On 28 September 2017 the German multiple sclerosis society and its competence network, the DMSG and the KKNMS, stated that in their view this protocol as an add-on therapy in multiple sclerosis is justifiable only within a study protocol [152]. A 2020 critical review by neurologists states that it is not based on study evidence and can cause life-threatening complications, and that vitamin D toxicity can show as fatigue, muscle weakness or urinary problems, resembling the natural course of progressive disease [124].

In most published reports of harm, whether supervision, baseline tests, the diet, the fluids and monitoring were in place is not stated [4][149][143][151], so they do not settle whether fully supervised care carries the same risk. They do establish that the harm is real, and that blood tests can show raised calcium before symptoms appear [153]. On the need for supervision, both sides agree. Amon and colleagues, who use the protocol, “strongly advise against the use of CP by patients themselves based on Internet information”, CP being their abbreviation for it [2]; Feige and colleagues, the neurologists of the 2020 critical review, who do not support it, conclude that vitamin D supplementation in multiple sclerosis is “a sensitive task which needs to be supervised by physicians” [124]. The Coimbra Protocol should never be attempted on one’s own, whatever doses, blood levels or schedules are read online.

Who should not take high-dose vitamin D?

High-dose vitamin D should not be taken by people with granulomatous disease such as sarcoidosis, kidney disease, raised calcium or parathyroid disease, or inherited differences in breaking vitamin D down, in pregnancy and breastfeeding, or with certain medicines such as thiazide diuretics or lithium. The published Coimbra Protocol papers screened people out before starting, and the strength of the evidence behind each exclusion differs.

• Granulomatous disease such as sarcoidosis. In sarcoidosis, tuberculosis, leprosy and fungal disease, activated immune cells make active vitamin D outside the normal pathway, a recognised cause of toxicity in a 2018 clinical review [153]; worsening after supplementation is a single case report [154].
• Kidney disease, raised calcium and parathyroid disease. Impaired kidney function, disturbed calcium metabolism, raised blood or urinary calcium and primary hyperparathyroidism were exclusions in the published papers, which also excluded a low fluid intake and refusal to restrict dietary calcium [1][2][3]. Kidney stones were an exclusion in neither, and only two published cases bear on them [155]; in our own practice we treat them as a reason not to start, or to start only with special care, a precaution rather than a research finding.
• Inherited differences in breaking vitamin D down. Where variants of the CYP24A1 enzyme slow that breakdown, a 2020 paper states that supplementation can precipitate hypercalcaemia and kidney stones [156]; beyond it there is one 2025 case of nephrocalcinosis and a 2024 review on genetic predisposition [157][158].
• Pregnancy and breastfeeding. No trial of protocol-level amounts in pregnancy was found; in women with a CYP24A1 mutation, pregnancy triggered hypercalcaemia [159]; pregnancy is among the reasons treatment stopped in the 2022 series [2]; and the European Food Safety Authority’s 2023 upper intake level applies to pregnant and breastfeeding women as to other adults [144].
• Certain medicines. The 2013 pilot study excluded thiazide diuretics and lithium, to avoid interactions with vitamin D on calcium metabolism [1]; a 2018 case study of milk-alkali syndrome in treated hypoparathyroidism lists sartans and thiazides among triggers [160]; and the man in the October 2023 notice was taking candesartan, a sartan [4].

What monitoring does published practice use?

Published practice reports frequent blood and urine testing, before treatment and throughout it, with the dose changed according to the results.

• The 2022 German series reports parathyroid hormone, total and ionised calcium, phosphate, kidney function including cystatin C, albumin, ferritin, thyroid stimulating hormone and 24-hour urinary calcium, with bone density and turnover markers decided individually and a yearly kidney ultrasound; biotin is stopped before parathyroid hormone testing because it interferes with the assay [2].
• The 2013 pilot study measured serum urea, creatinine and total and ionised calcium, which did not change, and urinary calcium excretion, which rose within the normal range [1].
• The 2021 paper describes parathyroid hormone as the measure used to find the dose [3].

The calcium-restricted diet and the high daily fluid intake are reported as part of treatment in both papers [1][2]. These are the measures the published papers name, reported as published practice: the doses on this page are facts about those studies, and this page gives no dose to follow and no target blood level. What any individual needs is decided by the treating physician from that person’s own results.

How we use supervised vitamin D therapy at Cure4Pain

At Cure4Pain, supervised vitamin D therapy is set, monitored and adjusted by the clinical team, inside an integrative and functional medicine plan, in coordination with your existing consulting physician.

• Assessment and tests first: your history, diagnosis, reports and medicines, any kidney, calcium or parathyroid history, and our standard panel of about 100 measures with ANA by the IFA method.
• The dose is ours to set, never copied from anyone else: there is no fixed dose for any person or condition. It comes from your condition, body weight and tests, with PTH as the main guide, and is adjusted at each review from your results [3]. We publish no dose and no target blood level.
• A calcium-restricted diet: dairy removed (small amounts of fermented dairy such as yogurt or kefir may be allowed within the calcium limit set for you), calcium-fortified foods and calcium supplements stopped, foods very high in calcium limited within an allowance set for you, so that less calcium is absorbed from food while vitamin D is high [2][1]. Ghee is usually allowed.
• Fluids: at least 2.5 litres a day, to keep the urine dilute, as in published practice [1][2].
• Cofactors, from your tests and the clinical picture. Vitamin D cannot be switched on by itself: the enzymes that activate it depend on riboflavin (vitamin B2) and magnesium, as set out above [36][38][44][47][48][50]. So we correct what your tests and clinical picture show: magnesium, always as elemental magnesium, with absorption varying widely by form, assessed from the clinical picture because according to the US National Institutes of Health less than 1% of the body’s magnesium is in the blood and blood levels do not reflect total body magnesium [161][53]; vitamin B2; vitamin K2, which carboxylates the proteins that direct calcium into bone [92]; zinc where your tests show the need; and, as separate nutrients that are not steps in the vitamin D pathway, B12, folate or selenium where your tests show the need, and omega-3, an essential nutrient judged from your diet history unless contraindicated. By mouth first. The riboflavin, magnesium, zinc and vitamin K links are established chemistry; whether adding each one as a supplement changes how a patient feels has not been tested in trials, and we say so.
• Vitamin K2: we use it as a cofactor so that calcium goes into the bone rather than settling elsewhere. This use is not proven: vitamin K2 has been studied for bone density and artery calcification, not as a safeguard during vitamin D therapy. We use it as a precaution, because the aim is immune modulation at the highest level of safety.
• Exercise: regular activity as advised; exercise and stress management are part of published practice [2].
• Gut and metabolic health in the same plan: gut health and absorption, thyroid and metabolic health, sleep and stress are treated alongside the therapy, not after it.
• Regular monitoring: a full panel including PTH, total and ionised calcium, kidney function and 24-hour urine calcium usually every 6 to 8 weeks (each condition page states its own interval), with the dose changed when results move; published practice also reports a yearly kidney ultrasound [2]. Outside India, tests are done near you.
• Your existing treatment continues: no prescribed medicine is stopped simply because this therapy is added. Dr Krushal Pabari, MD, PGCP prescribes and adjusts medicines as per guidelines, under clinical guidance from Team Cure4Pain, in coordination with your existing consulting physician; never stop or change them on your own.

This is our clinic practice; individual results vary, and further studies are needed.

If you would like us to read your reports and say whether this therapy suits your case, you can book a consultation.

Please do not try the Coimbra Protocol on your own

The Coimbra Protocol is not something to copy from an article, a forum or a video. The dose only means anything beside your own test results: we set it, monitor it and adjust it from those results, and the diet, the fluids and the cofactors belong to the same plan. Supervised care is available, in Mumbai and online from any country. AT. Chintan Dalal, N.D. repeats this warning in his teaching, and it applies just as much if you have already found a dose mentioned somewhere: please have it reviewed first.

Which conditions do we use it for, and where does it fit?

Cure4Pain uses supervised vitamin D therapy for autoimmune and immune-mediated conditions, including multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, lupus (SLE), Hashimoto’s thyroiditis, myasthenia gravis and others. The dose level differs by condition: the full supervised protocol for some, Coimbra Protocol-based methods at lower supervised doses for others, and standard supplement doses for some, such as ankylosing spondylitis and hypothyroidism. Each condition page states which level we use.

At Cure4Pain, supervised vitamin D therapy is never used alone, and it is added to guideline treatment, not used in place of it: guideline medicines are named on each autoimmune condition page, and this therapy has no published randomised trial behind it. It sits inside an integrative and functional medicine plan with functional nutrition, gut health, thyroid and metabolic health, sleep, stress and, where helpful, naturopathy, acupuncture and pain care, beside the treatment you are already on.

Consultations: Mumbai or online worldwide

You can consult Cure4Pain in person at the clinic in Malad West, Mumbai, or online from any country. Reports are reviewed before the therapy is considered, blood tests are done at a laboratory near you and read with you, and reviews usually continue every 6 to 8 weeks. Hands-on treatment needs a visit to Mumbai. The consultation fee is shown when you book.

Who treats you

• Dr Krushal PabariMD, PGCP - Rheumatic & Musculoskeletal Diseases. Assistant Professor, Cooper Hospital; Guest Professor, CMP Homoeopathic Medical College.
• AT. Chintan Dalal, N.D.BNYS, R.AP. Functional nutrition and Coimbra Protocol practitioner.

Consultations look at the whole person: alongside the medical and nutritional plan, we bring a strong interest in behavioural science to counselling on stress, sleep and lasting lifestyle change.

How consultations work: Mumbai or online worldwide

Book through our patient portal. You can see us in person at our clinic in Malad West, Mumbai, or online from anywhere. Your first consultation reviews your history and tests; we then agree a plan together and set the monitoring schedule.

Related conditions and articles

• Multiple Sclerosis (MS)Immune attack on the brain and spinal cord; supervised vitamin D therapy (Coimbra Protocol) with your neurologist.
• PsoriasisScaly, inflamed skin patches; vitamin D, nutrition and patient cases.
• Rheumatoid ArthritisJoint pain and stiffness; integrative care in coordination with your existing consulting physician.
• Lupus (SLE)A whole-body autoimmune condition; vitamin D, magnesium and monitoring.

• Autoimmune and inflammatory conditions
• Vitamin D and autoimmune disease: what the research shows

This page is for education and does not replace medical advice. Do not start, stop or change any medicine or supplement without medical guidance.

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