I would like to open a discussion on high dose vitamin D, order of magnitude of 1,000 IU / kg of body weight, so around 50,000 IU a day for an adult.
High dose vitamin D has put a number of patients with autoimmune diseases into remission, ranging from multiple sclerosis to psoriasis by practitioners in Brazil, also known as the Coimbra protocol, since the early 2000s. I have corresponded with a PSC patient who has put his PSC and UC into remission with this treatment, and I myself have seen symptomatic improvements on high dose vitamin D that I did not see with vancomycin (which brought my liver numbers down, but did nothing for my symptoms).
I compiled a document with some resources on high doses of vitamin D, which includes a spreadsheet with patient stories along with published case reports of patients with autoimmune diseases who have improved greatly.
It seems to me that this is similar to vancomycin for PSC. There are autoimmune patients who have clear improvements on this treatment, yet there’s no randomized controlled trials, so it’s not widely accepted. It could be helpful for PSC patients who do not have access to vancomycin, or for whom vancomycin doesn’t work.
Hello. As a physician, I would like to emphasize the following: This dose is extremely high and potentially dangerous, and it may result in serious vitamin D toxicity.50,000 IU/day of vitamin D is an extremely high dose if taken daily. It is about 12.5 times the usual adult upper tolerable intake of 4,000 IU/day and equals 350,000 IU/week.Main concern: vitamin D toxicity
The major danger is severe hypercalcemia, which can cause:
Nausea, vomiting, abdominal pain, constipation
Marked thirst and frequent urination
Dehydration and weakness
Confusion or drowsiness
Kidney stones and acute kidney injury
Cardiac rhythm disturbances
In severe cases, coma
Dr. Coimbra and the protocol physicians are well aware of the risk of hypercalcemia and contraindications (see the slides).
They require their patients do the following:
Be on a low-calcium diet
Drink at least 2.5 liters of water a day
Test PTH, ionized calcium, 24h urinary calcium, along with other blood tests
From what I have read, it seems that as long as patients monitor their testing levels and stay on the diet, extremely few patients have gotten hypercalcemia. There is a procedure in place (I’ll try to find resources about this) about what to do if it does happen.
However, with respect to all single measurements in 319 patients in over 3.5 years, we temporarily stopped vitamin D3 only in 27 situations, when calcium excretion exceeded more than 10 mmol/24 h (normal values: 2.50–8 mmol Calcium/24 h). In almost all cases, the dietary calcium intake was reviewed with the patient with emphasis on reducing calcium intake to less than 500 mg daily and they were encouraged to increase fluid intake. As a result, the patients were restarted on the CP four-to-eight weeks later without any further disruptions in their treatment. It is notable that a 24 h urine calcium as a marker is helpful for monitoring the possible side effects during CP, but finally not ideal, since the parameter could be under- or overestimated if the collection was less or more than 24 h. For further studies, the regular determination of the urine calcium–urine creatinine ratio might be a more sensitive measure to evaluate the need of protocol interruption.
How Much Vitamin D is Too Much? A Case Report and Review of the Literature – this is a review of patients who were on high doses of vitamin D, however, there is no mention of a low-calcium diet, drinking lots of water, monitoring levels like PTH, ionized calcium or urinary calcium, or pre-existing conditions of the patients, and in all cases except one (which did not report the blood levels) there was at least one indicative blood marker that was high that likely would have been indicated much earlier in 24 urinary calcium, but again, we don’t have much prior information about the patients. In the case report that is specifically reported in this paper, the patient had hyperparathyroidism, which is a contraindication for the protocol because it indicates that calcium will not be regulated properly.
Our patient’s baseline laboratory profile indicates secondary hyperparathyroidism, characterized by increased serum PTH alongside a severe deficiency of vitamin D.
The risks of this treatment are known and can be monitored and controlled. Thanks for opening the discussion on this, as it is something to be aware about and there are some dietary modifications and testing necessary.
Given the number of autoimmune cases of patients who have had a clear benefit from this treatment for many years, it is certainly worth a consideration for PSC.
There are a couple of videos in the spreadsheet of PSC patients in Brazil who seem to be doing better on high dose vitamin D in Portuguese (can be translated on Youtube), linked below:
Thank you for your response. I sincerely appreciate your sharing more detailed information about this study with us.
In clinical research, the level of evidence provided by a study is highly important when determining whether a particular method can move from an experimental approach to an accepted and clinically applicable treatment. The strongest evidence, generally considered to be Level A evidence, with high-quality and relatively consistent results, is provided by well-designed clinical trials, particularly multicenter randomized controlled trials, as well as high-quality systematic reviews and meta-analyses. These types of evidence provide greater confidence regarding the clinical application, efficacy, and safety of a treatment.
Other types of studies, such as case series, can certainly serve as valuable preliminary evidence and may provide the basis for conducting subsequent studies with a higher level of evidence, particularly Level A evidence. Therefore, the level and quality of evidence should always be carefully considered when evaluating the safety and clinical applicability of study findings. In such circumstances, the expert opinions of physicians and specialists directly involved in the relevant field should also be taken into consideration.
Given the rapid advances in medical science and technology, I am confident that more definitive and effective treatments for primary sclerosing cholangitis (PSC) will become available in the near future.
Thank you for your response. I sincerely appreciate your sharing more detailed information about this study with us.
In clinical research, the level of evidence provided by a study is highly important when determining whether a particular method can move from an experimental approach to an accepted and clinically applicable treatment. The strongest evidence, generally considered to be Level A evidence, with high-quality and relatively consistent results, is provided by well-designed clinical trials, particularly multicenter randomized controlled trials, as well as high-quality systematic reviews and meta-analyses. These types of evidence provide greater confidence regarding the clinical application, efficacy, and safety of a treatment.
Other types of studies, such as case series, can certainly serve as valuable preliminary evidence and may provide the basis for conducting subsequent studies with a higher level of evidence, particularly Level A evidence. Therefore, the level and quality of evidence should always be carefully considered when evaluating the safety and clinical applicability of study findings. In such circumstances, the expert opinions of physicians and specialists directly involved in the relevant field should also be taken into consideration.
Given the rapid advances in medical science and technology, I am confident that more definitive and effective treatments for primary sclerosing cholangitis (PSC) will become available in the near future.
Thank you for providing information about how medical evidence is evaluated. Please do share Level A evidence for PSC that you find promising. Part of posting about high dose vitamin D on this forum is to bring physicians and specialists into the discussion.
For PSC, I am aware of these studies that have either already gone through or are in phase 3 clinical trials, which I understand does not necessarily mean Level A evidence, but are a starting point to evaluate:
elafibranor (350 patients): beginning phase 3 trials, estimated completion in May 2031
norUDCA (301 patients): design flaws in phase 3 trials (e.g. only about 20% of patients were not on concurrent UDCA)
nebokitug (CM-101) (350 patients): looking for funding for a phase 3 trial, last I heard they are looking to use it for RA instead of PSC because of funding problems
vancomycin (82 patients): a phase 3 trial this year claiming it is not effective, but was not designed to match the way that PSC patients who are on vancomycin take vancomycin, whereas this real-world observational paper published around the same time shows an improvement in patients with PSC-IBD who took vancomycin
A treatment can take decades to go from case reports to clinical trials, in which time a PSC patient may have to undergo a liver transplant or develop CCA. For example, the first case report of oral vancomycin for PSC was published in 1998, and results from clinical trials are coming out this year (28 years later) in the U.S. and currently being done in Europe.
I am putting together different types of research papers, including trials, related to high dose vitamin D in the spreadsheet that contains the case reports. The same issue of the vancomycin studies in replicating patient method of taking treatment applies to vitamin D. Some trials of vitamin D for M.S. show some improvement but not at the extent that is being reported by patients because they give too low a dose of vitamin D and do not track PTH, and some M.S. trials do show benefit (such as this one).
As for why Dr. Coimbra has not conduct a randomized controlled trial, his reasoning in interviews is that an RCT would mean not giving 50% of patients a treatment that, from his experience, has worked well for many patients. The downside to this is that it is not medically established, so it does not become widespread, meaning that ultimately less patients may get treatment.
I understand the ethics involved in a physician treating patients. Of course if there was a medical established treatment option available to patients, we would take it. But what does a patient do in the face of no widely trial-established medical option?