One more nail in the coffin of the absence of evidence of the Protocol Coimbra
Since I prescribe the Protocol Coimbra I have been asked what the scientific basis for its prescription is. It is a naturally fair question, no doubt. Either because of the curiosity of those who want to know how vitamin D works and why it is necessary to take high doses, or because their doctors raise this question - in a more or less incisive or aggressive way -, the truth is that I find myself confronted with some variation of this question.
In my response I end up explaining the physiology of vitamin D, the way it works in the nucleus of cells, the genetic particularities involved in its metabolism and the rationale for requiring significantly higher doses than recommended. I try to provide as much information and data as is necessary to answer the questions I am asked and to ensure that the person who has decided to leave the most obvious therapeutic pathway and seek different routes feels that they have made the right decision and that they have the support they deserve.
The argument that the Protocol Coimbra has no evidence for its use is false. In this text I explain in detail the evidence behind the use of high doses of vitamin D.
"Not enough," say the critics,"there is no peer-reviewed paper published in a major journal that supports its prescription." Indeed true, until this year.
In April 2021 a paper entitled "Vitamin D Resistance as a Possible Cause of Autoimmune Diseases: A Hypothesis Confirmed by a Therapeutic High-Dose Vitamin D Protocol"..
It is a very important milestone because, for the first time, a paper has been published in a renowned journal, Frontiers in Immunology, reviewed by world leaders in the field of vitamin D research, supporting the use of the Protocol Coimbra in autoimmune diseases.
It is a dense and fascinating article, exposing in a structured and clear way the existing evidence. Anyone who likes to dive into the details and nuances of science, I highly recommend reading it.
These are the 3 main ideas of the article:
Polymorphisms in genes of the vitamin D system can create individual susceptibility to the development of low response to vitamin D, with acquired resistance to vitamin D being an extreme form, exacerbated by other factors causing blockages in the vitamin D receptor.
This point and all the scientific justification presented is particularly fascinating because it sheds light on why our patients answer the question 'why do you think the disease appeared or got worse'.
Invariably, the answer we get is "stress".
Over 95% of our patients tell us that their autoimmune disease was triggered or aggravated after a more or less intense period of stress, particularly physical or emotional stress. The most common examples are relationship breakdowns or stressful and difficult work conditions, although there are examples of supposedly happy moments as a trigger for aggravation, such as preparation for marriage or birth of the first child.
Different possible hypotheses for why this relationship exists had already been published, ranging from altered regulation of Treg cells (which I call "conductors of immunity") or the impact of chronically increased levels of cortisol, the stress hormone, though in my view without being able to clarify this relationship in detail, something this article has managed to do.
Trying to simplify the science described, increased glucocorticoids (cortisol, cortisone or derivatives) inhibit the vitamin D receptor, VDR. This inhibition prevents vitamin D from binding to the receptor and thus prevents the positive effect of this vitamin in optimising immune function. Put another way, increased levels of cortisol and company in response to stress (whatever that may be) create a blockage of the vitamin D receptor, creating the conditions for increased intensity of autoimmune responses.
This is most likely the reason why stress, particularly emotional stress, is the main barrier blocking the positive effect of the Protocol Coimbra.
Withdrawal of article
But this impact can, and perhaps even should, be extrapolated to any other factor that negatively influences the GDV, namely infections, once again supporting the observation that there is a clinical worsening during viral or bacterial infections.
2. "Blood parathyroid hormone level remains the key information for determining vitamin D dose in autoimmune diseases as long as there is no other way to determine the individual response to vitamin D"
It could not be put better: until there is a better way of measuring the real biological effect of vitamin D, we are forced to resort to measuring the parathyroid hormone (PTH).
PTH levels vary inversely as a function of the biological effect of vitamin D, not its blood concentration. Incidentally, a state of secondary hyperparathyroidism is an analytical indication of probable genetic resistance to vitamin D, particularly when blood vitamin D levels are "normal" (i.e. within reference levels).
For this reason, when the biological effect of vitamin D increases, PTH decreases. Just like a balance, when one of the plates goes up, the other goes down. So, to reach the therapeutic target of the Protocol Coimbra and achieve the maximum biological effect of vitamin D, we increase its dosage until PTH is low - preferably below the reference range.
As I often tell our patients, there is nothing magical about PTH and its values being low. It just means that we have achieved what we want: the maximum effect of vitamin D.
3. "Based on these data, high-dose vitamin D therapy should be included in therapeutic measures for all autoimmune diseases on an individual basis only."
If we are all different, it is absolutely logical that we need different amounts of the same compounds. It seems obvious to me. The same dose of any compound will work for some people and not for others. Insulin treatment will always be the most classic - and conventional - example of the need to personalise treatments.
Image taken from article
Itis not possible to generalise a dose of vitamin D: the same dose can be extremely toxic or downright ineffective when taken by different people.
Genetic characteristics, the existence of factors that may influence the metabolism of this vitamin influence the process and define which steps are necessary to achieve therapeutic success. It is not just a matter of prescribing supplements in certain doses, adjusted to analytical results. It is also about eliminating reasons that may negatively influence the course of treatment, in particular stress.
Experience over the years has taught me that the 'easy' part of prescribing the Coimbra Protocol is the technical part: managing vitamin D, its positive effect, its risks and ensuring that patients are safe.
More difficult but more challenging is to support the person who makes the courageous decision to leave the easy and obvious path and seek better solutions for their disease, reducing the doubts and insecurities inherent in the decision.
I predict that as time goes on, with more and more thousands of people being helped by vitamin D in one form or another, there will be more and more scientific recognition of the potential that vitamin D has in different autoimmune diseases.
This recognition will increase the security and certainty of those who initiate the Protocol Coimbra, no longer feeling like "rare birds" or heretics for having decided on an unusual path, decreasing the stress associated with the choice of treatment.
This article is a very important step in that direction.