Can an article on vitamin D and autoimmunity change the way you approach health and performance?
After I wrote the post"Another nail in the coffin of the lack of evidence for the Protocol Coimbra", I got the feeling that something had slipped my mind and I would not have paid attention to the real importance or impact that the research article I had focused on could have. I reread it again to try to find what I had missed.
The conclusion I've come to is that this work, focused on the use of high doses of vitamin D in autoimmune diseases , may force you to rewrite thousands of scientific papers, review how you interpret blood tests and even how you view (and reduce) the impact of stress on health and performance.
I don't think it's overkill, honestly. Here are 3 reasons.
1. all studies on the effect of vitamin D need to be rewritten.
It is not an exaggeration.
One of the criticisms that is made of vitamin D (well beyond the direct criticism of the Protocol Coimbra and the use of high doses in the treatment of autoimmunity) is the apparent lack of clinical efficacy when trying to prove the associations demonstrated by epidemiological studies.
According to the standards of 'evidence-based medicine', observing that treatment A is related to the improvement of situation X does not allow one to say that A has a positive effect on X. It only allows us to say that there is a correlation, and correlation is not the same as causation.
To conclude that there is a causal effect, intervention studies are needed. In this type of research, if treatment A is shown to have improved condition X, then it is possible to say that there is a causal effect between the intervention and the outcome.
This is where criticism comes in:
On the one hand, there are several hundred epidemiological observational studies linking low vitamin D levels with a range of clinical conditions, from chronic diseases such as mood disorders, metabolic alterations or oncological diseases, to reduced physical and mental performance.
On the other hand, intervention studies have failed to demonstrate the much desired causality.
It is, in fact, difficult to find articles that conclude that vitamin D has a positive effect in these same conditions. (Indeed, it is possible to infer causality without having intervention studies, using the Bradford Hill criteria).
Thus, the authors come to the conclusion that vitamin D has no direct effect on these clinical conditions, the associations found being only "coincidental".
This is exactly what is now changing, following the publication of the article Vitamin D Resistance as a Possible Cause of Autoimmune Diseases: A Hypothesis Confirmed by a Therapeutic High-Dose Vitamin D Protocol
Based on the VitDMed and VitDBol studies, which show that there is a significant percentage of people considered to be "low responders" to vitamin D, Lemke et al. tell us that the same amount of vitamin D can have a different real impact on different people and that increasing blood concentrations is not a reliable method of assessing the impact of taking this hormone.
They also describe what will be the most reliable mechanism for doing so: the variation of parathyroid hormone (PTH), as we do in the Protocol Coimbra. This hormone constitutes a direct feedback mechanism of vitamin D metabolism, and is highly associated with changes in the effective physiological effect of this vitamin (and not only its blood concentration).
Image taken from https://pubmed.ncbi.nlm.nih.gov/33897704/
When researchers want to assess whether taking vitamin D can improve disease X, they construct a research protocol in which they make two groups of people the same - one group takes vitamin D A and the other does not - and then compare the two groups on disease activity or severity, on the assumption that the same amount of vitamin D and the same increase in its blood concentration will always have the same effect, even in different people.
It is now known that these research protocols are fundamentally incorrect: the same amount and the same increase in its concentration has different clinical effects in different people.
The physiological effect of vitamin D is achieved when PTH is in the lower third of the reference range, regardless of its blood concentration.
"In other words, if 25(OH)D3 levels are high, PTH should be low and vice versa" (Lemke, et al.)
Logic dictates that
If PTH is not between 15 and 31.6ng/mL (considering the reference range of 15-65ng/mL), then vitamin D will not be having any real physiological impact;
If it won't be having any real impact, you can't really know if vitamin D hasn't had an impact because it really has no effect in those conditions or just because it doesn't yet exist in sufficient quantity to have an effect;
If the actual effect of vitamin D cannot be isolated, no conclusions can be drawn, either positive or negative.
For this reason, all studies using the same dose of vitamin D in all participants, without checking PTH, cannot conclude on the existence or absence of effect of vitamin D .
Let's then dive into some meta-analyses (papers that evaluate the conclusions of published articles, organising them in a rigorous and systematised way) to assess how many studies have taken this relationship into consideration or, in the opposite sign, will have to be redacted.
Cochrane, 2014 reviewed the evidence on the impact of vitamin D on mortality levels. Of the 159 studies included, only one studied variation in PTH (without considering it an efficacy marker). Although they concluded that vitamin D3 could reduce all-cause mortality, in particular from cancer, the studies and their conclusions need to be reviewed as they did not use PTH marker, not assessing the actual effect of vitamin D.
British Medical Journal, 2019 again on the impact of vitamin D on mortality, this time included 50 articles. Not a word about PTH. Although they also concluded a 15% reduction in mortality, the studies and their conclusions need to be reviewed as they did not use marker PTH, not assessing the actual effect of vitamin D.
Nutrients, 2018 on the impact of vitamin D on glycaemic control in type 2 diabetes. Twenty different studies were evaluated. Although they found positive results in reducing insulin resistance, the studies and their conclusions need to be reviewed as they did not use the marker PTH, not assessing the actual effect of vitamin D.
Nutrients, 2015 on the impact of vitamin D on polycystic ovary syndrome. Thirty studies were included. They found no positive effect but the studies and their conclusions need to be reviewed as they did not use marker PTH, not assessing the actual effect of vitamin D.
PLoS One, 2019 on the impact of vitamin D on muscle strength, where they studied 8 articles. Although they found positive results in some muscle groups, the studies and their conclusions need to be reviewed as they did not use the marker PTH, not assessing the real effect of vitamin D.
Sports Medicine, 2017 on the impact of vitamin D on sports performance in athletes included 13 studies. They found no positive effect but the studies and their conclusions need to be reviewed as they did not use marker PTH, not assessing the actual effect of vitamin D.
Look, I'm not saying that vitamin D would have a positive effect on the studies that didn't show it or that it would have a more positive effect on those that did.
Regardless of whether they obtained positive results or not, all articles that did not include PTH variation in their research protocol need to be rewritten and need to take into consideration the individual impact that vitamin D has.
Otherwise, the studies are not clinically useful and their conclusions are false.
It would be the same as saying "drinking water, in this quantity that we don't know if it is enough, is not capable of improving thirst". Or "inhaling less oxygen than is necessary to have an effect is not capable of improving breathlessness". It is obvious that insufficient intervention is not going to have sufficient effect!!!
2. Normal" blood values do not mean that there is a normal effect
The basic reasoning of the researchers is simple and logical: having a 'normal' amount of a compound in circulation only corresponds to an adequate effect if the system is functioning optimally. It is not enough just to measure its concentration in circulation, it is necessary to evaluate its practical physiological and clinical outcome.
Isn't this the same kind of reasoning that is used in different scenarios to assess the effectiveness of a system?
The success of a table factory depends on how many tables it can produce per day, as this is the real factor that will determine its financial viability. Your profitability will depend on how efficiently you can transform the wood coming into the factory into tables for the market.
In the ideal factory, efficiency is always 100%: all the machines are perfectly tuned, they work without any faults, they can produce tables without any waste of material. Because they work so efficiently, the number of chairs produced will be equal to the amount of wood entering the production line. Therefore, all that is needed is to maintain a constant adequate supply of raw material to guarantee success.
In the real factory the scenario is different.
Not all machines work well, their production is influenced by different factors - environmental, structural, human - and their efficiency is not perfect.
This means that, even using exactly the same raw material as the ideal factory - the same wood, in the same quantity - the outcome will be different: the number of tables produced will certainly be lower, compromising the company's viability.
The appropriate amount of "raw material entering the production line" is no longer the only metric needed to control because it can no longer accurately predict how many tables will be produced. It is not enough to know the amount of wood coming in, it is mandatory to measure the amount of tables going out: it is the only way to assess the sustainability and viability of the factory.
If we replace "wood" with "vitamin D" and "tables" with "PTH", we arrive at Dr Lemke's reasoning.
But we may not stop there, as there is a message between the lines that forces one to stop and think:
"normal or adequate blood analytical values do not automatically translate into optimal effect or balance".
There are many situations similar to Vitamin D / PTH where looking at a circulating product does not automatically predict its actual impact:
Optimal blood values of vitamin B9 and B12 may not be sufficient if the homocysteine value is not ideal
Glycaemia within reference values may not mean all is well ifinsulin is higher than it should be
Without DHEA-s value, the morning rise in adequate cortisol does not make it possible to ensure that the circadian rhythm is maintained
Normal' concentrations of vitamin C do not mean sufficient production of cellular glutathione (or cortisol)
These are some examples where assessing only one side of the equation does not give us the comprehensive view needed to know more accurately how the body is functioning, identify subtle signs of physiological change or implement early strategies to improve and optimise health and performance.
They are the difference between being 'normal' or ahead of the norm, or between not being sick and being healthy. It sounds the same but it is not.
3. How stress impacts health and human performance
This part is not hidden between the lines of the article but it is the glue that binds different pieces together, giving a further explanation to the impact of stress on the body
Dr Lemke's team was quite clear in describing howstress, particularly emotional stress, influences the efficacy of vitamin D by reducing the expression of the vitamin D receptor, the VDR .
The increase in cortisol levels, a typical event when there is more stress, inhibits the VDR and thus reduces the effect of the vitamin, resulting in what the authors call acquired resistance to vitamin D.
This relationship explains why the vast majority of our diseases who initiate the Protocol Coimbra report a clear association in stressful events or increases in stress levels and clinical worsening of their disease.
It also explains why most patients who unfortunately do not experience improvement with treatment have very high levels of chronic stress, particularly emotional stress.
Conclusion: increased cortisol levels decrease the biological efficacy of vitamin D.
The problem is that this effect is not limited to autoimmunity!
Image taken from https://www.mdpi.com/2072-6643/11/3/676/htm
In situations where there are chronically high levels of cortisol, there is a reduction in all the effects of vitamin D. This is because it exerts its effect by binding to the VDR and together they influence the gene transcription of over 1000 genes.
The impact is particularly significant in 3 systems:
Neurological
Immune system
Osteomuscular
Better health and performance requires the optimisation of these systems. Whatever the context - be it a corporate athlete, weekend warrior, professional athlete or wanting to be healthy to live better - we must all agree that brain, immune and muscle function are fundamental for success!
Without being able to think or make decisions, defend and recover or have structural strength and resilience, achieving goals will become much more difficult.
It turns out that vitamin D greatly influences how these systems act!
"Low vitamin D levels predict executive dysfunction, in particular mental shifting, information updating and processing speed."(article)
"The proper function of our body's defence system requires the presence of adequate levels of vitamin D for barrier integrity, production of antimicrobial compounds, chemotaxis of other immune cells and regulation of the innate and adaptive immune systems." (article)
"Poor vitamin D status affects muscle strength and vitamin D may participate in protein synthesis through the actions of the VDR in muscle tissue. It may also protect against overuse injuries, such as stress fractures, through its role in calcium metabolism. "(article)
So if high cortisol levels reduce the effectiveness of vitamin D, they will also reduce cognitive function, immune effectiveness and sports performance!
The work of Lemke et al, helps shed light on how stress decreases our health and reduces our performance. It's the glue that helps put these pieces together.
But it also raises a hypothesis on how to reduce this impact. If:
One of the reasons for the autoimmune process is the impact of high cortisol levels resulting from stress
By using higher doses of vitamin D we can improve its function to the point where it is possible to reduce or switch off autoimmune disease, reversing the effect of cortisol
Adequate vitamin D effect is achieved when PTH is low
So it's fair to think that taking vitamin D in effective personalised doses may be able to lessen the negative impact of stress, contributing to improved health and performance!
Which brings me to a question:
