Disputable studies

[Suikerbuik]

John's finding is a great example of bias on the internet. Instead of making a new thread for each study each time. Or even worse, just ignoring if it does not fit a certain perspectiv.. We could discuss it instead.

So to start with. Yesterday I was pointed to some new research about vitamin D - a subject I have been reading and posting about more often. Though I have been forming a standpoint over time. I still like to be unbiased, since no one is right and I can very well be wrong too.. Why not?
So saw the title of the article at sciencedaily:

Vitamin D shows promise for treating Crohn's disease

This sounds impressive doesn't it!? Up to this date there is not really any study that shows what's going except for studies that contradict vitamin D use, at least not support it.

So went to the reference underneath: http://ueg.sagepub.com/content/early/20 ... 6.abstract
Methods looks good, finally some useful research.

Then the results and conclusion:

Results At 3 mos., 25(OH)D concentrations were significantly higher in those whom were treated (p < 0.001). Intra-group analysis showed increased LL-37 concentrations (p = 0.050) and maintenance of IP measures in the treated group. In contrast, in the placebo group, the small bowel (p = 0.018) and gastro-duodenal permeability (p = 0.030) increased from baseline. At 3 mos., patients with 25(OH)D ≥ 75 nmol/L had significantly lower CRP (p = 0.019), higher QoL (p = 0.037), higher LL-37 concentrations (p < 0.001) and non-significantly lower CDAI scores (p = 0.082), compared to those with levels <75 nmol/L.

Conclusion Short-term treatment with 2000 IU/day vitD significantly increased 25(OH)D levels in CD patients in remission and it was associated with increased LL-37 concentrations and maintenance of IP. Achieving 25(OH)D ≥ 75 nmol/l was accompanied by higher circulating LL-37, higher QoL scores and reduced CRP. Registered at ClinicalTrials.gov (NCT01792388).

Wow sounds impressive.. did i miss something?? -- Research so far on antimicrobials shows the opposite.

Suspicion raised with the words inta-group analsysis and no word on a comparision between vitamin D suppleted group and placebo.. In fact going to the results, there is no difference at all. You can also doubt about differences in the intra-group analysises. The low numbers, as they themselves indicate, is a weak point and just because of 1 case they can say there is an increase in LL-37 expression.

I did not do a statistical analysis, however, the non-vitamin D treated group, which contains more smokers and probably disease of different etiology has lower baseline v.D levels (52 nmol/L) and higher LL-37 and hBD2 levels. Okay could be co-incidence.. But looking at the v.D levels after treatment (placebo) they dropped to 40 nmol/L but ll-37 on average increased (though, reduced standard deviation but that's in both groups). Makes me wonder why they not even make a tiny mention of that observation.

The drop in vitamin D and raise in intestinal permeability in the placebo group is not strange at all and supports the view to target > 50 to 75 nmol/L. Permeability in the intra-group analysis is not significant (even with all those <50 nmol/L cases includend in the <75 nmol/L group!)

To conclude I am a bit disappointed. I thought there was finally some study contradicting my view, not that I think I am wrong but I think that someone always has to try to disprove himself. So how they come this conclusion..? It seem like another group that does not grasp reality, plays with the numbers and needs publications.. And with reality I mean; highly individual reaction to vitamin D that makes it impossible to generalize v.D metabolism based on just 25D serum values, and that vitamin D shows to be immuno-modulative with a tendency to immunosuppression, which is also something open to debate.

To continue debate on the last aspect. This puts questions to elephanto's findings of inhibiting NLRP3 with fish oil, which might support the view that fish oil (esp. supplements) could promote cancer growth. Not because of the effect on NLRP3 action only, but the whole range of actions.

 

[narouz]

Wonderful analysis, Suik.
Thanks!

With the fish oils,
Peat did say that there could be short term anti-inflammatory effects,
much like radiation's short-term anti-inflammatory effects.
I would like to see a study over a longer time.

So, with this study,
seems like they contorted their "pitch" to conform to positive hopes for Vit D supplementation.

 

[gummybear]

 

[narouz]

Yeah...
In the US, with the FCC, you see that exact phenomenon.
But the head of the FCC earlier this year heard the outcry,
reversed course,
and is onboard with internet neutrality.

He used to be head of some big internet company....

 

[Wilfrid]

Thanks, Suikerbuik.
Very good analysis as always.
And any posted study on IBD ( thanks to Haidut too ) will always have a special place in my mind.
Thanks again.

 

[SQu]

It's a really great idea.thank you

 

[haidut]

John's finding is a great example of bias on the internet. Instead of making a new thread for each study each time. Or even worse, just ignoring if it does not fit a certain perspectiv.. We could discuss it instead.

So to start with. Yesterday I was pointed to some new research about vitamin D - a subject I have been reading and posting about more often. Though I have been forming a standpoint over time. I still like to be unbiased, since no one is right and I can very well be wrong too.. Why not?
So saw the title of the article at sciencedaily:

Vitamin D shows promise for treating Crohn's disease

This sounds impressive doesn't it!? Up to this date there is not really any study that shows what's going except for studies that contradict vitamin D use, at least not support it.

So went to the reference underneath: http://ueg.sagepub.com/content/early/20 ... 6.abstract
Methods looks good, finally some useful research.

Then the results and conclusion:

Results At 3 mos., 25(OH)D concentrations were significantly higher in those whom were treated (p < 0.001). Intra-group analysis showed increased LL-37 concentrations (p = 0.050) and maintenance of IP measures in the treated group. In contrast, in the placebo group, the small bowel (p = 0.018) and gastro-duodenal permeability (p = 0.030) increased from baseline. At 3 mos., patients with 25(OH)D ≥ 75 nmol/L had significantly lower CRP (p = 0.019), higher QoL (p = 0.037), higher LL-37 concentrations (p < 0.001) and non-significantly lower CDAI scores (p = 0.082), compared to those with levels <75 nmol/L.

Conclusion Short-term treatment with 2000 IU/day vitD significantly increased 25(OH)D levels in CD patients in remission and it was associated with increased LL-37 concentrations and maintenance of IP. Achieving 25(OH)D ≥ 75 nmol/l was accompanied by higher circulating LL-37, higher QoL scores and reduced CRP. Registered at ClinicalTrials.gov (NCT01792388).

Wow sounds impressive.. did i miss something?? -- Research so far on antimicrobials shows the opposite.

Suspicion raised with the words inta-group analsysis and no word on a comparision between vitamin D suppleted group and placebo.. In fact going to the results, there is no difference at all. You can also doubt about differences in the intra-group analysises. The low numbers, as they themselves indicate, is a weak point and just because of 1 case they can say there is an increase in LL-37 expression.

I did not do a statistical analysis, however, the non-vitamin D treated group, which contains more smokers and probably disease of different etiology has lower baseline v.D levels (52 nmol/L) and higher LL-37 and hBD2 levels. Okay could be co-incidence.. But looking at the v.D levels after treatment (placebo) they dropped to 40 nmol/L but ll-37 on average increased (though, reduced standard deviation but that's in both groups). Makes me wonder why they not even make a tiny mention of that observation.

The drop in vitamin D and raise in intestinal permeability in the placebo group is not strange at all and supports the view to target > 50 to 75 nmol/L. Permeability in the intra-group analysis is not significant (even with all those <50 nmol/L cases includend in the <75 nmol/L group!)

To conclude I am a bit disappointed. I thought there was finally some study contradicting my view, not that I think I am wrong but I think that someone always has to try to disprove himself. So how they come this conclusion..? It seem like another group that does not grasp reality, plays with the numbers and needs publications.. And with reality I mean; highly individual reaction to vitamin D that makes it impossible to generalize v.D metabolism based on just 25D serum values, and that vitamin D shows to be immuno-modulative with a tendency to immunosuppression, which is also something open to debate.

To continue debate on the last aspect. This puts questions to elephanto's findings of inhibiting NLRP3 with fish oil, which might support the view that fish oil (esp. supplements) could promote cancer growth. Not because of the effect on NLRP3 action only, but the whole range of actions.

Smoking has been shown to be protective against Chron's and UC, so if the smokers showed better results than the vitamin D suppleented group I am not surprised. Here is something to consider.
http://www.dailymail.co.uk/health/artic ... oking.html

Also, what antimicrobials were used for Chron's and found ineffective? Are you familiar with this hypothesis?
https://en.wikipedia.org/wiki/Mycobacte ... berculosis

Look at the section on the company Giaconda getting FDA approval for Phase 3 trial. Based on that I'd guess the bacterial origin of Chron's is looking more and more legit.
If vitamin D is beneficial, then agents that raise its concentrations through accelerated cholesterol metabolism should be helpful for Chron's and this has been found to be the case for DHEA and probably pregnenolone.
http://onlinelibrary.wiley.com/doi/10.1 ... 1433.x/pdf

 

[Suikerbuik]

Smoking has been shown to be protective against Chron's and UC, so if the smokers showed better results than the vitamin D suppleented group I am not surprised. Here is something to consider.
http://www.dailymail.co.uk/health/artic ... oking.html

Also, what antimicrobials were used for Chron's and found ineffective? Are you familiar with this hypothesis?
https://en.wikipedia.org/wiki/Mycobacte ... berculosis

Look at the section on the company Giaconda getting FDA approval for Phase 3 trial. Based on that I'd guess the bacterial origin of Chron's is looking more and more legit.

The low group, with less smokers (p=0,168 - not significant) does not do better. There is just no difference between vit. D suppletion and non-suppletion notable.

I was talking about the antimicrobials in the context of the article i.e. ll-37 and hBD2. I only support the view you propose:

Most experiments investigating susceptibility to a given autoimmune disease is, however, based on animal models. The question therefore remains whether these animal models which are executed in a pathogen free environment reflect the real life situation where humans continuously are bombarded with a variety of pathogens. It is slowly becoming apparent that the microbial environment has a greater influence on development of autoimmune diseases than previously anticipated. For example, certain microbes have been shown to slow innate immune defenses by dysregulating the VDR. One mechanism used by the innate immune system to clear a pathogen is VDR-induced production of the antimicrobial peptide cathelicidin which possesses antiviral, antibacterial, and antifungal activity. Therefore, any microbe capable of dysregulating expression of the VDR would enhance its chance for survival (Waterhouse et al., 2009; Proal et al., 2013). Klein and coworkers illustrated in vitro that Epstein-Barr virus (EBV) were able to effectively down-regulate expression of VDR in B cells (Yenamandra et al., 2009), Modlin and coworkers that Mycobacterium leprae inhibits VDR activity through down-regulation of CYP27B1 in monocytes (Liu et al., 2012), Wang and coworkers that Mycobacterium tuberculosis down-regulate expression of VDR in macrophages (Xu et al., 2003), and McElvaney and coworkers that the fungus Aspergillus fumigates secretes a toxin capable of down-regulating VDR in macrophages (Coughlan et al., 2012). This allows pathogens to accumulate in tissue and blood and the weakened innate defense further causes susceptibility to additional infections. As more pathogens are incorporated into this microbiome, people start to show symptoms characteristic of inflammatory and autoimmune diseases. Accumulating evidence now supports the observation that a number of autoimmune diseases can be reversed by restoring VDR function (using the VDR agonist olmesartan) along with antibiotics. This includes rheumatoid arthritis, systemic lupus erythematosis, sarcoidosis, scleroderma, psoriasis, Sjogren’s syndrome, autoimmune thyroid disease, and type I and II diabetes mellitus (Waterhouse et al., 2009; Proal et al., 2013). Knowledge of the regulation of VDR abundance and activity in immune cells potentially is of great therapeutic importance, and therapeutic enhancement of VDR should therefore be considered in the clinic today. -- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684798/

If vitamin D is beneficial, then agents that raise its concentrations through accelerated cholesterol metabolism should be helpful for Chron's and this has been found to be the case for DHEA and probably pregnenolone.
http://onlinelibrary.wiley.com/doi/10.1 ... 1433.x/pdf

DHEA has profound effects on cellular metabolism and with the downregulation of the mentioned inflammatory intermediates it is not strange that it is helpful for crohn's. How this translates to vitamin D I don't know.. (you may be assuming too much here - imo).

 

[haidut]

Smoking has been shown to be protective against Chron's and UC, so if the smokers showed better results than the vitamin D suppleented group I am not surprised. Here is something to consider.
http://www.dailymail.co.uk/health/artic ... oking.html

Also, what antimicrobials were used for Chron's and found ineffective? Are you familiar with this hypothesis?
https://en.wikipedia.org/wiki/Mycobacte ... berculosis

Look at the section on the company Giaconda getting FDA approval for Phase 3 trial. Based on that I'd guess the bacterial origin of Chron's is looking more and more legit.

The low group, with less smokers (p=0,168 - not significant) does not do better. There is just no difference between vit. D suppletion and non-suppletion notable.

I was talking about the antimicrobials in the context of the article i.e. ll-37 and hBD2. I only support the view you propose:

Most experiments investigating susceptibility to a given autoimmune disease is, however, based on animal models. The question therefore remains whether these animal models which are executed in a pathogen free environment reflect the real life situation where humans continuously are bombarded with a variety of pathogens. It is slowly becoming apparent that the microbial environment has a greater influence on development of autoimmune diseases than previously anticipated. For example, certain microbes have been shown to slow innate immune defenses by dysregulating the VDR. One mechanism used by the innate immune system to clear a pathogen is VDR-induced production of the antimicrobial peptide cathelicidin which possesses antiviral, antibacterial, and antifungal activity. Therefore, any microbe capable of dysregulating expression of the VDR would enhance its chance for survival (Waterhouse et al., 2009; Proal et al., 2013). Klein and coworkers illustrated in vitro that Epstein-Barr virus (EBV) were able to effectively down-regulate expression of VDR in B cells (Yenamandra et al., 2009), Modlin and coworkers that Mycobacterium leprae inhibits VDR activity through down-regulation of CYP27B1 in monocytes (Liu et al., 2012), Wang and coworkers that Mycobacterium tuberculosis down-regulate expression of VDR in macrophages (Xu et al., 2003), and McElvaney and coworkers that the fungus Aspergillus fumigates secretes a toxin capable of down-regulating VDR in macrophages (Coughlan et al., 2012). This allows pathogens to accumulate in tissue and blood and the weakened innate defense further causes susceptibility to additional infections. As more pathogens are incorporated into this microbiome, people start to show symptoms characteristic of inflammatory and autoimmune diseases. Accumulating evidence now supports the observation that a number of autoimmune diseases can be reversed by restoring VDR function (using the VDR agonist olmesartan) along with antibiotics. This includes rheumatoid arthritis, systemic lupus erythematosis, sarcoidosis, scleroderma, psoriasis, Sjogren’s syndrome, autoimmune thyroid disease, and type I and II diabetes mellitus (Waterhouse et al., 2009; Proal et al., 2013). Knowledge of the regulation of VDR abundance and activity in immune cells potentially is of great therapeutic importance, and therapeutic enhancement of VDR should therefore be considered in the clinic today. -- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684798/

If vitamin D is beneficial, then agents that raise its concentrations through accelerated cholesterol metabolism should be helpful for Chron's and this has been found to be the case for DHEA and probably pregnenolone.
http://onlinelibrary.wiley.com/doi/10.1 ... 1433.x/pdf

DHEA has profound effects on cellular metabolism and with the downregulation of the mentioned inflammatory intermediates it is not strange that it is helpful for crohn's. How this translates to vitamin D I don't know.. (you may be assuming too much here - imo).

I don't have a study showing direct effect of DHEA on vitamin D levels but the two seem to be correlated:
http://www.medicalnewstoday.com/opinions/177003
AFAIK, the beneficial effects of DHEA on bone are proposed to be mediated primarily through effects of DHEA on blocking cortisol-induced osteopenia and increasing levels of calcitriol in the cell. DHEA has been shown to accelerate cholesterol metabolism into all downstream metabolites, so my assumption was that it will affect vitamin D levels as well. But, like you said, it may be a too strong of an assumption.

 

[Suikerbuik]

so my assumption was that it will affect vitamin D levels as well. But, like you said, it may be a too strong of an assumption.

Hypotheses are good though Questioning is what makes us human!

Thanks for that study by the way. It says that dysfunctional vitamin D receptor, caused by for example mycoplasma, results in low DHEA. So it might be the way around (the study suggestes it is the other way around). But I am not convinced about that yet! Certainly not when speaking about Crohn's.

 

[Wilfrid]

Thank you both, Suikerbuik and Haidut for those good info.
In 2007, I tried to get this tri-antibiotics therapy and went to the London Bridge Hospital in London.
Dr. Jeremy Sanderson was OK to give me this treatment but unfortunately I couldn't find any M.D in France who was agreed to do it. ( the treatment in England was too costly...)
Despite the fact that, back then, only antibiotics put me in significant remission.
Anyway, keep up the good work guys.