7 replies to this topic

[s123]

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The US FDA currently encourages the addition of vitamin D to milk and cereals, with the aim of reducing rickets in children and osteoporosis in adults. However, vitamin D not only regulates the expression of genes associated with calcium homeostasis, but also genes associated with cancers, autoimmune disease, and infection. It does this by controlling the activation of the vitamin D receptor (VDR), a type 1 nuclear receptor and DNA transcription factor. Molecular biology is rapidly coming to an understanding of the multiplicity of roles played by the VDR, but clinical medicine is having difficulty keeping up with the pace of change. For example, the FDA recently proposed a rule change that will encourage high levels of vitamin D to be added to even more foods, so that the manufacturers can claim those foods reduce the risk of osteoporosis. The FDA docket does not review one single paper detailing the transcriptional activity of vitamin D, even though, on average, one new paper a day is being published on that topic. Nor do they review whether widespread supplementation with vitamin D, an immunomodulatory secosteroid, might predispose the population to immune dysfunction. This BioEssay explores how lifelong supplementation of the food chain with vitamin D might well be contributing to the current epidemics of obesity and chronic disease.

PMID: 18200565

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Low blood levels of vitamin D have long been associated with disease, and the assumption has been that vitamin D supplements may protect against disease. However, this new research demonstrates that ingested vitamin D is immunosuppressive and that low blood levels of vitamin D may be actually a result of the disease process. Supplementation may make the disease worse.

...

The VDR is at the heart of innate immunity, being responsible for expression of most of the antimicrobial peptides, which are the body's ultimate response to infection.
Molecular biology is now forcing us to re-think the idea that a low measured value of vitamin D means we simply must add more to our diet. Supplemental vitamin D has been used for decades, and yet the epidemics of chronic disease, such as heart disease and obesity, are just getting worse. "Our disease model has shown us why low levels of vitamin D are observed in association with major and chronic illness," Marshall added. "Vitamin D is a secosteroid hormone, and the body regulates the production of all it needs. In fact, the use of supplements can be harmful, because they suppress the immune system so that the body cannot fight disease and infection effectively."

Marshall's research has demonstrated how ingested vitamin D can actually block VDR activation, the opposite effect to that of Sunshine. Instead of a positive effect on gene expression, Marshall reported that his own work, as well as the work of others, shows that quite nominal doses of ingested vitamin D can suppress the proper operation of the immune system. It is a different metabolite, a secosteroid hormone called 1,25-dihydroxyvitamin D, which activates the VDR to regulate the expression of the genes. Under conditions that exist in infection or inflammation, the body automatically regulates its production of all the vitamin D metabolites, including            25-hydroxyvitamin D, the metabolite which is usually measured to indicate vitamin D status.

Vitamin D deficiency, long interpreted as a cause of disease, is more likely the result of the disease process, and increasing intake of vitamin D often makes the disease worse. "Dysregulation of vitamin D has been observed in many chronic diseases, including many thought to be autoimmune," said J.C. Waterhouse, Ph.D., lead author of a book chapter on vitamin D and chronic disease.

"We have found that vitamin D supplementation, even at levels many consider desirable, interferes with recovery in these patients."

"We need to discard the notion that vitamin D affects a disease state in a simple way," Marshall said. "Vitamin D affects the expression of over 1,000 genes, so we should not expect a simplistic cause and effect between vitamin D supplementation and disease. The comprehensive studies are just not showing that supplementary vitamin D makes people healthier."

ScienceDaily (Jan. 25, 2008)

So many studies show that supplementing vitamin D prevents cancer, diabetes type 2, auto-immune disease and cardiovascular disease.

Quote

Ecological and observational studies suggest that low vitamin D status could be associated with higher mortality from life-threatening conditions including cancer, cardiovascular disease, and diabetes mellitus that account for 60% to 70% of total mortality in high-income countries. We examined the risk of dying from any cause in subjects who participated in randomized trials testing the impact of vitamin D supplementation (ergocalciferol [vitamin D(2)] or cholecalciferol [vitamin D(3)]) on any health condition. METHODS: The literature up to November 2006 was searched without language restriction using the following databases: PubMed, ISI Web of Science (Science Citation Index Expanded), EMBASE, and the Cochrane Library. RESULTS: We identified 18 independent randomized controlled trials, including 57 311 participants. A total of 4777 deaths from any cause occurred during a trial size-adjusted mean of 5.7 years. Daily doses of vitamin D supplements varied from 300 to 2000 IU. The trial size-adjusted mean daily vitamin D dose was 528 IU. In 9 trials, there was a 1.4- to 5.2-fold difference in serum 25-hydroxyvitamin D between the intervention and control groups. The summary relative risk for mortality from any cause was 0.93 (95% confidence interval, 0.87-0.99). There was neither indication for heterogeneity nor indication for publication biases. The summary relative risk did not change according to the addition of calcium supplements in the intervention. CONCLUSIONS: Intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates. The relationship between baseline vitamin D status, dose of vitamin D supplements, and total mortality rates remains to be investigated. Population-based, placebo-controlled randomized trials with total mortality as the main end point should be organized for confirming these findings.

PMID: 17846391

The study seems to contain some errors:

Trevor Marshall:

"Vitamin D is a secosteroid hormone.."

Brian Wideman:

Wrong!  R. Veith states emphatically that Vitamin D is not a hormone.  A Vitamin D metabolite, 1,25-dihydroxyvitamin D, is a hormone.  Marshall himself states that the hormone is "a different metabolite, a secosteroid
hormone called 1,25-dihydroxyvitamin D."

Trevor Marshall:

Under conditions that exist in infection or inflammation, the body automatically regulates its production of all the vitamin D metabolites, including 25-hydroxyvitamin D, the metabolite which is usually measured to indicate vitamin D status.

Brian Wideman:

Wrong! According to Veith, the body can produce 25-hydroxyvitamin D, provided it has the Vitamin D precursor.  This precursor is produced by the action of UV B on cholesterol. It can also be ingested in oily fish. Lacking one of these, it is false that "the body automatically regulates its production of all the vitamin D metabolites, including 25-hydroxyvitamin D, the metabolite which is usually measured to indicate vitamin D status."

Edited by s123, 14 September 2008 - 02:58 AM.

[pro-d]

Trevor Marshall will never been taken seriously, because I don't think he's ever going to publish a peer reviewed study. Partly because he must be aware of mixed results in his protocol.

[Joe_Public]

Vieth states emphatically? That's hilarious  

Hey is Is D-Drops one word or two?

[caston]

Anyone seen this article and want to make some comments on it?

http://bacteriality....2009/08/10/iom/

[kismet]

caston, on Sep 29 2009, 10:22 AM, said:

http://bacteriality....2009/08/10/iom/

Wow, is this really one huge ad hominem and smear campaign against every known vitamin D researcher? (read "Researchers affiliated with the Vitamin D Council drive the science on vitamin D") I love scepticism and I love the ad hominem fallacy (it's so underused in the literature and on different fora) - should be good reading.

I just skimmed the whole thing: It really is a smear campaign, it's so chock full of ad hominems I lost count! And it even contains some genuinely intelligent remarks. Oh, how I love such combinations. Gonna read it tomorrow.

Edited by kismet, 29 September 2009 - 05:11 PM.

[kismet]

Ok, anyone who tries to follow my rambling should read the article. This post easily demonstrates that "I can play this game too" and that their counter-evidence is weak. Rhetorical tricks (and the deliberate use of logical fallacies) are (is) a lot of fun from time to time, but they're not evidence. I'll grant those guys, as expected I liked (some of) their sceptical remarks.
I think this opinion-piece is very enjoyable if you like well-placed logical fallacies and such stuff.

A committee to evaluate the DRI of vitamin D is convened
According to the report’s abstract: “The majority of the findings concerning vitamin D, calcium, or a combination of both nutrients on the different health outcomes were inconsistent.” "...unchallenged claims about vitamin D’s perceived benefits."
Interesting, what a little selection bias can do, isn’t it? Most recent independent reviews and meta-analyses I’ve read, however, state that the evidence is strong enough to support well-sized, interventional trials (eg. in the case of diabetes prevention, hypertension, cardioprotective effects and cancer mortality). "Inconsistent" does not mean the weight of evidence isn’t positive.

Dr. Barry Kramer sounds an early note of caution
Just reiterating the nature of evidence, nothing to see here, really. But wait 25OHD is a surrogate marker? What the hell? That’s blatantly false; it's just their (so far) unproven hypothesis.

However, there’s something interesting I get out of that paragraph. Medical decision making is reactionary to the core, too reactionary; we’ve seen it in the case of life extension research and we see it again. I think the medical establishement has fallen prey to the omission bias (“the tendency to judge harmful actions as worse, or less moral, than equally harmful omissions”).
I am not pushing to ignore the nature of evidence, not at all. But I’ve seen my fair share of ethical principles gone wrong in medicine, awfully wrong. Like for instance the Gonzalez cancer trial, which to paraphrase ORAC was the most unethical trial since Tuskegee and which spit into the face of clinical equipoise. Then there’s the principle of “primum non nocere” which often completely obliterates freedom of (patient) choice.

We should caution people to simply keep in mind that manslaughter by neglect is still manslaughter. In fact, sometimes jumping the gun will save more people than waiting.

Researchers affiliated with the Vitamin D Council drive the science on vitamin D
The influence of scientists affiliated or at least supported by the VD council is interesting, but that’s all. Well, unless you suggest a conspiracy theory or severe ethical misconduct by those people. The way this is extolled constitutes a bona fide ad hominem. What I find interesting is that the authors who strongly criticise epidemiology fall prey to one of the basic fallacies of observation. Correlation (people citing eachother or being cited by the council) does not imply causality (does not imply anything on its own actually). Evidently it could be a form of selection bias, if you arrive at a positive conclusion based on your own evidence, whom are you going to cite? (right, people who produced similar research)

”Despite a notable lack of data derived from RCTs…”
Not true at all.There’s merely a lack of data from meaningful, well-sized RCTs, not RCTs in general (big difference).  Sure, we need well-sized RCTs, but we have many smaller RCTs.

“We’re giving you high doses of a secosteroid that will adjust your hormonal and immune activity in ways not yet fully understood.”
Well played. If I explained metabolism of any nutrient to someone that way, I could scare anyone. Just imagine how scary fishoil and fish must look in this context or basically any type of food. Run for your life.

Similar could be said about vitamin K which causes thromboembolism. What? I thought VK does not cause “over-clotting”? Sure it doesn’t, but it can normalise a deficiency in clotting factors which would be protective. That, however, would ignore all other effects of VK.

Did our human ancestors really have extremely high levels of vitamin D?
”Dr. Robert Heaney [hey why not have a shot at poisoning the well and mention his affiliation in the first sentence?], a researcher affiliated with the Vitamin D Council, said…”

”Why then would just a few burns before the age of 20 dramatically increase[7] the risk of skin cancer? Did humans evolve to get skin cancer?”
First, the abstract does not support this statement and the full paper does not mention the word cancer at all. Didn’t those authors just warn against using surrogate outcomes?
And, yes, we evolved to develop cancer, fidelity of DNA repair is well-balanced against real world needs under which we evolved. We were not meant to get old. Therefore we get cancer; a benefit on cancer incidence would be hardly advantageous to naked apes (humans) dying at <30yo.

”At this point, it’s probably safe to say that we simply do not know how much sun early man got.” Fair enough, but very, very likely more than now.

Dr. Michael Holick speaks on sunscreen and vitamin D
Boys, such dirty tricks are disingenious. I don’t want to see that crap anymore. Downplaying somone'ss publication record?!
”[Holick] has authored or co-authored 59 publications appearing in PubMed on vitamin D (26 more than Dr. William Grant, who is second in that category and a frequent co-author)”
Holick has 348 publications indexed in MEDLINE and 253 refer to vitamin D (see for yourself: "Holick MF"[Author] "vitamin D"). I can only guess that they talk about original publications, but they do not explain it in the text – dishonesty par excellence. 

Most Xeroderma pigmentosum patients were deficient, I've looked at the study & it's very small. Their calcitriol levels averaged <40pg... Your dishonesty is showing if you ignore world-wide epidemiology showing great seasonal variation (eg. NHANES).

Now a red herring:
A review by Drs. Wolpowitz and Gilchrest states, “There is no evidence that customary sunscreen use causes vitamin D deficiency or insufficiency in otherwise healthy individuals.”
Do you see where I’m coming from? Yes, people fail at applying sun screen, fair enough. Sure it does not cause deficiency, but it definitely reduces cutaneous synthesis, which the authors almost admit (although, they try to tarnish the studies performed on the topic). Note: Dr. Glichrest has been know for her ignorance on Vitamin D (she’s right on the skin cancer thingy, though).

A concession: vitamin D is not for people with granulomatous disease
Correct and completely besides the point, unless they eventually prove their autoimmunity hypothesis.

Dr. Cedric Garland discusses vitamin D and cancer
To put things in perspective, you’d have to consume 20 eggs or four glasses of vitamin D fortified milk a day in order to get 400 IUs of vitamin D.
Red herring, you could as well spend 2 minutes in the sun. Still a red herring.

“There were literally scores, if not hundreds, of observational studies that showed almost beyond reasonable doubt that hormone replacement therapy would prolong women’s lives, if it were given routinely.”
I’m not an expert but I think that is exactly the reason why it was necessary to test the intervention. Because failing to provide benefical treatments leads to death by neglect (real world vs omission bias).

Observational data are “guilty until proven innocent.”
Well said.

They’re right about Garland’s graph with the skewed Y-axis. I hate such statistical trickery. If presented before health professionals it makes you look stupid. OTOH, I don’t think that Vitamin D was necessary the main culprit, but I’d need to check. 1000mg calcium was more likely the problem in the WHI finding increased rates of kidney stones.

Dr. Reinhold Vieth speaks about safety
Again, they’re right (apparently the article gets better from paragraph to paragraph). Lack of short term toxicity tells us nada, niente & nill about chronic exposure. Therefore we need well-sized RCTs, but the risk:benefit ratio is in favour of VD. And, hey, we're getting those RCTs!

They may be wrong about the calcitriol being the only active form. According to this review 25OHD binds to the VDR, but it's not sure what the effect of binding is (to me at least).
Dusso AS, Brown AJ, Slatopolsky E. Vitamin D. Am J Physiol Renal Physiol. 2005;
289(1):F8-F28.
http://ajprenal.phys...t/full/289/1/F8

25-D vs. 1,25-D and the long elusive search for biological plausibility
”It seems prudent then, that if a study measures 25-D levels, it should measure 1,25-D levels as well.” Yes.
”Thus, we would venture to say that studies absent levels of 1,25-D should at least be regarded with less rigor than those studies that test both metabolites.” No.

”Is this what passes for biological plausibility among pro-vitamin D researchers?” & related paragraphs constitute one heck of a straw man. There’s a myriad of mechanisms by which vitamin D could act (yes, vitamin D meaning calcitriol or calcidiol). Heck, even I know some of them, although, I never looked much into vitamin D mechanisms (I prefer to look at clinical evdience). MMP-Inhibition, cell cycle progression, expression of oncogenes/tumor suppressors. Plausibility is never a problem (other than if you try to peddle homeopathy...), but plausibility ain't enough.

...ok, I'm taking a break. Will finish bashing tomorrow.

Edited by kismet, 01 October 2009 - 03:25 PM.

[caston]

Hi Kismet: Thanks for reviewing that article. You are right in that the way they argue their points has a lot of flaws but can seem quite convincing to people that aren't trained enough to spot them.

I come from the perspective that I think that biological pathogens are far more strongly involved in the aging process than is accepted by the life extension community and indeed the existing medical professional but I don't understand all the crazyness about vitamin D. I don't supplement with it but I don't try to interfere with the so called VDR either because I just don't know enough about it. I think that most likely the MP people are right about some things and wrong about others and may be fighting the establishments dogma with yet another dogma only  some people religiously back them because they are the underdog(ma).

I more or less don't look at the arguments in regards to vitamin D from the evolutionary point because I also consider the possibility that the ruling classes of the first human civilizations were not the decedents of more primitive humans but actually of a more advanced and space faring civilization. I know that sounds crazy but that is my reason for not looking at evolutionary history to figure out the vitamin D mess there could be other more down to earth reasons for doing the same thing. I think we need to figure it out as we are here and now.

Edited by caston, 01 October 2009 - 03:03 PM.

[gattaca]

I look forward to the day that we finally and wisely decide to ban all Trevor Marshall protocol related discussion from this site. Until his protocol or some strong evidence supporting his hypotheses regarding vitamin D are published in a peer review journal, his ideas have no place in any serious discussion about health. It is disheartening that there are individuals with no scientific background or medical training who have been convinced that sunlight is poisonous and that undetectable microbes are making them sick in ways modern science cannot detect or understand. The fact that they feel the need to preach their views and recruit others, as I have seen in various medical discussion boards, is extremely disturbing, cultish behavior, reminiscent of how our species once behaved in the dark ages.

These people have nothing to contribute to any scientific discussion, and they have no place here.