Bacteriality

Exploring chronic disease

Category: vitamin D

Not every culture reveres the sun as Americans do. In our recent trip to Chengdu, China with a stopover in Hong Kong, we saw hundreds of people, women especially, blocking light on a daily basis.

We’re not sure if these people are supplementing with vitamin D (there is certainly no vitamin D added to the food chain!) but they’re certainly not getting a lot of sun.

The Vitamin D Council insists that people must expose themselves to sunlight and eat vitamin D-fortified products, yet these people are going about their daily lives without any apparent ill effect.

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  • Men who have excessive faith in their theories or ideas are not only ill prepared for making discoveries; they also make very poor observations. Of necessity, they observe with a preconceived idea, and when they devise an experiment, they can see, in its results, only a confirmation of their theory. In this way they distort observation and often neglect very important facts because they do not further their aim….

    Claude Bernard, An Introduction to the Study of Experimental Medicine

    This article discusses our experience at the one-day Institute of Medicine workshop on vitamin D and calcium. Both of us had an opportunity to make comments before the committee. Here are Paul’s comments and slides and here are Amy’s comments and slides. Note that our 2009 paper in Autoimmunity Reviews[1] discusses some of the science we allude to in further detail.

    On the cab ride to the IOM committee meeting on whether to change the dietary reference intake (DRI) of vitamin D, Amy practiced her speech.

    The cabbie had been silent for the whole ride, but broke character by talking to us. “So, let me ask you a question,” he said. “Do you take vitamin D?”

    “Actually, no, we don’t,” Amy said. Amy explained briefly how our data suggests that the form derived from supplementation is immunosuppressive, meaning that while it may temporarily improve signs and symptoms of disease, we have found it may do so at the cost of long-term health.

    We asked him if he took vitamin D. He said yes and explained that a few years back, he had a partially blocked artery. It scared him, so he searched the internet and found that high doses of vitamin D were being recommended for cardiovascular disease. He wasn’t clear about the evidence, but in his words, “I had to do something.”

    Which brings us to this point in time. At least in the United States, rates of chronic disease are rising. One recent study predicted that if current trends continue, all Americans will be obese by 2040.[2] Other studies have shown chronic disease is rising at rates faster than could otherwise be explained by an aging population and/or a general increase in population. One recent estimate says that by 2030, 171 million Americans will have a chronic disease. We have to do something, right?

    A committee to evaluate the DRI of vitamin D is convened

    The Institute of Medicine (IOM) is a non-profit organization that was first chartered in 1970. In 2008, IOM appointed a committee of experts whose charge is to reevaluate the DRI of calcium and vitamin D in light of recent research. The committee is expected to produce a report including these recommendations scheduled to be publicly released in May 2010.

    An IOM committee with the same purpose last met in 1997 and set the current standard of 400 IU of vitamin D per day for adults. But none of the members of the previous committee are on the current committee despite, collectively, hundreds of MEDLINE citations to their names. Perhaps this suggests that the IOM was trying to exclude scientists who most vocally tout vitamin D’s benefits from the committee.

    A great deal has happened since 1997. We learned that hormone replacement therapy (HRT) can cause disease (which led to thousands of premature deaths) even while early observational studies seemed to quite erroneously suggest the opposite.[3] Also, evidence-based medicine has come of age.[4]

    For those who are not from this planet or from a Western country anyway, it’s hard to really express how enthusiastic the support for vitamin D supplementation is – at least in the popular media. A quick search of Google News for “vitamin D” has led us to conclude that the few articles that allude to vitamin D’s risks are vastly outnumbered by stories repeating the same unchallenged claims about vitamin D’s perceived benefits.

    As part of their deliberation process, the IOM committee commissioned a report by the Tufts Evidence-based Practice Center. For this report, the Tufts group used a pre-existing set of criteria to identify only those studies meeting a certain standard of validity. Those studies that made the cut were independently analyzed.

    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.” For a variety of diseases, the report repeatedly finds few or no controlled studies showing an association between vitamin D intake and disease.

    Interestingly, Dr. Boullion, the sole speaker at the meeting from Europe (Belgium) conceded that he was confident that the European Union would not raise its recommendations regarding vitamin D intake based on vitamin D research to date.

    The complete list of presentations including audio and slides is available on the IOM website.

    Dr. Barry Kramer sounds an early note of caution

    Arguably the most illuminating speech of the day came before lunch. Dr. Barry Kramer, MD, MPH, works in the Office of Disease Prevention, a division of the NIH. His speech was somewhat dryly titled, “Weighing Scientific Evidence” (PDF of slides) but might just as well have been titled, “Hey, wait a second.”

    Invoking the work of Leon Gordis, PhD, Dr. Kramer discussed the “Levels of Decision Making,” and how the requisite amount of evidence for a non-conservative (our word) medical decision increases as the number of people it would affect increases. In other words, a person must make decisions for one’s family or even groups of patients with a different standard of evidence than he or she would when making decisions on behalf of the entire nation and possibly the world.

    The evidence-based pyramid. Higher levels of the pyramid have higher levels of validity. Note that while Dr. Kramer’s evidence-based pyramid contains a section for ideas and opinions, many evidence-based pyramids make no such provision.

    Dr. Kramer argued that some levels of evidence are not sufficient – at least not to make decisions on behalf of millions. The evidence must meet a minimum standard of validity:randomized controlled studies (RCTs), if not double-blind, placebo-controlled RCTs. According to Dr. Kramer, the history of research has shown in the cases of high-dose paclitaxel, encainide/flecainide, torcetrapib, and HRT, of course, that confounding variables have a way of compromising researchers’ most certain conclusions.

    A good example of a confounding variable is smoking in alcohol’s relationship with lung cancer. Alcohol consumption is strongly correlated with lung cancer, but only because people who drink are also more likely to smoke. Another commonly cited example: Volvos may be involved in fewer accidents, but that’s probably because people who choose to drive them are generally older and more safety-conscious.

    Dr. Kramer said in the case of observational studies with a relative risk of less than two, he could “spit them [confounding variables] out at the rate of one a second.” His slide lists a few obvious confounders for vitamin D studies: health consciousness, health insurance, and access to care.

    Dr. Kramer also made what should be an obvious point: surrogate outcomes do not substitute for reductions in mortality or disease. A surrogate outcome is a variable that is a substitute for a “true outcome”, used because it is easier, quicker or cheaper to measure – and the most common one used in vitamin D studies is serum 25-D although bone mineral density, polyps, and PTH levels are also used. But Dr. Kramer said that none of these surrogate outcomes, in his words, “measure up.”

    At the end of the speech Dr. Kramer showed the audience a classic Far Side cartoon, explaining, “Especially when you’re dealing with public health issues and millions of people, it pays you not to shoot first, because once you’ve shot, you can’t ask the questions any more, because your credibility is invested in your message. It pays to ask the questions before you shoot.”

    We’re not sure if Dr. Barry Kramer heard our five-minute remarks (we never saw him after lunch), but we were, in essence, presenting a set of explanations for how his note of caution could later prove to be well-justified or even prescient.

    Researchers affiliated with the Vitamin D Council drive the science on vitamin D

    Inarguably the most forceful voices for increasing the DRI of vitamin D come from researchers affiliated with the Vitamin D Council, a California-based organization. At the one-day workshop, a total of seven speakers were affiliated with the Vitamin D Council (only Drs. Hollis and Grant are board members; the remainder are listed as “Vitamin D scientists” on the website), and the balance of other speakers could be fairly characterized as strongly sympathetic to their aims.

    Many of the most influential papers on vitamin D are published by this group. We searched the online database, Web of Knowledge, for papers published since 2005 that mention “vitamin D” in the title or abstract, and then we sorted that list by number of times cited. The top four papers on that list are by researchers with the Vitamin D Council – as are a number more in the top twenty.

    These researchers have a habit of wholeheartedly agreeing with one another; throughout the day, we would hear at least several times something to the effect, “I agree with my colleague.”

    What does a bandwagon look like? If you search for the publications in MEDLINE on vitamin D since 2005 in GoPubMed.com and click on the statistics tab, you see how often Vitamin D Council researchers have co-authored each others’ papers. Below is an annotated screenshot (click for full-size PDF) of the professional collaborations in this relatively close-knit and like-minded group. Researchers affiliated with the Vitamin D Council are in red.

    Despite a notable lack of data derived from RCTs, those researchers associated with the Vitamin D Council are pushing the IOM committee to raise the DRI of vitamin D by a huge increase – around 5-6 times the current DRI. To achieve this goal, the Vitamin D Council markets the form of vitamin D derived from food and supplements to the public as a nutrient. What harm can high levels of a nutrient cause, right?

    Yet although we’re referring to it as vitamin D in this article so that you know what we are talking about, any molecular biologist would confirm that the two main forms of “vitamin” D are actually powerful secosteroids. The active form of vitamin D, 1,25-D, can also function as a hormone. We suspect that people would be less willing to take extremely large amounts of vitamin D if they were actually told, “We’re giving you high doses of a secosteroid that will adjust your hormonal and immune activity in ways not yet fully understood.”

    Yet rather than trying to help the public understand these true properties of “vitamin” D, a number of prominent vitamin D researchers still seem content to refer to it as nothing more than the “sunshine vitamin,” some with impressive consistency.

    Did our human ancestors really have extremely high levels of vitamin D?

    Late in his talk, Dr. Robert Heaney, a researcher affiliated with the Vitamin D Council, said, “We all agree and it is well-established that humans evolved in equatorial East Africa wearing no clothes.” This assumption is repeatedly invoked to justify supplementation with vitamin D at levels that would leave the average American with a 25-D level similar to that of a present-day farmer who works near the equator.

    We’re not sure anyone noticed, but in the next talk, Dr. Michael Holick would undercut this very argument. Dr. Holick said that according to his research, students of African descent need three to five times the exposure to ultraviolet light as Caucasians to “barely raise their blood levels” of 25-D. In short, their skin is “such a good sunscreen.” If ancient man had darkly pigmented skin, (according to a paper by Jablonski et al.,[5] man only evolved lighter skin pigment as he left the tropics) then why would he produce the copious levels of vitamin D referenced by Dr. Heaney?

    What about climate change? That ancient man evolved in a consistently sunny and hot environment makes no provision for several extended ice ages, which corresponded to key periods in hominid evolution.[6]

    What about skin cancer? Say that early man did not hunt and gather at dusk like so many other animals – that early humans did evolve in an unforested environment with no caves, no clothing, and no thick body hair, whiling away his hours sizzling like a big piece of Paleolithic bacon. 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?

    To clear up the confusion surrounding this issue, we recently contacted Dr. Peter Bogucki, an archaeologist at Princeton University, who is a leading expert on prehistoric man. We asked him to estimate how much sun prehistoric man actually got.

    Dr. Bogucki responded, and I trust he won’t mind us quoting him, “You raise a very good question, but I don’t know that there’s a good answer. All we have is skeletal remains. There’s no elemental isotope to track sun exposure.” In the absence of such a marker, our understanding of how much vitamin D early man actually synthesized is complicated by several factors including climate variability,[8] migration, and changes in skin pigment.

    Dr. Richard Potts sums up the evidence or lack thereof for inferring how man evolved from specific environmental scenarios:[9]

    The study of human evolution has long sought to explain major adaptations and trends that led to the origin of Homo sapiens. Environmental scenarios have played a pivotal role in this endeavor. They represent statements or, more commonly, assumptions concerning the adaptive context in which key hominin traits emerged. In many cases, however, these scenarios are based on very little if any data about the past settings in which early hominins lived.

    Dr. Richard Potts, Director of The Human Origins Program, Smithsonian Institution

    At this point, it’s probably safe to say that we simply do not know how much sun early man got.

    With this in mind, isn’t it a bit less plausible that, when it comes to the ability of the human body to naturally adjust its vitamin D levels for optimal health, current humans are a complete evolutionary bust and must be given truckloads of pills in order to remain healthy?

    Dr. Michael Holick speaks on sunscreen and vitamin D

    Dr. Michael Holick is a professor at Boston University, a medical doctor, and may be the world’s leading authority on vitamin D. Since 2005, he 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) and he has the distinction of being quoted on vitamin D in nearly every magazine, newspaper, television show and website ever. In his 10-minute statement, Dr. Holick was critical of dermatologists, a group which he singled out for advising the public to avoid creating vitamin D by direct sun exposure. As it happens, Dr. Holick receives large amounts of funding from the UV Foundation, which is in turn sponsored by the Indoor Tanning Association.

    Entitled The D-Lightful Vitamin for Health, Dr. Holick remarks sprinkled his speech with a number of pop culture references including mentions of Charlie Brown and Don King. And then there was the clip of Darth Vader telling Luke to come to the Dark Side. It has been a while since we have seen the Star Wars trilogy, but we don’t seem to recall Darth Vader’s evil stemming from his unnecessary prudence.

    Dr. Holick went on to claim that sunscreen use blocks 99% of vitamin D production in the skin. This claim is a featured part of his argument, because there has to be a reason why what he views as vitamin D deficiency is so widespread. If there’s evidence to back up this statistic, then our search of the literature cannot find it.

    What we did find were three small studies, one of which Dr. Holick authored himself.

    One of these studies measured the vitamin D3 (a precursor of 25-D) levels of only eight subjects[10] while another performed no intervention but simply measured the 25-D levels of 20 sunscreen users.[11] The third put only 27 subjects into tanning beds rather than into the sun, which could easily introduce bias.[12] All three are by the same lead author, Dr. Lois Y. Matsuoka.

    As it happens, several reviews have refuted the idea that real-world use of sunscreen entirely halts cutaneous production of vitamin D. By real world, we mean people putting sunscreen on themselves for extended periods of time while exposed to the actual sun.

    Dr. William L. Scarlett writes in his review, “Several large prospective studieshave shown that vitamin D deficiency does not result from regular sunscreen use.”[13]

    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.”[14]

    One research team, studying patients with xeroderma pigmentosum, a genetic disorder in which patients are unable to repair damage caused by ultraviolet light, found that vitamin D levels are maintained even when patients practice at least six years of rigorous photoprotection and not supplementing with vitamin D beyond their normal dietary intake. Most importantly, the researchers also concluded that the clinical manifestations of vitamin D “deficiency” were absent.

    In a 2007 review, Dr. Melanie Palm concludes real-world people tend not to consistently or repeatedly apply sunscreen.[15] She writes: “Most people’s real-life experience with sunscreen is that despite its application, they still sunburn or tan after casual sun exposure.” Dr. Palm goes on to explain, “SPF [sun protection factor] is a strictly defined and Food and Drug Administration (FDA)-regulated measurement based on applying 2 mg/cm2 of product. Studies have shown that most users apply insufficient amounts of sunscreen to meet this FDA standard, and the true SPF obtained is usually less than 50% of that written on the package.”

    Dr. Holick also proudly informed the committee of the manner and amount of his vitamin D intake. If you ask us, this is irrelevant. It’s nice that Dr. Holick believes what he says enough to try it on himself, but this kind of data falls to the very bottom of Dr. Kramer’s evidence-based pyramid – the opinion level that should never be used to guide public health decisions.

    In the remainder of his talk, Dr. Holick went on to say that no one living in a latitude north of Atlanta, Georgia can make vitamin D in their skin during the winter months. Based on everything else we have heard, maybe you can understand why we’re a bit dubious of this claim.

    It seems that one of the unspoken rules of publishing a study on vitamin D is that you must cite Michael Holick – geez, even we have done it. But in light of the conflicting data related to Dr. Holick’s claims, we have to wonder why the man has been accorded that authority and why more people don’t second-guess some of his more definitive statements.

    A concession: vitamin D is not for people with granulomatous disease

    From our perspective, one positive statement Dr. Holick made was when he conceded, as actually many of the pro-vitamin D researchers will do, that vitamin D is not for everyone, specifically not for people with granulomatous diseases such as Crohn’s or sarcoidosis.

    A granuloma is a ball-like collection of immune cells which forms when the immune system attempts to wall off substances such as bacteria. But it looks like patients with granulomatous diseases are going to have a tough time if Holick and his colleagues succeed in drowning us in vitamin D. Raising the DRI of vitamin D would inevitably mean that vitamin D would be added to another slew of foods.

    When Dr. Holick et al. were questioned about the fact that some people have been shown to develop kidney stones after taking extra vitamin D or that people with granulomatous disease could easily ingest excess levels of vitamin D and become significantly more ill, they seemed ambivalent. In their eyes, if a certain number of people are harmed by taking vitamin D, it should not matter, so long as more people benefit. We find this risk-benefit analysis difficult to stomach having seen first-hand the suffering associated with granulomatous diseases.

    Dr. Cedric Garland discusses vitamin D and cancer

    Another member of the Vitamin D Council, Dr. Cedric Garland, spoke in his remarks about vitamin D and cancer. After his remarks, a committee member, Dr. JoAnn Manson challenged him on his claim that vitamin D is protective against cancer at high levels of intake. She asked him about the Women’s Health Initiative-led randomized controlled study which trended in the opposite direction when it comes to breast cancer among women who start out with high intakes of vitamin D.[16][17]

    Dr. Garland brusquely and repeatedly dismissed the cancer study, saying that the dose of vitamin D administered to subjects, 400 IU – which happens to be the current adult DRI – was “not even a placebo.” In other words he believes that 400 IUs of vitamin D has no biological effect whatsoever. Dr. Manson responded, “I don’t buy it.” Actually, neither do we. 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.

    Interestingly, when you take a look at the five most frequently cited papers on vitamin D published in the last five years, the first four are authored by researchers affiliated with the Vitamin D Council. But study #5[18] derives its conclusion based on data collected by the Women’s Health Initiative, the same research group whose data Dr. Garland suggested should have no implication on the IOM Committee’s decision-making. That other vitamin D researchers are more than inclined to analyze data from the Women’s Health Initiative suggests that, although Garland may seem like he is an expert speaking on behalf of the entire vitamin D community, not all vitamin D researchers share his views.

    We have taken the liberty of annotating in red several of Dr. Garland’s slides to make points about the presentation of data especially as it pertains to vitamin D.

    Below is Dr. Garland’s slide showing a strong and consistent increase in the rate of breast cancer since 1935, which he used as a general indication for why it is important to significantly increase the amount of vitamin D added to the food supply.

    However, as you can see below, it is very easy to take that same data and “show” the opposite – that vitamin D consumption has led to a dramatic increase in breast cancer.

    Another example: Dr. Garland didn’t mention this publication in his speech, but in a 2008 study, his group found a significant association between “low UVB irradiance and high incidence rates of type 1 childhood diabetes.”[19]

    Data derived in this observational manner could just as readily be used to show something else entirely.

    As you can see in this graphic above, there is a strong apparent association between states that get more sun and teenage pregnancy. But does sun exposure actually cause teen pregnancy? We certainly hope not!

    Obviously, you can try to control for confounding variables, as Dr. Garland did in his ’08 publication, but so too did researchers who repeatedly concluded that hormone replacement therapy was safe. According to Dr. Kramer: “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.”

    In the words of Dr. David Ransohoff (who Dr. Kramer quoted in his talk), observational data are “guilty until proven innocent.”

    When discussing vitamin D, Dr. Garland put up another thought-provoking chart on the effect of vitamin D and calcium on the development of kidney stones (derived from the Women’s Health Initiative).

    Several things about Dr. Garland’s chart are of interest.

    • Although the y-axis could easily have gone up to only 10%, it goes all the way up to 55%. This visually minimizes the apparent negative treatment effect of calcium and vitamin D and barely impresses on the viewer that if the trend observed in the study is accurate and significant, approximately 1.2 million Americans will develop kidney stones if they continue taking vitamin D and calcium.
    • We probably should not be surprised that on this same slide, Dr. Garland opted to display absolute risk rather than relative risk.Absolute risk is a measure of what portion of a population have a disease in a given time period. Relative risk is that percentage increase divided by the risk in a placebo group, e.g. (2.5%–2.1%)/2.1%. In this case, patients who take calcium and vitamin D have an increased absolute risk of 0.4% of developing kidney stones but a relative risk of 19% of getting kidney stones. So by showing absolute risk, Dr. Garland again downplays the sheer number of people who could be negatively affected by taking extra vitamin D and calcium.

    Dr. Reinhold Vieth speaks about safety

    In his slot, Dr. Reinhold Vieth was asked to speak on whether there was a safe upper limit/level of vitamin D. As he has stated in at least one paper, his answer was no. In his words, “A prolonged intake of 250 mug (10,000 IU)/d of vitamin D(3) is likely to pose no risk of adverse effects in almost all individuals in the general population.”[20]

    Dr. Vieth’s comments echoed those of Dr. Garland, who had earlier concluded, “The benefit/risk ratio for 2,000 IU/day of vitamin D is infinite.”

    Obviously, we disagree. We take no comfort in the fact that a person, as demonstrated in case reports, can accidentally take several thousand times the recommended dose of vitamin D and still seem healthy after only several months – which is the only data Dr. Vieth provided. Our attention is directed towards long-term outcomes, time windows which correspond to the slow growth of chronic bacteria and other pathogens that may play a role in causing chronic disease. Also, the full negative effect of immunosuppressants (recall that we have found that 25-D acts as an immunosuppressant) can often only be noted after decades.

    25-D vs. 1,25-D and the long elusive search for biological plausibility

    Most of the talks had us scratching our heads, trying to figure out why, when 1,25-D is the biologically active form of vitamin D and the sole vitamin D metabolite able to activate the Vitamin D Receptor (VDR), almost every speaker focused on research and recommendations pertaining to 25-D levels. For a brief discussion of the different forms of vitamin D see my (Paul’s) speech.

    One of the points both of us tried to make in our own five minute presentations is that the levels of the different forms of vitamin D are jointly regulated by several feedback mechanisms. This means that if one alters the level of one form of vitamin D, levels of the other vitamin D metabolites will almost certainly shift to accommodate the change.

    It seems prudent then, that if a study measures 25-D levels, it should measure 1,25-D levels as well. Without the ability to examine the relationship between the two main vitamin D metabolites, how can a researcher fully understand the spectrum of the changes that occur when vitamin D supplementation takes place? Over a decade ago, even the FDA suggested that “1,25-D should be measured in order to support claims of a drug’s osteoporotic activity.” Yet few researchers seem to have heeded this advice. 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.

    At some point in a discussion with the Committee, one of the experts mentioned how 1,25-D is difficult to detect. We hope that doesn’t serve as an excuse for not testing 1,25-D. Since most major laboratories – including Quest Diagnostics – can easily perform the test, we would expect any vitamin D researcher would be able to do so as well. The real reason 1,25-D might be “hard” to test is that the 1,25-D test costs more than the 25-D test. But we’re all trying to do the best possible research… right?

    The potential significance of 1,25-D is suggested in a forthcoming study published in the Annals of the New York Academy of Sciences. In the study, Dr. Greg Blaney of Vancouver, Canada reported on the 25-D and 1,25-D levels of 100 patients with autoimmune disease.

    While many of the subjects had very low levels of 25-D, even more of the subjects (approximately 85%) had levels of 1,25-D elevated above the normal range. Under these circumstances can those subjects with low levels of 25-D but elevated levels of 1,25-D truly be considered vitamin D deficient? They are certainly not deficient in the sole form of vitamin D that actually activates the VDR to transcribe approximately 913 genes, TLR2, and the antimicrobial peptides vital to the innate immune response.

    When Dr. Heaney was asked to comment on 25-D’s actions by a member of the committee he admitted that he did not know, biologically speaking, how 25-D exerts any of the myriad beneficial effects that he claimed occur when it is elevated. All he could offer was that he knows that 25-D must be present in patients for them to get better.

    Is this what passes for biological plausibility among pro-vitamin D researchers?

    Later that afternoon, one committee member asked Dr. Cedric Garland, “Do you have a mechanism to explain the outcomes you’re reporting?”

    Dr. Garland proceeded to offer his analysis for how supplemental vitamin D, in his words, “eradicates” cancer. Garland pointed to a stack of his papers and asked that it be passed out. When members of the committee seemed hesitant to do so, he went on to explain the details of his model anyway. Dr. Garland shared that he had developed a novel pathogenesis for cancer in which cancer is caused by gaps between cells, which, in simple terms, he believes form as a body becomes vitamin D deficient. This line of inquiry was clearly only in its infancy and had not yet passed muster with cancer researchers. But even if Garland’s model proves to be valid, one would have hoped he would expose it to great scientific scrutiny before using it as the basis for making unequivocal recommendations regarding vitamin D supplementation.

    But as Dr. Garland went on to further describe what he believes are vitamin D’s cancer benefits (he was eventually cut off by a member of the committee), he provided a perfect example of the vitamin D expert that we have trouble following. The reason? He used the broad term “vitamin D” when making claims and by doing so, mixed up research that pertains solely to 25-D or 1,25-D. For example, Garland said that vitamin D is able to “upregulate tumor suppressor genes.” Most audience members probably thought he was referring to 25-D since that was the only vitamin D metabolite he ever mentioned. Yet, only 1,25-D is able to activate the Vitamin D Receptor to express Tumor Metastasis Suppressor 1 and other related genes.

    Similarly, another talk that we believe should have discussed 1,25-D levels but did not was Dr. Stephanie Atkinson’s remarks on vitamin D in pregnancy. That is because researchers have realized for some time now that 1,25-D is over-expressed during pregnancy.[21] Placental conversion was demonstrated in vitroin 1979,[22] over-expression of 1,25-D in vivo in 1980,[23] and the dysregulated vitamin D metabolism was described in 1981.[24] If 1,25-D becomes elevated during pregnancy, then isn’t it only prudent that studies on vitamin D and pregnancy should measure it and its relationship to 25-D?

    We find the relationship between 25-D and 1,25-D important, because it was by observing relationships between the two metabolites that our group was able to realize that in the majority of cases, when a subject’s 25-D level is low, their 1,25-D levels are actually high (AIDS is an exception because HIV completely co-opts the VDR).[25] And it was these relationships that led to our alternate hypothesis for the low levels of 25-D observed in patients with chronic diseases such as cancer. We have found that when 1,25-D is high, the vitamin D feedback pathways naturally downregulate levels of 25-D. This means that what is now viewed as “deficiency” could simply be a result of the chronic disease process. Under such circumstances, allowing people to create extra 25-D by raising the DRI is not only useless but harmful. We believe that our alternative hypothesis at least deserves consideration by the committee, yet are worried that when they are not presented with data on both 25-D and 1,25-D, they will not be able to recognize the pattern that makes our model plausible.

    Vitamin D and the evolving definition of autoimmune/inflammatory disease

    We also find it problematic that none of the experts who spoke at the meeting seem to be aware that microbial metabolites have a profound effect on the activity of the Vitamin D Receptor (VDR). The US NIH now estimates that 90% of cells in the human body are bacterial in origin while only a mere 10% of cells in the body are truly human.[26] Thus, many microbiologists now believe that humans are best viewed as superorganisms in which a plethora of bacterial gene products can effect the activity of our own receptors and genetic pathways.[27]Indeed, independent research teams have found that Mycobacterium tuberculosis downregulates VDR activity by approximately 3.3 times.[28] ActiveBorellia lowers VDR activity by about a factor of 50 and Epstein-Barr Virus by a factor of around 10.[29] HIV completely shuts down VDR activity. It’s quite likely that other pathogens yet to be fully characterized have also evolved ways to decrease VDR activity because by doing so, they slow important components of the innate immune response that might otherwise render them dead. That the experts who spoke before the committee have failed to factor this knowledge into their study designs suggests that they cannot fully account for the actions of the various vitamin D metabolites in an in vivo environment.

    Furthermore, no vitamin D researcher, of whom we are aware, makes provision for research which shows that the current view of autoimmune disease – in which the immune system is believed to attack itself – may be running its course.[30][31][32][33] Many microbiologists now believe that at least some, if not all, of the inflammation that drives the autoimmune disease state is caused by the presence of chronic pathogens.

    Inflammation is a clear potential link between infectious agents and chronic diseases.

    Siobhán M. O’Connor[31]

    With this in mind, the claim by many vitamin D researchers that vitamin D can help patients with autoimmune disease by slowing an “over-active” adaptive immune response no longer jives with an emerging view in the microbiology/immunology community – that both the adaptive and innate immune systems should be kept active in autoimmune disease in order to allow the body to best target disease-causing microbes.

    The possible presence of pathogens in autoimmune and other inflammatory disease states such as cancer and atherosclerosis makes our group’s findings on vitamin D’s actions more plausible. When the immune system is fighting a microbe, it continually releases inflammatory molecules in an effort to kill the pathogen.[34] If the pathogen dies, endotoxins[35] and cellular debris are generated. This leads to increased symptoms of malaise on the part of a person who harbors such microbes.

    It follows that any substance that slows the innate immune response will decrease this battle between man and microbe, causing the patient to feel better. The more the immune response is slowed, the greater the decrease in inflammation and inflammatory markers. But while such measures can make the patient appear as if they are getting better for years, ultimately the bacteria causing their disease are able to spread much more easily and exacerbate the disease state over the long-term.

    Our molecular and clinical data shows that 25-D, like the pathogens we describe above, binds the Vitamin D Receptor and slows its activity.[1] Since the VDR largely controls the innate immune response, increasing 25-D levels could easily display the pattern of immunosuppression described above. This begs the question – is 25-D a miracle curative substance or simply an excellent palliative?

    If we are correct and 25-D slows VDR activity then we have found that patients who are chronically ill benefit from decreasing their vitamin D intake. This is because their VDR activity already appears compromised by the pathogens they harbor. Yet this should not be interpreted to mean we think healthy people can’t consume vitamin D. However, our data suggest that healthy people can get the vitamin D they need by eating a well-rounded diet that does not include fortified foods and getting sun exposure similar to that of a person taking measures to avoid an increase in skin cancer risk.

    Our speeches and the reaction to them

    In our speeches, we raised the possibility that low levels of 25-D are caused by the inflammatory disease process and that taking vitamin D suppresses the immune response.

    In total, the two of us spoke for 600 seconds, and we’re not sure we convinced anyone of anything. By all indications, a discussion of molecular mechanisms was outside the committee’s comfort zone. Most would probably say that they are uninterested in software emulations of molecular interactions, no matter how provocative or far-reaching the conclusions they imply. If we had to pin the members of the committee down on it, I think they would say that when it comes to our clinical trial, we needed better controlled data such as the kind we intend to generate as a part of our West China Hospital collaboration. For this reason, we opted for a more measured tone.

    During Amy’s speech, a Dr. Holick sighting, seated in the front on the left.

    During Paul’s speech, there was some tittering in the audience (not the committee). He saw one prominent researcher, who shall remain nameless, chuckling. For a moment, he thought he had spinach in his teeth or was trailing toilet paper from his shoe, and then he realized that, oh yes, he was telling 50 PhDs and MDs that their conclusions have the potential to be very misguided.

    After the day’s business concluded, everyone began to file out. One woman though turned to us and said, “What a bunch of rebels!”

    Glad we could liven up the workshop for you, ma’am.

    Although during our speeches, we asked people to come by and ask us about our work, only Dr. Tony Norman did. He did not seem convinced, but did invite us to submit an abstract for a poster presentation at an upcoming vitamin D conference in Belgium.

    Anticipating what is to come

    If you ask most Vitamin D Council researchers, they would say that this is the “end game,” and there is already more than enough evidence to raise the level of vitamin D added to the food supply. During the question and answer sessions, some of these scientists such as Dr. Garland were dismissive of evidence to the contrary. It was as if many were saying, “Look – there is no downside here. It is demonstrably impossible that consumption of vitamin D can cause harm. If we don’t have all the requisite evidence, it doesn’t matter. Lives are at stake!” We suspect that even if the committee decides to maintain current vitamin D levels, there are other ways to convince the public to increase vitamin D intake.

    But despite the media’s stampede to promote the “sunshine vitamin,” the evidence is ambiguous and the issue of biological plausibility – not knowing how 25-D exerts its claimed benefit – is troubling as well. Dr. Kramer said that the root of science is the art of thinking hard about how you could be wrong. Is this something the vitamin D research community is actively doing? Looking through everything that was presented throughout the day, how many confounding variables might Dr. Kramer have identified? How many surrogate outcomes could he point to?

    It is difficult to anticipate exactly what decision the IOM Committee will arrive at. However, from this perspective, it would be hard to see how the group could raise the dietary reference intake in light of such an equivocal set of conclusions in the Tufts report – in spite of considerable pressure to do so.

    Will an IOM committee ever emerge from this climate of consensus and consider research that would cause them to lower the DRI of vitamin D?

    Here are a few possibilities:

    • An evolution in the understanding of disease raises new concerns about the risks of using immunosuppressants. The Human Microbiome Project shows that bacteria are not confined to the surfaces of the body, i.e. skin, mouth, gastrointestinal tract, etc. As chronic disease is increasingly characterized as an infection or at least having infectious components, researchers seriously question if reducing the inflammatory response needed to kill chronic pathogens is in a individual’s long-term interest.
    • After continuing to increase vitamin D consumption to historic levels, members of the public and some researchers begin to question the absence of the promised overall drop in rates of disease. In some respects, the decision of the IOM committee is immaterial. All indications are that the vitamin D “experts” are having a great deal of success communicating their message that it’s important to take 4-5 times or more the current DRI of vitamin D. People will take increasing amounts of vitamin D as food manufactures will add increasing amounts to their products. Many of the presenters at the Workshop essentially promised double-digit declines in disease. If this does not materialize, there will be questions. If we are right, this could be the hormone replacement therapy (HRT) saga redux, except with potentially broader ramifications.
    • Well-controlled long-term studies show that vitamin D consumption increases incidence and severity of chronic disease. To most people – probably in excess of 95% of people at the workshop – this is not even a possibility, but the history of HRT use proves such unexpected results can emerge, eventually, from well-controlled studies.

    Epilogue: The ride home

    After the meeting adjourned, we were approached by a nattily attired man in his thirties, originally from Barcelona. He offered us a ride home to New York. His Mercedes SUV looked quite appealing, so we skipped the bus and took him up on his offer.

    On the ride home, this fellow – who told us he had a PhD in oncology – told us he agreed with the sentiment of our remarks and expressed disappointment with the lack of rigor of the science presented. The word he used to describe the majority of presentations was “pseudoscience.” He told us that, based on what he saw, vitamin D was harmful and that it was only a matter of time before the hype surrounding vitamin D would fizzle.

    Although we felt validated, we wondered why he had attended the conference in the first place. It turns out that he was an entrepreneur, had just bought the patent for a new formulation of calcium, and wanted the discussion at the IOM workshop to help him decide how much vitamin D to add to his product.

    He seemed like a honest and honorable guy until, that is, he let us know that despite his negative view of vitamin D, he intended to add high levels of it to his supplement anyway, so long as the medical community and public viewed it as beneficial. Later on, he said, he planned to strategically remove it “just before the vitamin D bubble bursts.”

    Well, isn’t that wonderful? Some reassurance about the people behind products aimed at “improving our health.”

    In that vein, we couldn’t help remembering the short speeches delivered by members of the Dairy Council as well as a yeast company, whose goal in speaking before the Committee were simply to urge the Committee that, if more vitamin D is added to the food supply, it should be added to the food they market. This would give these interests the ability to claim more health benefits from their food and, of course, make more money.

    In sum, our adventure in the nation’s capital left us with a bad taste in our mouths. We’d like to wash it away but we’re worried that by the time we do so, no drink won’t be fortified with vitamin D.

    REFERENCES

    1. Albert, P.J., Proal, A.D. & Marshall, T.G. Vitamin D: the alternative hypothesis. Autoimmun Rev8, 639-644 (2009). [] []
    2. Wang, Y. & Beydoun, M.A. The obesity epidemic in the United States–gender, age, socioeconomic, racial/ethnic, and geographic characteristics: a systematic review and meta-regression analysis. Epidemiol Rev 29, 6-28 (2007). []
    3. Rossouw, J.E. et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA288, 321-333 (2002). []
    4. Sackett, D.L. Evidence-based medicine. Semin. Perinatol 21, 3-5 (1997). []
    5. Jablonski, N.G. & Chaplin, G. The evolution of human skin coloration. J. Hum. Evol 39, 57-106 (2000). []
    6. Petit, J.R. et al. Climate and atmospheric history of the past 420,000 years from the Vostok ice core, Antarctica. Nature 399, 429-436 (1999). []
    7. Dodd, A.T. et al. Melanocytic nevi and sun exposure in a cohort of colorado children: anatomic distribution and site-specific sunburn. Cancer Epidemiol. Biomarkers Prev 16, 2136-2143 (2007). []
    8. Maslin, M.A. & Christensen, B. Tectonics, orbital forcing, global climate change, and human evolution in Africa: introduction to the African paleoclimate special volume. J. Hum. Evol 53, 443-464 (2007). []
    9. Potts, R. Environmental hypotheses of hominin evolution. Am. J. Phys. Anthropol Suppl 27, 93-136 (1998). []
    10. Matsuoka, L.Y., Ide, L., Wortsman, J., MacLaughlin, J.A. & Holick, M.F. Sunscreens suppress cutaneous vitamin D3 synthesis. J. Clin. Endocrinol. Metab 64, 1165-1168 (1987).
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    11. Matsuoka, L.Y., Wortsman, J., Hanifan, N. & Holick, M.F. Chronic sunscreen use decreases circulating concentrations of 25-hydroxyvitamin D. A preliminary study. Arch Dermatol 124, 1802-1804 (1988). []
    12. Matsuoka, L.Y., Wortsman, J. & Hollis, B.W. Use of topical sunscreen for the evaluation of regional synthesis of vitamin D3. J. Am. Acad. Dermatol 22, 772-775 (1990). []
    13. Scarlett, W.L. Ultraviolet radiation: sun exposure, tanning beds, and vitamin D levels. What you need to know and how to decrease the risk of skin cancer. J Am Osteopath Assoc 103, 371-375 (2003). []
    14. Wolpowitz, D. & Gilchrest, B.A. The vitamin D questions: how much do you need and how should you get it? J. Am. Acad. Dermatol 54, 301-317 (2006). []
    15. Palm, M.D. & O’Donoghue, M.N. Update on photoprotection. Dermatol Ther 20, 360-376 (2007). []
    16. Chlebowski, R. et al. (2006). The Women’s Health Initiative Randomized Trial of calcium plus vitamin D: effects on breast cancer and arthralgias. Journal of Clinical Oncology, 24. []
    17. This comment was based on Figure 3 of Chlebowski et al on page 1587, strata entitled Baseline total vitamin D (supplements + diet). One can see that those who started out with an intake of 600 IU of vitamin D or higher had a hazard ratio of 1.34 (95% CI, 1.01-1.78), while those who started out low had a risk reduction (the p-value for interaction was significant at 0.003). This is one of the few examples of a randomized trial on vitamin D. []
    18. Jackson, R.D. et al. Calcium plus vitamin D supplementation and the risk of fractures. N. Engl. J. Med 354, 669-683 (2006). []
    19. Mohr, S.B., Garland, C.F., Gorham, E.D. & Garland, F.C. The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide.Diabetologia 51, 1391-1398 (2008). []
    20. Vieth, R. Vitamin D toxicity, policy, and science. J. Bone Miner. Res 22 Suppl 2, V64-68 (2007). []
    21. Ardawi, M.S., Nasrat, H.A. & BA’Aqueel, H.S. Calcium-regulating hormones and parathyroid hormone-related peptide in normal human pregnancy and postpartum: a longitudinal study.Eur. J. Endocrinol 137, 402-409 (1997). []
    22. Tanaka, Y., Halloran, B., Schnoes, H.K. & DeLuca, H.F. In vitro production of 1,25-dihydroxyvitamin D3 by rat placental tissue. Proc. Natl. Acad. Sci. U.S.A 76, 5033-5035 (1979). []
    23. Steichen, J.J., Tsang, R.C., Gratton, T.L., Hamstra, A. & DeLuca, H.F. Vitamin D homeostasis in the perinatal period: 1,25-dihydroxyvitamin D in maternal, cord, and neonatal blood. N. Engl. J. Med 302, 315-319 (1980). []
    24. Gray, T.K., Lowe, W. & Lester, G.E. Vitamin D and pregnancy: the maternal-fetal metabolism of vitamin D. Endocr. Rev 2, 264-274 (1981). []
    25. Haug, C.J. et al. Severe deficiency of 1,25-dihydroxyvitamin D3 in human immunodeficiency virus infection: association with immunological hyperactivity and only minor changes in calcium homeostasis. J. Clin. Endocrinol. Metab 83, 3832-3838 (1998). []
    26. Turnbaugh, P.J. et al. The human microbiome project. Nature 449, 804-810 (2007). []
    27. Proal, A.D., Albert, P.J. & Marshall, T. Autoimmune disease in the era of the metagenome.Autoimmun Rev 8, 677-681 (2009). []
    28. Xu, Y. et al. Chin. Med. J 116, 1070-1073 (2003). []
    29. Yenamandra, S.P. et al. Expression profile of nuclear receptors upon Epstein — Barr virus induced B cell transformation. Exp. Oncol 31, 92-96 (2009). []
    30. Kivity, S., Agmon-Levin, N., Blank, M. & Shoenfeld, Y. Infections and autoimmunity–friends or foes? Trends Immunol 30, 409-414 (2009). []
    31. O’Connor, S.M., Taylor, C.E. & Hughes, J.M. Emerging infectious determinants of chronic diseases. Emerging Infect. Dis 12, 1051-1057 (2006). [] []
    32. Relman, D.A. Detection and identification of previously unrecognized microbial pathogens.Emerging Infect. Dis 4, 382-389 (1998). []
    33. Rook, G.A. & Stanford, J.L. Slow bacterial infections or autoimmunity? Immunol. Today 13, 160-164 (1992). []
    34. Allie, N. et al. Protective role of membrane tumour necrosis factor in the host’s resistance to mycobacterial infection. Immunology 125, 522-534 (2008). []
    35. Hurley, J.C. Antibiotic-induced release of endotoxin. A therapeutic paradox. Drug Saf 12, 183-195 (1995). []
  • Comments Off on Second-guessing the consensus on vitamin D
  • Filed under: conferences and trainings, featured articles, medical research, vitamin D
  • In a recent prospective study appearing in Neurology, researchers at various scientific institutions including many in Korea set out to examine the relation between milk and calcium intake in midlife and the risk of Parkinson’s disease. The team analyzed data based on records of dietary intake observed from 1965 to 1968 in 7,504 men enrolled in a cohort called the Honolulu Heart Program. The men ranged from 45 to 68 years of age.

    Parkinson’s disease (PD) is a degenerative condition affecting movement and balance in more than one million Americans each year: its prevalence is expected to rise in aging populations.

    The men were followed for three decades. At that point, 128 men had developed Parkinson’s. But… cue drum roll… the risk of Parkinson’s disease increased as the amount of milk consumed each day rose. Heavy milk drinkers, who drank more than 16 oz a day, were 2.3 times more likely to develop Parkinson’s disease than those men who didn’t drink any milk. Milk was related to PD whether it was whole or skim.

    One may ask, “Why?” The beautiful person with the milk mustache in the latest magazine add told me milk was good for me!


    Perhaps it’s the calcium? Nope. The team, under Dr. Park, used careful statistical analysis to rule out the possibility that calcium could have caused the increased disease incidence. “In addition, calcium intake from non-dietary sources was not related to PD, further suggesting that a role for calcium in altering PD risk is absent,” states the paper, which was published in the March issue of the Journal of Neurology.

    Total fat and protein also had no relation with the risk of PD. Park and team suggest that neurotoxins such as organochlorine, tetrahydroisoquinoline, and heptachlor may be to blame, but even they would concede that this explanation is speculative at best. In fact, according to the study’s authors, “Unfortunately, there are no clear explanations for the relation between milk intake and the risk of PD.”

    What the researchers fail to even consider is that since the 1930′s, milk suppliers have been fortifying milk with vitamin D. According to, A. W. Norman in the book, Vitamin D: The calcium homeostatic steroid hormone, “There developed in the 1940′s, and continues to the present, a large business of industrial production of vitamin D3 used for the supplementation of foods for human consumption: milk (both homogenized and evaporated), some margarine and breads. Since the 1960′s vitamin D3 has been used also for the supplementation of farm animal and poultry food. In 1973 in the United States some 290 trillion (290 x 1012) International Units of vitamin D3 was manufactured and sold for over 3 million dollars. This vitamin D3 is the equivalent of approximately 8 tons.”

    This strongly suggests that the men in the Honolulu heart study were drinking vitamin D fortified milk. With this in mind, the powerful secosteroid incorrectly labelled “vitamin” D seems like an extremely logical culprit for the rise in PD amongst subjects drinking higher amounts of milk. As described in this recent paper, vitamin D’s steroidal properties allow it slow the innate immune response. While this allows for palliation and symptom reduction in the short-term, it causes chronic bacteria that very likely contribute to the progression of PD to proliferate more easily.

    When writing previously about vitamin D, I’ve argued that, “One of the abiding weaknesses of studies on vitamin D is that researchers do not follow subjects consuming the secosteroid for a sufficient period of time. Instead they track subjects over the course of weeks, months, or one or two years, during the period of time when study participants are usually feeling the palliative effects of the secosteroid. Researchers will rarely, if ever, track subjects over the course of decades, the length of time needed to begin to note the negative changes that chronic bacteria cause later in life.”

    So hooray for the authors of the Honolulu Heart Study who spent the time and money to monitor subjects for 30 years after their dietary intake was reported. Clearly, when it comes to vitamin D, patience is needed for the negative impact of consuming the secosteroid to be noted.

    Another clue that vitamin D likely caused the increase in PD risk among men drinking more milk in the Honolulu study was that consumption of cheese and ice-cream did not affect PD risk. The explanation? Although these products are made from milk, they are generally made from milk before it has been fortified with vitamin D.

    That Park and team did not even consider the vitamin D in milk as a possible cause for the increase PD among men consuming more of the substance speaks to the incredible strength of the current consensus that fails to recognize the immunosuppresive properties of vitamin D. This is bound to change, but in the meantime, vitamin D fortified milk should at least come with the message, “Immunosuppressive steroid included at no extra charge!!”

  • Comments Off on Milk consumption tied to Parkinson’s disease
  • Filed under: medical research, News Flash, vitamin D
  • For several years now, studies have emerged showing that breastfed babies often perform better on standardized tests and display higher overall levels of intelligence than their formula-fed counterparts. And since baby formula possesses, at least according to a number of mainstream researchers, many of the same basic characteristics as breast milk, the reality that breastfed babies tend to display higher levels of intelligence currently presents a conundrum for the medical community.

    Of course, theories have been proposed. One such theory is that women who breastfeed their babies possess different personality traits than those women who chose to feed their infants formula. It’s been postulated that women who take the time to feed their babies from their own breasts are smarter. Perhaps the fact that such women harbor the desire to breastfeed also indicates that they are more invested in the future of their infant. And if they are more invested their baby, then it could be proposed that they interact more closely with the baby and initiate a greater number of activities to foster its intelligence.

    The hypothesis is plausible and may be true to a certain extent. Yet a recent study by researchers at McGill University and conducted at a Belarrussian hospital has poked a serious hole in its accuracy, highly suggesting that other factors govern the level of mental development achieved by breastfed and formula fed babies.

    Key to the Belarussian study is that unlike any of the previous studies conducted on breastfed/formula fed infants, the mothers of the babies were randomly assigned to two different groups. Other studies on the same topic have instead allowed mothers to chose whether or not they want to breastfeed or formula feed their infants. Or, research teams have simply tracked the children of breastfeeding mothers and then compared them to the children of mothers who had independently made the choice to use formula instead. The problem with such study designs is that in each case, the mothers themselves chose how to feed their infant, making it impossible to test whether children’s intelligence levels later in life are due to the milk/ formula or the characteristics of the mother.

    However, in the Belarussian trial, about half the 14,000 babies under study were randomly assigned to a group in which prolonged and exclusive breastfeeding by the mother was encouraged at several hospitals and clinics. The mothers of the other babies received no special encouragement. The result was that those infants in the breastfeeding encouragement group were, on average, breastfed longer than the others and were less likely to have been given formula in a bottle, yet the decision to breastfed was largely influenced by the researchers conducting the study rather than the personalities of the mothers themselves.

    “The design of the study — randomly assigning babies to two groups regardless of the mothers’ characteristics — was intended to eliminate the confusion [of whether breastfed babies are given more attention],” state the team.

    At 3 months, 73 percent of the babies in the breastfeeding encouragement group were breastfed, compared to 60 percent of the other group. At 6 months, it was 50 percent versus 36 percent. In addition, the group given encouragement was far more likely to give their children only breast milk. The rate was seven times higher, for example, at 3 months.

    The children were monitored for about 6 1/2 years, at which point the researchers proceeded to measure the differences between the children in two groups using IQ tests administered by the children’s pediatricians and by ratings by their teachers of their school performance in reading, writing, math and other subjects.

    Interestingly, despite the fact that the study design had largely eliminated the “mothers who breastfeed are more likely to invest in their infants” variable, children who had been breastfed still scored higher on intelligence tests. In fact, the children in the group where breastfeeding was encouraged scored about 5 percent higher in IQ tests and did better academically.

    Although Kramer and team were able to identify a causal relationship between breastfeeding and measured intelligence, they admit to being somewhat flummoxed by exactly how this happens. A number of mechanisms are suggested including the notion that maybe there’s some constituent unique to breast milk, such as polyunsaturated fatty acids, which offers breastfed infants an advantage. However studies that have attempted to add polyunsaturated acids to formula have yielded inconsistent results when tested on infants. Others have proposed that breast milk may superior to formula because it contains more insulin-like growth factor I, but it’s difficult to connect a growth factor to cognitive function.

    One of the old refrains you hear on Bacteriality time and again is “What about the alternate hypothesis?” So, what about it? In this case, the variable which escaped the researchers’ consideration is right under their noses. Whereas natural breast milk is low in vitamin D, infant formula is fortified with the secosteroid,

    So, it’s very likely that the characteristics of the baby formula itself, rather than the characteristics of breastfeeding mothers or possibly even the properties of natural milk, are the driving factor determining intelligence levels among formula-fed children. The vitamin D added to baby formula is in the form of 25-D – the vitamin D metabolite that slows activity of the Vitamin D Receptor. Since the Vitamin D Receptor is key to controlling the activity of the innate immune response, those infants fed formula gradually ingest enough 25-D to slow the activity of the receptor. It follows that the chronic, intraphagocytic bacteria capable of infecting the brain and causing numerous mental deficiencies, learning disorders, and overall mental sluggishness (the very conditions and diseases correctable by removing vitamin D from one’s diet) are able to infect and persist in the heads of the formula fed babies with greater ease.

    Here then is a summary of the McGill study. People add unnatural substance to food for infants. Infants ingest said substance. Infants grow up to have lower intelligence.

    Mothers and their doctors privy to this study will probably opt to breastfeed their babies, albeit for the wrong reason. So at least, even if based on misinformation, most doctors currently recommend breastfeeding over formula feeding. Still, the number of formula fed babies reigns in the millions, compromising their later health and well-being.

  • Comments Off on Why are breastfed infants more intelligent? Examining the alternate hypothesis
  • Filed under: News Flash, vitamin D
  • The Indian sub-continent is situated between 8.4 degree N and 37.6 degree N latitude and has adequate sunshine throughout the year. So say researchers at the Apollo Hospital in New Delhi India. In fact, in their introduction to a recent study on vitamin D, the team postulated further, stating that “it has been presumed that Indians have ‘sufficient’ levels of vitamin D.”

    And who wouldn’t presume such a thing? Considering that the average temperature in India is quite high, it’s doubtful that natives would be deficient in a substance that is easily obtained from the sun. Nevertheless, with growing concerns of what mainstream medicine calls vitamin D “deficiency” at hand, the team set out to confirm that the staff from a hospital in north India did indeed possess levels of vitamin D (25-D) that the medical community has deemed healthy – specifically 25-D level between 35-50 ng/ml. Using a machine called dual energy X-ray absorptiometer, the Apollo Hospital team were able to measure the staff’s serum 25-D and 1, 25-D levels.

    In the end, the team was unnerved by their results. To their dismay, only 33.7 percent of subjects had 25-D concentrations above 15 ng/ml. And they were probably even more confused that 20.6% of subjects had 25-D levels < 5 ng/ml, 27.2% of subjects had 25-D levels between 5-9.9 ng/ml and 18.5% demonstrated 25-D levels in the range of 10-14.9 ng/ml. Rather than consider any possible alternate hypotheses for the fact that essentially all of their subjects displayed 25-D levels below the “normal range” – after all, the researchers themselves had once described the subjects as healthy – the team leapt to a sobering conclusion. Despite the reality that the subjects were getting adequate amounts of sunlight, they argued that vitamin D “deficiency” was rampant among the staff.

    The ease with which the Apollo team jumped to the conclusion that their subjects are vitamin D “deficient” goes a long way towards explaining why incorrect assumptions about vitamin D remain the norm among mainstream researchers. Few seem to truly consider the implications of the fact that 25-D is a secosteroid rather than a vitamin, or the consequences of altering levels of a substance that is controlled by myriad delicate feedback pathways. One would think that with such counterintuitive results at hand, the Apollo team would strive to consider alternate explanations. There are at least two rational alternate hypotheses for the low levels of 25-D observed among the hospital staff.

    First off, who’s to say that the current range used to determine what is considered to be a “healthy” level of 25-D is correct? Since the vast majority of the public whose data are used to create such a range consume large amounts of vitamin D fortified products, few people have a truly natural level of vitamin D in their bodies. Consequently, it’s only logical that over the past few decades, the “healthy” range for 25-D obtained from bloodwork has been adjusted upward to accommodate the rise in 25-D levels that results from the consumption of fortified products. The result is that the 25-D levels of people eating a diet without fortified foods – as is probably the case among the hospital staff – are inevitably considered to be too low, out of range, and ultimately a menace to their health.

    The possibility that the current “healthy” range for 25-D incorrectly tags people not consuming fortified products as vitamin D “defiecient” is strengthened by other studies including a study by researcher at who tested the level of 25-D in 90 “healthy, ambulatory Chilean women”. Testing revealed that 27% of the premenopausal and 60% of the postmenopausal women had 25-D levels under 20 ng/ml. Similarly, a study on healthy Bangladeshi women found that approximately 80% of the women had a level of 25-D under 16 ng/ml.

    The stark reality is that considering all the extra vitamin D we have added to the food chain, we no longer know what amount of 25-D the body would maintain under natural circumstances. Could it be that the people we call “Vitamin D deficient” actually have a normal level of 25-D and actually are, as the Apollo researchers first postulated of their subjects, vitamin D “sufficient?”

    Furthermore, among those familiar with the complexities of vitamin D metabolism, the concept of vitamin D “deficiency” is rapidly becoming obsolete. Armed with the knowledge that 25-D actually blocks, rather than activates, the VDR, it has become clear that people – particularly those suffering from chronic disease – are better off with low levels of the secosteroid. In a recent BioEssay, biomedical researcher Trevor Marshall details feedback pathways which show that among patients with chronic disease, 25-D levels are naturally downregulated by the disease process itself – a process driven by the ability of chronic, intracellular metagenomic pathogens to created VDR-blocking ligands.

    Although slow growing, these chronic pathogens can easily spread from person to person, particularly among people in close contact. So when one considers that the hospital staff examined by the Apollo research team are in constant contact with patients suffering from a plethora of illness caused by these bacteria, there is little doubt that each staff member has acquired at least some chronic pathogens from their patients.

    Perhaps then, the low 25-D observed in many of the staff members reflects the fact that they too are infected with the chronic bacteria that dysregulate vitamin D metabolism and cause 25-D levels to drop.

    Unfortunately, although discussed repeatedly on Bacteriality, such alternate hypotheses remain largely foreign to the mainstream medical community. So the concept of vitamin D “deficiency” continues to be spoon fed to the public, who, of course, proceed to supplement with vitamin D in order to keep their 25-D levels in an artificially high range. It’s clear that this trend can only be remedied by a rise in independent thinking. Surely when the results of a study fail to make sense in the light of a current model, it’s time to re-examine the model rather than rationalize the data. So go for it, vitamin D researchers– dare to consider alternate hypotheses for your observations. After all, the health of essentially the entire population is at stake.

  • Comments Off on Study finds that healthy Indian hospital workers display low levels of vitamin D despite adequate sun exposure, providing support for Marshall’s model of vitamin D metabolism
  • Filed under: News Flash, vitamin D
  • This month, researchers from several institutions including the University of Oulu in Finland and the Imperial College in London reported the results of a study which found an association between high-dose vitamin D supplementation in infancy and an increased risk of atopy, allergic rhinitis, and asthma later in life. Atopy, or atopic syndrome, is an allergic hypersensitivity affecting parts of the body not in direct contact with an allergen. It may involve eczema (inflammation of the upper skin layers), allergic conjunctivitis, allergic rhinitis and asthma.

    The team started collecting data in 1967. That year, every mother in the two most northern provinces of Finland – a group of mothers referred to as the Northern Finland Birth Cohort (NFBC) – who had given birth to a child during the previous year was required to report the level of vitamin D they were giving their infant. At the time, Finnish government recommendations stated that mothers should supplement their infants with 50 ug of vitamin D. Mothers were asked to report if they were giving their infant the recommended dose of vitamin D, no vitamin D, or an irregular dose of vitamin D. An irregular dose of vitamin D usually reflected the fact that the infant was given high levels of vitamin D rich cod liver oil.

    The infants were then tracked over the next 31 years of their lives. The exact age at which the study participants started to develop allergies and asthma was not specifically documented. However, the team did check in with subjects when they were 14 years old. At that point, subjects who had been taking the requisite 50 µg of vitamin D as infants were found to suffer from a higher prevalence of asthma and allergies. When the researchers checked in with the subjects at 31 years of age – the presence of atopy was determined by skin-prick test – the trend persisted. Prevalence of asthma and allergic rhinitis was greater in participants who had received vitamin D supplementation regularly than in those who had received it irregularly or not at all.

    Although the team did not keep track of specific levels of vitamin D supplementation higher than 50 µg, their data did suggest increases in the occurrence of allergic rhinitis and asthma among those participants who had taken the highest doses of vitamin D.

    The researchers believe that the NFBC population lends itself to a highly accurate study on the effects of vitamin D. Since during the Northern Finnish winter, daylight last for only 2 hours a day, the infants analyzed may have produced less vitamin D from sunlight. Also, during 1966, infant formula in Finland was not yet supplemented with vitamin D, meaning that lack of information on infant feeding was not likely to have affected estimates of vitamin D intake.

    Compliance to vitamin D supplementation recommendations (i.e., child received 50 µg regularly) was associated with several social and behavioral characteristics of the mother. It turns out that mothers who were more proactive, better educated, and of higher social class were most likely to correctly follow the government specified vitamin D supplementation guidelines for their infants. Ironically, the children born to such mothers were found to suffer from higher levels of asthma, atopy, and rhinitis by age 31. This means that, ironically, those children born to mothers who did not correctly comply with the supplementation guidelines were actually healthier 31 years later. As the team states, “Many of the same characteristics that were predictive of worse compliance to vitamin D recommendations were associated with reduced risk of allergies.”
    Of course, those of us familiar with the work of biomedical researcher Trevor Marshall understand why those infants given extra vitamin D during the first years of life were more likely to develop asthma and allergies as adults. Molecular and clinical data support the fact that the vitamin D derived from diet and supplements in a secosteroid that, at high levels, blocks the activity of the vitamin D Receptor – a fundamental receptor of the body that controls the activity of the innate immune system. A wide body of research has also confirmed that asthma and allergies are caused by chronic intraphagocytic biofilm-like bacteria. Thus, the innate immune function of those infants given extra vitamin D was depressed at an early age. The subsequent immunosuppression almost certainly made it easier for the infants to acquire the pathogens that cause asthma and allergies. Since L-form and biofilm bacteria grow very slowly, it took many years before the symptoms of their diseases became overt and problematic.

    When Dr. S.O. Shaheen of the National Heart and Lung Institute at the Imperial College London was alerted to the results of the above study, he wrote a letter to two researchers (A.A. Litonjua and S.T. Weiss of the Brigham and Women’s Hospital in Boston) who, unaware of the long-term immunosuppressive effects of vitamin D, are urging researchers to conduct more trials in which infants are administered high doses of vitamin D.

    “I would argue… that the vitamin D story is, at present, rather more confused than Weiss and Litonjua suggest, and that before rushing into prenatal nutrient supplementation trials, we need more convincing data to support their hypothesis, and greater confidence that such an intervention would be safe, states Shaheen. “Given the failure to translate observational associations between antioxidant deficiency and asthma into beneficial interventions in adults, we need to be more sure that observational links with prenatal nutrition are not confounded, and that longer term follow-up of birth cohorts does not reveal a positive relation between prenatal vitamin D status and [asthma].”

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  • Filed under: News Flash, vitamin D
  • Need proof that consuming high levels of vitamin D can curb your lifespan? Look no farther then a study published this month in theAmerican Journal of Clinical Nutrition which found that middle-aged men who ate seven or more eggs a week had a higher risk of earlier death from diabetes.

    More specifically, Dr. Luc Djousse and Dr. J. Michael Gaziano of Brigham and Women’s Hospital at Harvard Medical School found that men with diabetes who ate any eggs at all doubled their risk of death during a 20-year study period. The team studied 21,327 men taking part in the much larger Physicians’ Health Study, which has been watching doctors since 1981 who have agreed to report regularly on their health and lifestyle habits.

    “More egg on our faces? It’s really hard to say at this point, but it still seems, if you’re a middle-aged male physician and enjoy eggs more than once a day, then having some of the egg left on your face may be better than having it go down your gullet,” said Dr. Robert Eckel of the University of Colorado and a former president of the American Heart Association.

    Egg yolks are high in vitamin D.

    Although the study did not examine what about the eggs might affect the risk of death, the results of the study can almost certainly be explained by the fact that egg yolks are very high in vitamin D – a secosteroid with immunosuppressive properties when elevated. Molecular modeling data, that is supported by a large amount of clinical data from the Marshall Protocol study site, has confirmed that 25-D – the form of vitamin D obtained from foods such as egg yolks – binds and blocks the Vitamin D Receptor (VDR). The VDR is fundamental receptor of the body that controls the activity of the innate immune system, the production of many families of antimicrobial peptides, and the transcriptions of hundreds and possibly thousands of genes.

    Since, diabetes has now been linked to bacteria, blockage of the Vitamin D Receptor results in decreased immune function that allows the L-form and biofilm bacteria (collectively called the Th1 pathogens) that cause diabetes to spread with much greater ease. 25-D starts to cause immunosuppression via the VDR at levels at around 20 ng/ml, an amount that can be easily be obtained by eating only a moderate amounts of vitamin D.

    It goes with out saying then, that physicians consuming a high number of eggs over a twenty year period would easily accumulate enough “vitamin” D to substantially block their VDRs.

    Actually though, the extent to which 25-D blocks the VDR is related to another important factor – a person’s bacterial load. Biomedical research Trevor Marshall has used molecular modeling to show that at least one of the Th1 pathogens can create a substance that binds and blocks the VDR. Because slowing the VDR is such a logical survival mechanism for any form of pathogen, it’s almost certain that other species of the Th1 pathogens also create substances that block the receptor.

    In the Harvard study, the physicians with diabetes no doubt had high bacterial loads. Subsequently their VDRs were already substantially blocked by bacterial substances. Since their VDRs were already blocked, it’s clear that even a small amount of 25-D from egg consumption easily exacerbated the existing blockage. Not surprisingly then, even moderate egg consumption in these men increased VDR blockage to a point where the subsequent decrease in immune function more then doubled their risk of death.

    If the extent of VDR blockage generated by bacterial ligands is an important variable in determining how quickly 25-D contributes to VDR blockage, then healthy subjects with lower bacterial loads should not have been as negatively impacted by the immunosuppressive properties of the secosteroid. Indeed, the Harvard team found that healthy physicians without diabetes could eat up to six eggs a week with no extra risk of death.

    Yet even among healthy physicians, risk of death increased by 23% among those who consumed seven or more eggs a week. This suggests that healthy men have more leeway when it comes to consuming vitamin D because of the fact that their VDRs are not yet significantly blocked by bacterial substances. Yet, even among healthy subjects, eating a sufficiently high level of vitamin D (over six eggs) did allow 25-D to rise above 20 ng/ml – to a point where they also began to suffer from negative consequences of decreased immune function.

    The message is clear. Most healthy people are probably able to tolerate some vitamin D – moderate amounts of the substance that are found in non-fortified foods. Yet once a person develops symptoms of an inflammatory disease and their bacterial load starts to rise, consuming the secosteroid will only hinder immune function and exacerbate VDR blockage. Hence the Marshall Protocol guidelines, which state that patients on the treatment must remove all forms of vitamin D from their diet as they recover.

    As for the rest of the the medical community, how long will it take before they connect the consumption of egg yolks to vitamin D – the real villan at the scene of the crime? As of today, they appear to be largely oblivious.

    Take, for example, researchers in Finland, who recently discovered that the vitamin D content of an egg can be raised sevenfold by tripling the vitamin D in chicken feed, the hope being that such eggs could allow the public to consume ever higher amounts of vitamin D on a daily basis. The study was published in the Oct. 18 issue of the Journal of Agricultural and Food Chemistry.

    Sevenfold? I’m literally getting shivers down my spine, and clearly not the good kind. If the amount of vitamin D in a natural egg doubles the rate of death for the average diabetic male physician, then imagine how quickly consuming eggs with a seven-fold increase in vitamin D will send them to the grave? And this trend applies to the entire population.

    We are living in the midst of an epidemic of chronic disease that is fostered by nothing less then an epidemic of vitamin D delusion.

  • Comments Off on In men with diabetes, eating eggs – which contain vitamin D in the yolk – doubles the risk of death
  • Filed under: News Flash, vitamin D
  • Maybe vitamin D isn’t the answer after all.

    Not only does the above statement ring true, it’s also the title of a recent post on “Dr. Len’s Cancer Blog” – a website written by Dr. Len Lichtenfeld, Deputy Chief Medical Officer for the national office of the American Cancer Society, in order to facilitate communication with the public on important issues related to cancer.

    Dr. Lichtenfeld, as described by his website, is a frequent spokesperson on a variety of cancer-related subjects, and serves as a liaison for the Society with many professional and public organizations. He’s also a board certified medical oncologist and internist who was a practicing physician for nearly 20 years and serves on several national committees focused on physician payment, the quality of medical care, and the role of health information technology in healthcare delivery.

    In the blog entry described above, Lichtenfeld attempts to explain to the public why the American Cancer Society does not plan to advise the American public to take extra vitamin D supplements in the name of preventing cancer (this is in contrast to the Canadian Cancer Society which has, unfortunately, urged citizens to ingest more of the secosteroid).

    Dr. Lichtenfeld

    Lichtenfeld begins his discussion by taking a close look at one of the most recent studies on cancer and vitamin D – a study conducted by the National Cancer Institute. The first study to actually look at the relationship between measured vitamin D in the blood and subsequent total cancer deaths, it failed to show an association between baseline vitamin D status and overall cancer risk in men, women, non-Hispanic whites, non-Hispanic blacks, Mexican Americans, and persons younger than 70, or 70 years or older.

    “The key finding of the study was that there was no impact of vitamin D levels on the overall risk of dying from cancer, when comparing groups based on where they lived or what season their blood test was drawn (spring and summer would be expected to increase vitamin D levels, compared to winter),” Lichtenfeld explains. “Vitamin D had no impact on cancer deaths when various racial/ethnic groups were examined.”

    Of course, Lichtenfeld does acknowledge that the research team found a significant reduction in colorectal cancer among subjects with higher levels of vitamin D (25-D) in their blood. Yet, in a decision that reflects his neutrality on the subject, Lichtenfeld makes it clear that such findings will need to be confirmed by future studies before the American Cancer Society considers vitamin D as a possible remedy for colorectal cancer.

    No doubt he is aware of a similar study conducted by Jacques Rossouw at the National Institutes of Health, whose group tracked the effects of vitamin D on 46,282 postmenopausal women with colorectal cancer, while monitoring the women over a long period of time. Rossouw’s team found “absolutely no indication of an effect of calcium or vitamin D [on cancer] — zero.”

    With such conflicting data emerging on vitamin D and colorectal cancer, no wonder leaders such as Lichtenfeld are taking a step back to see if they might be missing part of the vitamin D puzzle.

    Such contradictions may also be why, with good reason, Lichtenfeld appears to be taking a long, hard, look at how several other studies on vitamin D have been conducted, with a keen eye towards bias.

    Many of the other studies have tried to infer vitamin D levels through a variety of means, such as asking about dietary habits or inferring a vitamin D level based on descriptions of outdoor activities.“Many of the other studies have tried to infer vitamin D levels through a variety of means, such as asking about dietary habits or inferring a vitamin D level based on descriptions of outdoor activities,” comments Lichtenfeld. His concerns about such research methods are well-grounded, as studies attempt to infer levels of vitamin D rather than measure them are notoriously bad at coming up with accurate results.

    Thus, Lichtenfeld suggests that the recent study by the National Cancer Institute, a study which found that vitamin D offers no overall benefit in fending off cancer, should bear more weight than other studies on the subject, as it was done prospectively – meaning that participants were followed looking forward, and actual blood tests were used to measure the amount of vitamin D in their blood.

    Futhermore, Lichtenfeld seems to understand the urgent need for long-term studies on vitamin D. He agrees with editorialists who have suggested that it may take longer than 6-12 years to accurately assess the effects of vitamin D on study subjects – especially since, as he comments, it can take many years for a cancer to develop.

    Those of us familiar with the Marshall Protocol wholeheartedly agree with Lichtenfeld in this regard. It’s clear that future studies on vitamin D and cancer will have to follow their subjects for at least a decade or two in order to accurately gauge the relationship between intake of the secosteroid and cancer rates. If such studies actually take place, they will almost certainly highlight the drawbacks of vitamin D rather than any purported “benefits”, as the negative consequences of immunosuppression become increasingly apparent over longer periods of time.

    Lichtenfeld proceeds to comment on several editorials written in response to the National Cancer Institute study, arguing they “point out that we need to know more about how vitamin D levels change from season to season, and how that impacts our health.”

    He also warns readers to heed the following editorial comment, stating that he “couldn’t agree more” with their conclusions:

    “Whether vitamin D reduces cancer risks and, if it does, whether these amounts suffice are actively being debated. Randomized clinical trials of the effects of vitamin D on the incidence of colonic polyps and invasive cancer are needed. While vitamin D may well have multiple benefits beyond bone, health professionals and the public should not in a rush to assume, in a rush to judgment, that vitamin D is a magic bullet and consume high amounts of vitamin D. More definitive data on both benefits and potential adverse effects of high doses are urgently needed.”

    Indeed, Lichtenfeld seems wise enough to have realized that treatment options that are suspiciously simplistic enough to be dubbed “magic bullets” have seldom if ever held up to medical scrutiny, especially when researchers start to examine the substance at the molecular level.

    When the studies were actually done, we discovered that the vitamins had either no effect or, for some people, may have actually increased their risk of cancer.“We have consistently called for more research into this topic [vitamin D],” he argues. This is especially important given our past experience with other vitamins, such as vitamin C and beta-carotene, where well-qualified experts touted the benefit of those vitamins in reducing cancer risk. When the studies were actually done, we discovered that the vitamins had either no effect or, for some people, may have actually increased their risk of cancer.”

    As with any other blog, readers are able to write responses to Dr. Lichtenfeld’s pieces. The very first person to respond to “Maybe Vitamin D isn’t the Answer After All” was none other then Dr. Jacob Cannell – head of the “Vitamin D Council” – an organization that seeks to promote the consumption of vitamin D, and when I say promote I mean promote. Although the group presents itself as a scientific body, even a quick glance at their website assures the reader that the members of this Council have failed to read, evaluate, or even consider any of the alternate hypotheses proposed about vitamin D – hypotheses based on research that clearly show that extra levels of the secosteroid are harming rather than helping people with chronic disease.

    “Perhaps you could explain what residual confounding is?” writes a livid Dr. Cannell. “If so, your readers might feel you fully understand the study. What was the relative risk of breast cancer? I know the sample size was too small for signifigance [sic] but you might want to say what it was? Is it true that the relative risk of breast cancer was almost four times higher in the group with the lower levels?…..What you are actually doing is defending the American Cancer Society’s decision not to follow the Canadian Cancer Society’s recommendation of 1000 IU per day of vitamin D. Say you are wrong and Canada is right? On whose hands will that blood be?”

    Apparently for the Vitamin D Council, this is what passes for professional discourse.

    Lichtenfeld kept his cool, responding, “What Dr. Cannell has not said is that similar circumstances in the past–with other vitamins that were thought to be harmless and able to reduce the risk of cancer–showed evidence of harm and/or lack of efficacy when subjected to appropriate study. To say that my opinion is equivalent to having blood on my hands is an ad hominem attack not worthy of consideration. His cause would be better served to advocate on behalf of people who need to be screened for colorectal cancer (which would save thousands of lives, based on solid evidence), and join us in encouraging appropriate review of the data and research to definitively answer the issue at hand.”

    Lichtenfeld then ended the discussion with a statement that just about sums up one of the biggest problems to result from the fact that the public is getting their information about vitamin D straight from the mouths of people like Cannell, stating:

    “When we succumb to making every medical decision solely on the basis of the strongest advocate’s voice, we run the risk of moving medical practice back into an era similar to that from which we are trying to emerge.“When we succumb to making every medical decision solely on the basis of the strongest advocate’s voice, we run the risk of moving medical practice back into an era similar to that from which we are trying to emerge. If the review and research studies confirm Dr. Cannell’s position, that will be welcome. But we need to once and for all establish the science-based evidence that will conclusively answer the question one way or the other, rather than relying on advocacy to establish dietary and medical practice recommendations for the world.”

    Steven Strauss takes a look the ethical issues affecting the bulk of vitamin D research.

    At about the same time that Lichtenfeld was advising the public to wait for more research before popping extra vitamin D supplements, author Steven Strauss was addressing similar issues in an entry published on the CBC News blog. To me, it is a remarkable piece, because it comes from one of the few voices that actually says in the midst of what can only be described as vitamin D hysteria, “Hey, wait a minute.” In his online bio, Strauss expresses admiration for the motto of Austrian writer Karl Kraus – “Say what is.” I think it’s pretty clear that Strauss does just that.

    Strauss begins his discussion of vitamin D by describing the pressures put not only on himself, but on the average Canadian citizen to purchase vitamin D. “It’s been cold and remarkably un-sunny in my neck of Canada recently — climatic conditions which I have been repeatedly told in the past year should lead me to start scarfing down vitamin D pills, and do it in amounts which likely exceed Health Canada’s daily recommended dosage,” he writes.

    Along with his fellow citizens, he’s also been urged by numerous vitamin D advocates – who might be better characterized as zealots – to ignore the Canadian government’s requirements about vitamin D. These advocates, who include researchers such as Reinhold Vieth, Michael Hollick and Cedric Garland, have encouraged Canadian citizens to “strike out on a vitamin D health path of their own” by taking five times the amount of vitamin D suggested by the government.

    “And if I don’t, it is my fault — well ‘my’ as in all the media — if you readers get cancer, multiple sclerosis, flu, autism, depression, diabetes, loose teeth, stroke, heart disease, osteoporosis, fractures and God knows what else,” remarks Strauss.

    Strauss’ comment is laced with sarcasm as he is well aware of an editorial published last year in the American Journal of Clinical Nutrition in which 15 of the top vitamin D proponents from around the world scolded journalists for not encouraging the public to consume the high amounts of vitamin D recommended by… themselves.

    “Well, one should take this kind of criticism to heart,” remarks Strauss. Indeed, the situation caused Strauss to examine other papers on vitamin D.

    Among these papers was a study by researchers at Creighton Univerisity in Nebraska, one of the papers cited by the Canadian government in an effort to rationalize its decision to recommend that people in Canada take much more — upwards of two-and-a-half times today’s recommended 400 International Units — vitamin D on a daily basis.

    The study, which looked at the cancer rates of women taking vitamin D, taking calcium without vitamin D, or taking nothing over a four year period reported a 60 per cent decrease in collective cancer rates for the vitamin D takers when they took what was something more than twice the currently recommended dosage.

    When Strauss took a better look at the study, he wasn’t pleased with what he discovered. Now, I would like to share with my readers an extended portion of Strauss’s post, in his own words, starting with his discussion of the Creighton study. The following is reproduced from the CBC Canada site. Strauss’s argument is too cogent, too compelling, not to share it.

    While the cancer numbers were small — only 50 cases in total — the CCS decision meant there was lots of coverage of the research. I found upwards of 50 reports in magazines, newspapers, radio and television, but absolutely zero coverage of the criticism of the paper that appeared in the journal in recent months.In one letter, three scientists in Texas pointed out a number of issues, not the least of which being an Iowa study which suggested that when breast cancer was looked at there was indeed a fall in cancer numbers for the first five years when a vitamin D supplement was taken. But this balanced out at 10 years and there actually seemed to be more breast cancers among women taking vitamin D after 15 years.It is precisely these sorts of yes/no/maybe results that make science and medical writers very, very, very, very cautious about blithely recommending dose rate increases.It is precisely these sorts of yes/no/maybe results that make science and medical writers very, very, very, very cautious about blithely recommending dose rate increases.Then there were the questions raised by Manish Sood of the Toronto General Hospital and Amy Sood of the University of Toronto faculty of pharmacy. They pointed out that some had suggested the incidence of heart disease might grow as a result of increasing the vitamin D dosages and recommending, as the CCS did, that supplements be taken year round or during fall and winter months depending on skin colour and other factors.

    In light of the CCS recommendation and a possible heart disease side-effect, they concluded their letter saying: “As Canadians, we ask the question — have we just traded one problem for another?”

    Sounds reasonable, but their concern was brushed back by paper authors Robert Heaney and Joan Lappe of Creighton, who responded that there is no evidence of heart problems with vitamin D doses up to 10 times what they had given people. They added, “The issue of vitamin D toxicity was exhaustively reviewed in this Journal just a few months ago and Sood and Sood may find some reassurance in that report.”

    Given this disagreement I, too, needed reassurance and so I went to the review where I found something very non-reassuring. Heaney and Vieth had co-authored the toxicity study with two employees of the Council For Responsible Nutrition, a Washington D.C.-based lobby group and trade association for ingredient suppliers and manufacturers in the dietary supplement industry — that is to say, the official representatives of the people who would make vitamin D.

    Ultimately what the four wrote looks extremely authoritative, and might well be so, but to my mind this collaboration represents not an apparent conflict of interest, but a genuine conflict of interest.And their roles were anything but minor. One applied “risk assessment methodology” to the results and the other “searched literature and summarized relevant findings.” Ultimately what the four wrote looks extremely authoritative, and might well be so, but to my mind this collaboration represents not an apparent conflict of interest, but a genuine conflict of interest.

    And let me explain it with a simple equation. Let us assume that one-third of the people in North America decide, based on the CCS recommendation, to more than double their vitamin D dosage and this costs a bare $20 per person a year. That translates into an extra $2 billion going to vitamin D manufacturers and sellers.

    All of this made me go back to the original Creighton paper and look to see if there was any indication of specific conflicts of interest among the researchers in it. The paper says no, with resounding vehemence: “None of the authors was affiliated in any way with an entity involved in the manufacture or marketing of vitamin D.”

    Then it goes on to mention that one author, Robert Recker, was on the scientific advisory boards of Roche and Proctor & Gamble, and Heaney was on the scientific advisory board for the International Dairy Food Association and the speaker’s bureau for P & G.

    It’s true that Roche doesn’t make vitamins today — but it sold the business in 2003, a time that the Creighton experiment was ongoing. The sale, by the way, was announced at the same time Roche said it had resolved lawsuits growing out of its involvement in vitamin price fixing.

    But Proctor remains in the business, in that it has licensed its Olay name to another company to produce Olay vitamins, which include vitamin D in a multivitamin supplement. Not to mention the fact that Heaney reported in 2006 that he had a “financial relationship with SmithKlineGlaxo” — a company which directly produces vitamin D.

    And oh, yes, it seems almost everyone doing vitamin D research — Vieth included — gets money from dairy farmers associations in either Canada or the U.S.

    So I sent Recker and Heaney an e-mail asking for an explanation and Recker responded: “Neither Dr. Heaney nor I have any affiliation with the company that supplied the vitamin D for the study. We have not had affiliation with the vitamin D work for the companies you mention. I have been a scientific adviser to Roche, P & G and Smith-Kline-Glaxo, but not in their vitamin D work.”

    Interestingly finely parsed, but when I Google “Recker and Glaxo” I find him quoted in a company press release endorsing an osteoporosis website the company supports — a site that advocates taking vitamin D and which points out that if you have problems getting it naturally, you can buy supplements that will fill in the gap.

    Recker responded in his e-mail to me that, “I do not include the statement in the press release as a potential conflict of interest since I was not making the statement out of any affiliation with GSK. I have not participated in any of the studies nor in any advisory capacity to GSK regarding any vitamin D product. There is often some confusion about what constitutes a potential conflict of interest, as might be the case here. My institution does not require that I list this as a potential conflict of interest in its management of faculty relations with industry.”

    Parsing a parse, if you ask me.

    I then had a lengthy discussion with Vieth who quite candidly said he had been delighted to join up with the manufacturers’ association employees in the toxicity review paper because he had long admired them for being good scientists. “I was honoured when they asked,” he told me.

    As to money conflicts he doesn’t think that was a big issue because vitamin D is a generic product and can be made for very little. He said the pure form of the substance costs about $3,000 a kilogram to make, a figure that translates into the dose each of the women in Nebraska took to ward off cancer costing about 3.5 cents a year to make.

    Then he told me he had been angered when his name had been taken off some scientific papers after he, in complete openness, told agencies and journals that he and his wife have set up a vitamin D company in Toronto called Ddrops Inc. She is now the company’s president and it sells a year’s supply of 1,000 IU liquid vitamin D for about $20. “I was told my name was being taken off papers because of my wife’s occupation. That is something I find infuriating and upsetting,” he said.

    A little additional research found that Elaine Vieth has told the Hamilton Spectator that pharmacies initially had little interest in selling her product, which can be sprinkled on food or in drinks, but that after the Creighton cancer study appeared she sold 30,000 bottles within two days.

    I am not often struck speechless by life’s contradictions, but here I am.Who would have thought that the research pertaining to what Ddrops markets as “the sunshine vitamin in just one drop” could be so conflicted?

    Nonetheless, let me be absolutely clear. I cannot say that any of the findings of any of the researchers I cite — particularly when it comes to vitamin D’s cancer preventative effects — are erroneous because of the scientists’ commercial connections. Vitamin D may indeed turn out to be the next best thing since free e-mail and ballpoint pens, but I will say that a careful journalist, a prudent journalist, a wise journalist would look at this tangled mess of conflicted interests and results and proceed exceedingly carefully in promoting a massive change in vitamin D dosage levels.

    I will say that Health Canada should not be stampeded into doing anything reflexive when it comes to raising vitamin D dosage levels.

    And I might also suggest that if university scientists are looking for a less conspiratorial explanation for their perception that media has been loath to join a crusade to raise the dosage levels, they would do well to consider how it looks to outside observers when researchers blithely associate with those who benefit financially from these changes.

    And that advice is good on both the sunniest and the cloudiest of days.

    In Strauss’ case, an inflamed Vieth wrote back in response to the piece, arguing that. “Is there any conceivable way that a new discovery in nutrition, health or therapeutics could make a difference to the public without involving a commercial interest? Compared to the private sector, government agencies usually move at a snail’s pace. If vitamin D is the example being discussed, then it is foolish to imagine that government will reflect anything newer than what was known ten years ago. Government does not make products for consumers. There can be no progress without the private sector.”

    I beg to differ. Mixing commercialism with science is a dangerous endeavor, one that is sure to mislead the public with biased opinions and deliberately cheerful results. It’s the attitude Vieth describes above that has taken the public to the place they are now. They are a group sadly misled by a handful of researchers who zealously advocate for their preconceived beliefs, while refusing to acknowledge even the most valid of scientific research if it proves them wrong.

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  • Filed under: featured articles, vitamin D
  • Disease or no Disease?

    A week ago, yet another study was published that casts serious doubt on a long-standing consensus among mainstream doctors and researchers – namely the idea if people are given extra vitamin D they will absorb more calcium, thus strengthening their bones.

    In a paper published in the Journal of Bone Mineral Research titled “Disease or No Disease?” researchers tested the effects of extra vitamin D on calcium absorption in a group of postmenopausal women. The women had been diagnosed with “vitamin D insufficiency” – a label given to those people mainstream medicine contends to have a “low” level of the secosteroid 25-D.

    The researchers put the consensus to the test by tracking the amount of calcium absorbed (called fractional calcium absorption) after subjects were administered 50,000 IU of vitamin D daily (a ridiculously high amount!) for 15 days. During the study, subjects also consumed their typical diet along with (44)Ca– the number 44 refers to the isotope of Calcium being consumed– orally with breakfast and (42)Ca administered intravenously each day.

    The team used a molecular technique called mass spectrometry to determine the amount of calcium in the subjects’ urine during the 15-day study period (urine samples were collected 24 hours a day). By keeping track of how much calcium each subject excreted, the team was able to subtract that amount from the level of the substance they ingested each day, allowing them to infer how much calcium had been absorbed by their bones.

    The data revealed that the rise in fractional calcium absorption after subjects ingested such massive amounts of vitamin D increased by only a paltry 3%, with a margin of error of 1%.

    According to the researchers, “in existing literature this small change in fractional calcium absorption does not associate with lower fracture rates nor consistently higher bone mass.”

    Such results make it crystal clear that even if postmenopausal women are given huge doses of vitamin D, the secosteroid will have no impact on their bone mass. And if 50,000 IU a day of “vitamin” D can’t increase calcium absorption by a statistically significant amount, then the average person popping even copious amounts of vitamin D tablets in the name of helping their bones is literally pouring money down the drain. The average vitamin D tablet contains about 400 to 1000 IUs of vitamin D, meaning that a person would have to consume well over 50 tablets a day in order to ingest 50,000 IUs of the substance.

    Hence the title of the team’s paper – “Disease or no disease?” Is vitamin D “insufficiency” really a problem?, the researchers ask. Are low levels of vitamin D something that should remedied or is it possible that levels are low for a reason, rendering supplementation useless and unnecessary?

    The answer to their questions lies in biomedical research Trevor Marshall’s recentBioEssays paper, which explains how the low levels of vitamin D observed in women with bone loss and other chronic diseases are a result rather than acause of the disease process. Vitamin D “insufficiency” is simply an indicator of Th1 disease, not a problem that needs to be remedied by supplementation. Imagine how the incidence of chronic disease would drop if all of mainstream medicine were able to embrace this alternate hypothesis.

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  • Filed under: vitamin D
  • Due to the hormonal changes that take place during recovery, many patients on the Marshall Protocol become sensitive to bright lights and sunlight. They are soon informed that dousing themselves with sunscreen does nothing to affect the production of vitamin D in their skin – hence the need to cover up with thick, dark layers when outside in the sun. “The majority of sunscreens are ineffective in blocking vitamin D production or blocking sun flare symptoms in Th1 patients,” states J.C. Waterhouse of Autoimmunity Research Foundation.

    Yet, proponents of high-dose vitamin D continue to blame what they interpret as vitamin D “deficiency” on the fact that the American public wears too much sunscreen. Because they mistakenly believe that sunscreen fully blocks vitamin D production, organizations such as the Vitamin D Council – an organization dedicated to promoting high levels of vitamin D – make a firm point of informing the public that, “The only way to be sure you have adequate levels of vitamin D in your blood is to regularly go into the sun, or use a sun bed (avoiding sunburn).”

    Yet dermatologists and other scientists who better understand the properties of sunscreen and vitamin D have been combating these claims for years – arguing over and over again that they are flat out wrong. Three years ago, at the American Academy of Dermatology’s Melanoma/Skin Cancer Detection and Prevention Month news conference, dermatologist Darrell S. Rigel, M.D., clinical professor, New York University Medical Center in New York City, did exactly that.

    Rigel’s message: sunscreens do NOT block all of the UV radiation hitting the skin, so that those wearing sunscreen are still able form vitamin D. There is simply no such thing as a total (or even near total) UV block. Even the most effective sunscreens currently on the market let through enough UV to allow for adequate vitamin D formation. According to Rigel, normal vitamin D levels are easily maintained through routine daily activities (even when wearing sunscreen) and a normal diet. “Supplemental vitamin D tablets are typically not needed,” states the scientist.

    To support his point he cited a 1997 study published in the Journal of the National Cancer Institute of patients with Xeroderma Pigmentosa (a disease that causes multiple skin cancers in persons exposed to the smallest amounts of ultraviolet radiation), who showed normal vitamin D levels despite virtually no UV exposure.

    Rigel went on to argue that no scientific studies exist which prove the statement that low vitamin D levels lead to increases in cancers and other diseases. “The claim is based on a study that finds that overall cancer rates are higher in the northeast United States, a location with lower sunlight levels than many other places in the country. Those making this claim conclude that since the Northeast has lower UV levels, this is the reason why cancer rates are higher in this region. However, several studies prove this theory is false,” says Rigel. These include studies which show that cancer rates are low in the Northern Plains states – areas of the United States that have lower UV levels then the states in the Northeast. Furthermore, several regional studies have shown that the increased levels of cancer observed in the Northeast states are tied to levels of industrial pollutants rather than levels of UV light.

    “When we take a close look at these myths and evaluate the facts, the course of action is clear,” said Dr. Rigel. “Until there is science that tells us otherwise, it is imperative that people protect themselves from the sun. Given the fact that the U.S. Department of Health and Human Services has declared UV radiation as a known carcinogen, exposing oneself to it for the sake of vitamin D is not the answer.”

    Rigel also challenged vitamin D proponents on their claim that skin cancer is not a dangerous disease, thus rendering protection from the sun unimportant. On the contrary, Rigel argued, one American dies every hour from melanoma, the most serious form of skin cancer.

    “As a dermatologist who treats the ravages of skin cancer on a daily basis, it is appalling to me that anyone in good conscience could make the claim that intentional sun exposure – for any length of time – is beneficial,” stated Dr. Rigel. “The fact is, skin cancer is increasing at an alarming rate and scientific research confirms that our best defense is avoiding excessive, unprotected sun exposure.”

    Dr. Rigel’s argument supports the fact that the low levels of vitamin D frequently observed in patients with chronic disease are not even the result of deficiency. As described by biomedical researcher Dr. Trevor Marshall in his upcoming paper “Vitamin D Discovery Outpaces FDA decision making”, the low levels of vitamin D observed in patients with chronic disease are simply a result of the fact that when the active vitamin D metabolite (1,25-D) rises as a result of bacterial-induced inflammation, it naturally downregulates levels of 25-D – the precursor form of the substance that is measured in order to detect “deficiency.”

    With this information at their disposal for over three years now, why do organizations such as the Vitamin D Council continue to blame what they incorrectly interpret as a “deficiency” of vitamin D among the American public on the use of sunscreen? Is it simply because if they acknowledge that the “sunscreen blocks vitamin D production” myth has been debunked, they will be at a loss to explain how the public could possibly be “deficient” in a substance that is so widely available? After all, the American diet is rich in vitamin D due to fortification of numerous products. Not to mention the reality that most people make about 10,000 units of vitamin D after about 20 minutes of summer sun -100 times more vitamin D than that needed to meet government nutritional requirements.

    Note: research by Dr. Waterhouse of Autoimmunity Research Foundation has shown that sunscreens containing the chemical zinc oxide do block vitamin D production in the skin to a certain extent. These sunscreens, particularly those with the highest zinc oxide content (17-20%) provide a means for patients on the Marshall Protocol to better tolerate the sun and participate in outdoor activities.

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  • About Amy Proal

    Amy and Zeus

    Amy Proal graduated from Georgetown University in 2005 with a degree in biology. While at Georgetown, she wrote her senior thesis on Chronic Fatigue Syndrome and the Marshall Protocol.