Bacteriality

Exploring chronic disease

Category: medical research

Second-guessing the consensus on vitamin D

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).
    []
  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). []

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!!”

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  • A “cure” to die for

    Several recent reports have made it abundantly clear that until drug companies understand the infectious pathogenesis of chronic disease, they will continue to churn out dangerous drugs with numerous side effects – drugs that only offer “Band–Aids” for symptoms at the cost of billions of dollars to the consumer.

    A few days ago, researchers at Stanford University released the results of a study that tracked the effects of a drug called Sutent on patients with kidney cancer or gastrointestinal stromal tumor (GIST). Sutent, which is widely being tested for the treatment of several other cancers, works by starving tumors — stopping them from growing blood vessels to feed themselves.

    Fifteen percent of study subjects taking Sutent developed heart failure, a chronic condition in which the heart loses its ability to pump blood properly. Sutent, made under the generic name sunitinib by Pfizer, has also been shown to damage heart cells.

    The study, presented at a meeting of cancer specialists, confirmed the results of previous studies, such as one published in the December issues of the Lancet, which found that half of 75 patients with GIST who took Sutent in a clinical trial developed high blood pressure, 8 percent developed heart failure, and two had heart attacks.

    Nevertheless, the American Society of Clinical Oncology still encourages the use of Sutent in patients with GERT and kidney cancer. Why? Because as they stated at a recent meeting, the drug causes “risky” but “reversible” side-effects. Apparently the council feels that while heart failure is serious, it can be treated with a variety of yet more drugs – each of which elicits its own plethora of side effects.

    How sad is the Society’s view on Sutent? The medical community’s ability to effectively treat patients with GERT and kidney cancer has sunk to such a low level that they are actually willing to give patients with the diseases a drug that will almost certainly destroy their cardiovascular system in the process of palliating their cancer. And cardiologists, the FDA, and the public actually accept this bleak reality, most without raising an eyebrow, because this is what we have come to expect from a medical world that fails to recognize bacteria at the heart of inflammatory diseases such as cancer.

    The Stanford study on Sutent came out just a week after Merck and Co., the makers of Vytorin, a combination of the cholesterol-lowering drug Zetia and the statin called Zocor, failed to meet the primary goal that the company intended – to slow the accumulation of fatty plaques in the arteries more than either drug alone.

    Similarly, a recent trial of Torcetrapib, a drug that both raises HDL and lowers LDL cholesterol, was halted midstream because the drug seemed to cause heart attacks and strokes rather than prevent them.

    Of course, Merck and Co are continuing to defend and promote Vytorin. The alternative is financial ruin. But the tragic reality is that even if Vytorin, Sutent, Torcetrapib, or any of the other drugs made by major drug companies end up pulling in less of a profit, they will make other palliative drugs in their place: drugs that still fail to target the root cause of chronic disease.

    When will mainstream medicine accept the reality that nearly all chronic inflammatory conditions can be treated with a selection of low dose antibiotics and one ARB? Few, if any side effects included.

    Certainly not while companies like Merck and Pfizer avert their glance from studies implicating bacteria in chronic disease and continue to churn out drugs that may kill patients but put money in their pockets. It certainly doesn’t help that the medical community and the public continue to maintain such low standards about how a drug should work – accepting as normal the idea that in many cases, even the dangerous side effects of a particular medication must simply be endured.

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  • For decades, scientists working with L-form bacteria have warned that the pathogens are not killed by the purification processes used when pharmaceutical companies creates vaccines. A recent drug trial by Merck and Co., Inc. suggests that the failure of mainstream medicine to take the presence of L-form bacteria seriously has put a large group of people of people for developing a wide range of chronic diseases.

    Several months ago, two international trials aimed at testing an experimental AIDS vaccine were stopped after it became clear that the vaccine did not prevent infection with the AIDS virus. The trials were conducted in the United States, Peru, Brazil, Dominican Republic, Haiti, Jamaica, Australia and South Africa. Today, the researchers conducting the trial are faced with another problem. Earlier this month they reported “worrying” indications that the thousands of people who received the vaccine are now at greater risk for infection. They have already begun counseling volunteers about the fact that they could be at higher risk for acquiring HIV – the fatal and incurable virus that causes AIDS.

    To test vaccines and new drugs, researchers always aim for what are called placebo-controlled, double-blinded trials. This means that neither the researchers nor the volunteers know who gets a placebo and who gets an active ingredient – the goal being to minimize any biases in determining whether the treatment works.

    But Merck and the academic researchers who conducted the vaccine trial are planning to “unblind” the study – meaning that participants will find out who got an active shot and who got a dummy injection.

    “All study volunteers will be encouraged to continue to return to their study sites on a regular basis for ongoing risk reduction counseling and study-related tests,” the researchers said in a statement.

    Were the vaccines contaminated with L-form bacteria? It’s quite probable. Especially since L-form bacteria are now known to create ligands that bind and block the Vitamin D Receptor (VDR). Since the VDR controls the activity of the innate immune system and the antimicrobial peptides, people who acquire L-form bacteria begin to suffer from immune dysfunction – much like the study participants in the trial described above.

    Ensuring that the vaccines, injections, and blood transfusions we receive are not contaminated by L-form bacteria only strengthens the reality that the pathogens need to be brought into the spotlight immediately. In the meantime, people such as those unlucky enough to receive the actual vaccine in the Merck trial will continue to get sick after taking a measure ironically aimed at preventing disease.

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  • What do Microsoft and medical research have in common?

    Let’s start with the simple fact that they have both been wildly successful. Microsoft has 79,000 employees, global annual revenue in the year 2007 exceeding $51 billion, and has made more than 12,000 of its employees millionaires simply by increases in stock valuation. Additionally, Microsoft’s market share for the operating systems on desktop computers, by one 2003 estimate, is 90%. Not bad for a garage startup.

    In the United States alone spending on medical research is at or near the $100 billion mark in the year 2007. That’s about $300 for every man, woman, and child and more than doubles what was spent just a decade ago. According to Dan Fox, president of the Milbank Memorial Fund, a philanthropic group that works on health policy issues, the data in a recent JAMA review makes it plain that “we are spending huge amounts of money, more than any other country, to develop new drugs and devices and other treatments.”

    Not bad for a profession that used to do double duty as barbers.

    But perhaps the strongest connection between the multinational and the medical profession may be that both are, in some very key respects, failures.

    Anyone who has ever seen the dreaded “Blue Screen of Death” or had their computer infiltrated by spyware, adware, or other kinds of malware knows the shortcomings of Microsoft software. Maybe Microsoft is an easy target for the technorati, too easy it would seem. But let’s face it– Microsoft has over the past few decades consistently churned out software which costs more, has more bugs, and hogs more memory than comparable software. Right up to the present, new software releases have been slow in coming and devoid of groundbreaking features. Certain releases, namely Windows ME and Vista– some versions of which retail in excess of $350– have inarguably added very little if anything to previous releases. One prominent commentator, John C. Dvorak, in his colorfully titled column, “Vista Death Watch” has argued that the latest operating system, Windows Vista should be completely scrapped.

    Modern medicine, specifically medical research, may be in the same boat. Let’s concede that we all are very pleased that medicine has advanced to the point that a burst appendix can be safely removed, catheters can spring open blood vessels, and that eliminating wrinkles surgically is just a series of injections away– and with a toxin no less!

    When it comes to chronic illness, at least in its traditional form, medicine has largely failed. According to mainstream medicine, what causes Parkinson’s Disease? What causes cardiovascular disease? What about fibromyalgia? Lyme Disease? Crohn’s, cancer, bipolar disease, depression? The consensus among medical researchers has been, “We don’t know.”

    Now, maybe these conditions are all too complicated to unravel over the course of mere decades even for a world that spends hundreds of billions on medical research annually. For that matter, maybe it’s the case that having stable software largely impervious to malware is no less a pipe dream.

    Even if these explanations are mostly true, the absence of real solutions for chronic illness is not good enough– not for the hundreds of millions of patients watching the best part of their lives pass them by. For all the sound and fury of medical discovery we catch wind of these days in breathless press releases (Eureka Alert!), what chronic diseases have been definitively cured in the last few decades? You can count them on one hand: stomach ulcers and cervical cancer.

    Few would argue that medical researchers aren’t highly intelligent and capable or that Microsoft’s software engineers are the same, or that both groups contain people who are quite possibly the most intelligent and the most capable at what they do. If a failure of smartness isn’t the problem, then what is?

    This essay examines the Open Source Software (OSS) movement as a model for a more evolved, more effective system of medical research. We look at four lessons from the OSS movement and try to apply them to medical research. Also, we look at how one treatment protocol for chronic disease, the Marshall Protocol, incorporates many of these lessons and may represent a model for future medical research in more ways than one.

    Lesson #1: Use open review.

    One of the most influential works in the history of open source development is Eric S. Raymond’s, The Cathedral and the Bazaar. In this essay Raymond argues that there are two contrasting software development models– the cathedral and the bazaar. In the cathedral model, represented by Microsoft, software is available for all to use, but the ability to contribute to the code is restricted to an exclusive group of developers– wizards Raymond calls them– who work in “splendid isolation.” In the bazaar model, the code for a project is developed over the Internet in full public view, Linux and Wikipedia being excellent examples. In theory, anyone so inclined can contribute.

    The cathedral model holds that the key to success of a software project is the judgment and experience of a limited group of well-vetted and talented experts. Most proprietary software is necessarily developed using the cathedral model. In contrast, the bazaar model says, “Let’s engage as many developers as are inclined and qualified to participate.” The theory here is that the mistakes and red herrings of inexperienced or confused contributors is more than counterbalanced by an ability to rapidly improve the code given the fact that, as Raymond puts it, “thousands of eager co-developers are pounding on every single new release.”

    Which model is more effective in software development? Raymond explains his thinking: “I worked hard… at trying to understand why the Linux world not only didn’t fly apart in confusion but seemed to go from strength to strength at a speed barely imaginable to cathedral-builders.” For Raymond, the advantage of transparency and openness is simple: “Given enough eyeballs,” he writes, “all bugs are shallow.”

    The track record of a number of large-scale projects like the production of an operating system such as Windows XP seems to support Raymond’s opinion. The day Microsoft released Windows XP, the company posted 18 megabytes of patches on its website: bug fixes, compatibility updates, and enhancements. Two patches fixed important security problems. Or actually, one of them did; the other patch didn’t work. Microsoft suggested that users back up critical files prior to installing the patches. Buyers of the home version of Windows XP, however, discovered that the system provided no way to restore these backup files if things went awry. As Microsoft’s online Knowledge Base blandly explained, the special backup floppy disks created by Windows XP Home “do not work with Windows XP Home.”

    Though it’s certainly not the case with all closed or proprietary software projects, really big systems are forever in danger of the “tar pit” as Fred Brooks called it in his book The Mythical Man-Month. A tar pit– I would argue that that phrase is as apt a description as any to describe the state of research into chronic disease.

    Is medical research a bazaar or a cathedral? At least when it comes to chronic illness, I think it’s pretty clear that it’s the latter– the reason being that the Academy is just not open enough to opposing ideas. The results, or lack thereof, speak for themselves.

    Not only are pulmonologists unwilling to consider infection as the cause of sarcoidosis, but many have actively suppressed publication of articles that are at odds with their points of view.One need look no further than the field of pulmonology. Not only are pulmonologists unwilling to consider infection as the cause of sarcoidosis, but many have actively suppressed publication of articles that are at odds with their points of view. Biomedical researcher Trevor Marshall, PhD, head of Autoimmunity Research Foundation explains, “Dr. Om Sharma from USC Medical Center has kept the lid on bacterial pathogenesis when dozens of researchers have implicated pathogens in the disease.” Marshall says, “Dr. Sharma has discouraged discussion about patients who received organs from people with sarcoidosis also developed the disease – evidence which strongly supports an infectious cause.”

    As is the case with a lot of these “experts,” Dr. Sharma has authored or co-authored over 500 journal articles, some 70 reviews and sits on the editorial board of all the key pulmonology journals. It’s this last line on Dr. Sharma’s resume that has allowed him to effectively act as a gatekeeper for new ideas about sarcoidosis. Yet, even now, there is growing evidence that Dr. Sharma is mistaken in the worst way. What provision does medical research have for reining in the myopia of the Dr. Sharmas of the world? Is it really acceptable for medicine to advance but one funeral at a time?

    Or, take the work of Dr. Alan Cantwell who has photographed L-form bacteria in the cells of people with cancer for decades now. Dr. Cantwell’s research into the so-called “cancer microbe” is strong. He makes a number of claims worth further investigation or, at the very least, outright rebuttal. Yet, the medical community has largely marginalized his work such that it hasn’t even attracted a fraction of the attention it deserves.

    According to Dr. Cantwell, most pathologists who saw his specimens would practically refuse to admit that what they were seeing was bacteria. Few, if any, were willing to co-author a paper to that effect. “For the most part,” Cantwell said, “they didn’t want to get involved.”

    Why the cold shoulder from all corners of medicine? Is it because we have figured out the “true cause” of cancer? Well, that’s not the case. Though we certainly know how diet and heredity can effectively change the odds, we still have only the faintest understanding of what actually causes cancer. Or, is it true that it’s simply impossible that bacteria can exist in the size and shape described by Cantwell? No, there’s no reason to think that it’s not bacteria, specifically L-form bacteria, to blame. Entire textbooks, namely Lida Mattman’s Cell Wall Deficient Forms– Stealth Pathogens, now in its third edition, have been devoted to the culture and life cycle of L-form bacteria.

    Dr. Cantwell was asked to explain his colleagues’ refusal to entertain the idea that bacteria may be involved in cancer. He responded, “I think it’s because finding bacteria in illnesses that are not [thought to be] attributed to infection is highly controversial, and most doctors shy away from controversy.” But if that’s what it takes to open up the dialogue, isn’t controversy exactly what sufferers of chronic disease need?

    If you paid attention to your bulk mail announcing fundraisers, you’d think that the only reason diabetes or sarcoidosis or any number of other diseases have not been cured is a lack of funds for research. This, in spite of the fact that the National Institute of Health alone spends $28 billion annually on medical research.

    You could spend ten times as much money on medical research and without changes to the process of how ideas get considered, that money would be better used as wallpaper.You could spend ten times as much money on medical research and without changes to the process of how ideas get considered, that money would be better used as wallpaper. One of the enduring lessons of open source software development is that the best way to tame complexity is to open up the discussion to as many people and ideas as possible.

    Andrew S. Grove is founder of the computer chip maker Intel. Now Grove is suffering from Parkinson’s Disease and a medical system that continues to test drugs on rats in the laboratory but offers little, if any, medical options for human beings who suffer from Parkinson’s and other chronic diseases. Recently, Grove has been publicly critical of the biomedical establishment, particularly academic researchers, who while successful in getting NIH grants and publishing research papers, seem to have little regard for whether their work leads to ideas or treatments that can actually cure disease.

    “The peer review system in grant making and in academic advancement has the major disadvantage of creating conformity of thoughts and values,” Grove told a correspondent from Newsweek. “It’s a modern equivalent of a Middle Ages guild, where you have to sing a particular way to get grants, promotions and tenure. The pressure to conform [to prevailing ideas of what causes diseases and how best to find treatments for them] means you lose the people who want to get up and go in a different direction. There is no place for the wild ducks. The result is more sameness and less innovation. What we need is a cultural revolution in the research community, academic and non-academic.”

    It should be a no-brainer: medical research, particularly when it comes to chronic disease, ought to be more like a bazaar. You could start with peer review. Peer reviewers are often well-intentioned, but the fact that only two or three anonymous “experts” can act as gatekeepers for what gets published in prestigious journals severely limits the dialogue. Let’s allow increasing numbers of self-selected people– amateurs, volunteers, marginalized scientists– to critique work too. Let’s then publish all reviews, positive and negative, online. To the extent that we can make medical research less like a guild, let’s do that too. Too often grants are awarded on the basis of past success in winning a grant. Do we really want to continue to reward old ideas? Not when those old ideas are failures! Is that any way to foster new ideas and new approaches? After all, until a researcher succeeds in curing a chronic disease, he is neither an authority nor an expert.

    Lesson #2: Write software for yourself.

    In 2005, BMG Music Entertainment started selling CDs that came with copy protection software. Unbeknownst to users, this software contained an evil bit of code called a rootkit. Rootkits are a set of programs or instructions that effectively subvert control of an operating system from its legitimate users. They might allow a third party to install keyloggers monitoring bank account information or turn your computer into a zombie and have it send out thousands of spam email messages. According to security researcher Dan Kaminsky more than half a million machines were infected by the rootkit. Since then, Sony BMG has been the subject of numerous lawsuits and eventually had to settle in a national class action suit.

    What would drive Sony BMG to include rootkits with their CDs to say nothing of notoriously restrictive copy protection software? It all has to do with the bottom line. The rootkit was Sony’s heavy-handed way of preventing users from copying songs they had purchased. For the multinational conglomerate, the bottom line was protecting the profitability of their music artists even if it meant trampling consumers’ rights.

    But, if you’re an open source software developer, your bottom line is straightforward as can be: solving your own technical problems. Eric S. Raymond writes in The Cathedral and the Bazaar, “Every good work of software starts by scratching a developer’s personal itch…. too often software developers spend their days grinding away for pay at programs they neither need nor love.”

    What if everyone researching Crohn’s Disease had Crohn’s Disease? What if all those investigating bipolar had that illness? How would research change?The open source model has been successful time and again.AWStats, the excellent log analysis program, was written by developers who needed to know the makeup and characteristics of visitors to their websites. VLC Media Player was written by programmers who wanted to play back a range of audio and video codecs unrestricted in the way that Windows Media Player or even iTunes is. It’s laughable to think that any open source developer would include anything on par with Sony BMG’s 2005 fiasco.

    So, what if everyone who studied a chronic disease had that chronic disease? What if everyone researching Crohn’s Disease had Crohn’s Disease? What if all those investigating bipolar had that illness? How would research change?

    To paraphrase Samuel Johnson, nothing focuses the mind so much as a trip to the gallows. In sum, I think you would see a greater sense of urgency, a better openness to new ideas, and an increased willingness to do away with ideas that have gone long past their expiration date (more on this last one later).

    The remarkable thing about being a researcher of chronic disease is that you can spend entire careers without actually contributing anything useful to the understanding of it.

    It’s not the fault of researchers, necessarily. It’s the way these professionals are rewarded for their contributions. As it stands, developing and investigating bonafide cures for chronically sick patients can all too easily take a back seat to getting published, getting funded, and getting promoted– “time, tender, and tenure,” Thomas Goetz calls it. As it stands, you are more likely to get funded if you have gotten funded. As it stands, you are encouraged to publish research which has positive results, even with the most tepid, toothless conclusions, because positive results get published.

    If there was the least bit of urgency, you might see the serious reconsideration of a variety of treatments, starting with the use of corticosteroids for sarcoidosis. The 2003 ACCESS study, which was funded by the NIH, shows that two-thirds of sarcoidosis patients do not get better on current treatments and those that do see improvement are in no way correlated to whether or not they received treatment.

    Given all this, you would think researchers would be interested in any broad reconsideration of what causes sarcoidosis. One such idea that sarcoidosis is actually an infection has been posed by Trevor Marshall among others. In fact, since 2002 when the Marshall Protocol treatment was first published– open source style, online– many patients have claimed recovery on the antibiotic-based treatment. Strangely, the response from sarcoidosis doctors, primarily pulmonologists, has been lukewarm at best. “We’re not even on their radar,” Marshall has said of the pulmo doctors.

    You would think that a new idea such as this one, which was backed by molecular data, would receive less of a chilly reception. You would think that this is exactly the kind of big idea sarcoidosis researchers should be looking for. If it was their own skin at stake maybe they would.

    Lesson #3: Openly and honestly size up failure.

    When it comes to chronic disease, there is no failure more categorical, more disastrous than the autoimmune model of illness. Autoimmunity is the idea that– contrary to the forces of natural selection or the dictates of basic common sense– the immune system *somehow* goes haywire and attacks the body.

    One way to measure the worth of a theory in medicine is to gauge how that theory can functionally improve what should be everyone’s ultimate bottom line: patients’ health. In short, all the anti-inflammatory, immunosuppressive, and palliative medications given to those suffering from “autoimmune illnesses” are failures. If I were being paid by the word, I could list hundreds of first line anti-inflammatory, immunosuppressive drugs that don’t cure hundreds of chronic diseases. Corticosteroids do not cure sarcoidosis. Neither hydroxychloroquine nor cyclosporine cures lupus. Prednisone does not cure multiple sclerosis.

    Of this class of drugs meant to treat autoimmune illness, prednisone is typical. Patients taking prednisone complain of weight gain along with any number of other symptoms including itching, increased sweating, irregular or absent menstrual periods, inappropriate happiness, and irregular heartbeat– and that’s just symptoms beginning with the letter I!

    First proposed in more general terms by Paul Ehrlich more than 100 years ago (horror autotoxicus he called it), this theory of autoimmunity has had a lot of time to be tested and refined. Instead, further investigations have only rendered the concept of autoimmunity more flawed and more complicated. Wikipedia lists five theories about what causes autoimmunity: the clonal deletion theory, the clonal anergy theory, the idiotype network theory, the clonal ignorance theory, and the suppressor population theory. What do all these mean?… Does it matter? The point is, as an idea, autoimmunity is a failure.

    A healthy sense of proportion– some would call it succumbing to realism– is much more common in the realm of programming especially of the open source variety. In fact, one of the colorful but enduring proverbs of the programming world, seen in a variety of forms is, “All software sucks.”

    Ron Avitzur has said during the development of his groundbreaking piece of software called Graphing Calculator that if your software was exceptional, fellow engineers would simply say, “This sucks less.”

    Maybe if the medical research community could be a bit more philosophical about failure, certain ideas that have gone long past their expiration, namely autoimmunity, could have been unceremoniously discarded long ago. Some would argue that any kind of operating system Microsoft produces is doomed to be underwhelming given its tens of millions of lines of “legacy code,” and maybe that’s not such a bad analogy for the concept of autoimmunity as they both share any number of fundamental flaws.

    Maybe if the medical research community could be a bit more philosophical about failure, certain ideas that have gone long past their expiration, namely autoimmunity, could have been unceremoniously discarded long ago.The problem for medical research is that it has made little to no provision for failure. With certain notable exceptions (i.e. Journal of Negative Results in Biomedicine) journals tend not to publish negative results, a phenomenon known as publication bias. The media tend not to cover studies showing the absence of a connection.

    If a negative result is based on good science, why confine it to obscurity? Why would we want to, in essence, encourage researchers to produce positive results even if those results make no significant contribution? You get what you ask for, and our system is, in essence, asking for such results.

    One thing medicine might quickly discover if, as a whole, it better embraced failure is just how ineffectual old approaches to chronic disease have been.

    Lesson #4: Seek to rapidly deploy multiple versions of software by iterating incrementally and openly.

    While Andrew S. Grove was at Intel, the number of transistors on a chip has gone from about 1,000 to almost 10 billion. Over that same period, the standard treatment for any number of chronic diseases has remained unchanged: L-dopa is still the standard treatment for Parkinson’s just as it was nearly half a century ago.

    “I picked the semiconductor [transistor] industry because it’s the one I know; I spent 40 years in it, during which it became the foundation for all of electronics. It has done a bunch of unbelievable things, powering computers of increasing power and speed,” says Grove.

    So, twelve years ago, when Grove was diagnosed with prostate cancer he immediately jumped into the advocacy movement, with the expectation that quick, deliberate action could push scientists in the field of cancer research in the same way that a drive for innovation and knowledge had inspired his team at Intel. But nothing happened. “I got disappointed with the lack of real output,” says Grove. “Not much has changed 12 years later.”

    In the last 20 years, there are only two common chronic illnesses for which the cause has been established. I’m thinking here about cervical cancer, caused by the human papillomavirus, and ulcers also found to be caused by bacteria. Is this pace acceptable?

    In January of 2007, Scott Rosenberg wrote a piece about the debacle that is Microsoft Vista. First began in 2002, the development of Vista was beset by a series of problems. Microsoft developers were ultimately unable to execute the original grand vision, which included a complete file system overhaul. As a result, the new operating system came in much later than scheduled and lacked many of the originally promised features. Rosenberg’s analysis: without discipline “too often, software teams get lost in what are known in the field as ‘boil-the-ocean’ projects — vast schemes to improve everything at once.”

    Where did Microsoft go wrong? Some of the failures of process are touched upon elsewhere in this essay, but I would suggest here one of those problems was an inability to iteratively build upon their project by harnessing the power of their natural community, their end users.

    Those who follow software development are familiar with the idea of “perpetual beta,” or that certain software is always being added to and improved upon. Popular examples of software that have had the label of perpetual beta include Gmail, Google Maps, and del.icio.us. For many developers, “perpetual beta” is an attitude as much as anything. It starts with the assumption that software should be better. Changes are rapid, but incremental. Testing and assessment are done frequently.

    Even those of us eager for cures to chronic disease recognize that magic bullets do not magically arise as if willed to exist. They need to be worked on, worked over, the subject of productive consideration. Dialogue is the order of the day.

    Jean-Claude Bradley practices something he calls open notebook science, which he describes as making his online laboratory notebook freely available and indexed by common search engines. The underlying philosophy, Bradley says, is as pithy as it is bold: “No inside information.” On his UsefulChem blog he and his collaborators share and discuss chemistry problems and on his UsefulChem wikiobservations from experiments in excess of 150 are described and logged.

    What do third parties do with this data? Maybe nothing. But then again, perhaps a failed experiment or an unanswered question– the programming equivalent of a feature request made before the open source community– could spark progress. It could be the key to new advances and new understanding.

    Bill Hooker on the excellent 3QuarksDaily blog writes that “From our current perspective we cannot predict more than a fraction of the ways in which openness will transform the culture and practice of science.” The advent of collaborative science and the openness that drives it has the potential to help us refine our understanding of medicine at increasing speed.

    We cannot predict more than a fraction of the ways in which openness will transform the culture and practice of science.A prime example of this openness is the world of genomics. Right now, anyone anywhere can search NCBI’s online gateway Entrez and dig into any number of mRNA, genomic DNA and protein sequences using some thirty interconnected and all freely available databases. It’s easy to see how these kinds of resources made freely available can really allow researchers to rapidly and iteratively build knowledge.

    Even in the field of chronic disease, we have seen promising developments where clinical data is posted online and made freely available for inspection. I’m speaking here about the Marshall Protocol site. As of December of 2007, the MP site has 5,000 members and 125,000 posts, the vast majority of which come in the form of self-reported statements of progress. When it comes to the sheer scale of open clinical experiments, the MP may be in a class of its own.

    Patients suffering from a variety of chronic diseases including fibromyalgia, sarcoidosis, multiple sclerosis, even autism are on the Marshall Protocol, a novel antibiotic-based treatment for chronic diseases which is in some respects the original inspiration for this essay. Using instructions that can be downloaded from the web, patients work in conjunction with their prescribing physicians to put the Protocol into practice: avoiding vitamin D and taking low-dose pulsed antibiotics as well as Benicar, a Vitamin D Receptor agonist.

    While the science behind the Protocol hasn’t changed much since 2002 when it was first made available to patients, the site is designed so that each patient reports symptoms and reactions to medications in a weekly progress report entry. Not only are these progress reports open to other patients who can ask questions about data, or on occasion offer advice, but they are also open to analysis by the FDA (who actively monitor the site) or any other health care agency, think tank or organization who wish view the data. Any doctor, scientist, or medical researcher can become a member of a special forum for medical professionals, which not only allows them to view progress reports, but gives them a place to actively engage in discussions about specific cases and share ideas about treatment and research.

    Another indication of this study site’s uniqueness is the chance to get feedback on one’s progress from nurses and researchers including, often enough, from the originator of the Protocol, Trevor Marshall. In fact, this is very similar to the open source software community where end users can be in direct contact with the developers from whom they downloaded the source code.

    This is in marked contrast to most other treatments where a patient’s reactions usually do not go much farther than the doctor’s office. Under such circumstances, each separate case history ends up in a different place, almost always at a metaphorical dead end. Such reports go hidden from the eyes of the public, other researchers, and medical professionals who might under many circumstances offer important feedback or learn something.

    With open clinical data, such as the kind on display atwww.MarshallProtocol.com, patients can discover a thing or two from researchers themselves but also from each other. How will I react to Benicar? Have patients who share my condition really experienced the telltale reaction to antibiotics? These are all questions that can be effectively and convincingly answered by fellow patients. Such insights make a tough treatment that much more manageable, and it’s the openness that allows it.

    Who can use this study site? The science behind the MP has broad application, so a range of patients with different conditions can participate. Almost no one is turned away. This is quite different from other clinical trials in which participants are required to fit specific inclusion criteria with the aim of accumulating the most homogeneous group possible.

    Had the Marshall Protocol followed that model, how much longer would it have taken to confirm that the Marshall Protocol works to treat other diseases besides sarcoidosis? Surely, since Marshall’s first model was based on sarcoidosis, any other clinical trial model would have carefully excluded patients with other diseases, ailments, and symptoms. But it was by allowing patients with a wide array of symptoms to join his open internet-based site that Marshall soon collected data demonstrating that symptoms other than those related to sarcoidosis respond to Benicar and antibiotic therapy – a reality that would have taken decades for a standard clinical trial to reveal.

    A parting thought

    If the research medicine were anything like the open source software movement, study sites like Marshall Protocol.com would be springing up left and right as other researchers jumped on the possibility that their data might also have a greater impact if freely available on the Internet. You might also see a greater number of bad ideas relegated to historical curiosity.

    Medical research today has all the turning radius of an oil tanker. As a whole, it is too slow to accept and instigate positive change, and any sensible person would be right to lay a good chunk of that blame on the process itself.

    Innovation: how can researchers better innovate in the field of chronic disease? I argue that when it comes to innovation, the open source software community is particularly inspired– and instructive.

    For those of us who truly care to fight chronic disease, what lessons can we learn? Release early and often. Iterate. Practice openness to the point of promiscuity. Collaborate. Embrace failure. No failed or failing system has to be as it is. We can be worlds more productive. Let’s get to work.

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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.

    Amy has spoken at several international conferences and authored several peer-reviewed papers on the intersection of bacteria and chronic disease.

    If you have questions about the MP, please visit CureMyTh1.org where volunteer patient advocates will answer your questions. Another good resource is the MP Knowledge Base, which is scheduled to be completed within the next year.