FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, Oct 1, 2018

Vitamin D acceptance delayed by Big Pharma following the Disinformation Playbook

Commentary by William B. Grant, Ph.D.

(OMNS Oct 1 2018) A "Disinformation Playbook" has been used for decades by corporations to delay government action on matters of public interest that would adversely affect their income and profit. Some well-known examples include the big tobacco companies, the coal and oil industries, the sugar industry, and the National Football League. The Union of Concerned Scientists has outlined five "pillars" of the Playbook [Disinformation Playbook], [Alvord 2017]. Big Pharma may be using the Playbook to slow the adoption of strong support for vitamin D. This article is the product of my further analysis.

The Disinformation Playbook

1. The Fake
Conduct counterfeit science and try to pass it off as legitimate research.

2. The Blitz
Harass scientists who speak out with results or views inconvenient for industry.

3. The Diversion
Manufacture uncertainty about science where little or none exists.

4. The Screen
Buy credibility through alliances with academia or professional societies.

5. The Fix
Manipulate government officials or processes to influence policy inappropriately.

Background and evidence that vitamin D improves health outcomes

Big Pharma and its allies in the U.S. and perhaps also in Europe are opposing major recommendations for increases in vitamin D intakes and higher serum 25-hydroxyvitamin D [25(OH)D] levels [above 30 or 40 ng/ml (75-100 nmol/l)], apparently because such measures can significantly reduce the burden of human disease and, therefore, would reduce income and profit from treating disease. Healthcare in the U.S. now consumes almost 20% of the gross domestic product.

Historically, vitamin D was associated with prevention and cure of rickets and osteomalacia, and later with calcium absorption and bone health. In the past two decades, evidence has accrued showing that higher 25(OH)D serum levels from diet, supplements, and/or solar UVB exposure, are associated and mechanistically linked to better health and longer life expectancy.

In 2009-2010, the Institute of Medicine (IOM) reviewed the evidence regarding vitamin D, and was instructed by the study sponsors, the Food and Drug Agency, the National Institutes of Health, and Health Canada, to use only the evidence from published high-quality vitamin D randomized controlled trials (RCTs). However, by that time, such trials had only found benefits for bone health. From these studies it was known that bone health 'normalizes' above 25(OH)D levels of~20 ng/ml (50 nmol/l). However, they also used evidence from purely observational studies to suggest that there were risks associated with vitamin D supplementation that raised serum 25(OH)D levels above 30 ng/ml [Ross, 2011a]. This was the basis for their hypothesis of a U-shaped serum 25(OH)D level vs. health outcome relationship (higher risk for both low and high levels). However, this concern was later shown to be largely unfounded since most of the studies reporting U-shaped risk vs. serum level had no data for subject vitamin D supplementation, or for when it had started, thereby confounding subject stratification [Grant, 2016].

Over the last two decades, evidence has accumulated that UVB exposure and vitamin D have many non-skeletal health benefits, mainly from ecological and observational studies and from mechanistic evidence. Recent evidence has accumulated from vitamin D supplementation studies, especially those showing a correction of deficiency [Martineau, 2016]. Such evidence is now strong for cancer [Moukayed, 2013], [Grant, 2017], [Grant, 2018], [McDonnell, 2018], cardiovascular disease [Zhang, 2017], [Wimalawansa, 2018], respiratory tract infections [Martineau, 2017], all-cause mortality rates [Grant, 2011], [Garland, 2014], [Grant, 2016], [Lindqvist, 2016], and pregnancy and birth outcomes such as preterm birth [McDonnell, 2017], [Wagner, 2018] and as now widely reviewed [e.g. Holick, 2007; Pludowski, 2013; Baggerly, 2015; Grant, 2018; Page, 2018; Sorenson and Grant, 2018].

Recommended vitamin D intakes and optimal 'target' serum 25(OH)D levels have increased since the IOM report. For example, The Endocrine Society subsequently recommended 1000-4000 IU/d (25-100 mcg/d) vitamin D supplement intakes and serum 25(OH)D levels >30 ng/ml (75 nmol/l) for patients with baseline insufficiency [Holick, 2011]. A more recent review of vitamin D supplementation guidelines also recommended >30 ng/ml [Pludowski, 2018]. However, such recommendations may be replaced in the near future by those recommending >40 ng/ml based on studies such as those reported recently for preterm birth [McDonnell, 2017] and breast cancer [McDonnell, 2018]. One reason for the low earlier recommendations was the large underestimate made by the IOM in calculating intakes for the average population, (i.e. in 50% of the population) rather than for 97.5% of the population for whom the recommendations were presumed to be aimed [Veugelers & Ekwaru, 2014].

Of course, Big Pharma and its allies must follow current research findings on vitamin D with trepidation since they also realize that the general public also follows the research and has increased its rates of self-supplementation with > 1000 IU/d vitamin D from 0.2% of the population in 2001-2002 to 18.2% in 2013-2014, and that supplementation with >4000 IU/d has also increased from 0.2% in 2007-2008 to 3.2% in 2013-2014 [Rooney, 2017].

Examples of the use of the five pillars of "The Disinformation Playbook" on Vitamin D

1. The Fake
Below are some papers reporting no benefit from vitamin D supplementation due to methodological flaws. These examples are for health outcomes for which well-designed and conducted studies have shown benefits.

JAMA recently published the results of a vitamin D plus calcium clinical trial using 2000 IU/d vitamin D3 plus 1500 mg/d calcium [Lappe, 2017]. The trial did not find a significant all-cancer risk reduction based on intention to treat (i.e. comparing outcomes on those who received the supplements vs. those who received the placebo) [Grant, 2017]. However, the trial did find a significant reduction in all-cancer incidence for those who achieved a level of >50 ng/ml 25(OH)D, despite the study being somewhat underpowered. But the journal did not let the authors present or discuss that finding in the printed paper, relegating the latter analysis on subjects who achieved repletion to an online supplement for the paper, which few people read, and issuing a press release stating that vitamin D supplementation did not reduce the risk of cancer [JAMA Media Advisory, 2017].

Cochrane systematic reviews were carried out that omitted some clinical trials with positive results. Thus, a Cochrane review of vitamin D supplementation during pregnancy published in November, 2017, found "There was no effect on preterm birth" and concluded "The evidence to date seems insufficient to guide clinical or policy recommendations." [Roth, 2017]. Overlooked in this review was mention of a paper published in July, 2017, that found a 60% reduction in preterm birth rates for those in a supplementation study who achieved >40 ng/ml [McDonnell, 2017],

2. The Blitz
The New York Times published a hit piece on Michael Holick by Liz Szabo of Kaiser Family Foundation on August 18, 2018. "Vitamin D, the Sunshine Supplement, Has Shadowy Money Behind It: The doctor most responsible for creating a billion-dollar juggernaut has received hundreds of thousands of dollars from the vitamin D industry." [Szabo, 2018]

This opinion piece took aim at Dr. Holick because he is considered the person most responsible for raising public awareness of the benefits of UVB exposure and vitamin D. The opinion piece agreed with the IOM report that vitamin D was good for bone health, but dismissed other benefits through quotes from three IOM committee members [JoAnn Manson, Clifford Rosen, and Catherine Ross]. It also stated "A Miracle Pill Loses Its Luster; Enthusiasm for vitamin D among medical experts has dimmed in recent years, as rigorous clinical trials have failed to confirm the benefits suggested by early, preliminary studies." However, it did report that some people in the "wellness-industrial complex," such as Professor Walter Willett of Harvard, support supplementation with vitamin D.

The main thrust of the opinion piece was to attack Dr. Holick for receiving several hundred thousand dollars from the vitamin D industry, including the indoor tanning industry, pharmaceutical companies and Quest Diagnostics, a major supplier of 25(OH)D assays. It is not unethical to be paid for one's work. It is, however, unethical not to disclose in journal publications any competing interests such as funding from the industry that might benefit from the publication. Dr. Holick has freely acknowledged his support from the vitamin D industry as he did in the Endocrine Society vitamin D guidelines paper [Holick, 2011].

While several vitamin D researchers submitted letters to the editor about the above publication, none were published. The submitted letters supported Dr. Holick and vitamin D supplementation. Here is the text of one submitted by Cedric F. Garland, Dr. P.H. and Camillo Ricordi, M.D.

"The New York Times is the beacon of truth. But we were shocked by an article (Aug 18) by Liz Szabo. Masquerading as exposé, it unfairly accused Dr. Michael Holick, who helped discover a form of vitamin D, of mostly monetary motivation. Dr. Holick's discovery of an important biomarker has enabled thousands of epidemiological studies. Using this biomarker, members of our group discovered that vitamin D3 helps prevent colorectal cancer, and, along with British researchers, that it also reduces the risks of breast cancer. Recently other investigators also have found that vitamin D reduces risk of diabetes and coronary heart disease, and reduces prematurity. These compelling findings suggest a vitamin D deficiency 'syndrome' based on converging data from hundreds of studies. The cost of correcting underlying vitamin D deficiency would be miniscule compared to the cost of drug treatment for cancer and diabetes. This article is, therefore, misleading. Dr. Holick is an honest, and widely respected researcher. If readers stop taking vitamin D based on this article, it would do great harm to the public health."

Letters to the editor are an important avenue for countering bias, misstatements, and omissions in newspapers and professional journals. To deny publication of such letters is poor journalistic practice, and in this case, considering the importance of vitamin D to the public, it is immoral. The most likely reason the Times did not publish any letters in response is that the revenue from Big Pharma for advertisements is a large part of its revenue.

Michael Holick is no stranger to controversy. In 2004, he was fired from Boston University's department of dermatology by Dr. Barbara Gilchrest, who was head of the department. "She called me into her office and said that she couldn't have somebody in her department recommending sun exposure." [Saul, 2006; Solomon, 2010]. Dermatologists advocate avoidance of indoor tanning devices and use of sunscreen as a way to reduce the risk of skin cancer and melanoma. They rarely consider the role of UVB exposure in producing vitamin D3, or, if they do, state that the little amount of vitamin D required (for bones) can be obtained though a few minutes of solar UVB exposure to the head and arms or diet. This, of course, is known to be inadequate, especially during the winter months and for those who have dark skin. That is the rationale for the need to take supplements.

3. The Diversion
This approach was explored in great detail by Naomi Oreskes and Erik M. Conway in their book Merchants of Doubt [Oreskes & Conway, 2011].

It has also been said that observational studies on vitamin D supplementation are invalid since they are not supported by randomized controlled trials. For example, the untested hypothesis goes, this must mean that low 25(OH)D is a result of disease, rather than a cause [Autier, 2014, Autier, 2017]. However this hypothesis has been debunked. "Published RCTs have mostly been performed in populations without low 25OHD levels. The fact that most [meta-analyses) on results from RCTs did not show a beneficial effect does not disprove the hypothesis suggested by observational findings on adverse health outcomes of low 25OHD levels." [Rejnmark, 2017]

In addition, many vitamin D clinical trials, including major ones currently underway, have not been based on measurements of the 25(OH)D level, but instead on the use of a single-sized dose of vitamin D. The reason for this is that they are based on the guidelines for clinical trials of pharmaceutical agents, which assume that 1), the trial is the only source of the agent; and 2), that there is a linear dose-response relationship. Yet neither assumption is satisfied for vitamin D. There are several sources of vitamin D including UVB exposure, diet, and supplements. Also health effects are not directly related to the dose of vitamin D (which is inert), but instead derive from the serum level of 25(OH)D, with large variations in outcomes with increases in initially low 25(OH)D at low levels, but reduced variation in outcomes with changes in higher 25(OH)D levels. Thus, clinical trials should be based on measurements of serum levels of 25(OH)D, not on vitamin D dosage [Heaney, 2014], [Grant, Boucher 2018], and open-label trials looking for significant health benefits in which participants know they are taking vitamin D and have sequential serum 25(OH)D measurements [McDonnell, 2017, McDonnell, 2018].

Other authors have implied that "vitamin D" is just another vitamin by designing studies as if it were a true vitamin [Fortmann, 2013], [Misotti, 2013] when, in fact, vitamin D is a hormone precursor provided either in the diet or made in the skin through the action of UVB on 7-dehydrocholesterol, though the definition of vitamin is a substance required for life that is NOT produced in the body. However, the definition of hormone is a regulatory substance produced in an organism and transported in tissue fluids to stimulate specific cells or tissues into action. Nearly every cell has a vitamin D receptor coupled to chromosomes. When the hormonal metabolite of vitamin D, 1,25(OH)2D, binds to the vitamin D receptor, gene expression can be up- or down-regulated.

4. The Screen
'Big Pharma' contributes to all major disease organizations, and none of these endorse vitamin D supplementation. In support of this statement, Google searches were conducted for corporate sponsors of some of the major disease-centered organizations in the U.S.

None of these organizations have position statements on vitamin D supplementation, based on a recent review of guidelines for vitamin D supplementation [Pludowski, 2018].

Disease organizations and pharma corporations that do not endorse vitamin D supplementation:

American Academy of Dermatology 2018 Corporate Partners:
The corporate partners are ordered by amount given to the Academy from Diamond (high) to Bronze (low).[American Academy of Dermatology, 2018]

Diamond

AbbVie, Lilly USA, LLC, Pfizer Inc., Sanofi Genzyme and Regeneron

Sapphire

Bristol-Myers Squibb Company, Celgene Corporation, Novartis

Ruby

Allergan, Amgen, Galderma Laboratories, L.P., LEO Pharma Inc., Merz North America, Inc., Ortho Dermatologics, SUN Dermatology, UCB Inc

Emerald

Bayer HealthCare | Coppertone, Janssen Biotech, Inc

Bronze

Aclaris Therapeutics, Inc., CareCredit, Dermira Inc., Endo Pharmaceuticals, Ferndale Pharma Group, ZO Skin Health, Inc. by ZeinObagi, MD

Supporters up to $24,999

Almirall, Amazon, EltaMD, Inc., Genentech, Great Lakes Advisors, JP Morgan, La Roche-Posay, SkinFix, Suneva Medical, UniteRx, Women's Health Magazine

American Cancer Society
Anthem BlueCross, BlueShield, CVS Health, Abbott Laboratories, Avon, Lilly, Merck, United Health Group, Walgreens, Walmart.[American Cancer Society, 2018]

March of Dimes
The March of Dimes is well-known for playing a role in ending the polio epidemic in the U.S. After that role, it turned its attention to reducing the rates of birth defects and premature births. GrassrootsHealth.net and vitamin D researchers at the Medical University of South Carolina showed that raising serum 25(OH)D concentrations of pregnant women early in pregnancy lowered the multi-racial preterm birth rate in Charleston County, SC (7.3% compared to 13.4% ) [Wagner, 2016]. Carole Baggerly of GrassrootsHealth.net told me recently that the March of Dimes is unwilling to discuss vitamin D supplementation for pregnant women.

Much of its support comes from Big Pharma: In 2012, the March for Babies national sponsors included their number one corporate supporter Kmart, along with top supporters of Farmers Insurance Group, Cigna, Famous Footwear, Sanofi Pasteur, FedEx, Mission Pharmacal, Watson Pharmaceuticals, First Response, and United Airlines.[March of Dimes, 2012]

A news account in Science August 10, 2018, reported that the March of Dimes curtailed support for 37 of 42 recipients of individual research grants due to reduced income [Servick, 2018].

National Medical Association
Abbott Laboratories, Amag Pharmaceuticals, Arbor Pharmaceuticals, Boehringer Ingelheim, Celgene, Gilead, Lilly, Merck, Novo Nordisk, Pfizer, UnitedHealth Group [National Medical Association, 2018]

Medical schools

Big Pharma also gives millions for research to medical schools. As a result, professors and students devote much of their time and effort to researching and promoting pharmaceutical drugs. This means that adequate health maintenance and disease prevention through lifestyle choices, nutrition, and vitamins, is rarely taught.

"Historically, nutrition education has been underrepresented at many medical schools and residency programs. Our surveys over a decade show that most medical schools in the United States are still not ensuring adequate nutrition education, and they are not producing graduates with the nutrition competencies required in medical practice. Physicians, residents, and medical students clearly need more training in nutrition assessment and intervention." [Adams, 2010].

Medical journals

Big Pharma also places many ads in medical journals and other media, thereby buying acceptance of the pharmaceutical drug model. Some journals manifest an anti-vitamin D bias:

JAMA; the editors of JAMA made the authors of the paper reporting results of vitamin D plus calcium supplementation to reduce risk of cancer [Lappe, 2017], discussed above, bury their most important finding in an online appendix with the excuse that since evaluating results in terms of 25(OH)D levels was not specified in the trial protocol, it could not be included in the printed version. This paper also suggested that the public was being harmed by taking large doses of vitamin D. But no such evidence exists.

The Lancet; the Lancet Diabetes & Endocrinology published two papers suggesting that since clinical trials largely have not found reductions in disease risk from vitamin D supplementation [Autier, 2014], "that low vitamin D status is a consequence of ill health, rather than its cause." [Autier, 2017]. However, this hypothesis was untested and unproven.

New England Journal of Medicine (NEJM) published this paper by authors of the IOM report [Ross, 2011b] questioning whether there is widespread vitamin D deficiency.

A recent paper found no benefit of vitamin D supplementation for pregnant women [Roth, 2018] though supplementation began quite late in gestation (mean of 20 weeks) and it takes many weeks for 25(OH)D increases to plateau.

However, The NEJM then declined to publish a paper reporting the benefits of measuring the serum 25(OH)D level and supplementing with vitamin D3 in Iran [Rostami, 2018], which did find significant benefits from vitamin D supplementation of pregnant women. [B. Hollis, private communication]

The fact that the major journals do not publish what appear to be valid, and useful, papers on the non-skeletal benefits of vitamin D gives the editors of the Vitamin D page at Wikipedia.org grounds for denying that vitamin D has many non-skeletal benefits.

5. The Fix
Big Pharma exerts significant control over the Centers for Disease Control and Prevention (CDC), The Food and Drug Administration (FDA), and the National Institutes of Health (NIH). The evidence is as follows.

CDC

"Many top executives and leaders at the CDC also leave the agency to take very lucrative positions with pharmaceutical companies, revealing a revolving door policy between the government and Big Pharma." [Shilhavy, 2018]

An example is that Dr. Julie Gerberding approved Gardisil vaccine and became head of Merck's vaccine division. [England, 2018]

The CDC's review on the effects of vitamin D predates the IOM report [Ross, 2011a] with the most recent references from 2007. It does not make any recommendations regarding vitamin D supplementation or desirable 25(OH)D levels. However, it does refer readers to other websites that give inadequate recommendations for vitamin D supplementation [CDC, 2018]:

For more information about vitamin D, see the Institute of Medicine's Dietary Reference Intake reports (Institute of Medicine 1997), fact sheets from the National Institutes of Health, Office of Dietary Supplements (http://ods.od.nih.gov/Health_Information/DS_WhatYouNeedToKnow.aspx), as well as information from the American Society for Nutrition (http://jn.nutrition.org)

FDA
The FDA is controlled by Big Pharma through the appointment of its leaders by the Federal Government and by the fact that Big Pharma funds many reviews of drugs up for approval. As noted in news accounts, there is a revolving door between Big Pharma and the FDA. Thus, those entering the FDA at the policy levels often come from Big Pharma and know that if they do Big Pharma's bidding while in office, they will be rewarded with a high-paying job in Big Pharma after leaving the agency.

(A Look at How the Revolving Door Spins from FDA to Industry - NPR [Lupkin, 2018])

FDA advisors are often rewarded financially after new drug approvals, a practice called "delayed incentives," yet the FDA has done nothing to restrict this practice. [Piller, 2018a,b]

FDA's information about vitamin D:

Vitamin	What it does	Where it is found	Daily value
Vitamin D Nutrient of concern for most Americans	Blood pressure regulation Bone growth Calcium balance Hormone production Immune function Nervous system function	Eggs Fish (e.g., herring, mackerel, salmon, trout, and tuna) Fish liver oil Fortified cereals Fortified dairy products Fortified margarine Fortified orange juice Fortified soy beverages (soymilk)	400 IU

[FDA, 2018]

"The authorization of user fees in 1992 has turned drug companies into the FDA's prime clients, deepening the regulatory and cultural capture of the agency. Industry has demanded shorter average review times and, with less time to thoroughly review evidence, increased hospitalizations and deaths have resulted. Meeting the needs of the drug companies has taken priority over meeting the needs of patients." [Light, 2013].

NIH
Big Pharma has arguably been captured by the One Percent [Zaitchik, 2018].

The NIH posted a Fact Sheet for Health Professionals regarding vitamin D. It basically endorses the IOM report [Ross, 2011a]. The most recent references (two) are from 2014, but more recent studies show that high 25(OH)D levels are beneficial in promoting health. [NIH, 2018]

A former worker in Big Pharma from 1984-95, who co-founded the Nordic Cochrane Collaboration in 1993, and is now a professor at the University of Copenhagen, published a book examining how Big Pharma corrupted health Care [Gotzsche, 2013];

In 2009, the Institute of Medicine was given the task of reviewing the guidelines for supplements of vitamin D and calcium. The study was funded by the Food and Drug Administration, the National Institutes of Health, and Health Canada. Among the guidelines was the requirement that the only evidence for beneficial effects had to come from clinical trials published by the time the report was published (end of 2010) [Chung, 2009]. By that time, randomized controlled trials had only shown beneficial effects for bone health. The report recommended 600 IU/d vitamin D for those up to 70 years of age, 800 IU/d for those over 70 years of age. The minutes of the meetings have never been made public, so we will probably never know what other considerations were used in making these recommendations. Interestingly, several of the members of this committee have continued to publish papers suggesting that there is little evidence of benefits of vitamin D, for example, disputing the recommendations of the 2011 of the Endocrine Society vitamin D [Holick 2011, 2012] and questioning whether there is a vitamin D pandemic [Rosen, 2012a, b; Manson, 2016].

Newspapers

Pharma Owns LA Times

The newspaper has been bought by a biotech billionaire, further entrenching Big Pharma's control of the media (ANH-USA, 2018).

From the LA Times:

Biotech billionaire Dr. Patrick Soon-Shiong on Monday will take control of the Los Angeles Times and San Diego Union-Tribune, two historic newspapers rooted in Southern California civic life for more than 135 years? that now must adapt for the digital age.

Soon-Shiong is spending $500 million to acquire the news organizations, along with Spanish-language Hoy and a handful of community newspapers, from Chicago-based Tronc.

Comment: "Usually Big Pharma influences the media through the billions the industry spends on advertising, but this time the tactic is outright ownership. Note too that Dr. Soon-Shiong is in the vaccine business, so we can expect the LA Times to be vocal supporters of what the state of California is doing to make it impossible for parents to deviate from the vaccination schedule. Not only has the state eliminated all non-medical exemptions to vaccination; they are cracking down on doctors offering medical exemptions, too."

Interested readers can find more information at these websites:

https://www.ncbi.nlm.nih.gov/pubmed. Over 27 million publications listed, most with abstracts, some with full text freely available.

https://scholar.google.com. This website can be easily searched and may have papers not listed at pubmed.gov. In addition, it has more links to full papers as well as listings of other papers that cited the papers found.

http://www.grassrootshealth.net. This organization, led by Carole Baggerly with Cedric F. Garland, Dr. P.H. as the scientific advisor, promotes the benefits of UVB exposure and vitamin D to the general public. It enrolls participants in voluntary vitamin D and omega-3 fatty acid prospective studies, which include semiannual blood spot tests.

http://www.vitamindcouncil.org, led by John J. Cannell, MD, has pioneered advances in the understanding of the role of vitamin D in reducing risk of influenza, reducing risk and treating those with autism spectrum disorders, and improving athletic performance, as well as fighting against criminal punishment of parents whose infants are found with broken bones and are falsely accused of baby abuse when the real cause is low serum 25(OH)D levels. It has reviews of the evidence for many adverse health outcomes. It sends out frequent emails regarding the benefits of vitamin D.

http://vitamindsociety.org/ is led by Perry Holman. It is a Canada-based vitamin D advocacy organization, with good information about vitamin D.

https://vitamindwiki.com/VitaminDWiki, is led by Henry Lahore. This website has a trove of information and papers on the benefits of vitamin D. Mr. Lahore works tirelessly to keep the site up to date.

http://sunlightinstitute.org is run by Marc Sorenson, Ed.D. It promotes sun and UV exposure and vitamin D.

(William B. Grant, PhD, directs the Sunlight, Nutrition, and Health Research Center http://www.sunarc.org. He was a senior research scientist at SRI International, the Jet Propulsion Laboratory, and the NASA Langley Research Center. He has authored or coauthored over 60 articles in peer-reviewed journals.)

[This commentary presents the findings and viewpoint of the author. The Orthomolecular Medicine News Service allows equal time for dissenting opinions, which may be submitted to the Editor at the contact listed further below.]