Recently, we protected the status of a qualified health claim for selenium, but in the process discovered that the U.S. Food and Drug Administration (FDA) is confused about both the basic biochemistry of selenium and the legal requirements for a qualified health claim (1). I will discuss the errors in basic biochemistry that the FDA made and constitutional attorney Jonathan Emord will chat with us about the legal mistakes the FDA committed.

The important part of this article is the interview with Emord, in which he discusses the FDA’s legal errors and gives a compelling message to all persons interested in protecting their health. I will begin with a discussion of selenium and the evidence that some selenium nutrients reduce the risk of some cancers. This is intended to provide background information for those who are not familiar with selenium and its role in cancer prevention. However, if you are already up to speed—or just bored with the science—please skip ahead and read the actual interview with Emord, which is the essence of this article. The importance of this discussion is that we have much at stake regarding protecting our rights to clearly disseminate truthful health information to the public.

Selenium Is Essential to Life
Selenium is essential to life. Selenium is the essential atom in several very important genetically programmed molecules called selenoproteins. A deficiency of any essential nutrient leads to disease and/or death, depending on the severity of the disease.

There are 25 known selenoproteins and most likely more, but we don’t yet fully understand the biological roles of several of the selenoproteins. The first selenoprotein discovered was identified in 1973 as glutathione peroxidase, an antioxidant that protects cellular membranes and maintains membrane integrity and function. There are now six known members of this glutathione peroxidase family. Selenoproteins are conventionally grouped as the glutathione peroxidases 1–6, iodothyronine deiodinases 1–3, thioredoxin reductases 1–3, selenoprotein P and other less understood and even unknown function including selenoproteins H, I, K, M, N, 0, R, S, T, V, W and 15. Selenoprotein P functions as a transporter of selenium between the liver and other organs.

Some of these selenoproteins are enzymes such as the six antioxidant glutathione peroxidases and the three thioredoxin reductases (TR1, TR2, TR3), the three deiodinases are involved in thyroid function by catalyzing the activation and deactivation of the thyroid hormones, while other selenoproteins are storage, transfer and transport agents (such as selenoprotein P), and some have direct roles in modulating immune response and other functions. We have neither identified all of the possible selenoproteins, nor determined all the roles of the 25 “known” selenoproteins.

Selenium Reduces Cancer Risk
It is well established that some forms of selenium reduce the risk of certain cancers. I have been conducting laboratory research with several selenium-containing compounds for 50 years. In the 1960s, I determined that dietary selenium reduced the risk of several cancers in a dose-dependent manner in a large series of laboratory animal studies. This discovery led to the granting of U.S. patent #6,090,414 to my research colleague, Dave Olson, and me for selenium in the prevention of cancer.

In the 1970s, Dr. Gerhard Schrauzer published a series of epidemiological studies linking selenium deficiency with increased incidence of several cancers. We discussed the inverse relationship between selenium and cancer with Dr. Schrauzer previously in this column (December 1991). Dr. Schrauzer and I were the only scientists who responded to the FDA regarding their “re-examination” of the qualified health claim for selenium for the reduction of risk of certain cancers (FDA-2008-Q-0323-0003[1]) (2).

The body of scientific evidence developed since these early observations convincingly supports these anticarcinogenic findings. A review by Combs notes that “some, but not all studies found selenium status to be inversely associated with cancer risk; hundreds of animal studies showed that selenium-treatment can reduce tumor yields; selenium was shown to inhibit growth and stimulate programmed cell death in a variety of cell culture systems. The consistent findings are that both inorganic and organic selenium-compounds can be antitumorigenic.” (3).

The plethora of mechanistic studies, laboratory animal studies and epidemiological studies provided the basis for funding for “nested” case-control studies.* These studies provided additional credible scientific evidence that selenium was protective against cancer.

The 1998 Harvard Health Professionals Cohort Study of 34,000 male health professionals (mostly physicians) found that the participants in the lowest quintile of selenium status had three times the risk of developing prostate cancer as those in the highest (43).

Also in 1998, Knekt et al. published their “nested” case-control study of 9,000 Finns. They found that there was a significantly higher relative risk of lung cancer between the lowest and highest tertiles of serum selenium (5).

A “nested” case-control study published in 1999 by Yu et al. determined that there was a significant inverse relationship between selenium levels in stored plasma and later development of liver cancer in 7,000 Taiwanese men (6).

In 1983, Willet et al. reported their “nested” case-control study of 10,000 American men and women. The study period ranged from 1973 to 1978. Blood samples were drawn from all participants at the start of the trial and analyzed for selenium (7). During the five-year trial period, 111 new cancer cases were observed. For each case, two “matched” control cancer-free patients were selected and their blood selenium levels were compared. A significantly greater than expected cancer incidence was found in the lower blood selenium group. The increased risk of cancer in the lower quintile of baseline was twice that in the highest quintile.

The additional support provided by “nested” case-control studies encouraged the funding of human intervention studies. In 1986, Willet and Stampfer reviewed the credible scientific evidence and concluded, “observational studies of blood selenium levels and cancer incidence are promising and randomized trials should be planned” (8).
This multitude of studies served as justification for a large gold-standard study of selenium and cancer sponsored by the National Cancer Institutes, American Cancer Society, American Institute of Cancer Research and Nutrition 21. This Nutritional Prevention of Cancer Clinical trial (NPC) was a prospective, randomized, placebo-controlled, double-blind study led by Dr. Larry Clark of the Arizona Cancer Center at the University of Arizona (Tucson) (9).

We chatted with Dr. Clark about the results of his study in this column in September and October 1998.
The large clinical study involved seven clinical centers and more than three dozen research physicians and other scientists. The results were published as the lead article in the Journal of the American Medical Association on Christmas Day 1996. The clinical study reported that selenium-yeast supplements cut cancer mortality in half! There was a 37% decrease in the incidence of cancer among patients who were assigned a selenium-yeast supplement. In addition, they reported a dramatic decrease in the incidence of lung, prostate and colorectal cancers.

In science, a result is deemed significant when a statistical measure called “p” is found to be less than 0.05. The NPC Trial showed that total cancer incidence was reduced 37% (p = 0.001) and total carcinoma incidence was reduced 45%. In addition, the three leading sites of cancer had significantly lower incidence: lung cancer incidence was reduced 46% (p = 0.04); prostate cancer incidence was reduced 63% (p = 0.002); and colon cancer incidence was reduced 58% (p = 0.03). Note the exceedingly high levels of significance for these results. There were also other interesting results, but they did not meet the scientific standards for significance. There was a 17% reduction in all cause mortality (p = 0.14), which when adjusted for sex, current smoking and age yielded a 21% reduction in deaths from all causes (p = 0.07).

Since this seminal clinical study, several other supporting studies have been reported, whereas a couple of flawed studies that did not use selenium-yeast as the selenium form do not support the study. At this time, we still cannot claim that the clinical studies supporting the protective effect of all forms selenium against all forms of cancer is conclusive; nonetheless we can state that the scientific evidence that selenium-yeast reduces the risk of certain cancers is definitely scientifically credible.

Additional studies that add support to the gold-standard NPC Clinical Trial were discussed in my petition to the FDA and include the following studies plus others.

• A French intervention trial, the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX), is a study of 13,017 French adults in the general population which gives additional support to the NPC Trial (10).

• The Linxian Trial, an intervention trial involving 30,000 adult Chinese found that supplementation of selenium combined with two other antioxidants significantly decreased mortality from stomach cancer (11).

• In 2004, Wei et al. published a 15-year follow-up study of 1,103 participants randomly selected from the larger Linxian trial cohort. They found a significant inverse association between baseline serum selenium concentrations and death from esophageal squamous cell carcinoma and gastric cardia cancer (12).

• In 2002, Knekt published his review of all prospective studies of selenium and cancer (13). He divided all existing studies into the following categories: “all cancers; lung cancer; colorectal cancer; gastrointestinal and stomach cancers; prostate cancer; female cancers; miscellaneous cancers that included cancers of the liver, bladder, mouth, pharynx, esophagus and melanoma.” He reviewed 72 prospective studies with 50 of the studies establishing lower risk of cancer associated with higher intake or status of selenium.

• A Harvard group examined the records of physician volunteers in the Harvard Physicians Study (14). In this study, 586 physicians were tested in 1982 and followed for 13 years. Among other tests was a determination of plasma selenium. The median age at testing was 60 years. These authors reported “a statistically significant inverse association between pre-diagnostic selenium levels and the risk of advanced prostate cancer.” They also reported that men with PSA levels greater than 4 ng/mL at the beginning of the study appeared to be protected from prostate cancer by a higher plasma level of selenium. They suggest, “selenium may influence tumor progression.” These data and others suggest that selenium can play a major role in the development and progression of prostate cancer.

• In 2005, a prospective study called the Etude du Vieillissement Arteriel (EVA) study was conducted in France (15). The EVA study was a nine-year longitudinal study with six follow-up periods. During the two-year period from 1991 to 1993 (EVAO), 1,389 men and women born between 1922 and 1932 were recruited. The effects of plasma selenium at baseline on mortality were determined by Cox proportional hazards regression analysis, adjusting for the following variables: sociodemographic characteristics, dietary habits, health and cognitive factors. The EVA study found a significant association between cancer-related mortality and low plasma selenium concentrations [increment = 0.2 µmol/L; RR = 1.61 (1.19 –2.13); p = 0.001]. Analysis by quartile of plasma selenium showed that mortality risk increased significantly in individuals with plasma selenium in Q1 and Q2 compared with those with plasma selenium in Q4 [Q1 versus Q4: RR = 4.06 (1.5110.92); p = 0.006; Q2 versus Q4: RR = 2.95 (1.06–8.18); p = 0.04]. Cancer-related mortality did not differ significantly between individuals who had plasma selenium concentrations in Q3 compared with those in Q4 [Q3 versus Q4: RR = 1.92 (0.63–5.86); p = 0.25]. The relative risk (RR) of cancer-related mortality associated with plasma selenium decreases in increments of 0.2 µmol/L, adjusting for all factors, was 1.79 (1.32–2.44); p = 0.0002.

• In 2006, a meta-analysis was undertaken to quantitatively determine if men with low selenium levels were at increased risk of prostate cancer. Twenty epidemiologic studies were selected. Mean differences were: –5.55 µg/1 (–9.82; –1.27; p = 0.01), –0.01 µg/g (–0.03; 0.006; p = 0.19), –0.52 µg/1 (–4.63; 3.58; p = 0.80) for serum, toenail and plasma studies, respectively. Overall, the pooled standardized mean difference between cases and controls were: –0.23 (–0.40; –0.05; p = 0.01) indicating an inverse association between selenium levels and risk of prostate cancer (16).

Also in 2006, a case-control study was undertaken to quantitatively determine if low selenium levels were associated with increased risk of bladder cancer (17). Eight epidemiological studies examined the association between serum selenium concentration and bladder cancer risk. A population case-control study in 178 cases and 362 controls was carried out to assess the relationship between bladder cancer risk and selenium serum concentrations. Unconditional logistic regression was calculated to determine odds ratios (OR) for bladder cancer occurrence with corresponding 95% confidence intervals (95% CI). Effect modification by smoking status, low fruit and vegetable intake, retinol equivalent, vitamin C, vitamin E and total antioxidant status were also assessed. The results were that serum selenium level was negatively associated with bladder cancer risk. After adjustment for sex, age, smoking and occupational exposure, the OR was 0.48 (95% CI 0.29–0.79) comparing the second with the lowest tertile (serum selenium concentration >82.40 µg/L). The adjusted OR for the highest tertile (serum selenium concentration >96.00 µg/L) was 0.30 (95% CI 0.17-0.52) (P-trend <0.001). An increase of 10 µg/L in serum selenium concentration was associated with a significant decreased bladder cancer risk (OR: 0.76; 95% CI 0.67–0.85). The researchers concluded that this case-control study demonstrated an inverse association between serum selenium concentration and bladder cancer risk.

Fortunately, other large selenium-yeast clinical trials are underway and their results will be known in three to five years. The important issue at this time is not whether or not there is conclusive scientific evidence that some selenium forms reduce the risks of some cancers, but whether or not the credible scientific evidence that some forms of selenium may reduce the incidence of some cancers can be accurately and truthfully disseminated to the public. The FDA seems to continue its policy of censoring all credible and truthful reports that some nutrients may decrease the risk of cancer.

FDA Censorship of Credible and Truthful Information
In the past, the FDA tried to ban all health books and scientific articles from health food stores. As was discussed in this column in an August 2005 interview with Frank Murray, few people realized the FDA went so far as to try to ban health books in health food stores. The FDA claimed that having books and articles near products was an illegal extension of labeling. Dr. Murray pointed out, “As a continuing vendetta against the health food industry, the FDA reasoned that, by curbing the sale of books, magazines, etc., in health food stores, it could severely hamper the stores’ ability to disseminate information about preventive medicine, natural foods, etc.”

Dr. Murray described a case in which the FDA entered the warehouse of Balanced Foods Co. in New York City and seized copies of Folk Medicine and Arthritis and Folk Medicine, two popular books by Dr. D.C. Jarvis, along with bottles of Sterling Cider Vinegar and Honey, which were mentioned in the books. This was said to violate FDA’s “labeling laws,” in that products and supporting literature could not be placed within five feet or so of each other. The FDA easily lost the case, and since then, has backed off somewhat from this approach.

However, it took sustained court action by constitutional attorney Jonathan Emord to allow truthful and credible scientific information to be disseminated about nutritional products. Such illegal censorship by a federal agency did not sit well with Emord. We have chatted with him recently in “The Rise of Tyranny” (October 2008), but I want to remind readers of our earlier discussions on qualified health claims.

In “Bringing the FDA into Compliance” (September 2003), we discussed how Emord’s efforts were forcing the FDA to obey the Constitution, discontinue illegal censorship of truth, and bring better, more accurate health information to the public.

In “Action is the Price of Freedom” (October 2003), we discussed the final report and recommendations of the FDA’s Task Force on Consumer Health Information for Better Nutrition. This task force was established to help American consumers obtain “accurate, up-to-date, and science-based information about the health consequences” of foods and dietary supplements. The FDA issued “guidances” for industry outlining the petition process for obtaining approval to use qualified health claims and how such petitions would be evaluated. Emord commented that the FDA must accept the First Amendment requirement that government favor disclosure over suppression as the rule and limit its use of censorship to those extremely rare instances when the words to be communicated are inherently misleading (incapable of being rendered non-misleading through the addition of more information). If the FDA gets that message, which comes from the federal courts in response to the legal challenges by Durk Pearson, Sandy Shaw, Pure Encapsulations, Inc., Dr. Julian M. Whitaker and others, it will implement the letter of the new rule in the spirit of the First Amendment. If it does not get that message, it will proceed like the former Soviet Union did in interpreting the civil rights protections of the Soviet Constitution: The First Amendment will be rendered meaningless and civil rights will be violated.

This new FDA guidance was intended to allow health claims (information) for important nutrient benefits that were not previously allowed on labels. Emord explained that the new FDA directive was to implement the “Pearson decision,” which Emord successfully argued before the courts. Instead of suppressing a claim because it is not proven to a near conclusive degree, it was intended to allow the claim with a disclaimer that alerts the consumer to the fact that the evidence is not conclusive. In short, far more claims would reach consumers along with qualifications stating the level of support in the science. The new category of “qualified claims” applied directly to nutrient–disease relationships. They were designed to be used in all instances when a health claim petition failed to satisfy the “significant scientific agreement” standard. Claims not satisfying that standard would be allowed nonetheless with disclaimers under the qualified claim regime the agency has adopted.

That regime is a direct response to the Pearson court’s command that FDA follow the First Amendment and allow qualified claims as a less speech-restrictive alternative to the suppression of claims that do not satisfy FDA’s significant scientific agreement (SSA) standard. In point of fact, the so-called SSA “standard” is still largely undefined and so, not a reasonable “standard” by any means.

Before I discuss the scientific errors that the FDA made about basic selenium biochemistry in Part 2, let’s chat again with Attorney Emord about the more important issue of how the FDA is still confused about qualified health claims. Let’s begin with reviewing some of the steps he and his clients took to bring the FDA into compliance with the constitution.

Emord has been practicing constitutional and administrative law before the federal courts and agencies since 1985. Having begun his career as an attorney in the Federal Communications Commission during the administration of President Ronald Reagan, Emord has maintained an abiding conviction to achieve full First Amendment protection for the freedoms of speech and press. In 1991, he authored the critically acclaimed Freedom, Technology, and the First Amendment, in which he chronicled the intellectual foundations of the First Amendment and advocated replacing government control over the airwaves with a title registry, private property rights approach. Emord has practiced law for a number of well-respected firms, including Wiley, Rein & Fielding, and served as a Cato Institute Vice-President.

Emord practices food and drug law, deceptive advertising law, and libel law, and he served as lead counsel in the Pearson v. Shalala (D.C. Cir. 1999); Pearson v. Shalala (D.C.D.C. 2001); Pearson v. Thompson (D.C.D.C. 2001); and Whitaker v. Thompson (D.C.D.C. 2002) cases, holding FDA censorship of nutrient-disease relationship claims unconstitutional. He also served as lead counsel in the Nutraceutical Corp. v. Crawford (D.Ut.2005). Emord is admitted to practice in the states of Illinois, Virginia, and the District of Columbia. He is admitted to practice before the United States Supreme Court; the United States Courts of Appeal for the D.C., Fourth, Seventh, Ninth, and Tenth Circuits; the United States Court of International Trade; and the United States District Courts for the District of Columbia, Eastern District of Virginia, Northern District of Illinois, and Western District of Wisconsin. He is a member of the Governing Council of the International Society of Regulatory Toxicology and Pharmacology. He is a 1982 graduate (B.A., Political Science and History) of the University of Illinois where he was an Edmund J. James Scholar and a 1985 graduate (J.D.) of DePaul University.

Emord’s professional publications include Freedom, Technology, and the First Amendment (1991), “The First Amendment Invalidity of FCC Ownership Regulations” (Catholic University Law Review, 1989), “Contrived Distinctions: The Doctrine of Commercial Speech in First Amendment Jurisprudence” (Cato Institute Policy Analysis, 1991), “The First Amendment Invalidity of FCC Content Regulations” (Notre Dame Journal of Law, Ethics & Public Policy, 1992), “Murder by Medicare: The Demise of Solo and Small Group Medical Practices” (Regulation, 1998) and “Pearson v. Shalala: The Beginning of the End for FDA Speech Suppression” (Journal of Public Policy & Marketing, 2000).

Passwater: What are the origins of “health claims” and “qualified health claims?” Did they originate with the will of Congress in the 1994 Dietary Supplements Heath and Education Act or did they originate as a result of your court actions wherein the Courts mandated that the FDA must accept the First Amendment requirement that government favor disclosure over suppression as the rule and limit its use of censorship to those extremely rare instances?

Emord: In 1990, President George H.W. Bush signed into law the Nutrition Labeling and Education Act. In that Act at 21 USC 343(r)(3)(B)(i), Congress mandated that nutrient-disease relationship claims be allowed for foods following the submission of a petition for claim approval backed by “significant scientific agreement.” By regulation, FDA applied that same standard to dietary supplements. “Significant scientific agreement” was left largely undefined, however, except that in practice it meant then (and still means now) near-conclusive proof in support of the nutrient-disease relationship. Because the great bulk of nutrition science concerns the potential of a nutrient to affect a disease, were the health claim regime the only one available, consumers would continue to be left in the dark concerning the vast majority of nutrient–disease relationships. To remedy that condition, my clients (including Durk Pearson, Sandy Shaw, Dr. Julian Whitaker, the former American Preventive Medical Association and others) filed a series of lawsuits against the FDA (six in all) that yielded five victories against FDA censorship.

At the start of this litigation, FDA took the remarkable position that the First Amendment largely did not apply to it and that were any claim allowed except that which it deemed conclusively true, consumers would be hopelessly beset with claims and bewildered by them. FDA viewed us, the consuming public, as Neanderthals, who would be led childlike to grab and quaff down any supplement that carried a health claim. The Pearson Court found this reasoning unfounded, fanciful, even laughable and certainly not the evidence it expected to justify an act of censorship. FDA even argued that the allowance of information on the potential of nutrition to treat disease, and I now refer to truthful information, would induce consumers to ingest dangerously high amounts of supplements, leading to a parade of horribles along a very slippery slope.

In short, FDA professed its role to be that of a Super Nanny for America—a protector of consumers who were too ignorant to perceive their own best interests and too gullible to protect themselves. We argued, to the contrary, that the First Amendment means nothing if truthful communication is banned from the market. We explained that inconclusive science can be accurately revealed just as conclusive science can and that the ultimate determinant on the relative worth of a speech offering is not the government under our First Amendment but the people. That, at any rate, is the theory of our Constitution, a theory the FDA still rejects despite the fact that all of its decision-makers swear an oath as a condition to employment that they will uphold the Constitution.

The litmus test we argued was truth, not certainty, and so long as we conveyed information that was truthful, by revealing its uncertainty, no government force could disallow it consistent with the First Amendment. The U.S. Court of Appeals for the D.C. Circuit in Pearson v. Shalala (Pearson I) agreed, and in 1999, a unanimous Court comprised of Judges Laurence H. Silberman, Patricia M. Wald and Merrick B. Garland ordered FDA to define “significant scientific agreement” (which FDA never really did) and to allow all claims to enter the market so long as they could be rendered nonmisleading through the addition of a reasonable disclaimer (e.g., the scientific evidence in support of this claim is inconclusive).

So, to answer your question, the FDA was required by constitutional mandate from the Court of Appeals to abide by a second, non-statutory health claims review process, one for qualified claims not backed by significant scientific agreement, in those instances where credible scientific evidence supported the nutrient-disease relationship claims and qualifications could render those claims nonmisleading. That decision did arise in response to our appeal, and no credit should be given FDA for its subsequent compliance, which came years later and only after a series of bitterly fought court battles in which the courts repeatedly demanded that FDA comply with the Pearson I decision. The agency has behaved badly and still seems oblivious to its place in our constitutional system, viewing itself as above the law.

The overarching principle in Pearson I that FDA has never adopted mandates that the agency favor disclosure over suppression. Instead, FDA has repeatedly avoided implementation of the First Amendment mandate, has saddled claims with excessive (and, often, excessively wordy and misleadingly negative) qualifications, and has largely prevented any commercial use of qualified claims through a rigid, Byzantine system of speech regulation. The classic example involves the omega-3 fatty acid qualified claim. We first won the right to have that claim enter the market from the Pearson I decision, itself. FDA, when finally compelled by court action to permit the claim, allowed it but with a paragraph-long disclaimer making it impossible to use. Thereafter, even when the Bush Administration issued a “prompt letter” from the Office of Management and Budget asking then Commissioner McClellan to allow the claim to reduce deaths from heart attacks because the evidence was so strong, McClellan over a year later allowed a revised claim to be made, but again saddled it with a disclaimer too long to permit the claim to appear generally in the market.

The battle to end FDA censorship, a censorship not unlike that of the Star Chamber Courts in 15th Century England, continues and will go on and on until the day arrives when this agency humbly accepts its proper place in the legal universe. It functions today as a law unto itself, arrogantly superseding the First Amendment with its edicts. If we are to restore constitutional governance in this country, we will have to reassert the supremacy of the First Amendment over the FDA.

Passwater: Is it correct to say that the distinction between a “health claim” and a “qualified health claim” is that the former requires essentially conclusive proof (SSA) whereas the latter requires only “credible scientific evidence?”

Emord: That is a fairly accurate shorthand description, but people need to understand that “credible scientific evidence” means plausibility, not probability. I prefer to recite the actual standard Judge Gladys Kessler gave FDA in Whitaker v. Thompson I. There, she made the meaning manifest for FDA after finding the agency derelict in disregarding the Court of Appeals’ command in Pearson I. When you read her words you will immediately realize that the Court’s standard differs fundamentally from FDA’s present one for qualified claims. FDA clings to an unconstitutional evaluative system where its prejudice against the relative worth of science dictates the treatment it accords claims. Under Judge Kessler’s standard, if a proposed claim is backed by scientific evidence, FDA may not ban it, regardless of its opinion of the value of the science. Instead, it must allow the claim and, in general, must recite that the evidence is inconclusive. Note that the statement evidence is “inconclusive,” the language recommended by the Court of Appeals is value neutral, yet FDA prefers instead to employ value laden terminology (e.g., the evidence is “weak”). The qualification FDA uses cannot constitutionally compel a private party to adopt and propound FDA’s bias. Under our First Amendment, the value to be accorded inconclusive science varies based on each person’s perception of its worth. It is the right of each person, not the government, under the First Amendment to assay the relative value of speech offerings, whether those offerings are in matters of politics or science. Under our First Amendment, the government may not condition claim allowance on the speaker’s acceptance and communication of the FDA’s view of the relative worth of the speech.

Bearing in mind that FDA requires near conclusive scientific proof to support a health claim, read carefully Judge Kessler’s definition of the standard for qualified health claim allowance: Pearson I identified two situations in which a complete ban would be reasonable. First, when the “FDA has determined that no evidence supports [a health] claim,” it may ban the claim completely. . . . Second, when the FDA determines that “evidence in support of the claim is qualitatively weaker than evidence against the claim—for example, where the claim rests on only one or two old studies, it may impose an outright ban . . . Even in these two situations, a complete ban would only be appropriate when [t]he government could demonstrate with empirical evidence that disclaimers similar to the ones [the Court] suggested [in Pearson v. Shalala] [“the evidence in support of this claim is inconclusive” or “the FDA does not approve this claim”] would bewilder consumers and fail to correct for deceptiveness.

Emord: FDA uses various yardsticks to measure scientific evidence (number of studies, human versus animal, double blind versus unblinded, etc.). That is not the right test under the First Amendment. The central issue is whether the representation made to the public accurately reflects the state of the scientific evidence (i.e., all of the evidence, not FDA’s preferred subset). Instead of favoring disclosure over suppression and an accurate statement of the state of the scientific evidence, FDA engages in a predetermined weighing of the evidence. Rather than look without bias at all of the science, FDA essentially disregards animal studies, in vitro studies and treatment studies and downgrades all other human intervention and observational studies except prospective randomized double-blind placebo-controlled clinical trials that are virtually nonexistent for the evaluation of healthy individuals, making outcomes largely a fete accompli. It is as if the FDA speech police put blinders on themselves, refusing to look at the totality of evidence, preferring instead to examine only evidence they have given decisional weight, skewing the picture and creating a result that either suppresses or misrepresents the truth.

The First Amendment compels a different approach. If FDA followed it, the issue would not be how many studies of a particular kind are submitted but (1) is there evidence to support the claim; (2) is the totality of the evidence for the claim qualitatively weaker than the evidence against; and, if 1 is answered affirmatively and 2 negatively, (3) can the claim be rendered nonmisleading through the addition of a disclaimer? The role of the disclaimer is not to propound an official orthodoxy on the science but to convey whether the science is conclusive or inconclusive.
To answer your question, there must be at least one study in support of a claim but if there is no study controverting it (i.e., disproving the supportive study), a claim associating a nutrient with a disease must be allowed with a qualification warning the consumer that the evidence is inconclusive.

Passwater: Most dictionaries define “credible” as “believable or plausible.” Is the FDA, by rejecting studies they don’t like and using other arbitrary and capricious standards, applying the standard of “conclusive” instead of “credible” to our qualified health claim petition for selenium?

Emord: The FDA categorizes science in a “go–no go” fashion rather than weigh the totality of all of it. In the case of the selenium claim, it separated animal studies and condemned them outright, not even considering them in its review. It separated in vitro studies and condemned them. It did the same with treatment studies. It then categorized the remaining intervention and observational studies, downgrading and largely rejecting all but a select few on largely subjective terms. It evaluated the remainder in the same manner as it does in a “significant scientific agreement” review. In the end, however, rather than hold SSA not met and condemn all claims, it makes a political decision, taking the few that it finds supported by intervention and observational studies not condemned in toto and affixing to those claims heavily negative value-laden disclaimers that force any who would use the claim to adopt and communicate the agency’s bias to the public. It does this because it presumes that if it allows some of the claims worded in a way that makes use of them impossible, it will not be viewed with as much disdain by the courts and will at least hold onto the argument that it allowed some of the claims. Probed by the slightest depth of reason, one can readily discern that FDA has in fact condemned all of the claims because it’s allowed ones are allowable only if very negative qualifications are attached. Its system makes a mockery of science and common sense.

Passwater: What can be done to correct the FDA’s “confusion?” Do we have to take them to court?

Emord: Three things. We must sue FDA relentlessly. Freedom requires eternal vigilance. Those who sit idly by while their freedoms are taken from them do not deserve them. It was Thomas Paine who said in words that still ring true today, “[t]he summer soldier and the sunshine patriot will, in this crisis, shrink from the service of their country; but he that stands by it now, deserves the love and thanks of man and woman. Tyranny, like hell, is not easily conquered; yet we have this consolation with us, that the harder the conflict, the more glorious the triumph.”

We must also enact the Health Freedom Protection Act. I have written an updated version of that Act for Congressman Ron Paul that focuses narrowly on stripping FDA of the power to impose a prior restraint on nutrient–disease claims. Under the bill, FDA has no power to require nutrient-disease claims to be reviewed in advance of use but is limited to proving the claims false by clear and convincing evidence in a federal court before it may act against them. This is as the Constitution prescribes. A core purpose of the First Amendment was to disarm this government of prior restraints; thus FDA’s censorship regime is a throw-back to an earlier day and has no place in a truly free society. Congressman Paul will introduce the bill before the August recess. Everyone who believes in our Constitution of liberty should rally behind it and urge its passage.

We must also enact the Congressional Responsibility and Accountability Act. This is another bill I have written for Congressman Ron Paul. At root, as I explain in The Rise of Tyranny (2008), the problems we are experiencing were predicted by the founding fathers who foresaw tyranny arising if ever in this country’s governing power (legislative, executive, and judicial power or any two of them) were combined in single hands. The FDA possesses legislative and executive power and advances an agenda that protects its principal regulatees’ interests, the pharmaceutical companies’ interests, at the expense of all others, including dietary supplement companies and the public (and public health). To bring about an ultimate solution, we need to prohibit independent regulatory agencies from enforcing rules (laws) unless the Congress passes them as laws in the way in which the Constitution prescribes. It is shocking to reflect on the fact that over three-quarters of all laws promulgated by the federal government are not the product of our elected representatives but of unelected heads of bureaucratic agencies. Through over 80 years of delegation, Congress has effectively moved governing power from the three constitutional branches of government to the unelected bureaucracy, transforming the United States from a republic to a bureaucratic oligarchy. The Congressional Responsibility and Accountability Act would restore constitutional government and would largely eliminate abusive regulation unpalatable to the electorate. Congressman Paul will also re-introduce this bill before the August recess.

Passwater: Thank you for your previous actions and your insight. Your comments are compelling! We must take the FDA to court to protect the health of the American people and call upon Congress to enact the Health Freedom Protection Act and the Congressional Responsibility and Accountability Act.

In Part 2, I will address the scientific errors made by the FDA in its June 19 letter concerning our petition on selenium and qualified health claims for specific cancers. The FDA is so confused about basic selenium biochemistry (Selenium Biochemistry 101), as well as the more advanced selenium biochemistry (Selenium Biochemistry 501), that one wonders about its capability to evaluate the qualified health claims for selenium. The FDA does show it understands the requirements for conclusive scientific evidence, but do not seem to understand the requirement for credible scientific evidence.

The FDA inappropriately relied totally on intervention studies, however, they arbitrarily and capriciously dismissed several credible intervention studies that confirmed selenium’s anti-cancer properties. We will also chat with Dr. Gerhard Schrauzer about a large clinical study (SELECT). WF

References
1. “FDA Docket No. 2007N–0464 Health Claims and Qualified Health Claims; Selenium and Certain Cancers; Revaluation; Opportunity for Public Comment,” Fed. Reg. 72 (245), 72738–72740 (2007).
2. B. Schneeman, “RE: Qualified Health Claim Petition—Selenium and a reduced risk of site-specific cancers ,” FDA CFSAN, Letter to Jonathan W. Emord Esq., June 19, 2009.
3. G.F. Combs, “Current Evidence and Research Needs to Support a Health Claim for Selenium and Cancer Prevention,” J. Nutr. 135 (2), 343–347 (2005).
4. K. Yoshizawa, et al., “Study of Prediagnostic selenium levels in toenails and risk of advanced prostate cancer,” J. Natl. Cancer Inst. 90 (16), 1219–1224 (1998).
5. P. Knekt, et al., “Is Low Selenium Status a Risk Factor for Lung Cancer among Finnish Men and Women?” Am. J. Epidemiol. 148 (10), 975–982 (1998).
6. M.W. Yu, et al., “Plasma Selenium Levels and the Risk of Heptocellular Carcinoma among Men with Chronic Hepatitis Virus Infection,” Am. J. Epidemiol. 150 (4), 367–374 (1999).
7. W.C. Willet, et al., “Prediagnostic Serum Selenium and Risk of Cancer,” Lancet 2 (8342), 130–134 (1983).
8. W.C. Willet and Stampfer, M.J. “Selenium and Human Cancer: Epidemiological aspects and implications for Clinical Trials,” J. Amer. Coll. Toxicol., 5 (1), 29-36 (1985).
9. L.C. Clark, et al., “Effects of Selenium Supplementation for Cancer Prevention in Patients with Carcinoma of the Skin: A Randomized Controlled Trial. Nutritional Prevention of Cancer Study Group,” JAMA 276 (24), 1957–1963 (1996).
10. S. Hercberg, et al., “The SU.VI.MAX Study: A Randomized, Placebo-controlled Trial of Antioxidant Vitamins and Minerals,” Arch. Intern. Med. 164 (21), 2335–2342 (2004).
11. W.J. Blot, et al., “Nutrition intervention trials in Linxian, China: Supplementation with Specific Vitamin/Mineral Combinations, Cancer Incidence, and Disease-Specific Mortality in the General Population,” J. Natl. Cancer Inst. 85 (18), 1483–1492 (1993).
12. W.Q. Wei, et al., “Prospective Study of Serum Selenium Concentrations and Esophageal and Gastric Cardia Cancer, Heart Disease, Stroke and Total Death,” Am. J. Clin. Nutr. 79 (1), 80–85 (2004).
13. P. Knekt, Selenium status and prevention of chronic diseases, Edited by E. Cadenas and L. Packer (Marcel Dekker Inc., New York, NY and Basel, Switzerland, 2002).
14. H. Li, J. Stampfer and E.L. Giovannucci, “A Prospective Study of Plasma Selenium Levels and Prostate Cancer Risk,” J. Natl. Cancer Inst. 96 (9), 696–703 (2004).
15. N.T. Akbaraly, et al., “Selenium and Mortality in the Elderly: Results from the EVA Study,” Clin. Chem. 51 (11), 2117–2123 (2005).
16. M. Brinkman, et al., “Are Men With Low Selenium Levels at Increased Risk of Prostate Cancer?” Eur. J. Cancer 42 (15), 2463–2471 (2006).
17. E. Kellen, M. Zeegers and F. Buntinx, “Selenium is Inversely Associated with Bladder Cancer Risk: A Report from the Belgian Case-Control Study on Bladder Cancer,” Int. J. Urol. 13 (9), 1180–1184 (2006).

Dr. Richard Passwater is the author of more than 40 books and 500 articles on nutrition. He is the vice president of research and development for Solgar, Inc. Dr. Passwater has been WholeFoods Magazine’s science editor and author of this column since 1984. More information is available on his Web site, www.drpasswater.com

Published in WholeFoods Magazine, Sept. 2009