Supplements

Dietary supplements occupy a special niche in the business of health, or life, enhancement. The variety of 'natural', mostly herbal, supplements on the market are intended to replace the present pharmacopeia mainly because of their virtue of being 'natural' (safer, milder), not because they are better at treating the underlying, biochemical problems.¹. In contrast, supplements are generally intended to treat an underlying deficiency or problem, and 'megadoses' are means to this end. Supplements are not given to intervene in a disease process, but 'boldly' aim to deconstruct this process. According to proponents of supplements, such as the influential American chemist Linus Pauling, one has to be orthomolecular in his interventions: the right molecules, in the right amounts, must be given back to the body to restore wholeness and the ability to eliminate disease.

The State of Play The History of Supplements : the Linus Pauling affair Moral development or medical education? Doctors, like Priests? 'Thou shalt not consume supplements' Defining evidence and refuting charges of 'quackery' A case study: depression Conflicting interests united against micronutrient research Financial conflicts of interest in leading journals Non-financial conflicts of interest with evidence-based medicine Non-financial conflicts of interest with specialists An enduring problem of cognitive dissonance Notes

The State of Play

In the past few years, several high-quality studies have failed to show that extra vitamins, at least in pill form, help prevent chronic disease or prolong life. According to an article, 'Major studies question value of vitamin supplements' recently in the International Herald Tribune²:

• A study as part of the Women's Health Initiative, published in The Archives of Internal Medicine, tracking eight years of multivitamin use among more than 161,000 older women found no evidence that multivitamins lowered the risk for heart disease and certain cancers.³

Critics replied that, based on the science of micronutients and old age, it was not surprising: it was too "little, too late."⁴

• Another study tracking almost 15,000 male physicians for a decade reported no differences in cancer or heart disease rates among those using vitamins E and C compared with those taking a placebo.⁵

Critics also replied that it was not suprising: that the dosage and posology of vitamin C, and the choice of a single vitamin E, the synthetic one, amongst the family of vitamins E that are required by the body, condemned this intervention to failure.⁶

• A survey of 35,000 men again found no evidence that high doses of vitamin E and selenium could lower the risk of prostate cancer.⁷Lippman SM, ⁸

Strangely, Eric Klein, the main author of this study comments: "The observations that, in previous trials, those who benefited most from selenium in reducing the risk of cancer had low baseline selenium levels and those who benefited from vitamin E in reducing the risk of lung cancer were primarily smokers who carry a high oxidant stress level appear to suggest that the observed biological effects result in clinical benefit only in those who have an easily correctable biological deficiency."⁹

Obviously, the very researcher who nourished this tide of disbelief is not a disbeliever himself...

This might seem to be an admission of an error in trial design¹⁰: why weren't the researchers aware when they designed the trial that they were mixing nutrient-deficient patients with non-deficient patients, thus obscuring the significance of the overall results?

Klein continues: "analyses of these groups (those who have an easily correctable biological deficiency) are underway in both SELECT and PHS, and future successes at chemoprevention are likely to rely on the identification of individuals with specific risk factors or molecular deficits that are correctable with targeted therapy".

40 years after Pauling coined it, mainstream research begins to understand the term "orthomolecular". Why this delay?

The History of Supplements : the Linus Pauling affair

Those crazy Nobel laureates

To fully comprehend the special perception that dietary supplements enjoy, we must understand the role of Linus Pauling, a two-time Nobel Prize winner and a key figure in modern biochemistry, in the dissemination and popularization of information about vitamin C in particular.

Pauling, who received worldwide praise for his work on a common metabolic disease, sickle cell anemia, struggled for the recognition of an even more common metabolic disease, which was termed by OMIM our "public inborn error of metabolism." This genetic disease is shared by 100% of higher primates like ourselves, but by less than 1% of other animals: it's the lost ability to produce 'vitamin C' (in so-called 'megadose' amounts: Pauling showed that a goat produced, in a single day, what humans are recommended to eat in a month or two).The response of the medical profession, by Pauling's account, was "astonishing."

Fear of ridicule and hubris
From being perhaps the major figure in modern chemistry, Pauling suddenly became, in the eyes of the Orthodoxy, little more than a well-meaning but misguided eccentric or even a quack. Meanwhile, masses began to follow Pauling's advice in what became one of the most important movements of citizen science; when asked how to assess the value of the safety warnings and the skeptical responses issued by medical authorities, he responded:

"I would trust the biochemistry of a goat over the advice of a doctor."

Moral development or medical education?

It is illuminating to analyze the medical profession as a group: how does it behave? How does it generally deal with critique from within and without?

It is recognized that higher education has a favourable impact on moral development: university students tend to reason more in societal and principled terms when faced with ethical issues, and less in terms of self-interest or peer approval, the more they advance in their university curriculum. The medical curriculum is a notable exception to this rule.

Many researchers have noted with concern that medical education, as it is today, hinders moral development. ¹¹The reason why medical education forms doctors that will be less able to take ethical decisions than other professionals with comparable levels of education is still not known with certainty, although the so-called "hidden curriculum" appears to be a likely culprit¹² (The "hidden curriculum" is the whole set of attitudes and mindsets that are promoted implicitly by teachers. Its role was eloquently expressed by Dr Albert Schweitzer: Example is not the main thing in influencing others. It's the only thing).

For an exploration of imitation learning, empathy and the crucial discovery of their neurological substrates, see cure-evil-mirror-neurons|Are we about to cure evil? Humanity in the mirror -- neurons.

Doctors, like Priests?

Galileo facing the Church

Goodwin and Tangum draw an interesting analogy with another case in the history of science. Based on the analysis by Giorgio de Santillana of galileo-s-thought-experiments | Galileo's impact in XVIIth century Italy, Goodwin and Tangum proposed to their fellow doctors, in American Medical Association's Archives of Internal Medicine, that Pauling's crime, like Galileo's, was not so much that he proposed a new paradigm, but that he proposed it directly to the people. ¹³ Pauling, by speaking to the population, just like he did when he fought to stop nuclear bomb trials (his success led him to receive his second Nobel Prize), committed the same crime as Galileo, who had chosen to write in the language of the masses (Italian), and who had to face the ire of the "scholarly elite, whom he had bypassed, usurped, and rendered irrelevant". They comment:

Of course, (speaking directly to the public) was precisely the course followed by many of the proponents of the benefits of micronutrients, the most famous of whom was Linus Pauling, the chemist who intruded into clinical matters. It is instructive to reread the review articles and editorials published in the 1970s ridiculing and condemning the ideas of Pauling. He was treated as a dangerous enemy, although a few years before his death, like Galileo, he was rehabilitated to the status of a genius with controversial ideas.

In effect, Pauling initiated one of the most significant critiques of the medical institution. By his own admission, Pauling's impetus was to communicate, as an educated citizen, the knowledge amassed by Irwin Stone,¹⁴ Abram Hoffer, Frederick Klenner and others before him. Pauling's "telescope" was his ability to read the literature that had been ignored by what could be called the pathocentric paradigm.

In the preface of The Healing Factor — Vitamin C Against Disease, Stone's magnum opus, as it were, Pauling summarizes:

As man has spread over the earth and increased in number, the supplies of ascorbic acid have decreased. It is possible that most people in the world receive only one or two percent of the amounts of ascorbic acid that would keep them in the best of health. The resulting hypoascorbemia may be responsible for many of the illnesses that plague mankind.¹⁵

to what Albert Szent-Gyorgyi, the discoverer of vitamin C, added:

'The medical profession itself took a very narrow and wrong view. Lack of ascorbic acid caused scurvy, so if there was no scurvy there was no lack of ascorbic acid. Nothing could be clearer than this. The only trouble was that scurvy is not a first symptom of lack but a final collapse, a premortal syndrome, and there is a very wide gap between scurvy and full health. But nobody knows what full health is! This could be found out by wide statistical studies, but there is no organization which could and would arrange such studies.¹⁶

While the debate about the most "luminously controversial of all biological, alternative cancer therapies" is slowly resolving, and as Pauling is regaining his reputation, the philosophical questions raised by the Nobel laureates, remain largely unaddressed: what is health?

'Thou shalt not consume supplements'

Being trapped at the level of peer approval (stages 3 and 4 of moral reasoning, in Kohlberg's scale) creates the need to protect the masses from the chaos caused by non-conformists and the dangers of ambiguity. To address these issues in the supposedly value-free field of science and medicine, scientists-priests will resort to indirect means. Instead of issuing commendments, scientists will leave to science reporters the dirty task of exaggerating the implcations of research: the typical good cop / bad cop routine, as we have seen above (see The State of Play).

It is for its good that scientists-priests want the population to avoid self-medication and to excommunicate medicine's paradigmatic Adversary, Linus Pauling. But rather than saying bluntly: don't trust yourself, trust us — the doctors, researchers and their industry sponsors (see below, Conflicts of Interest), the elites will, with one hand, create fear of self-medication and, with the other, turn against the population a century-old argument that it had against science: "After all, you were right: health is complex and we should trust nature without violating its complexity with reductionist therapies — such as supplementation".

Of course, normal-normative doctors and scientists won't apply the same standards when dealng with cholesterol, hypertension, depression, drugs e tutti quanti. It is simply propaganda.

Defining evidence and refuting charges of 'quackery'

The general population might think that medicine is concerned with what's wrong with a patient having a disease, and that most interventions are designed to normalize abnormal biochemical processes: serotonin reuptake inhibitors enhance mood, COX treat arthirits, beta-agonists and corticosteroids treat asthma, etc., and adverse or dissappointing effects are normal parts of life. However, this reassuring and familiar tale is just not true.

Maintream scientists and clinicians, those who are aligned with what is funded by Big Pharma's research consortia, will limit the quest for answers, both theoretically and clinically, to the 'problem solving' described by Kuhn, the search for the proximal biochemical triggers that, if turned down, can mimic healing and bring 'effects' (but not 'health'). In itself, this qualifies most of modern medicine as quackery:

At what point does the reference to science transform the conflict between "doctors" and "charlatans"? I will here put forward the hypothesis that what allows medicine to lay claim to the title of science is not this or that medical innovation, but rather the way it diagnosed the power of the charlatan and explained the reason to disqualify his power. According to this hypothesis, "scientific medicine" (appears) when doctors "discover" that not all cures are equally valid. A cure as such proves nothing; a popular cure-all or a few magnetic passes can have an effect, but they do not qualify as a cause. The charlatan is thereby disqualified as someone who takes this effect as a proof.¹⁷.

What applies to the pre-scientific "charlatans" (quacks) applies as well to the post-scientific Evidence-based medicine practicioners, who claim, in a typical post-modern stance, that they can do without those old-fashioned, repressive 'theories' on causes, and devote their cares to effects using trials involving millions of dollars and thousands of patients.

A case study: depression

According to the US Surgeon General, "the etiology (i.e. cause(s)) of depression, the mood disorder most frequently studied, is far from ideally understood".¹⁸. This governmental body doesn't suggest that monoamine abnormalities (those that are adressed by the usual mood drugs) are the root causes of depression, and presents an overview of the other usual suspects (GABA, acetylcholine, neurotrophic (I.e.neural growth) factors, and the hormones and glands of the stress system (the HPA axis)). For the Surgeon General,

What drives research is the determination to find which of the biological abnormalities in depression are true causes, especially ones that might be detectable and treatable before the onset of clinical symptoms. (...) The genetic complexities of the common depressive disorders ultimately may rival their clinical heterogeneity

What about 'supplements advocates'?

The functioning of the brain is affected by the molecular concentrations of many substances that are normally present in the brain (...) The optimal concentrations for a person may differ greatly from the concentrations (...) genetically determined (by his) biochemical machinery. (...) This therapy, to be successful, should involve the thorough study of, and attention to, the individual (...).¹⁹

The surgeon general, in 2009, says about the same thing as Pauling, in 1968. What differentiates the Orthodoxy from the 'Quacks' (except the delay) is the following edited text: "(substances) such as glutamic acid, nicotinic acid, and some other vitamins. Some of these substances are non-toxic" and "(may differ greatly) from the concentrations provided by his normal diet." (For the unedited text, see ²⁰) In other words, the number of patents that can be expected from the respective approaches.

What would help the US Surgeon General, for instance, to more 'ideally' understand the etiology of depression? Perhaps the recognition that non-orthomolecular substances such as lead ²¹, volatile organic compounds, trichloroethylene, PCBs,²² bisphenol (a),²³ are often elevated in depression, or that orthomolecular substances such as folic acid, ²⁴ glutathione,²⁵ EPA (the fatty acid),²⁶ potassium²⁷ magnesium,²⁸ iron,²⁹ zinc,³⁰ choline, ³¹ creatine,³² and, of course, vitamin C³³ are frequently low in depression?

Conflicting interests united against micronutrient research

The quacks, today, are those who have supposedly unproven and untested ideas about the biochemical roots of diseases.. But who decides which ideas are 'unproven' and 'untested'?

Financial conflicts of interest in leading journals

When patients ask about nutritional treatments, many a family physician has replied, "I've never seen any studies supporting the safety or efficacy of vitamin supplements in my professional journals. The research is simply not there."


Sadly, they are right. And now we know why.³⁴

There is a strong negative correlation between pharmaceutical advertising in a journal and its coverage of positive results in trials of dietary supplements (as well as a positive correlation with reports of adverse health effects).³⁵

"the ultimate impact of this bias on professional guidelines, health care, and health policy is a matter of great public concern."

As if the pervasive influence of 'Big Pharma' wasn't enough, the research on nutrients is also attacked from within: from the field of clinical nutrition. A recent analysis of the bias in the publication of studies related to nutrition showed that positive results were more likely to be published when they supported nutrients provided in products of the industry (in this first study of its kind, common beverages, soft drinks, juices and milk, were the focus of investigators).³⁶ This reporting bias strengthens the 'Thou shalt not consume supplements' commendment of scientists-priests.

Non-financial conflicts of interest with evidence-based medicine

A subspeciality of medicine, called clinical epidemiology, emerged in the 1990s as a panacea to the complexities of science and the rising costs of managing this complexity : it was called by its proponents 'Evidence-based medicine' (as if medicine was before EBM era, an obscurantist theoretical practice). Initially a small an iconoclastic group opposed to the priest-like authority of specialists, it quickly appealed to laypersons and governement officials, because it promised to provide simple 'yes or no' answers to specific questions of immediate interest — instead of the cryptic responses of specialists.

With this enthusiasm for 'pure scientific facts', came a gradual disinterest for ideas. A notion like oxidative stress has become artificially obscured by badly interpreted and mostly contradictory "evidence-based" speculations. Moreover, these speculations are not merely 'random theoretical abstractions', but are politically motivated. For instance, as of 2009, almost a century after the discovery of free radicals by biology, the science reporter of a most trusted newspaper, the International Herald Tribune, claims that "The selling point of antioxidant vitamins is that they mop up free radicals". How could one of the pillars of biochemistry become a quack's sales pitch? Did the excommunication of the founder of quantum chemistry, author of the monumental Nature of the chemical bond, Linus Pauling, invalidate Orthodox Science itself?

While the ideal, carefully practiced, evidence-based medicine would not fall into the trap of anti-intellectualism, today's EBM has a created a set of beliefs, and especially disbeliefs, that remain unchallenged because of the magnitude of the trials they are based on, not because of their quality. One could argue that quackery is back, helping masses and their leaders cope with complexity. In this context, the idea that each of us could have a a unique set of molecular deficiencies and excesses of an exquisite complexity is both unaffordable and unthinkable.

Practically, the definite test of supplements, or orthomolecular medicine, would involve the measurement of a wide variety of biochemical parameters, as in a crime scene investigation. But, as Szent-Gyorgyii complained, who would pay for that, in our eugenist era — in the Genome Project era?

Non-financial conflicts of interest with specialists

For the general context, see also paradigms | Paradigms, Falsification, and Unscientific methods

A closely related phenomenon is the lack of interest and indeed aversion of specialists for abstract thinking. Abstract thinking carries the risk of causing devastatingly untrue extrapolations from one cell type to another, from one disease subtype to another, and so forth. To escape these risks and attain excellence, specialists will each occupy a very tiny, cleanly defined area in the unthinkable complexity of biology and sign an implicit pact of non-agression with neighbor. This is how the Normal Science of problem-solvers functions.

In this context, a researcher who will identify a molecule present in most cells as a general cause of disease or health will be treated as a quack: simplistic, sensationalist, regressive. However, there exists good scientific reasons to consider some molecules as the usual suspects, and some others as the paramounts determinants of health. Specialists (normal specialists) will rather conceive of these as misplaced attempts to find a panacea or holy grail.

An enduring problem of cognitive dissonance

Negative attitudes about micronutrients did not evolve recently; they have deep roots. The resistance of the medical community to the concept that scurvy, beri-beri, and rickets were caused by vitamin deficiencies has been well documented. ... The pathologists who dominated academic medicine in the late 19th and early 20th centuries lacked the vocabulary to integrate the public health observations of vitamin deficiency into a pathophysiology dominated by the germ theory. A popular term used to describe vitamin deficiency disease, negative causality, evidenced the pathologists' awkwardness in grappling with the idea.³⁷

The awkwardness of pathologists is no laughing matter: as an argument against supplements, scientists will effectively create 'negative causality' protocols to test their misguided theories. For instance, they will try to investigate if malnutrition could be deleterious to cancer cells as much as to cancerous hosts — are we geared towards malnutrition clinics?

(...) But some free radicals are essential to proper immune function, and wiping them out may inadvertently cause harm.

In a study at the University of North Carolina, mice with brain cancer were given both normal and vitamin-depleted diets. The ones who were deprived of antioxidants had smaller tumors, and 20 percent of the tumor cells were undergoing a type of cell death called apoptosis, which is fueled by free radicals. In the fully nourished mice, only 3 percent of tumor cells were dying.

In truth, it is as ludicroous to "mop up" free radicals as it is to wipe out free radical scavenging vitamins — but those who learned about vitamins by studying beri beri, scurvy, pellagra, and other XIXth century diseases, don't seem to realize it.

see also alternative-medicine | The origins, theories of, and influence of Alternative Medicine

Could the history of philosophy ... explain the present debate between alternative and conventional approaches to nature and health?

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Notes