A Challenge to the Criticisms of Nutritional Therapy.

-Dr. Neville S. Wilson  –  March 2007

Attacks on the nutritional health industry are not uncommon and can be expected to continue since they represent a lobby intent on undermining the growing interest in and widespread use of nutritional supplements by health conscious people who desire optimum levels of well-being and protection against disease.

Such attacks are often thinly disguised by medical studies which purport to be scientifically based, unbiased, and authoritative, yet whose methodology may be riddled with credibility gaps and whose conclusive pronouncements may not only be invalid but potentially harmful.

It is understandable that the media will seize upon eye-catching pronouncements from journals that report controversial outcomes to clinical trials.  The sensationalism of such reports, regardless of their accuracy or validity, will undoubtedly serve to raise levels of uncertainty and anxiety in the general public.  They may also serve to promote the interests of groups whose supportive role in such trials are in conflict with their declared purpose.

Such was the case with misleading newspaper headlines suggesting harmful effects from taking anti-oxidant supplements.  These were based on a meta-analysis study recently published in the Journal of American Medical Association (JAMA) entitled, “Mortality in Randomized Trials of Anti-Oxidant Supplements for Primary and Secondary Prevention, Systematic Review and Meta-Analysis.

Prof. William Reville, writing “Under the Microscope” (IT 15/3/07) seized upon this sensationalist reporting in The Scientist, and denounced the merits of vitamin supplements using this meta-analysis to support his argument. Several statements made by Prof. Reville may serve to confuse and unnecessarily alarm readers who use anti-oxidant vitamins for health protective and health enhancement reasons.

He writes “large doses of fat-soluble vitamins should be avoided as they can be harmful,” and the findings of the study “clearly contradict claims that anti-0xidants improve health.”

Had Prof. Reville put the meta-analysis in its entirety under the microscope he might be compelled to conclude otherwise, and be less assertive in his sweeping statements which are not supported by epidemiological studies, scientific fact, or the universal experience of countless people who testify to the benefits and safety of anti-oxidant supplements.

The gross limitations of the meta-analysis study that Prof. Reville uses in support of his sweeping dogma have not gone unnoticed by critical observers inside and outside the dietary supplement industry.  The Canadian Health Food Association has questioned the findings because the researchers ignored a large body of scientific evidence supporting the benefits of anti-oxidants when drawing their conclusions.

Dr. Meir Stampfer, Professor of Nutrition and Epidemiology at the Harvard School of Public Health, told the Associated Press that the studies were too different to be able to pool them together.  “This study does not advance our understanding, and could easily lead to misrepresentation of the data,” Prof. Stampfer told Associated Press.

Putting this meta-analysis under the microscope for the purpose of clearly exposing its skewed methodology and unfounded conclusions is a public service which is now demanded by the sensationalist and misleading media headlines.

The study in question is not new clinical research in the sense that new and relevant data have been uncovered.  A meta-analysis is merely a review of pre-selected clinical trials and represents a particular interpretation of existing data which may or may not be driven by pre-determined conclusions.  It would thus be easy to conduct a meta-analysis of those trials which serve to provide supportive evidence for any pre-determined conclusion.

Goran Bjelakovic, from Copenhagen University, was the lead author of this new meta-analysis, and, with collaborators from Siberia and Palmero, collected 815 previously conducted studies of which 747 were excluded for several reasons, leaving 68 randomised trials in which beta-carotene, alpha-tocopheral (Vit. E), Vitamin A, Vitamin C, and Selenium were used in various combinations and dosages in a diverse group of subjects with varying degrees of long-standing illness and using also the appropriate prescribed medicines.

The trial results reflected a 16% association of Vit. A with mortality, 7% for beta-carotene, and 4% for Vitamin E.  There was no increased mortality risk associated with Vitamin C and Selenium use was associated with a 9% decreased risk.

It is important, in assessing the significance of these statistics, that the difference between association and cause is clearly understood.  There is no evidence whatsoever that mortality was caused by any of these anti-oxidants as alluded to by the injunction, “large doses of fat soluble vitamins should be avoided as they can be harmful.”

The association with mortality can mean that any one of several factors in isolation or in combination, could be implicated as contributory to such an outcome.  And the fact that in 66 of the 68 studies subjects were afflicted with a variety of longstanding pathological conditions such as diabetes, heart failure, hypertension, etc, and were on a variety of medical cocktails for such ailments, means quite clearly that any one of these conditions, or their prescribed medication, which included Beta Blockers (blood pressure reducing), diuretics, anti-hypertensives (blood-pressure reducing) and statins (cholesterol reducing), was equally associated with mortality, and more likely the cause than any one of the anti-oxidants taken in addition to the cocktails of presription drugs.

This fact alone serves as a serious limitation in the meta-analysis and flaws its conclusions about the safety of anti-oxidants.

Further limitations of the meta-analysis are evident which severely undermine its scientific credibility and practical value.  A closer scrutiny under the microscope reveals the following limitations:

1.            The diverse nature of the pooled studies robs it of the specificity which an objective analysis demands in any honest scientific endeavour.  Pooling together studies that differ vastly in respect of nutrients used, their dosage, their duration of use, the varied population groups studies, the range of pathologies involved and the mix of medical cocktails being swallowed together with various anti-oxidants is simply too vast and too vague for a precise and unbiased comparison to be made.  It would be easier to compare apples with oranges than to compare these studies and derive a valid conclusion.

2.            The dissimilarity of the time-frame for each study included in the meta-analysis introduces a variable that robs it of legitimacy and scientific credibility.  The duration of the trials studies ranged from several years to a one-off, single dose study with Vitamin A.  More apples and oranges?

3.            The distinction between primary prevention (those who have not had a heart attack) and secondary prevention (those who have had a heart attack and seek to prevent a second heart attack) has been blurred in this meta-analysis.  Combining such contrasting groups of subjects with a single end point in mind, such as mortality, defies the tenets of good science.  The study received harsh criticism from the US based Council for Responsible Nutrition for this particular methodological error, and stated, “misused meta-analysis methods to create generalised conclusions that may inappropriately confuse and alarm consumers who can benefit from supplementation with anti-oxidants.”

Dr. Andrew Shao, PhD., VP of CRN noted also that most of the trials in the meta-analysis tested for secondary prevention, looking at how a nutrient worked in diseased populations instead of primary prevention studies in healthy populations.  “Combining secondary prevention and primary prevention trials when making conclusions for the entire population is an unsound scientific approach.”

4.            Inaccurate reporting by the researchers of at least one study in the meta-analysis serves to further skew the results and casts a shadow over the credibility of the exercise.  One study involving the assessment of vitamins in relation to increased risk of gastrointestinal cancer in actual fact showed a benefit, rather than the reported risk, according to Dr. Pelayo Camera, the author of the cancer study, who in a response to enquiries by Patrick Holford, declared that his study looked at cancer and not mortality!

5.            Exclusions from the meta-analysis of other studies which have shown clear evidence of benefits from Vit. E supplements is likewise a limitation.  A Harvard study of more than 80,000 nurses found a 41% reduction in the risk of heart disease by those who had used Vit. E supplements for at least two years, and a second study involving 40,000 male health professional found a 37% risk reduction for heart disease.

Other studies have, however, concluded otherwise, such as the John Hopkins meta-analysis looking at studies conducted between 1993-2004 involving the use of high dose Vit. E (average 400 i.u. daily and looking at all case mortality).  Despite the media frenzy caused by the reported conclusions of this meta-analysis the authors were forced to admit that “Vitamin E supplements do not affect all-cause mortality.”

So much for the limitations of the study.

What is particularly important about the failure of this study is that it does not take account of the manner in which health conscious individuals use anti-oxidant supplements for the primary prevention of disease.  Anti-oxidants act synergistically, in that they replenish each other and thus continue to remove harmful free radicals after being damaged by oxidation, thereby providing ongoing protection to cells, tissues, and body organs.

Vit. E, on its own, can be damaged by oxidation and may thus cause harm (alpha-tocopheral) unless replenished by Vitamin C, with which it works synergistically to regenerate itself and become active again.

Furthermore, alpha-tocopherol does not occur in isolation in nature, but occurs as part of a family of tocopherols and tocotrienols which together disarm potentially harmful free radicals.  Gamma-tocopherol,an important component of the tocopherol family, has been shown to have powerful anti-oxidant and anti-inflammatory properties and can prevent free radical damage in the arterial wall, brain, kidneys and the organs.

Most clinical trials have used synthetic Vit. E. in the form of alpha-tocopherol, which has limited anti-oxidant properties, and on its own may be harmful, thus giving rise to outcomes showing limited benefit in risk reduction.  Vitamin E supplements should therefore include gama-tocopheral, or naturally occurring tocotrienols in combination, in order to produce the benefits supplied by dietary anti-oxidants.

Bjelakovic and colleagues have acknowledge the properties of anti-oxidants by stating that “anti-oxidant supplements may show interdependency and may have effects only if given in combination.”

This fact highlights the weakness of this meta-analysis and other similar studies which test single nutrients in isolation, for by so-doing, a drug model is employed, which is not appropriate for nutritional analysis, in which nutrients are seen to act in concert and are interdependent in their function.

Given the limitations of this meta-analysis there is nevertheless a positive message with practical implication for anti-oxidant consumers, and this is to avoid synthetic nutrients in isolation and use only natural anti-oxidants in combination which have been produced by credible manufacturers.

A further implication is that natural anti-oxidant supplement should not replace foods that contain balanced combinations of anti-oxidants.

Prof. Reville is correct to highlight the importance of a “balanced diet”, but I seriously doubt that this ideal is achieved in a typical modern-day lifestyle, and for this reason supplementing an inadequate or impoverished diet with balanced anti-oxidants makes good sense for purposes of protection and prevention of diseases linked to free radical damage.

Using mega-doses of nutritional supplements to reverse or halt pathological processes and improve health and longevity is quite possible, but these protocols are best understood within the context of Orthomolecular Medicine, Epigenetics and Nutrigenomics, which recognise the influence of nutrients on gene expression in acute and chronic illness.

Recent advances in Molecular Biology have demonstrated some of the mechanisms whereby nutritional intervention, directly or indirectly, is able to alter gene expression or structure, and offer a potential strategy for preventing, mitigating or curing chronic disease.

Medicine, as we know it, is in crisis, and new frontiers lie ahead beyond which a new paradigm will demand a review of our currently held perceptions about nutrition.

The use of vitamin D3, now becoming increasingly popular (at last ) in traditional medical practice, is one example of a shift in therapy from simply treating disease to optimizing health and human function.

The same mind shift is slowly occurring in respect of the n-3 fatty acids (omega 3), and these revisions of perception and practice are not only timeous, but long overdue !

The old paradigm of diagnosis and classification of disease into organ systems will soon pass away as molecular biology challenges the conventional views of nutrient therapy, and calls for a new understanding of the nutritional deficiencies that underlie chronic disease.

We are on the verger of a new frontier in medicine, and opportunities are emerging for individualising medical care through the appropriate and optimum use of macro-nutrients for a wide range of chronic disorders.

The  traditional abdication of the science and practice of Nutrition by conventional medical practitioners is now being judged and challenged by the science of Nutrigenomics, and the use of optimum dosages of nutrients may well be part of our therapeutic arsenal in the near future.

Denouncing the merits of Nutritional therapy, as noted in the meta-analysis report, is without scientific credibility.