Where we have a clear diagnosis and a well tested therapeutic option, then the role for any other treatment is less clear. However even with statins as one of the best studied medications we are faced with surprises. We have recently (recent in the history of the drugs use) found that it may hasten the onset of diabetes in susceptible individuals. The benefit of taking statins had been estimated to remain, despite the presence of diabetes. And the fact that this phenomenon was even discovered is a tribute to the many careful trials that have been carried out on statins alone (more than 1/4 million participants randomized in RCTs). For nutrients we do not have these data although vitamin D has been well studied and overall, it's use does not appear to have been associated with harm.
With a powerful placebo effect why are we so hard on the homeopathic approach? My great uncle Stanley Verity, a founding member of the British Medical Association, was general practitioner in Ross-on-wye, a country town (on the England and wales boarder) who used the placebo effect in the 1930s.
My Father when he graduated from the Middlesex Hospital Medical School in London (founded as a Med school in the early 18th century but now merged with University College Hospital) went to work as a locum with my great uncle while he decided what to do with his life (what specialty he wanted to enter). When he arrived my great uncle opened his medicine cabinet and showed my father what he had available that might not be readily available at the pharmacist. Amongst the medications was a large stock of medicine bottles containing blue, green or pink tablets. One has to remember that at that time we had no antibiotics, blood pressure meds, statins or diabetes meds as we have today. My great uncle informed my father that he used these colored pills when confronted with a patient with a relatively minor complaint, such as a troublesome cold for which he could do nothing. After careful examination of the patient he would prescribe a green, blue or pink bottle of tablets and the patient would depart. To return later for follow up. If for inexplicable reasons the cold persisted, again after thorough examination to look for other causes, he would again prescribe the tablets but select a different color. On the other hand, if, as was usually the case the patient was getting better he would prescribe a repeat of the same color to the great satisfaction of the patient. Further, if in the years to come the patient returned with a repeat of the same complaint, again after a careful history and physical examination he would check his notes and after confirmation with the patient he would prescribe the same colored medication that had worked previously.
My father was fascinated and enquired what exactly was in these green, blue and pink tablets? My great uncle replied that he had had them specially formulated. They were glucose tablets colored with vegetable colors. My father was shocked and disgusted with this deception and immediately left returning to his medical school.
At that time, we did not appreciate the power of the placebo effect. Combined with the lack of reasonable alternatives one might view my great uncle in a more favorable light. One might even say in the age of over prescription of antibiotics, antibiotic resistance, antibiotic use and related C difficile infection, my great uncle may have even been ahead of his time. The deception would still have got him into trouble today. Nevertheless, is there still a role for the first principle of Hippocrates and the medical oath named after him, translated from the Greek as "primum non nocere" or " first do no harm". My great uncle was certainly guided by this principle.
In terms of nutrient supplements there are certainly authorities who advocate a multivitamin/multimineral tablet to make up for dietary deficiencies in the eating habits of western nations. The case is a strong one. But trials do far have failed to provide compelling reasons in terms of CVD, cancer or all cause mortality reduction. One asks therefore if this lack of obvious effect is due to the fact some are getting too much of a particular nutrient that they were not deficient in and their lack of benefit may mask the benefit of those who needed the "top up"?
If this were the case then lower doses all round would not harm those who were replete, but over time would still help those who were deficient. Obviously, the bioavailability, storage and turnover of specific nutrients and the level of intake in the population would be additional issues to consider in one’s formulation of the new age "green, blue and pink tablets". But perhaps a more homeopathic approach on some circumstances is still warranted. This concern links with the current state of vitamin and mineral supplements where positive effects have been relatively few, even when seen, and for the most part coincide with relatively small trials.
An exception has been the CSPPT trial from China of over 20,000 participants. This trial demonstrated that folic acid supplementation reduced CVD and specifically stroke in a jurisdiction with no folate fortification. This fact may be all important since it may be key. We need to know what the status of a nutrient is in a population when one assesses its effects on that population. The effect of folate had not been clearly demonstrated in western populations where folate supplementation of white flour is mandated. However, the folate story is one bright light in an otherwise somber landscape of trials on nutrient supplementation. However even here there are concerns. High serum folate levels have been associated with prostate cancer. This problem had been downplayed in that the stroke benefit has been seen to outweigh the prostate cancer concern. Nevertheless, the concern remains, heightened by the fact that the large associated trial publication that the CSPPT group has subsequently put out on cancer incidence and folate contained all cancers except prostate. Perhaps this omission was because prostate cancer was irrelevant or because it did not fit with the picture of a harmless supplement. Either way we need the prostate cancer data to go forward.
Perhaps the other great hope had been vitamin D. However, although it has not shown the major preventive effects that one had hoped the "Sunshine " vitamin might do, nor has it shown evidence of harm. It could therefore fulfill my great uncle's indication for a placebo medication for problems for which we have no clear solution.
At the other end of the spectrum are the functional foods or food components. At one stage or other they have received approval from health Canada and the FDA to use health claims as part of their marketing strategy for CVD risk reduction. This approach has allowed a therapeutic strategy to be put together for dietary cholesterol reduction that is now referenced in the dietary guidelines of the Canadian Cardiovascular Society, Heart UK and the European Guidelines for statin intolerance. This dietary portfolio contains viscous fibers found in oats, barley and psyllium husk that increase bile acid output, similarly to cholestyramine. Soy protein inhibits cholesterol synthesis as do statins, plant sterols block cholesterol absorption like Ezetimibe and nuts function through many of the mechanisms mentioned above. Together these four components make up a dietary portfolio which is the subject of current recommendations. If each were to provide a meager 5% reduction in LDL -C then together with the 10% expected from a good diet, a 30% reduction would be predicted that is what you find. As a result, we may conclude that some supplements related to functional foods have definite use, vitamins and minerals may, but the placebo effect should not be disregarded where no harm is likely but possible good could be achieved.