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Monday, February 25, 2013

Nutritional epidemiology ~ Faith or facts

In the course of a recent lecture on the subject of obesity, an issue arose in the discussion about an incremental approach to solutions for obesity. Thus individual action plans might seem very modest but a suite of such action plans could be successful in treating obesity. Allied to this viewpoint about incremental solutions came the old chestnut that sometimes, in epidemiology, we need to take action even if we don’t have definitive proof of the efficacy of that action. This chestnut, hankers back to the founder of modern day epidemiology, John Snow, who disconnected the tap from the water pump in Broad Street London, thereby ending a cholera outbreak. It is argued that Snow did not have definitive proof and this is the root of the view that sometimes, epidemiology needs to take a leap of faith. However, as Snow himself points out, of the 71 deaths he investigated, 61 were of people living in the vicinity of Broad Street and thus users of the pump. Three deaths occurred in children who lived nearer another pump but who went to school close to the Broad Street pump. Five others “preferred” the water at Broad street over their local pump. Only two deaths could not be linked to the guilty pump. All of this happened prior to our understanding of pathogenic microorganisms so Snow clearly couldn’t have used culture techniques to verify the organisms presence. He could have asked persons living away from the pump in question to drink the water in question but even in Snow’s time, the unwritten ethical position was: “First do no harm”. And so, armed with a dot map and his 71 case histories, the pump was disabled. This may have been a leap of faith in that definitive proof of cause and effect wasn’t to hand, but the quality of Snow’s data was excellent and compelling.

So in the field of human nutrition, how much of our public health nutrition policy is based on fact and how much on faith. In the early 1950’s. Ancel Keys studies the relationship between dietary fats, plasma cholesterol and the rate of heart disease in seven countries across the globe. Keys and his colleague Paco Grande then completed a series of human intervention studies in which patients in a psychiatric hospital were fen on reconstituted milk with a wide variety of fats and oils. The net outcome was definitive proof that the effects of dietary fat on plasma cholesterol could be accurately predicted using equations derived in their studies. But was there proof that lowering cholesterol would reduce the risk of heart disease. Endless studies ensued and all showed that high levels of plasma cholesterol were , at a population level, predictive of a higher risk of heart disease. Thus the dietary lipid hypothesis was upheld and entered the policy arena of public health nutrition.

A contrasting story is that of antioxidant micronutrients, particularly vitamins C and E. In the early 1980s, there was a widespread belief that plasma antioxidant levels played a major role in cardiovascular disease, in cancer and in ageing. The data was dominated by associations studies linking published levels of plasma antioxidant status in different countries with national disease rates. The relationships were most impressive. Animal studies also added to the theory and in vitro studies abounded showing how anti-oxidant vitamins could protect fractions such as low-density lipoprotein from oxidative damage which would otherwise render them very atherogenic. As often happens in the field of health research, someone wanted to cut to the chase and head for glory with a human intervention study. And so the ATBC (alpha tocopherol {vitamin E} beta carotene) study was designed and implemented. It failed to uphold the hypothesis and many reasons were put forward as to why the study was “unsuccessful”. Based on knowledge of these flaws, more intervention studies were rushed along and, all in all, the antioxidant theory was abandoned.

We can look at some other “successes” and “failures” in nutritional epidemiology. The protective role of folic acid in reducing the risk of a neural tube defect birth was shown in a randomized controlled trial leading to a major initiative in public health nutrition with the fortification of flour with folic acid. Trans fatty acids were removed from the food chain wherever possible on the basis of a strong human intervention study. In contrast, notwithstanding the strong evidence from correlational studies in humans of a link between fish oil fatty acids and cognitive decline, endless intervention studies have failed to show a protective effect.

Thus we have an excellent track record in human nutrition in translating observational studies that show an association between some aspect of diet and some health attribute into dietary intervention studies and then basing our policy interventions on food of those intervention studies.

Taxing sugar-sweetened beverages to reduce the incidence of obesity requires data from human intervention studies that show a direct link between weight gain and consumption of such beverages at rates that correspond to reality before anything is done. There are intervention studies and meta-analyses of such studies and the evidence is very weak if non-existent. To suggest that we trust these data so much and that we are fully confident that fiscal measures will be always positive and rarely negative is simply wrong and is bad science. To argue that sometimes we need to take leaps of faith in nutrition policy flies in the face of 6 decades of rigorous research on which nutrition policy has been built. Facts and not faith should drive policy. Facts are universal but faith is a subjective value.

Tuesday, February 19, 2013

Dietary supplements ~ useless or useful?

There is a general tenet in human nutrition that if one eats a healthy diet, then there is no incremental benefit from taking additional nutrients either as fortified food or as supplements. A healthy diet should provide all of one’s nutrient requirements. I would go so far as to say that, among nutritionists, this is more a doctrine than a mere tenet. In recent times, several papers have been published which challenge this concept. A good place to start is with a major survey of 12,000 US adults to ascertain and characterise usage of dietary supplements[1]. In 2011, Americans spent $30 billion on dietary supplements, which, to put it into perspective is equal to or greater than the annual GDP of Ethiopia, Jordan or Bolivia. Some 77% of the users of dietary supplements do so through their own choice with 23% doing so on professional advice. In general, users of supplements are happier with their health than non-users, which suggests that they use supplements as some sort of insurance. The vast majority of respondents stated that they took supplements to “improve” or “maintain” health. So, are they wasting their money?  A recent meta-analysis would say that indeed they are wasting their money where the end point was mortality. In this study, the authors completed a meta-analysis of dietary supplement (multi-minerals and multi-vitamins) intervention studies, which involved a final list of 21 publications, involving 91,074 adults, with a mean age of 62 and a mean duration of supplement use of 43 months. A total of 8,794 deaths was recorded. When the death rate of those assigned to intervention with the supplements was compared to that of those receiving a placebo, no statistically significant differences in death rate were seen. So, taking dietary supplements doesn’t make you live longer. But do they make you healthier?
Late in 2012, two papers were published from the “Physicians’ Health Study II Randomized Controlled Trial”. This began in 1997 with 14,641 male physicians aged 50 years or greater entering the study. There were several treatments. One involved a multi-vitamin supplement. Two others involved either vitamin E alone or vitamin C alone. A final group received a placebo. After an average follow up of 11.2 years, 1,732 cases of major cardiovascular events (non-fatal serious heart attack or stroke) were observed[2]. No statistically significant differences were observed in cardiovascular events between treatment and placebo. So supplements wont make you live longer and wont make your heart any healthier. However, a second paper from the same Physicians Health Study Randomized Controlled trial did show that the overall risk of cancer was moderately reduced in those assigned to the vitamin supplements as opposed to those assigned to the placebo[3]. The authors conclude that: “Although the main reason to take multivitamins is to prevent nutritional deficiencies, these data provide support for the potential use of multivitamin supplements in the prevention of cancer in middle-aged and older men.” What a pity these studies didn’t employ modern genomics and metabolomics technology to look at responders and non-responders. When will nutritional epidemiology enter the 21st century?

The issue of vitamin supplementation was the subject of yet another recent paper, this time with a focus on folic acid supplementation in the pre-natal period and during pregnancy. Normally the end-point of such interventions would be neural tube defects such as spina bifida but in this case it was autism. The study was within the Norwegian Mother and Child Cohort study, which recorded the use of folic acid prior to conception and in the first 8 weeks of pregnancy[4]. Among the 85,176 children born in the cohort after exclusion of some births (12,000) for reasons such as premature delivery or lack of data on folic acid use, some 114 cases of autism were observed, equating to a rate of 0.14%. Among women who took folic acid supplements the rate was 0.10% while among women who didn’t take folic acid supplements the rate was 0.21%. This difference was statistically significant even when controlled for maternal and paternal education and age, a planned pregnancy, parity, year of birth and maternal BMI and smoking habits.
Clearly, some people benefit from dietary supplement use and the challenge to nutritional science must be to use modern technologies to ascertain those that do and don’t benefit with a view to customizing supplement use to optimise health. The doctrine that states that you should get all your nutrients from foodstuffs is codswallop.

[1] Bailey RL et al (2013) JAMA Int Med, On line February 4th
[2] Sesso et al (2012) JAMA, 308, 1751
[3] Gaziano JM et al (2012) JAMA, 308, 2012
[4] Suren P et al (2013) JAMA, 309, 570