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Heaney 2008 Atwater Lecture[read entire text here]
"Nutrients, Endpoints, and the Problem of Proof"[Notes]
Robert P. Heaney

...Less than a century ago, E. V. McCollum had to struggle with the prevailing notion that food was primarily fuel. The idea that not eating something could make one sick was considered laughable. Now, it is taken for granted that the quality of what we eat is at least as important as the quantity, an understanding that leads naturally to the determining of nutrient intake requirements...

...The original nutrient deficiency diseases were all of short latency and involved discrete body systems and dysfunctions. Rickets, pellagra, and beriberi are good cases in point...

...there is no inherent reason why inadequate intake of the same nutrients involved in short-latency diseases could not be producing long latency deficiency disease as well...low intakes might be expected to lead to disorders quite distinct from the disease originally connected with the nutrient. Vitamin D is a good case in point. Total body inputs closer to those that must have prevailed during hominid evolution are associated with reduced risk of disorders as varied as Type I diabetes, hypertension, osteoporosis, various cancers, multiple sclerosis, and periodontal disease, to name only some ...

Endpoints and the nature of nutrition

Much discussion, and even controversy, today centers around the question of whether these newly recognized endpoints should be considered when determining nutrient intake requirements. This controversy arises out of what seems to me to be three distinct operative models of what nutrition is all about.

For the news media and governmental regulators, nutrition seems concerned mainly about killing oneself with a fork....

In much the same vein, news stories in the general media concerning research studies involving nutrients are almost always negative, i.e. their message is "you will be harmed if you eat too much of this," ...

Nutritional policymakers, on the other hand, seem to be operating out of a model which, in effect, focuses on determining the lowest intake one can get by on without developing explicit disease. Such recommendations used to be called "minimum daily requirements," a term that has been dropped but a concept that appears still to be dominant. Once again, vitamin D serves as an apt example. The recommended intake up to age 50 is 200 international units/d. That quantity is sufficient to prevent rickets in children and probably osteomalacia in adults. However, it is an input that has been shown to be inadequate even to sustain serum 25-hydroxyvitamin D during winter at most U.S. latitudes (25) and in many cases it is insufficient to produce the other benefits associated with vitamin D, alluded to briefly above [e.g. osteoporotic fracture reduction (4)]. It is difficult to understand the rationale for this approach, but it may partly be due to the fact that there is a bias toward intake recommendations close to intakes that prevail in the population currently and, for at least some nutrients, intakes that should be readily achievable with currently available foods, if only better choices among them were made.

A model better than either of the foregoing, it seems to me, arises out of whole-organism physiology and rejects the simplistic, primary school approach to nutrition that can be caricatured as "one nutrient – one disease." It is based on the understanding that most nutrients act in all tissues, that all tissues need all nutrients, and that inadequate intake impairs all body systems (though obviously some more prominently than others). In brief, nutrition may be better conceptualized as the equivalent of preventive maintenance in a complex mechanical apparatus (such as an automobile). ..

Vitamin D again illustrates this point nicely. The wide variety of vitamin D effects can be reduced to what is probably a single mechanism. 1,25-dihydroxyvitamin D3 serves as a key component of the signaling system by which many cells access their DNA libraries to produce cell-specific proteins important for functional response to a wide variety of stimuli. The circulating 25-hydroxyvitamin D concentration is rate limiting in this system and thus low vitamin D status results in blunted or inadequate tissue responses such as the regulation of epithelial proliferation or the production of antibacterial peptides by macrophages...

it would seem to make better sense to presume the appropriateness of primitive inputs (where they can be known with some certainty) and to shift the burden of proof to those who say that such intakes are unsafe (rather than unnecessary) and that lower intakes would be more beneficial.

This approach to nutrition also plays into what has been termed the "squaring of the survival curve." Several years ago, Fries (27) noted that mean survival for humans was ~85 y, with a SD of ~4 y. Accordingly, excluding deaths from war, natural disasters, and the like, human survival ought to be close to 100% up to the mid 70s. ..over one-half of the breast cancer mortality in Europe and North America has a nutritional basis...

However, the success of the RCT in evaluating medical treatments has, perhaps, blinded nutritionists, regulators, and editors to the fact that it is a method ill-suited for the evaluation of nutrient effects. As a consequence, I submit that the field of nutrition needs to devise alternative designs to provide the required evidence base for its recommendations... [read entire text here]

 

 

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