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Healthy Eating and the Molecular Model of Medicine

by Geoff Moore, MD

In my blog on exercise as a medicine, I discussed how, 100 years ago, advocates of exercise had to learn how to think of exercise as biochemistry, and nutrition science underwent the same transition. At the turn of the 20th century, chemists were exploring the notion that there are substances in food that prevent diseases such as scurvy, beri beri, pellagra and rickets –nutritional deficiencies are spectacular examples of molecular causes of disease.

Because the first of these compounds were amines, Casimir Funk published a paper in 1912 calling them “vita” (life) + “amine”, or vitamines. This idea was adopted (though without the “e”) by Elmer McCollum and Harry Steenbock who had isolated a fat-soluble compound that prevented xerophthalmia, which they called vitamin A, and a water-soluble compound that prevented beri beri, which they called vitamin B. It was soon found that there were other water-soluble vitamins, giving a group of B vitamins, and then came more fat-soluble vitamins C, D and E. In 1933, Albert Szent-Györgyi isolated ascorbic acid (vitamin C) as the nutrient that prevents scurvy, which earned him the 1937 Nobel Prize in Physiology or Medicine and provided an exclamation mark to the molecularization of nutrition.

Knowing the importance of specific dietary compounds in preventing what Funk called “deficiency disorders”, in 1941 the National Academy of Sciences development of the Recommended Daily Allowances (RDA). The RDAs codified the idea that one needed a particular amount of specific nutrients in one’s daily diet. A chain of such recommendations over the decades, under various names, culminating in today’s Recommended Dietary Intake.

Sometimes people think that if some is good, more might be better. The most notable proponent of such thinking in nutrition was Linus Pauling, In 1966, Pauling advocated that humans need a very large intake – megadoses – of vitamin C. Pauling’s expertise had nothing to do with nutrition, but many people gave him benefit of the doubt…largely because he had won 2 Nobel Prizes (Chemistry and Peace).

Unfortunately, “more is better” thinking is often not true. Ultimately, large doses of vitamin C were found to have no benefit. Worse, large doses of vitamin A and vitamin E were shown to be harmful. High doses of vitamin A increases the risk of lung cancer in smokers, and high doses of vitamin E increase the risk of developing congestive heart failure in persons with coronary artery disease. Everything, even water, is toxic if you ingest too much of it. More is not always better.

Aside from diseases of deficiency, attributing health to specific dietary compounds is probably spurious logic. Humans tend to be biased by what we know, while we ignore complex phenomena we don’t understand. The truth is that nutrition is exquisitely complicated and far beyond our current insight.

In any food, there are thousands if not tens of thousands of compounds, but only a handful of them have been identified. The metabolome of food – compounds derived from foods after digestion and metabolism by body and gut microbiota – has at least 50,000 circulating metabolites and perhaps as many as 200,000 or more! The overwhelming majority of these compounds have never been identified. How they affect health is completely unknown. Moreover, in the molecular model of deficiency disorders, nutrients are considered in isolation, not in combinations of nutrients…which is how we eat them.

Aside from diseases of deficiency, what we know about diet is fairly limited. Alice Lichtenstein and Robert Russell openly declared that we mostly know about the benefits and hazards of dietary patterns, and not so much about nutrients in our diet. They called for dietary guidelines to be more focused on dietary patterns and less focused on nutrients, and the 2015 Dietary Guidelines for Americans (led by Lichtenstein) did just that. So what dietary pattern is best?

We know, with little disagreement among experts, that whole food plant predominant diets are associated with longevity and low prevalence of chronic conditions. We know that other dietary patterns, such as the “standard American diet”, are associated with a high prevalence of chronic diseases, particularly heart disease, diabetes and cancer. Dive in much deeper to diet, and disagreements arise over details like the amount of protein, the composition of fat, the risks of dietary cholesterol and other controversies.

The most elegant advice about diet comes not from a nutritionist but from journalist Michael Pollen, from his book In Defense of Food:

Eat food. Not too much. Mostly plants.

First, avoid what Pollen calls “edible food-like substances”, products sold as food but which consist of highly processed derivatives of foods. For corn, as an example, choose foods where the ingredient list simply says “corn”, and does not derivatives of corn such as “corn oil”, “corn meal”, or “high fructose corn syrup”.

Next, Pollen admonishes the reader about portion control. Actually, if you follow the third bit of Pollen’s advice, eating too much is hard to do!

Lastly, Pollen concludes that the closer one can come to being vegetarian or vegan, the better off one will be in terms of health and well-being. Human dentition is that of omnivores that eat both flesh and plants, but the less flesh one eats, the longer one is likely to live.

I’ll discuss food again in subsequent blogs, but for today we’ve come full circle. Nutrition science has adopted a molecular perspective, yet we’re a long way from having detailed understanding of how the nutrients in a diet produce health and well-being. As a starting point though, Michael Pollen’s advice is brilliant.


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