No such thing as a macronutrient

Monday, May 16th, 2011

Metabolism is complicated, so the scientists studying nutrition — like all scientists — make simplifying abstractions.

For instance, nutritionists see foods as composed of three macronutrients — carbohydrates, fats, and proteins — and numerous micronutrients — vitamins and minerals.

We’re used to hearing the word carbohydrate thrown around these days, but it was originally a highly technical term, referring to the carbon, hydrogen, and oxygen that form sugars and starches — and fibers.

Certainly these things seem like they belong in a group together when viewed through a chemical lens. The three monosaccharides — glucose, fructose, and galactose — all share the same chemical formula — C6H12O6 — and the other sugars and starches are made up of these monosaccharides.

But not all simplifying abstractions are created equal, and not all carbohydrates are metabolized the same way. This seems to get swept under the rug though.  In my basic nutrition textbook — used in med schools and vet schools — it briefly mentions that fructose gets converted to glucose in the liver, so it will be treated as glucose throughout the rest of the text. My advanced nutrition textbook only addresses fructose on two pages, according to the index.

Kurt Harris suggests that maybe there is no such thing as a macronutrient, and we should be treating individual nutrients, like fructose, individually:

Fructose is special. I would argue that fructose is so special that even calling it a “carbohydrate” is misleading. Later on I’ll discuss cellulose, which like starch is a polymer of glucose, but which, as the main component of indigestible sawdust, could not be metabolically more different than starch. So we can have polymers made of the very same LEGO-like building blocks, but because they are attached to each other in a different way, it is really a completely different substance.

In the case of fructose, we have a monosaccharide that has the same chemical formula and a caloric content equivalent to glucose, but is treated quite differently by the body because it has a different 3-dimensional structure.

Fructose is found in plants foods only, and especially in their fruit. Plants use fructose to attract animals like us to the fruit, so we will eat it and spread their digestion-resistant seeds about via our feces. The plant is not thinking of us when it does this. Fructose is fructose and is tolerated in reasonable amounts (whether you get it from table sugar, honey or high fructose corn syrup), but because fructose is tasty we have bred fruit and cultivated plants in order to increase its availability dramatically. Fructose has easily become an order of magnitude more abundant in our diets in the past few hundred years than it was at any time in the preceding several million years of human evolution. If fructose were as benign as saturated fat or starch, this would be no problem, but I am pretty sure it is not.

Like glucose, there is no dietary requirement for fructose, but unlike glucose, we do not require fructose for use as an internal fuel. There is no organ like the brain that has an absolute fructose requirement. In fact, our body has mechanisms that evolved specifically to keep most cells from being exposed to too much of it.

Because fructose spends more time than glucose in the unstable and reactive open configuration, it can react with proteins in a chemical reaction known as the maillard reaction. This results in glycation — attachment of a sugar — to other molecules, especially proteins. As proteins can be important structurally or as enzymes, this can have pathologic consequences. These glycated compounds are known as advanced glycosylation end products — AGEs.

Fructose absorption in the gut is most efficient when paired with equimolar (one-for-one equivalent) amounts of glucose.

When there is fructose in excess of glucose, or even when there is a large amount of fructose with glucose, there is often malabsorption in the small bowel — this can lead to rapid fermentation by bacteria in the colon, or abnormal overgrowth of bacteria in the distal small bowel. I speculate that fructose malabsorption is actually a defense mechanism to keep the liver from being overwhelmed by this metabolic poison, and the fact that we have not evolved a mechanism to handle big-gulp doses of fructose to the small bowel indicates modern quantities are likely outside of our evolutionary experience — the EM2.

When fructose is absorbed, it goes via the portal vein directly to the liver, and the liver attempts to clear it completely so it cannot get into the general circulation. This is good, as fructose seems to be about 10 times more likely to cause glycation than glucose. Even small amounts of it can wreak havoc.

To keep fructose out of the general circulation, it must be immediately burned or stored as fat. Fructose is related to the spectrum of serious diseases known as NAFLD (non-alcoholic liver disease), including fatty liver and cirrhosis.

Excess fructose, chiefly via the liver volunteering to “taking one for the team” causes a variety of negative effects that are linked to pathologic insulin resistance, metabolic syndrome, a general inflammatory state, and of course obesity.

Finally, fructose has no immediate effect on insulin release, but is linked to pathologic hyperinsulinemia via it’s effects on the liver. This is the exact opposite of glucose, which requires insulin to partition it when eaten, but for which there is no good evidence to relate it to chronic pathologic hyperinsulinemia.

(Note: This does not mean eating glucose is harmless once you have metabolic syndrome. You also have to be careful of large boluses of fat once your gallbladder is diseased. This doesn’t mean eating fat caused your gallstones, though — quite the opposite in fact.)

So fructose is a “carbohydrate” that has the same chemical formula as glucose, but unlike glucose, is very highly reactive with other molecules, is obligately metabolized by the liver, is malabsorbed by the majority of the normal population, can lead to NAFLD including fatty liver and cirrhosis, and in my view, is thus partly accountable for the current epidemic of metabolic syndrome, obesity and all the related diseases of civilization, including coronary disease and epithelial tumors.

Why do we lump harmless starch and possibly toxic fructose together and say they are equivalent macronutrients? They seem to have very little in common metabolically. Who cares about the paper chemical formula?


  1. Ben says:

    Ah, we want mystifing complexity, eh?

    Well, we might as well keep it simple, and start with “water”.

    Even liquid water itself, with no solutes at standard temperature and pressure, is not “water”.

    Look up bulk water, interfacial water, liquid crystalline water. Look up Martin Chaplin, Gerald Pollack, and Gilbert Ling.

    Damn mystifying.

  2. Dregs says:

    The first half of Gary Taubes’ Good Calories, Bad Calories also explores the metabolic treatment of various sugars with detailed summaries of many key studies and a good combination of sufficient technical detail and clear prose. Reading Taubes was eye-opening for me.

    As for Harris, his blog is simply great. His “Archevore diet” principles (previously labeled “12 steps to eating paleo”) is the clearest and easiest to follow exposition of how to eliminate the neolithic agents of disease from one’s diet that I have found.

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