Isegoria

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?

Equal amounts of glucose and fructose may be isocaloric but not isometabolic:

This means we can eat 100 calories of glucose (from a potato or bread or other starch) or 100 calories of sugar (half glucose and half fructose), and they will be metabolized differently and have a different effect on the body. The calories are the same, but the metabolic consequences are quite different.

The fructose component of sugar and H.F.C.S. is metabolized primarily by the liver, while the glucose from sugar and starches is metabolized by every cell in the body. Consuming sugar (fructose and glucose) means more work for the liver than if you consumed the same number of calories of starch (glucose). And if you take that sugar in liquid form — soda or fruit juices — the fructose and glucose will hit the liver more quickly than if you consume them, say, in an apple (or several apples, to get what researchers would call the equivalent dose of sugar). The speed with which the liver has to do its work will also affect how it metabolizes the fructose and glucose.

In animals, or at least in laboratory rats and mice, it’s clear that if the fructose hits the liver in sufficient quantity and with sufficient speed, the liver will convert much of it to fat. This apparently induces a condition known as insulin resistance, which is now considered the fundamental problem in obesity, and the underlying defect in heart disease and in the type of diabetes, type 2, that is common to obese and overweight individuals. It might also be the underlying defect in many cancers.

If what happens in laboratory rodents also happens in humans, and if we are eating enough sugar to make it happen, then we are in trouble.

A recent study examines sports-injury lessons from the circus — or, more specifically, the link between confidence and injury rate in Cirque du Soleil performers:

When they arrived at the tryout camp, each newcomer completed a series of health questionnaires, including one that assessed feelings of stress, competence, preparedness and general mood. Then they trained for eight and a half hours a day, five days a week, for 16 weeks. Conditions were trying, Dr. Hallé said. The athletes were beginners again after years of being among the best in the world at their sports.

During the four months, more than half of the athletes sustained an injury severe enough to require a visit to the on-site physical trainer. Some injured themselves multiple times.

Hoping to discern what traits separated the injury-prone from the impervious, Dr. Hallé and colleagues from McGill University in Montreal compared data from the athletes’ psychological questionnaires with their medical charts. What they found was that a person’s level of confidence could significantly affect his or her risk of sustaining an injury.

This raises the obvious question of which way the causality runs:

Those athletes who had a low self-efficacy score on the health questionnaire were almost twice as likely to be injured as those who had scored high on that measure.

Dr. Hallé suspects that low self-efficacy lessens a person’s ability to focus. “Instead of focusing all of your attention” on the task at hand, she said, a nervous athlete will waste some of his limited attentional resources on, well, worrying, and stumble or falter during the activity, hurting himself.

What’s interesting is that the athletes who considered themselves unready for the demands of Cirque were not necessarily right. Some of those with low self-efficacy were not physiologically and technically up to the job. But others with low scores excelled.

“How do you differentiate someone who has appropriate self-efficacy because they are not actually as good as others” from those who lack confidence despite being better, asked Dr. Ian Shrier, an associate professor in the department of family medicine at McGill and lead author of the Cirque study.

The distinction matters, he continued, because interventions designed to prevent injury would almost certainly need to differ, depending on whether someone’s perceptions of his or her abilities and risks were accurate. If you’re correct that you’re not physically ready to perform a skill, then the best intervention is going to be augmented coaching and physical training. But if you have the ability but simply don’t believe that you do, intercessions should probably focus on building psychological coping skills, rather than physical technique.

For more than 30 years, Gina Kolata reports, Dr. Benno Nigg, a professor of biomechanics and co-director of the Human Performance Lab at the University of Calgary in Alberta, has asked how orthotics affect motion, stress on joints and muscle activity. His overall conclusion:

Shoe inserts or orthotics may be helpful as a short-term solution, preventing injuries in some athletes. But it is not clear how to make inserts that work. The idea that they are supposed to correct mechanical-alignment problems does not hold up.
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In his studies, he found there was no way to predict the effect of a given orthotic. Consider, for example, an insert that pushes the foot away from a pronated position, or rotated excessively outward. You might think it would have the same effect on everyone who pronates, but it does not.

One person might respond by increasing the stress on the outside of the foot, another on the inside. Another might not respond at all, unconsciously correcting the orthotic’s correction.

“That’s the first problem we have,” Dr. Nigg said. “If you do something to a shoe, different people will react differently.”

The next problem is that there may be little agreement among orthotics makers about what sort of insert to prescribe.

In one study discussed in his new book, “Biomechanics of Sport Shoes,” Dr. Nigg sent a talented distance runner to five certified orthotics makers. Each made a different type of insert to “correct” his pronation.

The athlete wore each set of orthotics for three days and then ran 10 kilometers, about 6 miles. He liked two of the orthotics and ran faster with them than with the other three. But the construction of the two he liked was completely different.

Then what, Dr. Nigg asked in series of studies, do orthotics actually do?

They turn out to have little effect on kinematics — the actual movement of the skeleton during a run. But they can have large effects on muscles and joints, often making muscles work as much as 50 percent harder for the same movement and increasing stress on joints by a similar amount.

As for “corrective” orthotics, he says, they do not correct so much as lead to a reduction in muscle strength.

In one recent review of published papers, Dr. Nigg and his colleagues analyzed studies on orthotics and injury prevention. Nearly all published studies, they report, lacked scientific rigor. For example, they did not include groups that, for comparison, did not receive orthotics. Or they discounted people who dropped out of the study, even though dropouts are often those who are not benefiting from a treatment.