Fructose Tolerance is a Concept Gaining Diagnostic Ground
A small study looking both at people with metabolic syndrome as well as healthy adults has identified a hormone that rises sharply in response to eating fructose. The hormone, fibroblast growth factor 21 (FGF21), has been on the fat metabolism radar for some time, mostly due to studies on fasting and weight regulation in mice. Now, its role in fructose sensitivity in humans is being carefully explored.
The study found that fructose ingestion “acutely and robustly” increases circulating FGF21 levels in humans. This response is exaggerated in subjects with metabolic syndrome and is distinct from the FGF21 response to an equivalent amount of oral glucose.
The results are intriguing because of the quite different ways they may be interpreted.
A little like the nuanced debate over the function of inflammation in the healing process, we might conclude that a.) in essence, fructose is overstimulating the hormone, which because it is overstimulated is the cause of the weight gain, or b.) the hormone is simply a biomarker indicating the good fight is on to get rid of the unneeded fructose.
In other words, it is possible to say, as some do, that fructose may promote obesity and diabetes by overstimulating a hormone that helps to regulate fat accumulation. But what if the lesson is rather that fructose stimulated the sharpest rise in the hormone in people who were obese because they are resistant to the actions of FGF21 and so the exaggerated response to fructose ingestion may be, as the study authors put it, a compensatory response.
What is clear is that the hormone behaves in relation to fructose intake like insulin does in its relation to glucose intake. The elevated FGF21 levels were significantly correlated with circulating insulin-and-glucose levels in response to oral glucose loads in the subjects.
The study measured serum FGF21, glucose, insulin and triglyceride levels in 10 lean, healthy adults and 11 adults with metabolic syndrome following oral ingestion of 75 grams of glucose, fructose or a combination of the two sugars—which at 75 grams is similar to the sugar content of a 20 oz. bottle of Pepsi. The metabolic syndrome group was obese and at high risk of developing diabetes (as determined by a glucose tolerance test).
Glucose had a minimal impact on FGF21 but the highest does of fructose increased the hormone’s levels by nearly four times on average. Note that both baseline and fructose-stimulated FGF21 levels were two to three times elevated in subjects with metabolic syndrome.
The rise in sugar consumption that began in the 1970s is widely considered to be one of the most significant contributors to the nation’s obesity problem. The New York Times reports that between 1970 and 2000, the amount of added sugars in the food supply rose by 25%.
Sucrose accounts for much of this (a molecule of fructose bound to a molecule of glucose, producing table sugar). But what’s clear now is that much of the increase stemmed from the introduction of high-fructose corn syrup into the American diet. This is a cheaper sweetener that usually contains slightly more fructose than glucose, and it does not behave the same way.
Glucose goes from the bloodstream into fat and muscle tissues, with help from insulin. Fructose, on the other hand, mostly goes to the liver, where it stimulates the production of the storage form of excess calories in fat cells, triglycerides. Some of these are packaged into lipoproteins with cholesterol and secreted back into the bloodstream. Fructose, then, is a particularly bad actor in the development of metabolic syndrome and type 2 diabetes.
From Biomarker to Medication?
The study authors write, “Our findings here identify FGF21 as a measurable circulating biomarker to assess an individual’s acute hormonal response to fructose ingestion which may constitute a ‘fructose tolerance test.’ Future studies are needed to further elucidate whether this FGF21 response might contribute to or characterize risk for the development of fructose-associated physiology or metabolic disease.” [Emphasis added.]
The ideas here suggest spinning off research in several worthy directions. First, just as we now have glucose tolerance tests for determining risk of diabetes, a “fructose tolerance test” could employ FGF21 level monitoring to look for a related but subspecified set of disease risks. Next, we are unsure whether FGF21 response contributes to or merely characterizes such risk, and we should find out. But the characterization itself is important: it is useful as a biomarker in any case.
We know that people respond quite differently to fructose intake: meaning both “differently to fructose intake versus glucose intake,” and “differently to other individuals who intake fructose.” And so a third area worth exploring is the idea that it may be possible to test a person for weight gain-related illness susceptibility using the fructose sensitivity biomarker.
And finally, it may one day be possible to develop medications that regulate the hormone FGF21. This depends on many factors but notably for now, it depends on the ability of future research to illuminate this hormone’s exact causal role in weight gain-related illnesses.