Study suggests high fructose corn syrup is uniquely fattening, a that a calorie is not a calorie after all

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Variously on this site I’ve discussed the notion that ‘a calorie is a calorie’. Simply put, this concept, widely populated by doctors, dieticians and other health professionals, is that when it comes to their effects of weight, all forms of calorie are the same. In terms of its impact on body weight, a kilogram of fat will have the same as a kilogram of carbohydrate. Same for protein.

There is a certain logic to this, I suppose, but on the other hand, one could argue that it assumes that all forms of calorie are metabolised with equal efficiency. Imagine for a moment within your body you have a lit barbeque (this represents your metabolism). If you put petrol (gasoline) and charcoal briquettes on the barbeque, would they burn at the same rate and as completely? Of course not. Could this be at all true for fuel (food) in the body?

One way to test this theory is to feed individuals diets of the same calorific value but different composition (e.g. high-fat/low-carb, and low-fat/high-carb) to see if the effects on weight over time are the same. Some studies have yielded results which suggest that the composition of the diet does indeed have a bearing on their impact on body weight, while other studies have not. One of the problems with these studies is that it can be difficult to ensure individuals are eating what they’ve been instructed to eat, even when cooped up in a hospital ward. And even if the diet can be completely controlled, it can be difficult to conduct such studies for long enough for any real difference between the diets to emerge.

One way round such problems is to do relevant experiments in animals, as I describe here. In this post I describe and experiment in mice which shows very clearly that it is possible for a diet to offer weight loss advantages (a so-called ‘metabolic advantage) in a way that has to do with not just the number of calories it contains, but the form they come in [1]. Specifically, this study found that mice eating a high-fat, low-carb diet lost weight, while those eating a high-fat, high-sugar diet of the same number of calories gained weight.

One fundamental difference between these diets was the amount of carbohydrate (in the form of sucrose, maltodextrin and starch).

I was interested to read about a study published this week which assessed the effects of different dietary composition on weight in rats [2]. This study came in two parts. In the first part, rats were fed:

1. sucrose (table sugar) solution for 12 hours a day and rat chow in unlimited quantities

2. high fructose corn syrup (HFCS) for 12 hours a day and rat chow in unlimited quantities

3. high fructose corn syrup for 24 hours a day and rat chow in unlimited quantities

4. rat chow alone and in unlimited quantities

Rats eating the HFCS for 12 hours a day gained more weight than those consuming the sucrose solution, despite the fact that overall both groups of rats ate the same number of calories. The HFCS group did, however, consume fewer calories from HFCS than the sucrose-group consumed in the form of sucrose.

In the second part of this experiment, male rats were fed either diet 2, 3, or 4 (above) for a period of 6 months.

Also, female rats were fed one of diets 3 or 4 for a period of 7 months.
Over the same period, female rats were also fed either HFCS and chow for 12 hours or sucrose and chow for 12 hours.

In summary, compared to controls (chow only), male rats:

gained significantly more weight on both HFCS diets (diets 2 and 3).

gained significantly more fat on both HFCS diets.

this excess weight tended to accumulate around the abdomen (it is abdominal fat in humans that is most strongly linked with chronic diseases such as heart disease and type 2 diabetes).

saw significant rise in levels of unhealthy blood fats known as triglycerides on both HFCS diets.

In female rats, all the above was true for rats eating diet 3 (HFCS for 24 hours a day plus regular chow).

Overall, what these results suggest is that high-fructose corn syrup had special capacity to induce fat accumulation, particularly around the abdomen, as well as high levels of triglycerides in the bloodstream. Importantly, these effects (including those on weight) are to do with something other than mere calories.

How much relevance these results have to humans is not clear. However, my suggestion is that these results have at least some relevance, particularly as there is clinical research in humans which has linked fructose with adverse effects on health, and quickly too. See here for more about this.

What this study reminds us of is the potential hazards of consuming high fructose corn syrup, a sweetening agent that, increasingly, is pervading our diet. It should also remind us that, when it comes to the impact foods have on weight and fatness, a calorie is not necessarily a calorie, after all.


1. Kennedy AR, et al. A high-fat, ketogenic induces a unique metabolic state in mice. Am J Physiol Endocrinol Metab 2007;292:E1724-E1739

2. Bocarsly M, et al. High fructose corn syrup causes characteristis of obesity in rats: In creased body weight, body fat and triglyceride levels

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