Paul from Facebook asks:

What are your thoughts on fructose? Is it really as bad as Paleo is making it out to be?

Dr. Robert Lustig has worked hard in recent years to demonize fructose, and his efforts have paid off. His YouTube video “Sugar: The Bitter Truth” has over 2.5 million views as of this writing. Lustig et al. claim that fructose is a uniquely fattening poison (when compared to glucose) that is as toxic to the liver as alcohol.

But is this true? Does the current evidence support this position? I’ve changed my views on this over time as I’ve become better acquainted with the literature, so I’d like to share my current understanding with you.

When it comes to fructose, calories matter

There’s no doubt that refined sugar – including fructose – can be problematic. But studies suggest that this is only true when calories are in excess.

This may be the most dangerous aspect of refined sugar: it leads to unintentional overeating. In a recent post on fructose, obesity researcher Stephan Guyenet points out that most people in these studies aren’t deliberately overfeeding. They are inadvertently overfeeding because they aren’t spontaneously compensating for the calories added to the diet via a large fructose- or glucose-sweetened beverage.

This doesn’t happen with fruit or other whole foods that contain glucose or fructose.

When people add fruit to their diet, they reduce their calorie intake elsewhere to compensate. Not so with liquid-sweetened beverages like soft drinks.

When people add a soda or two a day to their diet, they tend not to reduce consumption of other foods, and thus their calorie intake increases.

This is where fructose does appear to be more harmful than glucose. Although people don’t compensate for calories added via glucose or fructose, the fructose-sweetened beverages have more serious metabolic effects.

Is fructose uniquely fattening?

Dr. Lustig argues that, when compared to glucose, fructose is uniquely fattening. He claims that fructose is the most efficient substrate for de novo lipogenesis (DNL), which is the process by which the liver converts carbohydrates to fat.

However, Dr. Lustig relies on animal evidence that doesn’t apply to humans. There’s a big difference between mouse carbohydrate metabolism and human carbohydrate metabolism. When mice are on a high-carbohydrate diet that doesn’t provide excess calories, it’s common to see DNL rates of 50 percent and up. In other words, they are efficient at converting carbohydrates into fat, even when they’re not overeating. (1)

But in humans on an isocaloric diet (without excess calories), de novo lipogenesis falls into the range of 10 to 20 percent. The conversion of carbohydrate is less efficient in humans than it is in mice.

The research in this area is robust and uncontroversial. Nearly 50 controlled feeding studies have been performed on various aspects of cardiometabolic control. Most investigators working in this field believe that DNL in humans is negligible in response to fructose, and doesn’t comprise a significant source of dietary calories.

There’s another problem with extrapolating the animal evidence to humans in this case. The mice in the studies Lustig cites are eating huge amounts of fructose: up to 60 percent of total calories. You’d have to drink more than four 44 ounce Super Big Gulps a day to get that much fructose. Ain’t gonna happen.

According to researcher Dr. Sievenpiper in an interview with science writer David Despain at Evolving Health, the 50th percentile intake for people in the U.S. is 49 grams per day, which works out to 10 percent of total calories. Even the 95th percentile intake of 87 grams per day doesn’t exceed 20 percent of calories. That’s a lot of fructose, but it’s nowhere near the 60 percent of calories fed to mice.

Is fructose an evil toxin?

Dr. Lustig refers to fructose is a “poison” that is nearly as toxic to the liver as alcohol. But again, human evidence doesn’t support this claim.

In a recent paper, Dr. Luc Tappy and colleagues labeled acetate, fructose and different metabolites with stable isotope tracers so they could see how fructose is metabolized in the human body. (2) They found that 50 percent ends up as glucose, 25 percent goes to lactate and greater than 15 percent goes to glycogen. The remainder is oxidized directly (to CO2 through the TCA cycle) and a small portion – as low as 2-3% – is converted to fat via de novo lipogenesis.

Glucose and glycogen are easily processed by the body, and 2-3% conversion to fat is not significant. And while some have claimed that lactate may be problematic, a paper published more than a decade ago contradicts this. (Hat tip to Evelyn from CarbSane.) According to the authors:

The bulk of the evidence suggests that lactate is an important intermediary in numerous metabolic processes, a particularly mobile fuel for aerobic metabolism, and perhaps a mediator of redox state among various compartments both within and between cells… Lactate can no longer be considered the usual suspect for metabolic ‘crimes’, but is instead a central player in cellular, regional and whole body metabolism.

Translation: lactate from fructose isn’t a problem.

What does this mean for you and fructose?

Fructose-sweetened beverages like soft drinks and juice cause metabolic problems when calories are in excess, and studies have shown that people are not likely to compensate for the additional calories they get from such beverages.

This is why soft drinks and other beverages sweetened with fructose aren’t a good idea. That said, an occasional glass of fruit juice within the context of an isocaloric diet is unlikely to cause problems – unless you have a pre-existing blood sugar issue.

I don’t think there’s any basis for avoiding whole fruit simply because it contains fructose. As I’ve shown in this article, there’s nothing uniquely fattening or toxic about fructose when it isn’t consumed in excess. And since whole fruit contains fiber and other nutrients, it’s difficult to eat a lot of fruit without simultaneously reducing intake of other foods.

Fruit has been part of the human diet for longer than we’ve been, er, human. We’re well-adapted to eating it, and capable of processing the fructose it contains. (Unless you are FODMAP intolerant – but that’s a different issue entirely.)