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Are All Sugars Created Equal? Let’s Talk Fructose Metabolism

By Chris Radlicz

According to NHANES (National Health and Nutrition Examination Survey) 2005-2010 the average American consumes about 20 teaspoons of sugar per day, with sugar consumption being the highest in teens and men (1). Interestingly, 33% of calories from added sugars come from beverages, and the majority of those beverages are sweetened with high fructose corn syrup (HFCS) (1).

But what is the novelty of HFCS? Aren’t the grams of sugar on the package all that matters? Although calorically equivalent, not all sugars are metabolized the same way.

Previous papers have established epidemiological links between fructose consumption, obesity, and metabolic disease. To take this further, recent literature has indicated that fructose, particularly in high concentrations, as present in high fructose corn syrup and sucrose, are proving to be toxic. HFCS is composed of about 60% fructose and 40% glucose (2). Prior to the processing of sugars, it was nearly impossible to find such high concentrations of sugar in the diet, but it now seems to be commonplace.

Dr. Kimber Stanhope out of University of California Davis published a recent review paper that touched on the metabolic dysregulation that occurs with high consumption of fructose.

Dr. Stanhope’s group has previously shown that subjects consuming fructose-sweetened beverages for 10 weeks, in addition to their normal diet, had increased de novo lipogenesis, dyslipidemia, circulating uric acid levels, visceral adiposity, reduced fatty acid oxidation, and insulin resistance. In contrast, subjects who consumed glucose-sweetened beverages, had comparable weight gain to the fructose group, but did not exhibit the aforementioned metabolic changes (3). These adverse effects seen in the fructose group all increase the likelihood of chronic diseases such as obesity, fatty liver, type-2 diabetes, and cardiovascular disease.

When consuming glucose, the liver is initially bypassed and the glucose reaches systemic circulation to be used by tissues such as the brain and muscles. If excess glucose is consumed in the diet, it will first be stored as glycogen, and secondarily as fat. Fructose on the other hand, takes a different path. When fructose is consumed, it is exclusively metabolized in the liver, where a particular enzyme, fructokinase, will allow for the uptake of fructose (3). Fructose metabolism as a whole lacks many of the cellular controls that are present in the glucose metabolism, which allows for unrestrained lipid synthesis (2).

Significant metabolic issues arise when a high concentration of fructose is consumed, such as in HFCS. An overload of fructose in the liver will lead to de novo lipogenesis and subsequent lipid droplet accumulation in the liver. With these high levels of fructose, the increase in lipid accumulation consequently decreases the breakdown of fat in the liver (3).

This intra-hepatic lipid will promote the production and secretion of very low-density lipoprotein 1 (VLDL1) leading to an increase in post-prandial triglycerides. A vicious cycle occurs effecting insulin resistance as well. The lipid in the liver will increase insulin resistance resulting in increases in circulating diacylglycerol. Additionally, the insulin resistance will lead to further lipid deposit in the liver with sugar having a greater propensity to turn to fat (3). A downstream effect of increased apoCIII and apoB will lead to muscle lipid accumulation, and end in whole body insulin resistance. All of this metabolic dysregulation results from the direct route fructose initially takes to the liver.

Although there is this well-defined and unique pathway for fructose metabolism, many industry-funded studies, haven’t shown the negative metabolic outcomes of consuming HFCS or sucrose (3). More research is certainly needed, but it is best to remember that added sugar in such high concentrations, no matter the culprit monosaccharide, is not favorable for overall health.

It is interesting to note a possible evolutionary perspective, which proposes the advantage of enhanced fructose to fat conversion. At the end of a growing season, ripened fruit will tend to have high levels of fructose. Therefore the fruit consumed at the end of the season may allow for increased fat storage, which would have been beneficial because of the low food availability in the ensuing months (2).

1.U.S. adults, 2005– 2010. NCHS data brief, no 122. Hyattsville, MD: National Center for Health Statistics. 2013.

2.Lyssiotis CA, Cantley LC. F stands for fructose and fat. Nature. 2013; 508:181-182.

3.Stanhope KL. Sugar consumption, metabolic disease and obesity: The state of the controversy. Crit Rev Clin Lab Sci. 2015;1-16.

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The Sugar Debate: ACCN Day Two

By Sheela Sinharoy, Student Blogger

Do you consider sugar to be controversial? From reading the mainstream media, where it is not uncommon to see “sugar” and “toxic” in the same sentence, one might assume that any debates about sugar have been resolved. However, Friday’s session on sugars and health made it clear that questions remain about sugar’s role in body weight, cardiovascular disease, insulin resistance, and dental caries.

In many people’s mind, a clear relationship exists between sugar and body weight. However, as Dr. John Sievenpiper explained, a 2013 systematic review and meta-analyses of dietary sugars and body weight (http://www.bmj.com/content/346/bmj.e7492) found no relationship between sugar and weight in isoenergetic comparisons (i.e., in trials where researchers substituted sugar with other carbohydrates, but held total calories equal). The study did find that an increased sugar intake was associated with increased weight, but Sievenpiper argued that this was simply due to increased calories, not to any unique properties of sugar. As he stated, when addressing weight gain, it is important to focus on overconsumption of all caloric food, including those high in added sugars.

Focusing next on cardiovascular disease, Dr. James Rippe shared evidence from a series of trials investigating the relationship of sugars with LDL, HDL, total cholesterol, triglycerides, blood pressure, total body fat, and abdominal fat. The trials found no relationship between sugars and any of the outcomes except for HDL and triglycerides. For these latter two outcomes, Dr. Rippe, like Dr. Sievenpiper, argued that these findings were due more to the excess calories than to any unique contribution of sugars.

The story with sugar and insulin resistance was, again, similar. Dr. Ian Macdonald explained that in animal models, evidence exists of large doses of fructose and sucrose leading to insulin resistance. However, this does not necessarily translate to human nutrition, and randomized controlled trials in humans have been inconclusive. Some studies have shown an effect of high doses of fructose on insulin resistance and liver fat, while others show no relationship.

The most conclusive evidence of an effect of sugar exists in relation to dental caries, which Dr. Paula Moynihan pointed out is the most prevalent chronic disease worldwide. As part of the World Health Organization (WHO) guideline development process, Dr. Moynihan led a systematic review on the relationship between sugar intake and dental caries. Based on the results, WHO has issued strong recommendations for reduced intake of free sugars throughout the life course and for intake of free sugars to be no more than 10% of total energy.

Throughout the conference, a number of speakers have referenced Americans’ changing dietary patterns and increases in consumption. This session was no different, as the overall message seemed to be that sugars alone cannot explain increases in overweight and obesity, cardiovascular disease, insulin resistance and diabetes. Rather, sugars are part of a larger constellation of factors that include dietary patterns and lifestyle patterns as a whole, which should be researched and addressed together in order to reduce the prevalence of chronic disease.