Rippe Review on Added Sugars and Disease Risk Factors

On November 4, a review by James M. Rippe and Theodore J. Angelopoulos was published in Nutrients. The review entitled, “Relationship between Added Sugars Consumption and Chronic Disease Risk Factors: Current Understanding,” examines the latest, high quality science to address the ambiguity of the relationship between sugar consumption and various health related conditions.

Rippe and Angelopoulos first examined the literature pertaining to the metabolism of fructose. It has been established that more than 90% of ingested fructose is absorbed in the small intestine and metabolized in the liver on its first pass through the digestive tract. Approximately 50% of absorbed fructose is converted to glucose in the liver, about 15-20% of fructose is converted to glycogen, and 20-25% is converted to lactate. Isotope studies suggest that a small percentage of fructose is converted to carbon dioxide. Additionally, about 1-5% is converted to free fatty acids, which are then esterified to create triglycerides, a process termed de novo lipogenesis (DNL), and are either stored in the liver or circulate in the bloodstream. Reviewers note that the DNL pathway is a major pathway in mice but is minimal in humans; this difference has resulted in many instances of misinterpretation of data. However, some human studies demonstrate that high fructose diets (25% of total calorie intake) promotes DNL while replacing high fructose foods with items like vegetables, breads, and pastas reduced fat accumulation in the liver. Reviewers also highlight here the paradox that while obesity rates continue to rise in the United States, Britain, Canada, and Australia, the consumption of sugar has actually declined.

Next, reviewers discussed the effects of sugars on body weight and body composition. Reviewers noted various studies which test isocaloric exchange of sugar or fructose with other dietary components. Isocaloric replacement of sugars had no effect on body weight signifying that there is no unique property of sugars in terms of weight control. Reviewers noted that most other studies did not control for total energy intake and therefore, weight gain or weight loss could not be contributed solely to sugar intake. Similarly, when looking specifically at visceral abdominal fat, researchers found that diets high in glucose and fructose resulted in increased abdominal adiposity. In these studies, the participants gained weight and therefore, demonstrate excess caloric intake, which is a confounding variable for these studies.

Reviewers then shifted gears to examine the potential risk of sugar consumption on the development of diabetes. Rippe and Angelopoulos identified ecological studies and market availability studies which correlated the availability of sugar to diabetes. Reviewers noted availability does not equal consumption and therefore, these studies prove nothing. Reviewers then looked at prospective cohort studies. It was found that sugar sweetened beverage consumption was associated with an increased risk of diabetes, but only when comparing the highest and lowest levels of consumption. Interestingly, “pooled analyses for these cohorts, however, for total sugars, total sucrose, and total fructose have not yielded the same relationship.” When reviewers examined randomized control trials (RCTs), they found mostly neutral, and in one case positive, effects of free sugar consumption on markers of diabetes such as insulin, glucose, and glycated blood proteins.

Next, reviewers looked at the literature which attempted to define a relationship between sugars and cardiovascular disease. Reviewers point out that a number of studies suggest that diets containing 20% or more of total calorie intake from simple sugars may result in elevated triglyceride levels. However, they also pointed out that recent systematic reviews and meta-analyses demonstrate isocaloric substitutions of fructose for other carbohydrates does not result in elevated triglycerides. Reviewers found a number of studies which associated sugar intake with elevated low density lipoproteins (LDL); however, in these cases, added sugars were provided in excessively large doses, often times higher than the 90th percentile population. Conversely, a number of RCTs providing between the 25th and 95th percentile population consumption showed no changes in LDL. The Framingham Heart Study showed an increased risk of developing high blood pressure when consuming one or more sugar sweetened beverage daily. Interestingly, one meta-analysis showed that high sugar consumption had no effect on systolic blood pressure but did increase diastolic blood pressure by 1.4 mm/hg. Another meta-analysis which included 18 studies “showed slight decreases in both diastolic and mean blood pressure when fructose was substituted either isocalorically for other carbohydrates or in hypercaloric trials.” The collective RCT data shows that the association between sugar intake and blood pressure is minute and only occurs when doses are high (> 90th percentile population).

Lastly, reviewers examined the data for the effects of sugar on the brain. Studies using animal models suggest that fructose and glucose act differentially in the brain, particularly within the hypothalamus and reward pathways. When similar trials using sucrose and high fructose corn syrup were conducted, there were no differences. There still seems to be much controversy around stimulation of reward pathways in relation to fat and sugar intake. There also seems to be an unclear answer to the theory of sugar “addiction.”

Reviewers concluded that single nutrients should not be studied in isolation and that the food matrix is likely more important than a single nutrient. They also concluded that in terms of sugar sweetened beverages, the high quality literature “does not suggest signals for harm within the normal range of human consumption at least in short-term studies lasting six months or less and in longer term cohort studies where fructose containing sugars are substituted isocalorically for other carbohydrates.” Rippe and Angelopoulos also “agree with the assertion in the Dietary Guidelines for Americans (2010) that overconsumption of calories represents the single greatest health threat to individuals in the United States and elsewhere.”