Lustig RH, Mulligan K, Noworolski SM, et al. Isocaloric fructose restriction and metabolic improvement in children with obesity and metabolic syndrome. Obesity (Silver Spring). 2016;24(2):453-460.
This was an observational, single-arm study to determine whether isocaloric substitution of starch for sugar as the primary carbohydrate source in the diet would improve metabolic parameters of obesity and metabolic syndrome.
Latino (n=27) and African American (n=16) children aged 8-18 years old. All participants were obese and had at least one other co-morbidity including hypertension, hypertriglyceridemia, impaired fasting glucose, alanine aminotransferase (ALT) >40 U/L, or severe acanthosis nigricans. Exclusion criteria included known diabetes, steroid medication use, any medication that affected insulin secretion or resistance, alcohol use, pregnancy, or neuroactive medications.
Study Medication and Dosage
For 9 days participants consumed a diet that delivered comparable percentages of protein, fat, and carbohydrate as in their self-reported baseline diet. The UCSF Clinical Research Service prepared all the food consumed by participants during the study period. In the intervention meals, mean daily dietary sugar consumption was reduced from 28% to 10% by substitution with starch. The starches used in the prepared meals were fully digestible and not the “indigestible starches” sometimes promoted for weight loss. Participants recorded daily weights; calories in the prepared meals were adjusted to maintain the weight of the participants. These increases in calories supplied by the meals were to compensate for the inaccuracy of using self-reported diet diaries to calculate daily caloric requirements. The menu was planned to restrict added sugar, while substituting other carbohydrates such as those in fruit, bagels, cereal, pasta, and bread so that the percentage of calories consumed from carbohydrate was consistent with their baseline diet, but total dietary sugar and fructose were reduced to 10% and 4% of total calories, respectively.
Fasting blood specimens, and oral glucose tolerance were measured on days 0 and 10 of the study. Dual-energy X-ray absorptiometry (DXA) scanning was also performed to determine bone, fat, and fat-free mass on these days.
A number of key biomarkers of metabolic syndrome improved significantly; diastolic blood pressure dropped (-5 mmHg; P=0.002), lactate dropped (-0.3 mmol/L; P<0.001), triglyceride dropped by 46%, and LDL-cholesterol dropped by 11.6 mg/dL (P<0.001). Fasting glucose and glucose AUC improved, implying improved glucose tolerance. Fasting, peak, and insulin AUC reduced, implying enhanced insulin sensitivity. These improvements were unrelated to calories or weight change. Glucose tolerance and hyperinsulinemia improved (P<0.001). Weight reduced by 0.9±0.2 kg (P<0.001).
The impact of dietary fructose in the diet of children and teenagers is significant and occurs quickly. During the study, participants obtained 47% of their daily calories from carbohydrates. Of these carbohydrates, mean sugar consumption was decreased from 27.7% at baseline to 10.2% of daily calories. Mean daily calories from fructose decreased from about 12% to about 4%. Replacing sugar with starch in effect replaces the fructose from sugar with additional glucose derived from the rapid breakdown of starch. Although this study lasted just 10 days start to finish, the results show significant changes in biomarkers predictive of a number of serious chronic disease.
Past epidemiologic studies have reported a positive association between fructose consumption as either white sugar or high fructose corn syrup with metabolic syndrome, cardiovascular disease, and type-2 diabetes.1,2,3
Yet actually proving that fructose causes metabolic syndrome has been difficult for several reasons:
- Long-term randomized controlled trials of dietary fructose consumption are difficult because in the real world, there is no integrated biomarker for dietary fructose or measure of consumption.4
- Past short-term experiments have added very high doses of fructose as an intervention and tell us little about the effect of relatively small decreases.5
- Recall bias on dietary questionnaires always seems to underestimates sugar consumption, so collecting accurate data is difficult.6
- The effects of fructose are often confused with its effect on adiposity, so it is difficult to differentiate between fructose, glucose, and starch effect.7
This study bypassed many of these problems by supplying isocaloric meals. As a result the researchers were relatively sure they knew what participants were eating. Starch replaced the majority of dietary sugars (glucose-fructose and fructose) so that although fructose was drastically reduced to 4% of total calories, the total calories and total carbohydrate consumed each day remained the same.
These same researchers reported in March 2015 that in adults, a high fructose diet (25% calories) caused a significant increase in lipogenesis by the liver.8
Animal and human experiments suggest that high fructose diets increase blood pressure by disruption of the sympathetic/parasympathetic balance,9 decreasing urinary sodium excretion,10 and increasing gut sodium absorption. Fructose also increases uric acid, which is an inhibitor of endothelial nitric oxide synthase.11
Past studies have taken the opposite approach to determining the effect of dietary fructose; they have increased dietary fructose and seen the opposite effects as in these low fructose diets. These results are compelling. First, because significant improvements are seen so quickly and secondly, the isocaloric diets tell us the reduction in fructose was fully responsible for the changes. These benefits appear to outweigh any possible negative effect that increasing starch might have been predicted to have. Remember, starches were substituted calorie for calorie for sugar and fructose.
Admittedly this idea does not come easy to those of us long focused on glycemic indexes and glycemic loads.
These results suggest that even substituting simple starch or glucose for fructose is a step in the right direction when it comes to preventing metabolic syndrome. Thus increasing pasta, bagels, and other starches—an idea that we have thought long outdated—is still an improvement over white sugar and even more so over high fructose corn syrups.
Admittedly this idea does not come easy to those of us long focused on glycemic indexes and glycemic loads, always mindful of the impact diet has on insulin production. It was not that many years ago when fructose was considered a “healthy” sweetener by health-minded consumers, and health food stores purposefully and proudly carried brands of soft drink that were fructose sweetened. Many consumers still believe that agave syrup, the chemical equivalent of high fructose corn syrup, is a healthy alternative sweetener. This study would suggest that white sugar and white flour might be better for a child’s health than any fructose-sweetened choices.
We might argue that reducing both glycemic index and total glycemic load along with total fructose would be a better approach. No one is arguing that it isn’t. Yet if the goal is to quickly change the hallmark markers of metabolic syndrome, lowering fructose should be our primary focus.
In explaining this study’s results to patients, it may help to review a bit of sugar chemistry. What people commonly call sugar (ie, sucrose) is a disaccharide, a molecule made of 2 sugar molecules, 1 of glucose and 1 of fructose. One might imagine that a pound of sugar when digested yields half a pound of glucose and half a pound of fructose. Starches are composed of long chains of glucose. When digested, starch pretty much all turns to glucose; a pound of starch breaks down to about a pound of glucose. Both sugar and starch are rapidly digested and broken down to their component sugars.
Patients will ask whether eating fruit is still a good idea. Fruits contain varying ratios of sucrose and fructose. The idea that fructose, often called fruit sugar, is the only sugar in fruit is erroneous. The ratio of fructose compared to glucose in fruits varies greatly by type of fruit. The website FoodIntolerances.org provides a list of fructose-to-glucose ratio in various fruits. For example, an apple’s fructose-to-glucose ratio is nearly 3. Dates in contrast contain equal amounts of fructose and glucose, and plums contain less fructose than glucose, to the degree that their ratio is only 0.6.
Paying attention to this fructose/glucose ratio and choosing low-ratio fruits may prove useful in treating metabolic syndrome.
Fructose does not stimulate insulin production, so the glycemic index of higher sugar foods may be lower than that of foods higher in simple starches. These 2 methods for evaluating foods, glycemic index vs fructose/glucose ratio, may yield conflicting results. This will trouble people who want clear answers as to which foods are best.
The data suggest that to reduce metabolic syndrome biomarkers, patients should reduce consumption of high fructose foods. High fructose corn syrup remains the primary problem. Tell patients to stop consuming it. Sucrose is a secondary source of fructose, and these data suggest that reducing consumption of sugar, because doing so lowers dietary fructose, will also have benefit.
- Basu S, Yoffe P, Hills N, Lustig RH. The relationship of sugar to population-level diabetes prevalence: an econometric analysis of repeated cross-sectional data. PLoS One. 2013;8:e57873.
- Yang Q, Zhang Z, Edward Gregg E, Flanders WD, Merritt R, Hu FB. Added sugar intake and cardiovascular diseases mortality among U.S. adults. JAMA Int Med. 2014;174:516-524.
- Ouyang X, Cirillo P, Sautin Y, et al. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol. 2008;48(6):993-999.
- Hedrick VE, Dietrich AM, Estabrooks PA, Savla J, Serrano E, Davy BM. Dietary biomarkers: advances, limitations and future directions. Nutr J. 2012;11:109.
- Stanhope KL, Havel PJ. Endocrine and metabolic effects of consuming beverages sweetened with fructose, glucose, sucrose, or high-fructose corn syrup. Am J Clin Nutr. 2008;88:1733S-1737S.
- Rangan A, Allman-Farinelli M, Donohoe E, Gill T. Misreporting of energy intake in the 2007 Australian Children’s Survey: differences in the reporting of food types between plausible, under- and over-reporters of energy intake. J Hum Nutr Diet. 2014;27:450-458.
- Sievenpiper JL, de Souza RJ, Mirrahimi A, et al. Effect of fructose on body weight in controlled feeding trials: a systematic review and meta-analysis. Ann Int Med. 2012;156:291-304.
- Schwarz JM, Noworolski SM, Wen MJ, et al. Effect of a high-fructose weight-maintaining diet on lipogenesis and liver fat. J Clin Endocrinol Metab. 2015;100(6):2434-2442.
- Brito JO, Ponciano K, Figueroa D, et al. Parasympathetic dysfunction is associated with insulin resistance in fructose-fed female rats. Braz J Med Biol Res. 2008;41(9):804-808.
- Rebello T, Hodges RE, Smith JL. Short-term effects of various sugars on antinatriuresis and blood pressure changes in normotensive young men. Am J Clin Nutr. 1983;38(1):84-94.
- Johnson RJ, Segal MS, Sautin Y, et al. Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am J Clin Nutr. 2007;86(4):899-906.