Fructose restriction improves metabolic syndrome in obese children
Jacob Schor ND, FABNO
November 27, 2015
Two papers have come out in the last six months that suggest dietary fructose has a bigger impact than we imagined on blood markers of metabolic syndrome. Metabolic Syndrome is the current name for a group of risk factors that increases risk for heart disease, diabetes and stroke. Symptoms of metabolic syndrome, which for awhile in past years was called “Syndrome X”, can be thought of as early warning signs of these serious conditions. There are five conditions commonly listed to define metabolic syndrome:
1. Abdominal obesity
2. High triglyceride level.
3. Low HDL cholesterol
4. High blood pressure
5. High fasting blood sugar
The first paper came out last March and looked at the effect fructose has in adults. Eight healthy men were fed two weight maintaining isocaloric diets for 9 day stretches. One diet was high fructose (25% of total energy content) and the other substituted complex carbohydrates for the fructose. Eating the high fructose diet significantly increased the amount of fats being created in the liver. This wasn’t a big surprise as the link between fructose and elevated triglycerides and cholesterol has been talked about for decades. [see earlier 2005 newsletter below]
It’s the second paper, one that came out at the end of October that caught my interest and really advances our understanding.
Lustig and colleagues at University of California, San Francisco recruited a group of obese kids who ranged in age form 8 to 18 years old. Twenty seven of the kids were Latino, and 16 African-American. As mentioned they were all obese. They also had one or more other conditions, things called comorbidities, that included high blood pressure, high triglycerides, elevated blood sugars or signs of liver damage (that is fatty liver disease).
For nine days these participants consumed a diet that delivered comparable percentages of protein, fat, and carbohydrate as in their normal self-reported diets. What was interesting is that the UCSF Clinical Research Service prepared all of the food consumed by the kids for the 9 days of the study period. Kind of a meals on wheels program though I think it was self-service, pick up the food. In these prepared meals, dietary sugar was reduced from 28% to 10% and substituted with starch. Participants recorded daily weights, and calories in the prepared meals were adjusted to maintain weight of the participants. 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.
Remember this study only lasted 9 days. When blood and other tests were compared on day 10 to day 0, the day prior to starting the diet, a number of significant changes had occurred. Diastolic blood pressure dropped, lactate dropped, triglyceride dropped by 46%, and LDL-cholesterol dropped by 11.6 mg/dL. 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. Weight dropped on averabe by almost two pounds.
The impact of dietary fructose in the diet of children and teenagers is significant and occurs quickly. Remember this study lasted only ten days start to finish and yet demonstrated 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. [3, 4, 5]
Yet actually proving that fructose causes metabolic syndrome has been difficult for several reasons:
1. 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. 
2. 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. 
3. Recall bias on dietary questionnaires always seems to underestimates sugar consumption so collecting accurate data is difficult. 
4. The effects of fructose are often confused with its effect on adiposity, so it is difficult to differentiate between fructose, glucose and starch effect. 
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.
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 starch was substituted calorie for calorie for fructose.
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 of us would dare suggest.
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.
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.
It is also unclear how we should interpret these findings when it comes to cancer. In cancer patients our concern is often total glycemic load and its resultant increase in insulin that in turn may bind to and stimulate tumor cell IGF-1 receptors. If a high starch diet increases insulin sensitivity and thus decreases total insulin production, one might argue for a diet at odds with our current recommendations that reduce simple starches. At this point we are unaware of a prospective study supplying data to clearly answer this question.
I thought I had written something about fructose and obesity a few years ago. After searching through my files I see that the earlier article was written about ten years ago. I’ll paste it below.
Fructose and Obesity
Subject: Over consumption of high fructose corn sweeteners may be one of the triggers to the current epidemic in obesity.
Fully twenty-five years ago I recall sitting in a lecture hall, first row, third seat from the left, listening the professor of my nutrition 101 class go off on a small tirade. She was answering a question, which I may have asked, about fructose. At that time high fructose corn syrups were just becoming popular in food manufacturing. I was a food science major, specializing in product development; I saw no downside to fructose. The corn derived fructose syrups were far cheaper than other sugar sources. Fructose tastes sweeter than sucrose lowering the number of calories needed to produce a perceived level of sweetness in a food. Most important, fructose does not stimulate insulin production so conceivably could be used by diabetics. Food scientists, a title which I aspired to at the time, thought fructose was one of the most exciting developments to come along.
I seem to have blotted out the name of the professor; she was the Department Chair and had the manner and authority that goes with the office. Whatever the lame question had been, our esteemed lecturer shifted gears and was off talking about some recent research about feeding fructose to baboons. It seems adding fructose to a baboon’s diet radically changed their triglyceride and cholesterol levels, shoving them rapidly in the direction of liver problems and a heart attack. “What makes you think people are any different than baboons?” she asked. Though in memory the question has become more personal, “Mr. Schor what makes you think you are any different than a baboon?”
So it is no wonder that over these intervening years I have noticed fructose’s fall from grace. Fructose, the ‘natural sweetener found in fruits, was the sweetener of choice that even health food stores use in sodas. Times have changed; pasta and bagels are no longer considered the foundation of a good diet and fructose is now blamed for no end of health problems. Not just in esoteric circles of radical Ivy League nutritionists but, heck, even in this week’s AARP bulletin.
This month’s issue of the American Journal of Clinical Nutrition features a good article linking fructose consumption to the obesity epidemic. I’ll paste an abstract of the article below. Part of the article’s explanation as to why fructose promotes obesity is because it doesn’t stimulate insulin. Without the insulin stimulation, the consumer does not feel any sense of satiety. Fructose calories don’t fill people up the same way sugar does, prompting them to increase their overall caloric intake. This gives a whole new meaning to the phrase empty calories. Add this to the effect fructose has to blood lipids and heart disease risk and fructose should start to leave a bad taste in your mouth.
Not that I am saying that sugar is good for you, but it might be safer over the long run than fructose. The dollar cost may be higher but the health cost lower.
American Journal of Clinical Nutrition, Vol. 79, No. 4, 537-543, April 2004
Consumption of high-fructose corn syrup in beverages may play a role in
the epidemic of obesity1,2 George A Bray, Samara Joy Nielsen and Barry M Popkin
Obesity is a major epidemic, but its causes are still unclear. In this article, we investigate the relation between the intake of high-fructose corn syrup (HFCS) and the development of obesity. We analyzed food consumption patterns by using US Department of Agriculture food consumption tables from 1967 to 2000. The consumption of HFCS increased > 1000% between 1970 and 1990, far exceeding the changes in intake of any other food or food group. HFCS now represents > 40% of caloric sweeteners added to foods and beverages and is the sole caloric sweetener in soft drinks in the United States. Our most conservative estimate of the consumption of HFCS indicates a daily average of 132 kcal for all Americans aged 2 years, and the top 20% of consumers of caloric sweeteners ingest 316 kcal from HFCS/d. The increased use of HFCS in the United States mirrors the rapid increase in obesity. The digestion, absorption, and metabolism of fructose differ from those of glucose. Hepatic metabolism of fructose favors de novo lipogenesis. In addition, unlike glucose, fructose does not stimulate insulin secretion or enhance leptin production. Because insulin and leptin act as key afferent signals in the regulation of food intake and body weight, this suggests that dietary fructose may contribute to increased energy intake and weight gain. Furthermore, calorically sweetened beverages may enhance caloric overconsumption. Thus, the increase in consumption of HFCS has a temporal relation to the epidemic of obesity, and the overconsumption of HFCS in calorically sweetened beverages may play a role in the epidemic of obesity.
References for 2015 newsletter:
1. Schwarz JM, Noworolski SM, Wen MJ, Dyachenko A, Prior JL, Weinberg ME, Herraiz LA, et al. Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat. J Clin Endocrinol Metab. 2015 Jun;100(6):2434-42.
2. Lustig RH, Mulligan K, Noworolski SM, Tai VW, Wen MJ, Erkin-Cakmak A, Gugliucci A, Schwarz JM. Isocaloric fructose restriction and metabolic improvement in children with obesity and metabolic syndrome. Obesity (Silver Spring). 2015 Oct 26.
3. 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
4. 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
5. Ouyang X, Cirillo P, Sautin Y, McCall S, Bruchette JL, Diehl AM, Johnson RJ, Abdelmalek MF. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol. 2008 Jun;48(6):993-9. PMID: 18395287
6. Hedrick VE, Dietrich AM, Estabrooks PA, Savla J, Serrano E, Davy BM. Dietary
biomarkers: advances, limitations and future directions. Nutr J 2012;11:109.
7. Stanhope KL, Havel PJ. Endocrine and metabolic effects of consuming beverages
sweetened with fructose, glucose, sucrose, or high-fructose corn syrup. Am J Clin
8. 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
9. Sievenpiper JL, de Souza RJ, Mirrahimi A, Yu ME, Carleton AJ, Beyene J, Chiavaroli L, 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.