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Keywords:

  • Fructose;
  • health risks;
  • randomized clinical trials;
  • sugar

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. The biological effects of fructose
  5. High-fructose corn syrup vs. fructose in the US food supply
  6. Discussion
  7. Conflict of interest statement
  8. Acknowledgements
  9. References

What is already known about this subject

  • Consumption of high-fructose corn syrup (HFCS) beverages may play a role in the epidemic of obesity.
  • Fructose from sugar (sucrose) is just as bad as from HFCS.
  • Soft Drink consumption related to risk of obesity, diabetes, and CVD in adults and children.

What this study adds

  • Non-alcoholic fatty liver increased by consuming fructose in containing beverages.
  • Consumption of sugar sweetened beverages, fruit drinks and probably fruit juice may mimic metabolic syndrome.
  • Reducing intake of calorically sweetened beverages slows weight gain.

Background

Sugar-sweetened drinks and the fructose they provide are associated with several health problems.

Methods

Data from the Nielsen Homescan and product content were analysed for sweetener type using the Gladson Nutrition Database. Meta-analyses and randomized clinical trials were used to evaluate outcomes of beverage and fructose intake.

Results

Over 70% of all foods contain some amounts of added sugar, and consumption of soft drinks has increased fivefold since 1950. Meta-analyses suggest that consumption of sugar-sweetened beverages is related to the risk of diabetes, the metabolic syndrome and cardiovascular disease in adults and in children. Drinking two sugar-sweetened beverages per day for 6 months induced features of the metabolic syndrome and fatty liver. Randomized, controlled trials in children and adults lasting from 6 months to 2 years have shown that lowering the intake of soft drinks reduced weight gain. Genetic factors influence the weight gain when drinking soft drinks.

Conclusion

Consumption of calorie-sweetened beverages and the fructose they contain has continued to increase and may play a role in the epidemic of obesity, the metabolic syndrome and fatty liver disease. Reducing intake of soft drinks is associated with less weight gain and metabolic improvement as well.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. The biological effects of fructose
  5. High-fructose corn syrup vs. fructose in the US food supply
  6. Discussion
  7. Conflict of interest statement
  8. Acknowledgements
  9. References

Ten years ago, we wrote a paper with the title ‘Consumption of high-fructose corn syrup (HFCS) in beverages may play a role in the epidemic of obesity’ which attracted considerable attention [1]. It was correctly noted by others that the association between the epidemic of obesity and the increasing use of HFCS does not prove causation and that the intake of sugar and HFCS have levelled off since that time [2]. However, this paper did highlight the potential importance of sugar-sweetened beverages and the fructose they provide as potential causative agents in the epidemic of obesity in adults and children, and this has been highlighted frequently since [3-6].

The data which have accumulated in the last 10 years from both meta-analyses of epidemiological studies and from randomized clinical trials in adolescents along with the experimental studies on the effect of fructose would suggest that this earlier paper might have been retitled: ‘consumption of calorie-sweetened beverages and the fructose they contain may play a role in the epidemic of obesity, the metabolic syndrome and fatty liver disease’. We will briefly examine each of these issues. In addition, we provide some insights into the continued use of HFCS and other newer caloric sweeteners containing fructose, mainly fruit juice concentrate.

Fructose is a sweet-tasting sugar that is found naturally in fruits and some vegetables and which in modest amounts has been part of the human diet for eons [7]. The consumption of sugar has dramatically increased in the US and worldwide, and with it our exposure to fructose [2, 8-11]. Sugar consumption in the US has risen more than 40-fold since the Declaration of Independence was signed 250 years ago, and more than 40% of the added sugars in our diet are in sugar-sweetened beverages and fruit drinks [12]. In addition, over 74% of all foods contain some amounts of added sugars [13]. Thus, the principal sources of fructose in our diet are now sugar, which is 50% fructose, and HFCS, which in its most commonly used form in beverages is 55% fructose, although a prior study of popular beverages found that some contained 65% of sugars as fructose [14]. The intake of soft drinks has risen fivefold since 1950 [15, 16], and with it the intake of fructose. Most of this increase occurred since 1980. Similarly, the major rise in the consumption of HFCS in beverages has paralleled the rise in the prevalence of obesity and the metabolic syndrome and is associated with the appearance of non-alcoholic fatty liver disease [17]. With the high intake of sweetened beverages by adolescents and young adults, these observations are particularly important.

Over the past decade, fructose from either sucrose or HFCS has received growing attention as it has been associated with a widening group of health-related problems. Several meta-analyses have shown a relationship between consumption of sugar-sweetened soft drinks and obesity [18-20]. The relation of these beverages to obesity can be attributed to an increased caloric intake and to the fact that beverages do not suppress the intake of other foods to an appropriate degree – thus beverage calories serve as ‘add-on’ calories enhancing the risk of obesity. The path-breaking work by Mattes and Rolls has led to dozens of replications highlighting this relationship [21-27].

Meta-analyses have also suggested that the consumption of sugar-sweetened beverages is related to the risk of diabetes, the metabolic syndrome and cardiovascular disease [28].

Several short-term clinical trials have provided insights into the metabolic consequences of ingesting sugar-sweetened beverages. In one study, there was an increase in body weight, blood pressure and inflammatory markers [29, 30], in another an increase in triglyceride levels, particularly at night, a stimulation of de novo lipogenesis and an increase in visceral fat [31, 32]. In the third study, which compared daily intake of 1 L per day – approximately two 16 oz. servings of cola, diet cola, milk and water, the sugar-sweetened beverage increased liver fat, visceral fat and triglycerides over the 6 months of beverage intake [33]. The latter study suggests that consuming two 16 ounce sugar-containing beverages per day for 6 months can mimic many of the features of the metabolic syndrome and non-alcoholic fatty liver disease (Fig. 1) [10]. A more recent study showed that ingesting sugar-sweetened beverages for only 3 weeks was sufficient to alter lipid metabolism by decreasing low-density and increasing high-density lipoproteins which is a marker of increased cardiovascular disease risk [34]. From a public health perspective, it is of concern that drinking two sugar-sweetened beverages per day for 6 months can induce features of the metabolic syndrome and fatty liver. These studies certainly need to be repeated, but if replicated, the public should be warned about the hazards of drinking the beverages in much the same way as the Food and Drug Administration warns people about risk of medications.

figure

Figure 1. Model showing some potential consequences of increasing fructose and energy intake from sugar or high-fructose corn syrup in beverages.

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A recent series of randomized, controlled trials in children and adults lasting from 6 months to 2 years have been conducted. The two most noteworthy are the Boston [35] and Amsterdam [36] studies among children. After 1 year, the control group in the Boston Study gained significantly less weight than the group receiving the sugar-sweetened beverages. The Amsterdam study went further and provided either 250 mL of low caloric-sweetened beverage or a sugar-containing beverage providing 104 kcal to 641 youth over an 18-month period. The body mass index, weight, skinfold-thickness and fat mass increased significantly less in the low-caloric beverage group. A third 6-month adult study with three arms – low calorie beverage, water and normal beverage intake – found significantly greater likelihood of a 5% weight loss among the first two groups compared to the normal beverage group, but all lost weight as this was part of an active weight loss regime [37].

The biological effects of fructose

  1. Top of page
  2. Summary
  3. Introduction
  4. The biological effects of fructose
  5. High-fructose corn syrup vs. fructose in the US food supply
  6. Discussion
  7. Conflict of interest statement
  8. Acknowledgements
  9. References

At the time of the original Bray and Popkin [1] paper, there was little known about the relative effects of HFCS vs. fructose beyond the fact that fructose was metabolized differently than from glucose. Subsequently, a large number of studies have begun to allow us to understand the mechanisms by which fructose – be it from HFCS or any other form of sugar – affects our livers, kidney and overall cardiometabolic health.

The work of Stanhope et al. [31, 32] and many others [29-32] have been instrumental in pushing forward our knowledge. In an earlier study comparing the effect of glucose, fructose and sucrose on plasma triglycerides Schall and Cohen [38] found in young adults that both fructose in the amount found in sucrose and sucrose increased triglycerides following a meal, but that glucose did not lead them to conclude that the effects on lipids were due to the fructose either alone or as part of sucrose (table sugar), and not glucose. The recent study by Aeberli et al. [39] adds to the information about the role of fructose either from sucrose (ordinary table sugar from cane sugar or beet sugar or other sources) or from HFCS in initiating liver dysfunction and possibly leading to non-alcoholic fatty liver disease and the metabolic syndrome which have become increasingly prevalent [11, 17]. Figure 2 pulls the findings from the studies described above together in a single model [29, 31-33, 39]. The increasing intake of soft drinks [2, 11] is viewed as the driver for the increase in energy and fructose which may play a part in the development of obesity and the metabolic consequences depicted here [40]. The caffeine present in these beverages is viewed as a positive feedback signal due to its ability to stimulate the central nervous system.

figure

Figure 2. Proportion of total calories in foods and beverages purchased in the US food supply sweetened with any caloric sweetener and with high-fructose corn syrup (HFCS) 2000–2011. NS = Nutritive Sweetener; NFP = Nutrition Facts Panel data.

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Two other meta-analyses of crystalline fructose added to the diet appeared to reach different conclusions. Livesey and Taylor [41] and Sievenpiper et al. [42] examined the effect replacing carbohydrate in the diet with crystalline fructose. Both excluded HFCS, and thus the beverage form of fructose which seems to play the central role in the response to the fructose in beverages. Crystalline fructose added to the food supply represents only a few percent of total ‘added sugars’ and behaves differently from the fructose which is in beverages. The largest amount of dietary fructose comes from the fructose in sucrose or HFCS both of which are the major components of calorie-sweetened beverages, but which were excluded from these meta-analyses. In addition, there was major heterogeneity among the often small and short-term studies included in the meta-analyses of Sievenpiper et al.. Thus, these conclusions need to be interpreted cautiously.

One key question which Aeberli et al. [39] begin to address is whether the detrimental effects of fructose are simply the result of a linear dose-response to our increasing dietary intake of fructose, or whether there is a threshold below which fructose is without harm. The current data suggest that it is a ‘linear’ response and that the reason we are now detecting the pathophysiological consequences of fructose is that its dietary load has continued to increase, largely as a consequence of increased soft drink and fruit drink consumption as well as proliferation of HFCS in the food supply as detailed below. This is particularly important as many studies have shown that there is a group of adolescents and young adults that consume large amounts of sugar-sweetened beverages both in the US and across many other countries [12, 43-48].

High-fructose corn syrup vs. fructose in the US food supply

  1. Top of page
  2. Summary
  3. Introduction
  4. The biological effects of fructose
  5. High-fructose corn syrup vs. fructose in the US food supply
  6. Discussion
  7. Conflict of interest statement
  8. Acknowledgements
  9. References

To examine the current patterns of usage of all caloric sweeteners in the US food supply, we utilized a nationally representative scanned data on purchases of foods and beverages in the US from 2005 to 2009 [13]. We identified 85 451 uniquely formulated foods and beverages. Of these, 68% were sweetened with caloric sweetener only and 6% with both caloric and non-caloric sweeteners. Across unique products, HFCS was the most commonly listed added caloric sweetener in three major food categories: Cakes, cookies, pies; Fruit, fresh, frozen, canned, or dried; and Yoghurt and one major beverage category – all sugar-sweetened beverages.

We went further for this paper to ask the question: has the discussion about HFCS, which led to a number of blogs that demonized this sweetener, to legal suits whereby the cane and beet sugar industry are stating they are natural sugars and suggesting HFCS is unnatural, and many other approaches which all attempt to suggest that consuming a beverage or food with a natural sugar is healthful? One aspect of this push is to promote that natural sugars have a marked increase in the role of fruit juice concentrate as an added sweetener in many foods, particularly those labelled natural or organic [13]. Fruit juice concentrate is used as a sweetener in 7% of the 85 451 unique consumer packaged products [13]. It is commonly used not only in juices but also in sugar-sweetened beverages, low caloric-sweetened diet beverages, granola and energy bars, ready-to-eat cereals, and even infant formula and other infant foods (see table 2 of Reference 14, available online at http://www.andjrnl.org).

The final issue we explored was whether there has been a decline in the use of HFCS as a result of all the adverse publicity. Figure 2 shows for the hundreds of thousands of foods in the US food supply, the calories of foods with any added caloric sweeteners and those with any HFCS. The results for 2000, 2005 and 2011 are weighted to be nationally representative. For beverages, there is a marked decline (2.9 percentage points) in the proportion of calories from HCFS-containing drinks. The shift in the proportion of HFCS over all calorically sweetened foods, however, is minimal.

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. The biological effects of fructose
  5. High-fructose corn syrup vs. fructose in the US food supply
  6. Discussion
  7. Conflict of interest statement
  8. Acknowledgements
  9. References

This last decade has brought a sea change in understanding the health impact of caloric beverages in general and at the same time of the health impact of fructose in any form – be it food or beverage – on the health of children, adolescents as well as adults. Our review highlighted some of the key aspects of fructose from any form of sugar, particularly in beverages but also in foods in general. The beverage effect is particularly important because of the lack of caloric compensation when a beverage is consumed. However, we have seen that a very large proportion of the US food supply contains added caloric sweeteners and it is most likely that similar patterns exist in the global food supply.

The most important issue is to understand the impact of fructose on cardiometabolic health, be it from food or beverages, when consumed in any meaningful quantity. Figure 1 highlighted the effects on fatty liver disease [49-51], kidney function and kidney stones and functioning [52, 53], visceral fat and many other cardiometabolic problems [51, 54-56].

We noted earlier that the effect of beverages was highlighted by two recent randomized controlled trials in adolescents. There is an interesting additional adult study. Three recent clinical trials have shown that reducing beverage consumption in adolescents [35, 36] can slow the rate of increase in weight compared to a control group. Using genetic analysis, another group showed that the more risk genes an individual had for obesity, the higher the weight gain with drinking sugar-sweetened beverages [57]. Jointly, these and other studies noted earlier point out that the potentially detrimental health effects of drinking sugar-sweetened beverages and the fructose that they contain are substantial.

The concern with HFCS in our diet has led to a reduced proportion of HFCS in beverages compared to other sugars. This paper shows that this is a misplaced shift. In general, we show that any beverages – be it sweetened with HFCS or any other caloric sweetener – contains fructose. While there might be small differences in the proportions of fructose in various sugars, the key cardiometabolic difference is between drinking a beverage with and without any caloric sweetener. This argument however, hinges on knowing how much fructose relative to glucose is in beverages made with HFCS. One recent study [14] showed that in popular beverages the ratio is 65:35 which is vastly different from 50:50 ratio found in sugar and the widely circulated level of 55% fructose which is often attributed to HFCS.

As other papers in the volume of Pediatric Obesity and our paper shows, fructose remains a major component of our global diet. To date, to the best of our knowledge every added amount of fructose – be it from fruit juice, sugar-sweetened beverages, or any other beverage or even from foods with high sugar content – adds equally to our health concerns linked with this food component. It is not possible to use glucose as a sweetener in foods, so as long as the US and global food supply sees increasing quantities of caloric sweeteners in our foods and beverages, this problem will only worsen. Obesity, diabetes, hypertension, fatty liver disease, and many other cardiovascular and cancer concerns related to obesity or each of these problems will only worsen until we begin to arrest consumption of caloric sweeteners in the US and globally.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. The biological effects of fructose
  5. High-fructose corn syrup vs. fructose in the US food supply
  6. Discussion
  7. Conflict of interest statement
  8. Acknowledgements
  9. References