Background
In Europe, the prevalence of obesity (BMI > 30 kg/m2) has tripled in many countries since the 1980s, and the numbers continue to rise. Presently, more than 50% of the population is overweight (BMI > 25 kg/m2) or obese, and more than 20% are obese.40 This translates into more than 200 million overweight or obese Europeans.
In the United States, the prevalence of overweight and obesity is 69%, and the figure for obesity alone is as high as 35% (or 79 mio adults).41 Also, childhood obesity is increasing at an alarming pace. Obesity is the most important known risk factor for type 2 diabetes, but obesity gives also rise to other serious complications, such as cardiovascular diseases, hypertension, and certain cancers (particularly in breast and colon), as well as psychosocial problems (e.g., depression, anxiety, loneliness, discrimination, mobbing). Further health consequences of obesity include dyslipidemia, insulin resistance, osteoarthritis, sleep apnea, asthma, lower back pain, gallbladder disease, reproductive hormone abnormalities, polycystic ovarian syndrome, impaired fertility, and childbirth complications. Taking action against the current obesity pandemic is therefore most important. A major approach is to initiate changes in food intake and eating behavior.
Weight-stable obesity is characterized not only by abnormally increased fat stores, but also by increased fat-free mass (FFM). The higher FFM of obesity results in higher levels of total energy expenditure, due to both an increased basal metabolic rate and increased energy expenditure (EE) for a given physical activity. Thus, FFM is strongly and positively correlated to EE, and it is the most important determinant and predictor of individual energy requirements. The size of the FFM can account for 70%–90% of the variability in EE between subjects.42,43 The higher EE due to overweight and obesity suggests that, in order to avoid weight loss, obese subjects must maintain a higher energy intake than nonobese subjects; consequently, the key question may be whether dietary composition (in particular, an increased sugar content) promotes excessive energy intake and hyperphagia in susceptible individuals. This can be examined by epidemiological surveys, by short-term studies on appetite control and energy balance, and by longer-term dietary intervention studies.
Epidemiological Studies
Methodological and Analytical Pitfalls
When reviewing the literature on cross-sectional surveys and longitudinal studies, a number of common methodological and analytical flaws can be identified. These must be taken into consideration in order to achieve a consistent picture of the relationship between dietary sugars and body weight. A source of possible error, more important than nonrepresentative sampling, lies in the difficult task of self-observation and reporting of food intake, as well as of body weight and height.
Undoubtedly, errors of this kind have resulted in an exaggerated range of individual variation in the response data and have therefore increased the standard errors of group means. If the response and translating errors are randomly distributed, however, the group means should still be useful measures and permit meaningful differentiation among the groups. Knowing the difficulties associated with the process of gathering valid information about food intake in the overweight and obese, one should establish a number of conditions to be fulfilled before accepting a study as valid.
It is well established that a major pitfall is the systematic under-reporting of energy by overweight and obese individuals, which has been clearly demonstrated by simultaneous measurement of free-living EE by the doubly labeled water method and of energy intake.44 Prentice et al.45 found that obese women under-reported their energy intake by 30%, and others have reported similar figures. 46 Further, selective underreporting of foods is most likely also taking place, making interpretation of dietary records and recall very complicated.47 One way to circumvent this uncertainty is to exclude studies in which substantial underreporting by overweight and obese subjects is evident from the analysis. These studies can be identified by a lack of positive relation between body fatness and energy expenditure. The same procedure should be followed when addressing the question of whether diet composition plays a role for type 2 diabetes, not least because the majority (80%–90%) of these patients are overweight or obese.
It is also important in the testing of the relationship between sugars and body fatness that dietary sugar content expressed in E% is used to examine possible associations. When intakes are expressed in grams per day, a positive correlation will occur even if the subjects compared are consuming the same diet.
This apparent relationship is due to the fact that subjects with high energy requirements consume higher amounts of all nutrients compared to subjects with low energy requirements.48 Another confounder problem is the fact that food items and nutrients often go together in a positive or negative way. Even after adjustments, there will still be a big likelihood for this so-called residual confounding.
Besides underreporting of energy intake, over-weight and obese subjects have a larger propensity to underreport their weight and to over-report their height.49,50 This has a large influence on the body mass index (BMI) and has been shown to produce significant errors in estimating the prevalence of overweight and obese subjects; therefore, the investigators should preferably measure weight and height themselves instead of the subjects doing it, or appropriate corrections should be made.51
Cross-Sectional Studies
In valid cross-sectional studies where obvious underreporters are omitted, case-control analyses of dietary composition in obese versus nonobese subjects have shown that obese individuals consume a diet with a higher fat and a lower carbohydrate content than do the nonobese. The diets of obese groups have been found to be 5–8 fat E% higher than those for the control groups. A proxy for dietary macronutrient composition can indirectly be obtained by measuring substrate oxidations, because the oxidative pattern seems to be relatively undisturbed by changes in dietary fat content in the first 24 h. Using a 24 h calorimeter, oxidative fat energy in the overweight and obese was found to be higher than in normal-weight controls (40.2% vs. 36.0%, p < 0.02).52 Unfortunately, this method only provides information about total fat and carbohydrate intakes.
Larger population studies have previously shown that as sugar intake (expressed in E%) increases, fat intake decreases, and vice versa.53,54 This phenomenon has been referred to as the fat–sugar seesaw. A number of cross-sectional population studies have also demonstrated that a higher sugar or sucrose intake (in E%) is related to a lower body weight or BMI, and vice versa.55–64 This would indicate that a low intake of sugars (or sucrose) produces overweight and obesity and that a high sugar intake may prevent weight gain. In some studies, the associations, however, have disappeared when obvious misreporters have been excluded.61 There are also some indications that differences exist between different genders and age groups; thus, stronger correlations have been found for men than for women in some studies,60,61,63 and in one study age was the strongest predictor of sugar intake, followed by BMI and energy intake.62
The form in which sugars are consumed also seems to influence the results, since sugars in drinks have been shown to produce increased energy intake and weight gain in the long term. In general, energy from drinks has been found to be less satiating compared with energy from solid foods. It is therefore easier to obtain an exaggerated energy intake when drinking compared with eating the source of energy. In one of the earlier landmark studies in this field, it was found that 1880 kJ/day from soft drinks increased body weight after 4 weeks whereas the weight was unchanged when the same energy came from jelly beans.65
A meta-analysis of 42 studies also showed that compensation was much less precise when fluids were ingested as compared to solid foods.66 This theory was supported by data from, among others, the NHANES-III study of 2- to 19-year-old children that showed that overweight children had a significantly higher percent energy intake from soft drinks compared with normal-weight children.67 The suggested mechanisms are primarily related to fewer satiating-producing signals after the intake of fluid energy sources, more specifically related to less chewing, less stimulation of the cephalic phase, faster gastric emptying, less contact with receptors in the intestinal tract, and less of an increase in satiating hormones. Finally, it could be that higher energy expenditures after solid versus fluid foods contribute to a lower propensity for gaining weight when consuming primarily solid foods.68
Cross-sectional studies can, however, only give a momentary picture of the situation and cannot reveal what produced the actual overweight. Thus, people with clinical conditions may change dietary habits and thereby spurious associations or reverse causality can arise. Findings from cross-sectional studies should therefore be interpreted with great caution. Instead, longitudinal population studies with follow-up data (prospective cohort studies) or randomized controlled trials (RCTs) should be considered with regard to how a certain dietary intake pattern may affect human health.
These types of studies provide the highest level of evidence together with meta-analyses on previously well-conducted studies.
Prospective Studies
In the past few years, several reviews, meta-analyses, and pro–con papers on the role of sugar intake for body weight regulation have been published.69–75 Some reviews and papers have also focused on the role of consuming beverages with and without added sugars. 70,71,76,77,78 They are not all in agreement, but do point in a similar direction.
One of the papers (Te Morenga et al. 2013) was produced in connection with the revision of the WHO guidelines for sugar intake.69 This paper comprises a thorough selection and evaluation of all studies according to relevant guidelines (e.g., WHO, Cochrane Collaboration, PRISME, and GRADE assessment). With regard to adults, a total of 16 prospective cohort studies were found that looked at associations between different measures of sugar intake (sweet foods, drinks) and obesity. The studies covered data from almost 500,000 subjects, including both gender, a wide age range (18–74 years), and most of the world (Europe, the United States, and China). Some data were from the same individuals (e.g., Nurses’ Health Study, United States) but were analyzed and published in different decades.
Out of the 16 studies, 11 showed a positive association between sugar intake and measures of adiposity. Although the picture was not crystal clear, it appeared that this was especially true for intake of sugar-sweetened beverages (SSBs) (including fruit drinks, iced tea, soft drinks, energy drinks) or sugar-sweetened soft drinks. Some differences in outcomes were seen in distinguishing between soft drinks and fruit juice, but this was also not consistent.
In one of the largest cohort studies (Nurses’ Health Study I and II and Health Professionals Follow-Up, United States), a total of 120,877 women and men were studied in 4-year intervals over 20 years, from 1986 to 2006. A number of factors were investigated, but after multivariate adjustments (age, baseline BMI, and all lifestyle factors), it was found that intake of SSBs was positively associated (+1.3 kg/4 years), whereas the intake of diet soda was negatively associated with body weight changes (−0.1 kg/4 years).79
For children and adolescents, 21 cohort studies were identified in this review.69 The studies covered almost 30,000 individuals of both gender (1–18 years) and derived from data in Europe, the United States, and Canada. A positive association between body fatness or weight gain and intake of sugar was seen in 15 of the 21 studies, with reported sugar intake coming from SSBs in 14 of these. In four studies, a negative association was reported, with reported sugar exposure being fruit juice in two of these. Recommendations to reduce sugar-sweetened foods and beverages showed no overall change in body weight. However, these studies had low participant compliance to the dietary advice given.
In a further quantitative meta-analyses based on five cohort studies in children/adolescents, with seven comparisons, a comparison of the higher intake with lower intakes suggested a significantly increased risk of being overweight associated with higher intakes of free sugars from SSBs (odds ratio 1.55). All five studiesshowed a positive association.
One earlier study in children is worth mentioning. The study was performed in 548 children (12 years old) in the United States. It showed that the intake of sugar-sweetened drinks increased the risk of weight gain over 19 months.82 For every extra sugarsweetened soft drink, the risk of becoming obese increased 60% (BMI ≤ 30.0 kg/m2). This study constitutes one of the milestones in the debate on sugars and obesity, since it was the first of its kindwith a longitudinal design that showed that sugary drinks may be fattening.
To summarize, most prospective cohort studies showed a positive association between a high intake of sugar and increased body weight, especially when SSBs were involved.
Intervention Studies
When assessing the results of intervention studies, it is important to consider the study design, study subjects, use of liquid versus solid sources of sweeteners, types of sugars, and other factors. Ideally, only the sugar in question is changed when manipulating the diet. However, keeping all dietary factors fixed, but one, is a huge and classic challenge in food and nutrition research. If one uses real foods as they are normally eaten, many factors beyond the one studied (e.g., sucrose) will normally differ. If one specific characteristic of a meal or diet (e.g., sucrose) is going to be investigated and all other factors are to be kept identical, this will often mean the investigation of less natural or adapted foods that would not normally be eaten in real life. Both designs have a purpose, depending on whether the focus is on mechanisms or on real-life situations. But it must be considered and decided upon each time before a study is conducted and also when a study is evaluated by others afterward.
Short-Term Intervention Studies
Short-term intervention studies lasting a few hours or days are interesting when studying physiological mechanisms, whereas longer-term intervention studies are more interesting when studying the impact on health of longer-term changes in dietary habits.
For weight maintenance, an energy balance must persist; that is, energy intake must equal energy expenditure. Dietary composition probably influences energy intake more than energy expenditure, although diet-induced thermogenesis may vary slightly according to macronutrient composition.85 Macronutrients compete with each other in an oxidative hierarchy with the following order: alcohol > protein > carbohydrate > fat. A high oxidation rate may promote satiety; therefore, a satiety hierarchy of the same order has been proposed.85 This has not, however, been proven correct in all studies.
Another view is that energy density rather than macronutrient-specific mechanisms determines energy intake86; hence, overeating may be encouraged by energy-dense foods, which may consist of both fat and sugars. The question is which position sugars (or sucrose) take? Do they promote excessive intake by being palatable or energy dense, or do they suppress energy intake through carbohydrate-induced satiating mechanisms—increased hepatic glycogen stores, oxidation in the peripheral tissues, or satiating hormones, such as gastric inhibitory polypeptide (GIP), GLP-1, and insulin?
Sugars, in general, increase palatability, and increased sugars in the diet could therefore stimulate energy intake and cause overeating. Some studies indicate, however, that sweet carbohydrates, including sucrose, exert a suppressing effect on appetite for a limited period after consumption,87,88 while others have not found this effect.89–91 The latter could be due to the use of quite small preloads of 20–40 g given in the form of a sweetened drink. Thus, food form (solid or fluid) seems important.
A recent meal test study92 showed that after drinking SSSD total energy intake (energy from the drink plus energy from the following ad libitum meal) was higher than compared to diet soft drink (aspartame) or water. In this study, the energy from the SSSD was not compensated at all at the following meal. The effects on appetite scores, GLP-1, GIP, and ghrelin levels were similar between the diet beverages and water. Thus, it was concluded that SSSD was not compensated by decreased energy intake at the following meal, emphasizing the risk of generating a positive energy balance by consuming energy containing beverages. Furthermore, there were no indications that the AS, aspartame, increased appetite or energy intake compared to water.
In another review of short-term studies, where sucrose and HFCS were compared, no differences were found with regard to effects on appetite and energy intake.93
In a 14-day study in normal-weight subjects, three different diets were compared with regard to appetite, ad libitum energy intake, body weight, and energy expenditure. One diet was rich in starch, one in sucrose, and one in fat.94 Subjective appetite ratings showed that on the sucrose diet, subjects felt more full and had less desire to eat compared with the fat diet, and they felt more satisfied on the sucrose diet compared with both the fat and starch diets. Despite this, ad libitum intake was lowest on the starch compared with the sucrose diet, and body weight decreased on the starch, but was stable on the sucrose diet. This could be related to quite large amounts of sugary drinks (fruit syrup and soft drinks) on the sucrose diet or to the higher dietary fiber content on the starch diet. Palatability ratings were highest on the sucrose diet, which may also have promoted energy intake.
Lawton et al.95 compared the effect of different types of snacks (± sweet or fat) on energy intake and body weight for 21 days. They found that subjects consumed more energy per day from a sweet snack than from a nonsweet snack and that most energy was consumed from a combined high-fat/sweet snack. Although fat energy percent in the diet decreased with the low-fat snacks, no differences between total energy intake and body weight were observed after 21 days.
Another factor to consider is that carbohydrates and sugars can stimulate EE, an effect that could counteract a slight increase in energy intake. Normally, the level of diet-induced thermogenesis for the main macronutrients is ranged with protein > carbohydrate > fat. Protein is more efficient in raising EE than carbohydrate and fat is the least potent macronutrient in this regard.
Considering the different types of carbohydrates, an increased intake of sucrose has been shown to stimulate thermogenesis compared with glucose or starch in an acute situation.96–98 This may be explained by the fructose moiety of sucrose, due to the increased cost of converting fructose to glucose in the liver or perhaps increased activation of the sympathetic nervous system.96
Only a few studies have looked at the effect of the long-term intake of different carbohydrates on energy expenditure. One was the 14-day ad libitum study in normal-weight, postobese subjects and matched controls mentioned earlier.94 Here, it was found that 24 h energy expenditures were 3% and 4.5% higher on a sucrose-rich diet compared with a high-fat or a starch-rich diet, respectively, mainly due to an increase in EE in the postobese subjects. Also, noradrenaline and adrenaline were increased on the high-sucrose diet, indicating a stimulatory effect of this diet on the sympathetic nervous system.
Another was a 10-week study comparing sucrose with ASs.99 In this study, the sucrose group consumed significantly more energy during the 10 weeks and body weight increased compared with the AS group. Surprisingly, 24 h EE was not increased, although basal metabolic rate after 10 weeks was significantly higher on the sucrose diet.
In the long-term Carbohydrate Ratio Management in European National diets (CARMEN) trial, no differences in 24 h EE were observed after 6-month ad libitum diets high in simple carbohydrates, high in complex carbohydrates, or high in fat.100 The lack of difference could be related to the small sample size (n = 7–9 per group), the specific study group (overweight and obese), or perhaps adaptation to the diets in the long term.
Long-Term Clinical Intervention Studies
Several dietary intervention trials have shown that the recommended high-carbohydrate, high-fiber diet that is low in fat and energy density ad libitum can cause a spontaneous weight loss, especially in overweight subjects.101–104 According to previous and newer meta-analyses, a reduction of 10% in the proportion of energy from fat is associated with a reduction in body weight of 2.0–2.8 kg over 6 months.102–105
These weight losses may seem small, but when compared with the gradual increase in body weight many people now experience over time, a weight loss of even a few kilograms over 6 months is important, especially when no energy restriction is involved in obtaining this weight loss. A spontaneous reduction in energy intake due to a low energy density (great volume) and a high fiber intake is probably a major reason why such a diet decreases and helps maintain body weight in the long term.
The effects may, however, also differ depending on whether the fat is substituted by carbohydrate or protein. Thus, protein has been found to be even more efficient than carbohydrate in producing spontaneous weight loss on ad libitum fat-reduced diet.106
The question is whether sugars act like starch or whether, because of a possibly higher energy density and palatability, they assume an intermediate position between fat and starch. Intervention studies with a weight-maintaining or weight loss design cannot disclose how sugars affect appetite and body weight in a real-life situation; therefore, it is relevant to focus mainly on studies using an ad libitum design.
The large-scale, long-term, randomized, controlled multicenter trial CARMEN involved a total of 316 overweight subjects in 5 different countries.107 Here, it was found that 6 months’ ad libitum intake of low-fat diets rich in either simple or complex carbohydrates reduced body weight and fat mass by 1.6–2.4 kg compared with a higher-fat, control diet, with no significant differences between the simple and complex carbohydrate diets.
In the meta-analyses by Te Morenga et al.,69 a total of 30 intervention trials in adults were included. The analyses based on these studies consistently showed that with ad libitum diets, increasing or decreasing intake of sugars was associated with corresponding changes in body weight in adults. Thus, in these trials with ad libitum diets and no strict control of food intake, reduced intake of dietary sugars was associated with a decrease in body weight (0.8 kg), whereas an increased intake was associated with a comparable weight increase (0.75 kg). Isoenergetic exchange of dietary sugars with other carbohydrate showed no change in body weight.
No intervention trials in children were identified for that review. However, another recent review on SSBs and weight gain analyzed 20 studies in children (15 cohort studies and 5 trials) and 12 studies in adults (7 cohort studies, 5 trials).70 In cohort studies, an increase of one daily serving of SSB increased BMI and weight in both children and adults. RCTs in children showed reductions in BMI gain when SSBs were reduced and RCTs in adults showed increases in BW when SSBs were added. Thus, the conclusion from this review and meta-analyses was that SSB consumption promotes weight gain in both children and adults.
Glycemic Index, Appetite, and Body Weight Regulation
Classifying carbohydrates according to their chemical composition (monosaccharide, disaccharide, sucrose, or starch) does not always reflect the physiological effect of the carbohydrate; therefore, it is more relevant to consider the glycemic and insulinemic impacts when trying to evaluate the health effects of carbohydrates. It has been suggested that LGI foods increase satiety and reduce body weight compared with HGI foods108,109; however, controversies exist.110–112
In a previous ad libitum study, where macronutrients, dietary fiber, and energy density were well matched and only GI was manipulated, there were no significant differences in 10 weeks’ body weight or fat mass in the overweight study subjects.113
Thus, both energy intake body weight and fat mass decreased similarly on the HGI and LGI diets. In a subsample, there were also no differences in 24 h EE or substrate oxidation rates. However, after 10 weeks on the LGI diet, fasting LDL cholesterol and postprandial plasma glucose, serum insulin, and GLP-1 were significantly reduced compared with an HGI diet.114
In the Diogenes study, a design including both the ad libitum principle and weight maintenance after weight loss was used. Here, it was shown that a combination of an ad libitum LGI, high-protein diet maintained body weight loss better and had a favorable effect on glycemic control and insulin sensitivity than other protein and GI combinations after 6 months.115,116 Still, at the 12 months’ follow-up in a subgroup of subjects, the opposite pattern for GI and body weight maintenance was seen, making interpretation of the role of GI in long-term weight maintenance quite difficult.117
Further, the recent GLYNDIET study could not prove any differences in body weight after 6 months.118 Here, 122 overweight or obese adults were randomized to one of three isocaloric, energy-estricted diets for 6 months. The diets were a moderate-CHO and HGI diet, a moderate-CHO and LGI diet, or a high-carbohydrate and HGI, low-fat diet. After 6 months, BMI was reduced in all three groups and more so in the LGI group compared with the low-fat diet. But there was no significant difference between the HGI and LGI diets. Fasting insulin, HOMA-IR, and HOMA-beta cell function followed a similar pattern, but no other differences were observed in fasting or postprandial appetite sensations, blood lipids, or inflammatory markers after 6 months. Therefore, this study does not support a role for dietary GI per se in body weight regulation and risk factors for metabolic diseases. The GLYNDIET study was of a reasonably long duration and performed in large groups of subjects. However, the energy restriction and isocaloric design may have blurred possible differences between diets of HGI and LGI, which could perhaps have been seen if an ad libitum design and thereby appetite regulation had been involved.
Conclusion
Recent meta-analyses and reviews suggest that regular intake of sugary drinks should be avoided in order to maintain energy balance and body weight. Sugary drinks consumed ad libitum in free-living subjects add energy that does not seem to be compensated adequately for and can therefore easily lead to overconsumption of energy.
The influence on body weight of sugars from solid foods is less clear. Isoenergetic exchange of sugars for other carbohydrates does not seem to produce different effects on body weight. GI has not consistently been shown to be important in appetite and body weight regulation. However, methodological problems with the GI concept could play a role.
Finally, it is possible that the impact of different diets differs between more and less vulnerable individuals (e.g., subjects ± obesity, obesity prone, ± impaired glucose tolerance).
Notes
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By Anne Raben, Ian A. Macdonald, and Mikael Fogelholm in "Carbohydrates in Food", third edition, edited by Ann-Charlotte Eliasson, CRC Press (imprint of the Taylor & Francis Group), USA, 2017, excerpts pp. 102-115. Adapted and illustrated to be posted by Leopoldo Costa.