Diet Drinks May Not Be So ‘Diet’ After All

On average, one-fifth of daily energy intake for UK adults is from sugar [1]. Not only does this affect dental health, but sugar consumption is associated with increased risk of obesity. One 330ml can of cola can contain more than the recommended daily intake of sugar, with few additional nutrients [2], therefore the government consider sugar sweetened beverages to be of high priority to public health. The ‘soft drink industry levy’ is driving reformulation by businesses, using artificial sweeteners to mimic the taste and mouthfeel of beverages, yet offer a healthier alternative. A recent study by Huang et al. reported a positive association between consumption of both sugar sweetened and artificially sweetened beverages and risk of diabetes [3]. After discussing these findings within wider research, it has been concluded that reducing consumption of sugar sweetened and artificially sweetened beverages may lower risk of diabetes and obesity, and that they should be replaced with unsweetened tea, coffee or water.

Current UK recommendations are that daily free sugar intake should not exceed 5% of total energy due to their association with increased risk of dental caries and excess calorie intake [1]. This means that adults should have no more than 30g, and children aged 4-6 and 7-10 years no more than 19g and 24g respectively [4]. Free sugars are define as those added to foods by the manufacturer, cook or consumer, and sugars naturally found in honey, syrups and unsweetened fruit juices [1]. In children and adolescents, who consume on average three times the recommended amount of sugar [2], the main contributor to intake is sugar-sweetened beverages (SSB) [1]. Consequently, they are being targeted by the government, with enforcement of a ‘soft drink industry levy’ from April 2018, taxing producers and importers of soft drinks containing added sugar [5].

The term SSBs includes carbonated soft drinks, fruit-flavoured drinks, sports and energy drinks, and ready to drink teas and coffees [6]. They generally contain either sucrose (50% glucose and 50% fructose) or high fructose corn syrup (45% glucose and 55% fructose) [7], greater sweetness perception offered by the additional fructose making the latter of popularity [8]. The sugar in SSBs contributes to total calorie intake [6] and stimulates a significant postprandial rise in blood glucose concentration, yet they are termed ‘empty calories’ due to their lack of essential nutrients. 

In an effort to reduce the sugar content of soft drinks, industries are focussing on innovation and reformulation, with sugar being replaced by artificial sweeteners such as aspartame, acesulfame K and sucralose, mimicking the organoleptic properties of SSBs but contributing minimal energy [6]. This action maintains supply of soft drinks and imposes a healthier product on the consumer, but does not promote behavioural change or educate individuals to be able to make rational food choices. With the likely shift in the availability of SSBs to artificially sweetened beverages (ASB), it is important to ascertain whether the direct replacement of SSBs with a ‘diet’ alternative should be promoted. A recently published study be Huang et al. investigated the association between consumption of both SSBs and ASBs and risk of diabetes, and the potential benefits of replacing SSBs with either ASBs or water [3]. This review will discuss their conclusions within wider research, considering the biological mechanisms that may make any effect plausible, to determine whether the action by industry to reformulate SSBs may reduce risk of obesity and associated comorbidities, or whether education and encouragement of replacement with other beverages may be a more effective public health strategy.

Method

Study population

Women aged 50-79 years recruited for the US Women’s Health Initiative (WHI) prospective observational study were studied.

ASB, SSB and water consumption

ASB consumption was assessed at the 3-year annual visit, with a unit of measurement as 355ml (12-ounce can). Four frequency categories were formed, and data was also used as continuous variables.

SSB consumption from the WHI food-frequency questionnaire (FFQ) was used. Frequency of consuming fruit juice and other fruit drinks was questioned as 177ml (6-ounce glass) servings. Data was used as categorical and continuous variables.

Tap and bottled water consumption frequency was questioned at the 3-year annual visit, with a serving size as 237ml (8-ounce glass). Serving size was adjusted for comparison and data was used as continuous variables.

Diabetes mellitus incidence

DM cases were self-reported at enrolment and follow-up to identify cases of DM but they were not classified as Type 1 or Type 2.

Statistical analysis

The association between beverage consumption and incident DM was analysed using Cox proportional hazards regression, adjusting for known risk factors and using follow-up duration as the interval between the 3-year annual follow up and the date of reporting DM, last data collection from the study or death. Analysis using BMI stratification was also conducted.

SSB consumption was modelled as total SSB and three subtypes. Substitution analysis modelled the potential replacement of ASB and SSB with water.

Sensitivity analysis used inverse probability weighting analysis to assess the implication of missing ASB data and lag analysis to exclude cases of DM that developed in the first 2-4 years of follow-up.

Results

Subject characteristics

Data from 64,850 women was analysed. Subjects consuming ASB most frequently were less physically active with a higher BMI, energy intake and greater abdominal adiposity.

Results of statistical analysis

After adjustment, a positive dose-response relationship between ASB consumption and DM was observed. SSB consumption significantly increased the risk of DM. ASB consumption was most significantly associated with incident DM for obese women (BMI≥30).

A stronger association was found between consumption of ≥1 serving/day of fruit drinks and risk of DM than fruit juice and regular soda. A 5% risk reduction was suggested from substitution of 1 serving of ASB per day and a 10% risk reduction for 1 serving of SSB per day with water. There was a non-significant risk reduction from substitution of SSBs with ASBs.

No differences were found in the sensitivity analysis. 

Discussion

The prospective observational study by Huang et al. concluded that SSB intake was associated with an increased risk of DM, independent of BMI, change in BMI and energy intake, which are all known risk factors for DM [3]. This positive association is frequently reported within the literature. Meta-analyses have found a 13% greater incidence of T2DM per serving increase of SSB [9], a 21% increased risk of type 2 DM (T2DM) per 250ml intake of SSB [10], and both a 26% [11] and 30% increased risk of T2DM for higher SSB consumption [12]. In children, a positive association between SSB consumption and change in BMI has been observed, and in adults each serving increase in SSBs per day has been associated with weight gain of 0.12-0.22kg throughout a year [7]. Moreover, higher intake of SSB has been associated with higher intake of energy and almost all food groups [13]. This suggests that SSB consumption causes increased adiposity as a result of inadequate energy compensation due to the inability of beverages to effectively suppress intake of other foods [14], an effect that may be augmented by the postprandial rise in blood glucose level, hyperinsulinemia and rapid removal of glucose from the bloodstream leading to increased hunger. Moreover, fructose and glucose are metabolised by separate physiological mechanisms [15], with fructose bypassing the rate regulating steps of glycolysis, being converted to fructose-1-phosphate, a process with no negative feedback control. Further steps produce glyceraldehyde-3-phosphate, which is an intermediate in gluconeogenesis and can be synthesised to glycogen. However, when glycogen stores are replenished it undergoes decarboxylation to acetyl coA [16] and hepatic lipogenesis [17]. The consequential increase in triacylglycerols (TAG) can increase very low-density lipoprotein (VLDL), leading to hypertriglyceridemia and visceral adipose deposition [16]. Not only does weight gain occur, but visceral adiposity is a major risk factor for T2DM.

Nonetheless, although Papier et al. reported 23% of the total association between SSB intake and T2DM to be mediated by obesity [18], many studies still report a positive association between T2DM and SSB consumption after adjustment for BMI [19], therefore it could be said that additional mechanisms exist by which SSBs elevate risk of T2DM above that of adiposity alone [20]. This may primarily be due to the high glycaemic load of the drinks causing recurrent high insulin levels, impairing β-cell function [18], and an increase in inflammatory biomarkers such as C-reactive protein, which contributes to insulin resistance [11]. However, it has been found that the proportion of the association mediated increases with increasing BMI, meaning that adiposity cannot be discounted as a significant contributing factor [18].

Similar to the observations regarding T2DM risk, Barrio-Lopez et al. reported those in the highest quintile of SSB consumption to have a higher risk of developing metabolic syndrome (MetS), which refers to a cluster of factors that increase risk of cardiovascular disease and DM when occurring simultaneously. It was reported that an increase in consumption by more than one serving per week doubled the risk of MetS. Moreover, a high intake of SSB was associated with elevated risk of developing high blood pressure, central adiposity, hypertriacylglycerolaemia and impaired fasting glucose, all of which are diagnostic criteria [21]. This conclusion was supported by a meta-analysis reporting a 20% greater risk of MetS with higher SSB consumption [11], and Chan et al. finding a 1.9-fold and 2.7-fold increase in risk for adolescents drinking >500ml of SSB per day. An association was also observed with increased serum TAG, waist circumference and adiposity index [22], suggesting the benefits of lower SSB consumption are significant and may extend beyond reducing risk of T2DM.

Although there has been a vast increase in the availability of ASB in an attempt to offer a healthier alternative beverage to consumers, Huang et al. found that ASBs were also associated with an increased risk of DM [3]. The wider literature supports this conclusion, with a meta-analysis reporting an 8% increase in incidence of T2DM per additional serving of ASB [11], and Sakurai et al. observing a 70% greater risk of DM for those consuming at least one diet soda per week compared to non-consumers [23]. This may seem to conflict with the previous discussion regarding the role of SSBs in the pathogenesis of DM, however it may be that there is an overestimation of the calories saved by substituting SSB with ASB, resulting in excess intake of other foods [23]. Additionally, both nutritive and non-nutritive sweeteners interact with taste receptors of the T1R family, which are present in taste buds on the tongue and GLP-1 secreting cells of the gut mucosa [24]. It is said that uncoupling sweetness with energy intake can cause metabolic dysregulation [19] and affect appetite, and it may be that continued exposure to sweet tastes results in an increased preference to high sugar energy-dense foods due to adaptation and decreased sensitivity. This may explain the dose-response relationship that has been observed between incidence of obesity, a risk factor for T2DM, and ASB consumption [25].

The association between T2DM and ASB consumption is frequently attenuated to a greater degree than that with SSBs [9][26], suggesting the potential for reverse causality to explain the relationship. ASB consumption in dieters has been reported to be higher than in non-dieters [20] and for ASB consumers to be more likely to be obese [26]. Such individuals may have increased risk of chronic disease such as T2DM due to adiposity and may consume ASBs as part of adopting a healthier lifestyle. This could imply that normal weight individuals, for which sufficient research is lacking, may not experience the increased risk of T2DM from ASB consumption. It is also important to consider the potential for residual confounding by lack of adjustment for lifestyle factors that may be significant in the pathogenesis of T2DM [9].

A further explanation for the similarity between T2DM risk for both SSBs and ASBs may be the caffeine content of such drinks, which has been shown to increase blood glucose concentration and decrease insulin sensitivity. Additionally, it is thought that there may be a synergistic effect of carbohydrates and caffeine in SSBs, with a resulting impairment of postprandial blood glucose homeostasis. However, Bhupathiraju et al. found both caffeinated and caffeine-free SSBs to be associated with higher risk of T2DM, with no change in risk when replacing caffeinated beverages with those that are caffeine-free [27]. Consequently, it could be said that any influence of caffeine on insulin response does not translate to long term risk of T2DM, potentially due to an accumulated tolerance to its effects, and that the sugar or sweetener in the beverages is the cause of the association.

There is great heterogeneity between studies in relation to the classification of SSBs. Many separate 100% fruit juice from sugar-sweetened fruit juices, although the SACN definition of free sugars incorporates both types. An association between sugar sweetened fruit juices and T2DM but not 100% fruit juice has been reported [28][29] which may be due to the additional nutrients it provides [30], such as antioxidants. This could suggest that replacing SSBs with fruit juice may reduce risk of T2DM. Nonetheless, the high sugar content should not be ignored when considering energy intake and risk of dental caries [1]. Huang et al. suggested a superior alternative beverage to be water, with a reduction in risk of DM observed [3]. However, research has also found that replacing SSBs with tea or coffee may offer similar, if not greater, health benefits [26] as flavonoids in tea can reduce oxidative stress, which causes enzyme and cellular damage, resulting in insulin resistance and the development of diabetic complications [27]. Further to this, it has been suggested that replacing 1 serving of SSB per day with 1 cup of coffee could reduce T2DM risk by up to 17% [20] due to its chlorogenic acid content, a component improving glucose metabolism and inhibiting glycation end product formation [27]. Despite this, it would be essential to ensure that excess sugar is not added to replacement beverages as this may attenuate any potential benefits experienced.

Impacts

To conclude, comparing the results of the study by Huang et al., which reported that consumption of both SSB and ASB was associated with increased risk of T2DM in post-menopausal women [3], it has been discussed that other studies have found similar results within other demographics. Clear evidence of the adverse effects of SSB intake has been identified, and it is has been suggested that that replacing these products with ASBs would not be of significant benefit. However, based on the physiological mechanisms by which these beverages increase risk of adiposity, MetS and T2DM, it is probable that frequency rather than quantity is of greatest importance as the regular elevated glucose and insulin concentrations, and stimulation of sweet taste receptors, affects appetite control, stimulates lipogenesis, causes insulin resistance and impairs β-cell function. This means it could be recommended to limit consumption of both SSB and ASB, opting for healthier alternatives such as tea, coffee and water to quench thirst, which instead reduce risk of T2DM.

As a result of this review, it could also be argued that the ‘soft drink industry levy’ enforced by the government may not translate to a significant reduction in obesity. Despite the promotion of reformulation of SSBs by businesses, there is potential for ASBs to cause excess energy intake by overestimation of saved calories and a reduction in sweet sensitivity, with a consequential greater consumption of energy-dense foods. It is therefore essential that the action is accompanied by education campaigns to empower consumers to make appropriate lifestyle choices to maintain a healthy weight and reduce risk of chronic disease.

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