Sugar-sweetened or artificially-sweetened beverage consumption, physical activity, and risk of cardiovascular disease in adults: a prospective cohort study.

BACKGROUND: Whether physical activity could mitigate the adverse impacts of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) on incident cardiovascular disease (CVD) remains uncertain. OBJECTIVES: This study aimed to examine the independent and joint associations between SSB or ASB consumption and physical activity and risk of CVD, defined as fatal and nonfatal coronary artery disease and stroke, in adults from 2 United States-based prospective cohort studies. METHODS: Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs between SSB or ASB intake and physical activity with incident CVD among 65,730 females in the Nurses' Health Study (1980-2016) and 39,418 males in the Health Professional's Follow-up Study (1986-2016), who were free from chronic diseases at baseline. SSBs and ASBs were assessed every 4-y and physical activity biannually. RESULTS: A total of 13,269 CVD events were ascertained during 3,001,213 person-years of follow-up. Compared with those who never/rarely consumed SSBs or ASBs, the HR for CVD for participants consuming ≥2 servings/d was 1.21 (95% CI: 1.12, 1.32; P-trend < 0.001) for SSBs and 1.03 (95% CI: 0.97, 1.09; P-trend = 0.06) for those consuming ≥2 servings/d of ASBs. The HR for CVD per 1 serving increment of SSB per day was 1.18 (95% CI: 1.10, 1.26) and 1.12 (95% CI: 1.04, 1.20) for participants meeting and not meeting physical activity guidelines (≥7.5 compared with <7.5 MET h/wk), respectively. Compared with participants who met physical activity guidelines and never/rarely consumed SSBs, the HR for CVD was 1.47 (95% CI: 1.37, 1.57) for participants not meeting physical activity guidelines and consuming ≥2 servings/wk of SSBs. No significant associations were observed for ASB when stratified by physical activity. CONCLUSIONS: Higher SSB intake was associated with CVD risk regardless of physical activity levels. These results support current recommendations to limit the intake of SSBs even for physically active individuals.

Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality.

Importance: Approximately 65% of adults in the US consume sugar-sweetened beverages daily. Objective: To study the associations between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality. Design, Setting, and Participants: A prospective cohort with 98 786 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative from 1993 to 1998 at 40 clinical centers in the US and were followed up to March 1, 2020. Exposures: Sugar-sweetened beverage intake was assessed based on a food frequency questionnaire administered at baseline and defined as the sum of regular soft drinks and fruit drinks (not including fruit juice); artificially sweetened beverage intake was measured at 3-year follow-up. Main Outcomes and Measures: The primary outcomes were (1) liver cancer incidence, and (2) mortality due to chronic liver disease, defined as death from nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% CIs for liver cancer incidence and for chronic liver disease mortality, adjusting for potential confounders including demographics and lifestyle factors. Results: During a median follow-up of 20.9 years, 207 women developed liver cancer and 148 died from chronic liver disease. At baseline, 6.8% of women consumed 1 or more sugar-sweetened beverage servings per day, and 13.1% consumed 1 or more artificially sweetened beverage servings per day at 3-year follow-up. Compared with intake of 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more servings per day had a significantly higher risk of liver cancer (18.0 vs 10.3 per 100 000 person-years [P value for trend = .02]; adjusted HR, 1.85 [95% CI, 1.16-2.96]; P = .01) and chronic liver disease mortality (17.7 vs 7.1 per 100 000 person-years [P value for trend <.001]; adjusted HR, 1.68 [95% CI, 1.03-2.75]; P = .04). Compared with intake of 3 or fewer artificially sweetened beverages per month, individuals who consumed 1 or more artificially sweetened beverages per day did not have significantly increased incidence of liver cancer (11.8 vs 10.2 per 100 000 person-years [P value for trend = .70]; adjusted HR, 1.17 [95% CI, 0.70-1.94]; P = .55) or chronic liver disease mortality (7.1 vs 5.3 per 100 000 person-years [P value for trend = .32]; adjusted HR, 0.95 [95% CI, 0.49-1.84]; P = .88). Conclusions and Relevance: In postmenopausal women, compared with consuming 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more sugar-sweetened beverages per day had a higher incidence of liver cancer and death from chronic liver disease. Future studies should confirm these findings and identify the biological pathways of these associations.

Artificially Sweetened Beverages and Health Outcomes: An Umbrella Review.

The consumption of artificially sweetened beverages (ASBs) is increasing in some countries. However, some meta-analyses have found that habitual consumers of ASBs (compared with low or no consumption) had an increased risk on some health outcomes. We performed an umbrella review of meta-analyses to grade the credibility of the evidence of claimed observational associations between ASBs and health outcomes. Data were searched in Web of Science, Embase, and PubMed for systematic reviews published up to 25 May 2022, examining association between ASBs and any health outcomes. Certainty of the evidence for each health outcome was obtained based on statistical results of tests used in umbrella reviews. The AMSTAR-2 tool (16 items) was used to identify high-quality systematic reviews. Answers of each item were rated as yes, no, or partial yes (for a partial adherence to the standard). We included data from 11 meta-analyses with unique population, exposure, comparison group, outcome obtained from 7 systematic reviews (51 cohort studies and 4 case-control studies). ASBs were associated with higher risk of obesity, type 2 diabetes, all-cause mortality, hypertension, and cardiovascular disease incidence (supported by highly suggestive evidence). Evidence for other outcomes (colorectal cancer, pancreatic cancer, gastrointestinal cancer, cancer mortality, cardiovascular mortality, chronic kidney disease, coronary artery disease, and stroke) was weak. Results of the quality assessment of systematic reviews using AMSTAR-2 showed some notable deficiencies: unclear sources of funding of eligible studies and lack of predefined study protocols to guide authors. The consumption of ASBs was associated with a higher risk of obesity, type 2 diabetes, all-cause mortality, hypertension, and cardiovascular disease incidence. However, further cohort studies and clinical trials in humans are still needed to understand the impact of ASBs on health outcomes.

Sugar-Sweetened and Artificially Sweetened Beverages Consumption and Risk of Cardiovascular Health.

INTRODUCTION: Sugar-sweetened and artificially sweetened beverages are routinely consumed worldwide. Given their popularity, there has been much debate about the effect that these beverages have on cardiovascular health. We sought to determine the exact relationship between sugar-sweetened and artificially sweetened beverages consumption on cardiovascular health. METHODS: All studies that reported an association between sugar-sweetened/artificially sweetened beverages consumption and cardiovascular health were extracted from database inception to September 2022 using keywords from several databases. We used the DerSimonian & Laird random-effects method for the analysis. RESULTS: Of the total 16 prospective studies, 1,405,375 individuals were followed for a median follow-up of 14.8 years. Compared with low sugar-sweetened and artificially sweetened beverage consumption, a higher consumption of sugar-sweetened and artificially sweetened beverages was associated with greater cardiovascular outcomes (hazard ratio [HR] of 1.27, 95% confidence interval [CI] of 1.16-1.40 and risk ratios of 1.16, 95% CI of 1.02-1.33). Similarly, compared with low artificially sweetened beverages consumption, a higher consumption of artificially sweetened beverages was associated with greater cardiovascular outcomes (HR of 1.32, 95% CI of 1.12-1.57). Likewise, compared with low sugar-sweetened beverages consumption, a higher consumption of sugar-sweetened beverages was associated with greater cardiovascular outcomes (HR of 1.21, 95% CI of 1.07-1.37 and risk ratios of 1.22, 95% CI of 1.09-1.35). CONCLUSIONS: Increasing consumption of sugar-sweetened and artificially sweetened beverages may be correlated with an increased risk of developing cardiovascular/vascular complications and mortality, albeit without causality of cardiovascular/vascular morbidity.

Artificially Sweetened Beverage Consumption and Cancer Risk: A Comprehensive Dose-Response Meta-Analysis of Prospective Studies.

The impact of artificially sweetened beverages (ASBs), alternatives to sugar-sweetened beverages, on cancer incidence remains controversial. We conducted a meta-analysis of prospective studies to assess the association of daily ASB intake with cancer risk. A systematic search was performed between January 1967 and September 2022. Risk ratios (RR) or hazard ratios (HR) were extracted and pooled. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used for the assessment of the certainty of evidence. The study was registered at PROSPERO (CRD42022312171). Overall, 14 articles with 17 cohorts were included. There was no significant association between daily ASB consumption and risk of overall cancer (highest versus lowest category: n = 17, RR = 1.03, 95% CI: 0.96-1.11, p = 0.407). For site-specific cancer analysis, the risk of non-lymphoid leukemia was elevated with high ASB intake (n = 3, RR = 1.35, 95% CI: 1.03-1.77, p = 0.030), while risk of colorectal cancer was decreased (n = 3, RR = 0.78, 95% CI: 0.62-0.99, p = 0.037). Dose-response analysis indicated a positive linear association between ASB intake and the risk of leukemia (p-linear = 0.027). The risk increased by 15% per one serving (355 mL) daily ASB intake increment (RR = 1.15, 95% CI: 1.02-1.30). In conclusion, ASB consumption might be positively associated with the risk of leukemia and negatively associated with the risk of colorectal cancer.

Sweetened beverage consumption and risk of cardiovascular mortality: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Several studies have reported the association of sweetened beverages (SB) with cardiovascular disease. However, the relationship between SB and cardiovascular mortality has not been clearly established. This systematic review and meta-analysis investigated the association between SB consumption and cardiovascular mortality. METHODS: PubMed/MEDLINE, Web of Science, and Embase were systematically searched up to July 31, 2021, for prospective cohort studies investigating this association in adults. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were used to assess the strength of association between SB: sugar-sweetened beverages (SSB)/artificial-sweetened beverages (ASB) exposure and cardiovascular mortality. RESULTS: A total of eight cohort studies comprising 1.2 million participants exposed to SB, reported 15,831 (1.2%) cases of cardiovascular mortality with a median follow-up of 12.2 years. Consuming at least one glass (250 ml) of SB per day (RR: 1.06; 95% CI: 1.00-1.12, P < 0.001) or ≥2 glasses per day (RR: 1.24; 95% CI: 1.16-1.31, P < 0.001) was significantly associated with increased risk of cardiovascular mortality. SSB and ASB intake of ≥2 glasses per day increased the risk of cardiovascular mortality by 21% (RR:1.21, 95% CI: 1.09-1.33, P < 0.001) and 33% (RR: 1.33, 95% CI: 1.12-1.55, P < 0.001), respectively. CONCLUSIONS: Our findings reveal that high SSB and ASB consumption are associated with an increased risk of cardiovascular mortality. Policymakers and public health practitioners should work on multisectoral strategies to reduce the consumption of sweetened beverages around the world and among all population groups.

Sugar- and Artificially Sweetened Beverages Consumption Linked to Type 2 Diabetes, Cardiovascular Diseases, and All-Cause Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Although studies have examined the association between habitual consumption of sugar- (SSBs) and artificially sweetened beverages (ASBs) and health outcomes, the results are inconclusive. Here, we conducted a dose-response meta-analysis of prospective cohort studies in order to summarize the relationship between SSBs and ASBs consumption and risk of type 2 diabetes (T2D), cardiovascular diseases (CVDs), and all-cause mortality. All relevant articles were systematically searched in PubMed, Embase, and Ovid databases until 20 June 2020. Thirty-four studies met the inclusion criteria and were eligible for analysis. Summary relative risks (RRs) and 95% confidence intervals (95% CI) were estimated using random effects or fixed-effects model for highest versus lowest intake categories, as well as for linear and non-linear relationships. With each additional SSB and ASB serving per day, the risk increased by 27% (RR: 1.27, 95%CI: 1.15-1.41, I2 = 80.8%) and 13% (95%CI: 1.03-1.25, I2 = 78.7%) for T2D, 9% (RR: 1.09, 95%CI: 1.07-1.12, I2 = 42.7%) and 8% (RR: 1.08, 95%CI: 1.04-1.11, I2 = 45.5%) for CVDs, and 10% (RR: 1.10, 95%CI: 0.97-1.26, I2 = 86.3%) and 7% (RR: 1.07, 95%CI: 0.91-1.25, I2 = 76.9%) for all-cause mortality. Linear relationships were found for SSBs with T2D and CVDs. Non-linear relationships were found for ASBs with T2D, CVDs, and all-cause mortality and for SSBs with all-cause mortality. The findings from the current meta-analysis indicate that increased consumption of SSBs and ASBs is associated with the risk of T2D, CVDs, and all-cause mortality.

Sugar-sweetened beverage, artificially sweetened beverage and sugar intake and colorectal cancer survival.

BACKGROUND: The influence of a high sugar diet on colorectal cancer (CRC) survival is unclear. METHODS: Among 1463 stage I-III CRC patients from the Nurses' Health Study and Health Professionals Follow-up Study, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC-specific and all-cause mortality in relation to intake of post-diagnosis sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), fruit juice, fructose and other sugars. RESULTS: Over a median 8.0 years, 781 cases died (173 CRC-specific deaths). Multivariable-adjusted HRs for post-diagnosis intake and CRC-specific mortality were 1.21 (95% CI: 0.87-1.68) per 1 serving SSBs per day (serving/day) and 1.24 (95% CI: 0.95-1.63) per 20 grams fructose per day. Significant positive associations for CRC-specific mortality were primarily observed ≤5 years from diagnosis (HR per 1 serving/day of SSBs = 1.59, 95% CI: 1.06-2.38). Significant inverse associations were observed between ASBs and CRC-specific and all-cause mortality (HR for ≥5 versus <1 serving/week = 0.44, 95% CI: 0.26-0.75 and 0.70, 95% CI: 0.55-0.89, respectively). CONCLUSIONS: Higher post-diagnosis intake of SSBs and sugars may be associated with higher CRC-specific mortality, but only up to 5 years from diagnosis, when more deaths were due to CRC. The inverse association between ASBs and CRC-specific mortality warrants further examination.

Sugar-sweetened soft drink consumption acutely decreases spontaneous baroreflex sensitivity and heart rate variability.

In healthy humans, fructose-sweetened water consumption increases blood pressure variability (BPV) and decreases spontaneous cardiovagal baroreflex sensitivity (cBRS) and heart rate variability (HRV). However, whether consuming commercially available soft drinks containing high levels of fructose elicits similar responses is unknown. We hypothesized that high-fructose corn syrup (HFCS)-sweetened soft drink consumption increases BPV and decreases cBRS and HRV to a greater extent compared with artificially sweetened (diet) and sucrose-sweetened (sucrose) soft drinks and water. Twelve subjects completed four randomized, double-blinded trials in which they drank 500 mL of water or commercially available soft drinks matched for taste and caffeine content. We continuously measured beat-to-beat blood pressure (photoplethysmography) and R-R interval (ECG) before and 30 min after drink consumption during supine rest for 5 min during spontaneous and paced breathing. BPV was evaluated using standard deviation (SD), average real variability (ARV), and successive variation (SV) methods for systolic and diastolic blood pressure. cBRS was assessed using the sequence method. HRV was evaluated using the root mean square of successive differences (RMSSD) in R-R interval. There were no differences between conditions in the magnitude of change from baseline in SD, ARV, and SV (P ≥ 0.07). There were greater reductions in cBRS during spontaneous breathing in the HFCS (-3 ± 5 ms/mmHg) and sucrose (-3 ± 5 ms/mmHg) trials compared with the water trial (+1 ± 5 ms/mmHg, P < 0.03). During paced breathing, HFCS evoked greater reductions in RMSSD compared with water (-26 ± 34 vs. +2 ± 26 ms, P < 0.01). These findings suggest that sugar-sweetened soft drink consumption alters cBRS and HRV but not BPV.

Consumption of Sweet Beverages and Cancer Risk. A Systematic Review and Meta-Analysis of Observational Studies.

The consumption of sweet beverages, including sugar-sweetened beverages (SSB), artificial-sweetened beverages (ASB) and fruit juices (FJ), is associated with the risk of different cardiometabolic diseases. It may also be linked to the development of certain types of tumors. We carried out a systematic review and meta-analysis of observational studies aimed at examining the association between sweet beverage intake and cancer risk. Suitable articles published up to June 2020 were sourced through PubMed, Web of Science and SCOPUS databases. Overall, 64 studies were identified, of which 27 were selected for the meta-analysis. This was performed by analyzing the multivariable-adjusted OR, RR or HR of the highest sweet beverage intake categories compared to the lowest one. Random effects showed significant positive association between SSB intake and breast (RR: 1.14, 95% CI: 1.01-1.30) and prostate cancer risk (RR: 1.18, 95% CI: 1.10-1.27) and also between FJs and prostate cancer risk (RR: 1.03, 95% CI: 1.01-1.05). Although the statistically significant threshold was not reached, there tended to be positive associations for the following: SSBs and colorectal and pancreatic cancer risk; FJs and breast, colorectal and pancreatic cancer risk; and ASBs and pancreatic cancer risk. This study recommends limiting sweet beverage consumption. Furthermore, we propose to establish a homogeneous classification of beverages and investigate them separately, to better understand their role in carcinogenesis.

Maternal consumption of artificially sweetened beverages during pregnancy is associated with infant gut microbiota and metabolic modifications and increased infant body mass index.

Artificial sweetener consumption by pregnant women has been associated with an increased risk of infant obesity, but the underlying mechanisms are unknown. We aimed to determine if maternal consumption of artificially sweetened beverages (ASB) during pregnancy is associated with modifications of infant gut bacterial community composition and function during the first year of life, and whether these alterations are linked with infant body mass index (BMI) at one year of age. We studied 100 infants from the prospective Canadian CHILD Cohort Study, selected based on maternal ASB consumption during pregnancy (50 non-consumers and 50 daily consumers). BMI was higher among ASB-exposed infants. Infant stool (16S rRNA gene sequencing) and urine (untargeted metabolomics) were acquired in early (3-4 months) and late (12 months) infancy. We identified four microbiome clusters, of which two recapitulated the maturation trajectory of the infant gut bacterial communities from immature (Cluster 1) to mature (Cluster 4) and two deviated from this trajectory (Clusters 2 and 3). Maternal ASB consumption did not differ between clusters, but was associated with community-level shifts in infant gut bacterial taxonomy structure and depletion of several Bacteroides sp. in Cluster 2. In the complete dataset, urine succinate and spermidine levels at 3 months were higher in ASB-exposed infants, and urine succinate was positively associated with BMI at one-year-old. Overall, gestational exposure to ASB was associated with gut microbiota structure in infants from Cluster 2, and gut microbiota structure was associated with infant BMI. Gestational exposure to ASB was positively associated with infant urine succinate and spermidine. Succinate was found to mediate 29% of the effect of ASB exposure on BMI at one-year-old, revealing a potential role of this metabolite in increased infant weight linked to gestational ASB consumption. As we face an unprecedented rise in childhood obesity, future studies should evaluate the causal relationships between maternal ASB consumption (a modifiable exposure), gut microbiota and metabolites, infant metabolism, and body composition.

Sweetened beverages and risk of frailty among older women in the Nurses' Health Study: A cohort study.

BACKGROUND: Consumption of sugar-sweetened beverages (SSBs) has been consistently associated with a higher risk of obesity, type 2 diabetes, cardiovascular disease, and premature mortality, whereas evidence for artificially sweetened beverages (ASBs) and fruit juices on health is less solid. The aim of this study was to evaluate the consumption of SSBs, ASBs, and fruit juices in association with frailty risk among older women. METHODS AND FINDINGS: We analyzed data from 71,935 women aged ≥60 (average baseline age was 63) participating in the Nurses' Health Study (NHS), an ongoing cohort study initiated in 1976 among female registered nurses in the United States. Consumption of beverages was derived from 6 repeated food frequency questionnaires (FFQs) administered between 1990 and 2010. Frailty was defined as having at least 3 of the following 5 criteria from the FRAIL scale: fatigue, poor strength, reduced aerobic capacity, having ≥5 chronic illnesses, and weight loss ≥5%. The occurrence of frailty was assessed every 4 years from 1992 to 2014. During 22 years of follow-up, we identified 11,559 incident cases of frailty. Consumption of SSBs was associated with higher risk of frailty after adjustment for diet quality, body mass index (BMI), smoking status, and medication use, specifically, the relative risks (RRs) and 95% confidence interval (95% CI) for ≥2 serving/day versus no SSB consumption was 1.32 (1.10, 1.57); p-value <0.001. ASBs were also associated with frailty [RR ≥2 serving/day versus no consumption: 1.28 (1.17, 1.39); p-value <0.001]. Orange juice was associated with lower risk of frailty [RR ≥1 serving/day versus no consumption: 0.82 (0.76, 0.87); p-value <0.001], whereas other juices were associated with a slightly higher risk [RR ≥1 serving/day versus no consumption: 1.15 (1.03, 1.28); p-value <0.001]. A limitation of this study is that, due to self-reporting of diet and frailty, certain misclassification bias cannot be ruled out; also, some residual confounding may persist. CONCLUSIONS: In this study, we observed that consumption of SSBs and ASBs was associated with a higher risk of frailty. However, orange juice intake showed an inverse association with frailty. These results need to be confirmed in further studies using other frailty definitions.

Sugar and artificially sweetened beverages and risk of obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies.

Although consumption of sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) has increasingly been linked with obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality, evidence remains conflicted and dose-response meta-analyses of the associations are lacking. We conducted an updated meta-analysis to synthesize the knowledge about their associations and to explore their dose-response relations. We comprehensively searched PubMed, EMBASE, Web of Science, and Open Grey up to September 2019 for prospective cohort studies investigating the associations in adults. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated for the dose-response association. Restricted cubic splines were used to evaluate linear/non-linear relations. We included 39 articles in the meta-analysis. For each 250-mL/d increase in SSB and ASB intake, the risk increased by 12% (RR = 1.12, 95% CI 1.05-1.19, I2 = 67.7%) and 21% (RR = 1.21, 95% CI 1.09-1.35, I2 = 47.2%) for obesity, 19% (RR = 1.19, 95% CI 1.13-1.25, I2 = 82.4%) and 15% (RR = 1.15, 95% CI 1.05-1.26, I2 = 92.6%) for T2DM, 10% (RR = 1.10, 95% CI 1.06-1.14, I2 = 58.4%) and 8% (RR = 1.08, 95% CI 1.06-1.10, I2 = 24.3%) for hypertension, and 4% (RR = 1.04, 95% CI 1.01-1.07, I2 = 58.0%) and 6% (RR = 1.06, 95% CI 1.02-1.10, I2 = 80.8%) for all-cause mortality. For SSBs, restricted cubic splines showed linear associations with risk of obesity (Pnon-linearity = 0.359), T2DM (Pnon-linearity = 0.706), hypertension (Pnon-linearity = 0.510) and all-cause mortality (Pnon-linearity = 0.259). For ASBs, we found linear associations with risk of obesity (Pnon-linearity = 0.299) and T2DM (Pnon-linearity = 0.847) and non-linear associations with hypertension (Pnon-linearity = 0.019) and all-cause mortality (Pnon-linearity = 0.048). Increased consumption of SSBs and ASBs is associated with risk of obesity, T2DM, hypertension, and all-cause mortality. However, the results should be interpreted cautiously because the present analyses were based on only cohort but not intervention studies.

Consumption of Diet Soda Sweetened with Sucralose and Acesulfame-Potassium Alters Inflammatory Transcriptome Pathways in Females with Overweight and Obesity.

SCOPE: Low-calorie sweetener (LCS) consumption is associated with metabolic disease in observational studies. However, physiologic mechanisms underlying LCS-induced metabolic impairments in humans are unclear. This study is aimed at identifying molecular pathways in adipose impacted by LCSs. METHODS AND RESULTS: Seven females with overweight or obesity, who did not report LCS use, consumed 12 ounces of diet soda containing sucralose and acesulfame-potassium (Ace-K) three times daily for 8 weeks. A subcutaneous adipose biopsy from the left abdomen and a fasting blood sample were collected at baseline and post-intervention. Global gene expression were assessed using RNA-sequencing followed by functional pathway analysis. No differences in circulating metabolic or inflammatory biomarkers were observed. However, ANOVA detected 828 differentially expressed annotated genes after diet soda consumption (p < 0.05), including transcripts for inflammatory cytokines. Fifty-eight of 140 canonical pathways represented in pathway analyses regulated inflammation, and several key upstream regulators of inflammation (e.g., TNF-alpha) were also represented. CONCLUSION: Consumption of diet soda with sucralose and Ace-K alters inflammatory transcriptomic pathways (e.g., NF-κB signaling) in subcutaneous adipose tissue but does not significantly alter circulating biomarkers. Findings highlight the need to examine molecular and metabolic effects of LCS exposure in a larger randomized control trial for a longer duration.

High-fructose corn syrup-sweetened soft drink consumption increases vascular resistance in the kidneys at rest and during sympathetic activation.

We first tested the hypothesis that consuming a high-fructose corn syrup (HFCS)-sweetened soft drink augments kidney vasoconstriction to sympathetic stimulation compared with water (study 1). In a second study, we examined the mechanisms underlying these observations (study 2). In study 1, 13 healthy adults completed a cold pressor test, a sympathoexcitatory maneuver, before (preconsumption) and 30 min after drinking 500 mL of decarbonated HFCS-sweetened soft drink or water (postconsumption). In study 2, venous blood samples were obtained in 12 healthy adults before and 30 min after consumption of 500 mL water or soft drinks matched for caffeine content and taste, which were either artificially sweetened (Diet trial), sucrose-sweetened (Sucrose trial), or sweetened with HFCS (HFCS trial). In both study 1 and study 2, vascular resistance was calculated as mean arterial pressure divided by blood velocity, which was measured via Doppler ultrasound in renal and segmental arteries. In study 1, HFCS consumption increased vascular resistance in the segmental artery at rest (by 0.5 ± 0.6 mmHg·cm-1·s-1, P = 0.01) and during the cold pressor test (average change: 0.5 ± 1.0 mmHg·cm-1·s-1, main effect: P = 0.05). In study 2, segmental artery vascular resistance increased in the HFCS trial (by 0.8 ± 0.7 mmHg·cm-1·s-1, P = 0.02) but not in the other trials. Increases in serum uric acid were greater in the HFCS trial (0.3 ± 0.4 mg/dL, P ≤ 0.04) compared with the Water and Diet trials, and serum copeptin increased in the HFCS trial (by 0.8 ± 1.0 pmol/L, P = 0.06). These findings indicate that HFCS acutely increases vascular resistance in the kidneys, independent of caffeine content and beverage osmolality, which likely occurs via simultaneous elevations in circulating uric acid and vasopressin.

Beverage Consumption and Longitudinal Changes in Lipoprotein Concentrations and Incident Dyslipidemia in US Adults: The Framingham Heart Study.

Background Limited data are available on the prospective relationship between beverage consumption and plasma lipid and lipoprotein concentrations. Two major sources of sugar in the US diet are sugar-sweetened beverages (SSBs) and 100% fruit juices. Low-calorie sweetened beverages are common replacements. Methods and Results Fasting plasma lipoprotein concentrations were measured in the FOS (Framingham Offspring Study) (1991-2014; N=3146) and Generation Three (2002-2001; N=3584) cohorts. Beverage intakes were estimated from food frequency questionnaires and grouped into 5 intake categories. Mixed-effect linear regression models were used to examine 4-year changes in lipoprotein measures, and Cox proportional hazard models were used to estimate hazard ratios for incident dyslipidemia, adjusting for potential confounding factors. We found that regular (>1 serving per day) versus low (<1 serving per month) SSB consumption was associated with a greater mean decrease in high-density lipoprotein cholesterol (ß±standard error -1.6±0.4 mg/dL; Ptrend<0.0001) and increase in triglyceride (ß±standard error: 4.4±2.2 mg/dL; Ptrend=0.003) concentrations. Long-term regular SSB consumers also had a higher incidence of high triglyceride (hazard ratio, 1.52; 95% CI, 1.03-2.25) compared with low consumers. Although recent regular low-calorie sweetened beverage consumers had a higher incidence of high non-high-density lipoprotein cholesterol (hazard ratio, 1.40; 95% CI, 1.17-1.69) and low-density lipoprotein cholesterol (hazard ratio, 1.27; 95% CI, 1.05-1.53) concentrations compared with low consumers, cumulative average intakes of low-calorie sweetened beverages were not associated with changes in non-high-density lipoprotein cholesterol, low-density lipoprotein cholesterol concentrations, or incident dyslipidemias. Conclusions SSB intake was associated with adverse changes in high-density lipoprotein cholesterol and triglyceride concentrations, along with a higher risk of incident dyslipidemia, suggesting that increased SSB consumption may contribute to the development of dyslipidemia.

Sugar-sweetened and artificially-sweetened beverages and changes in cognitive function in the SUN project.

Background: Sugar-sweetened beverages (SSB) and artificially-sweetened beverages (ASB) have been inconsistently associated with declines in cognitive function. Because of their low caloric content and replacement of sugar, ASB are often seen as 'healthy' alternatives to SSB. Objective: We longitudinally assessed the association between the consumption of SSB or ASB and cognitive function. Design: A subsample of the 'Seguimiento Universidad de Navarra' (SUN) cohort of university graduates aged over 55 years old was evaluated with the Spanish Telephone Interview for Cognitive Status (STICS-m) at two-time points, separated by 6 years. Consumption of SSB and ASB was appraised using a validated food-frequency questionnaire. Linear regression models were fitted, adjusting for potential confounders, including cardiometabolic variables, with the change in the STICS-m score at year 6 as the dependent variable. Results: A significant association between the consumption of SSB and changes in cognitive function as measured by the STICS-m was observed in the total sample, with a change of -0.43 (95% CI -0.85, -0.02, p = 0.04) in those that consumed >1 beverage/month compared to never/seldom consumers. The association was not significant for the consumption of ASB, but point estimates showed negative values, suggesting declines in cognition. Conclusions: Only the consumption of SSB, but not ASB, was significantly associated with a decline in cognitive function after 6 years. Further longitudinal studies are needed to explore the relationship between these beverages and cognitive function and the potential mechanisms through which they might be harmful.

Nutraceutical Potential of Diet Drinks: A Critical Review on Components, Health Effects, and Consumer Safety.

Background: The purpose of this review paper was to explore the components and their respective health effects and safety aspects regarding the consumption of diet drinks (DDs).Methods: A wide variety of the relevant publications (published before 2018) were identified through searching electronic databases (ScienceDirect, PubMed, SciELO, Google Scholar, Springer Link, and ResearchGate) on the basis of different keywords such as diet drink, market status, consumption pattern, composition, health effects, and regulations related to DDs. After the search of suitable literature, 139 papers were screened and reviewed.Results: Numerous brands of DDs have been introduced in the market along with a wide variety of modifications in order to attract the consumers of all age groups along with their respective professions. The major components of DDs are caffeine, taurine, ginseng, guarana, sodium, potassium, and sweeteners that contribute to the good taste, stimulating effect, increased performance and cognitive function, and reduced stress. However, ingestion of DDs over a prolonged course of time can pose multiple deleterious effects, i.e., intoxication, affective disorder, hypertension, reproductive toxicity, and neurological disorders. Consequently, different regulatory bodies of respective countries have formulated and enforced rules and regulations regarding the composition, consumption, labeling, distribution, and sales of DDs.Conclusions: An awareness regarding the components, consumption, and health effects is greatly required in the present era, and authors have tried to fill this gap.Key teaching pointsRise in socio-economic status, health awareness and change in dietary lifestyle are the major factors that fuel the demand of diet drinks; which has been witnessed by a drastic increase in the consumption pattern of the diet drinks among young to middle-age adults since last decade.A wide variety of the ingredients are used in the preparation of diet drinks including caffeine, ginseng (Panax ginseng), guarana (Paullinia cupana), taurine, artificial sweeteners, B Vitamins, sodium, potassium etc.Diet drinks are generally served cold and contain high levels of caffeine and other artificial sweeteners; which based on dosage, have been known to be beneficial as well as harmful.These ingredients possess numerous health benefits including anti-hypertensive, anti-oxidant, anti-cancer properties, improved metabolic functions, stress reduction and enhanced endurance, exercise and performance and increased cognitive function.A wide range of the adverse health effects such as nervousness, sleeplessness, behavioral changes, decreased appetite, heart palpitations, nausea, vomiting, dehydration etc. is being possessed by diet drinks upon the ingestion of these drinks over a prolonged course of time.Regulatory bodies should determine the safe limits of all ingredients for different age groups to get maximum health benefits.

Changes in Consumption of Sugary Beverages and Artificially Sweetened Beverages and Subsequent Risk of Type 2 Diabetes: Results From Three Large Prospective U.S. Cohorts of Women and Men.

OBJECTIVE: We evaluated the associations of long-term changes in consumption of sugary beverages (including sugar-sweetened beverages and 100% fruit juices) and artificially sweetened beverages (ASBs) with subsequent risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: We followed up 76,531 women in the Nurses' Health Study (1986-2012), 81,597 women in the Nurses' Health Study II (1991-2013), and 34,224 men in the Health Professionals' Follow-up Study (1986-2012). Changes in beverage consumption (in 8-ounce servings/day) were calculated from food frequency questionnaires administered every 4 years. Multivariable Cox proportional regression models were used to calculate hazard ratios for diabetes associated with changes in beverage consumption. Results of the three cohorts were pooled using an inverse variance-weighted, fixed-effect meta-analysis. RESULTS: During 2,783,210 person-years of follow-up, we documented 11,906 incident cases of type 2 diabetes. After adjustment for BMI and initial and changes in diet and lifestyle covariates, increasing total sugary beverage intake (including both sugar-sweetened beverages and 100% fruit juices) by >0.50 serving/day over a 4-year period was associated with a 16% (95% CI 1%, 34%) higher diabetes risk in the subsequent 4 years. Increasing ASB consumption by >0.50 serving/day was associated with 18% (2%, 36%) higher diabetes risk. Replacing one daily serving of sugary beverage with water, coffee, or tea, but not ASB, was associated with a 2-10% lower diabetes risk. CONCLUSIONS: Increasing consumption of sugary beverages or ASBs was associated with a higher risk of type 2 diabetes, albeit the latter association may be affected by reverse causation and surveillance bias.

Cumulative intake of artificially sweetened and sugar-sweetened beverages and risk of incident type 2 diabetes in young adults: the Coronary Artery Risk Development In Young Adults (CARDIA) Study.

BACKGROUND: Epidemiological evidence has demonstrated a positive association between artificially sweetened beverage (ASB) and sugar-sweetened beverage (SSB) consumption and type 2 diabetes (T2D) risk. However, research informing this topic in young adults is limited. OBJECTIVE: This study examined the association between ASB, SSB, and total sweetened beverage (TSB; combined ASB and SSB) consumption and T2D risk in young adults. METHODS: A prospective analysis of 4719 Black and White men and women aged 18-30 y at baseline was conducted from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Each participant's beverage intake was assessed using the CARDIA Diet History at baseline and at study Years 7 and 20. Multivariable Cox proportional hazards regression models were used to examine cumulative average ASB, SSB, and TSB intakes and risk of T2D. RESULTS: During the 30-y follow-up period, 680 participants developed T2D. ASB consumption was associated with a 12% greater risk of T2D per serving/day (HR 1.12, 95% CI 1.04-1.20) in a model adjusted for lifestyle factors, diet quality, and dieting behavior. Further adjustments for baseline BMI (HR 1.07, 95% CI 0.99-1.14) and weight change during follow-up (HR 1.04, 95% CI 0.97-1.12) attenuated the association. SSB and TSB consumption as continuous variables per 1 serving/day of intake were associated with 6% and 5% increased risks of T2D, respectively (HRSSB 1.06, 95% CI 1.01-1.10; HRTSB 1.05, 95% CI 1.01-1.09), in the model accounting for lifestyle factors, dieting behavior, baseline BMI, and weight change. Results were consistent when the exposures were modeled in categories of consumption and quintiles. CONCLUSIONS: In young adults, long-term ASB, SSB, and TSB consumption were associated with increased risks of T2D. However, the estimates for ASB were attenuated when accounting for weight changes.