-
1.
Erythritol: An In-Depth Discussion of Its Potential to Be a Beneficial Dietary Component.
Mazi, TA, Stanhope, KL
Nutrients. 2023;(1)
Abstract
The sugar alcohol erythritol is a relatively new food ingredient. It is naturally occurring in plants, however, produced commercially by fermentation. It is also produced endogenously via the pentose phosphate pathway (PPP). Consumers perceive erythritol as less healthy than sweeteners extracted from plants, including sucrose. This review evaluates that perspective by summarizing current literature regarding erythritol's safety, production, metabolism, and health effects. Dietary erythritol is 30% less sweet than sucrose, but contains negligible energy. Because it is almost fully absorbed and excreted in urine, it is better tolerated than other sugar alcohols. Evidence shows erythritol has potential as a beneficial replacement for sugar in healthy and diabetic subjects as it exerts no effects on glucose or insulin and induces gut hormone secretions that modulate satiety to promote weight loss. Long-term rodent studies show erythritol consumption lowers body weight or adiposity. However, observational studies indicate positive association between plasma erythritol and obesity and cardiometabolic disease. It is unlikely that dietary erythritol is mediating these associations, rather they reflect dysregulated PPP due to impaired glycemia or glucose-rich diet. However, long-term clinical trials investigating the effects of chronic erythritol consumption on body weight and risk for metabolic diseases are needed. Current evidence suggests these studies will document beneficial effects of dietary erythritol compared to caloric sugars and allay consumer misperceptions.
-
2.
The Dose-Response Effects of Consuming High Fructose Corn Syrup-Sweetened Beverages on Hepatic Lipid Content and Insulin Sensitivity in Young Adults.
Sigala, DM, Hieronimus, B, Medici, V, Lee, V, Nunez, MV, Bremer, AA, Cox, CL, Price, CA, Benyam, Y, Abdelhafez, Y, et al
Nutrients. 2022;(8)
Abstract
Increased hepatic lipid content and decreased insulin sensitivity have critical roles in the development of cardiometabolic diseases. Therefore, our objective was to investigate the dose-response effects of consuming high fructose corn syrup (HFCS)-sweetened beverages for two weeks on hepatic lipid content and insulin sensitivity in young (18-40 years) adults (BMI 18-35 kg/m2). In a parallel, double-blinded study, participants consumed three beverages/day providing 0% (aspartame: n = 23), 10% (n = 18), 17.5% (n = 16), or 25% (n = 28) daily energy requirements from HFCS. Magnetic resonance imaging for hepatic lipid content and oral glucose tolerance tests (OGTT) were conducted during 3.5-day inpatient visits at baseline and again at the end of a 15-day intervention. During the 12 intervening outpatient days participants consumed their usual diets with their assigned beverages. Significant linear dose-response effects were observed for increases of hepatic lipid content (p = 0.015) and glucose and insulin AUCs during OGTT (both p = 0.0004), and for decreases in the Matsuda (p = 0.0087) and Predicted M (p = 0.0027) indices of insulin sensitivity. These dose-response effects strengthen the mechanistic evidence implicating consumption of HFCS-sweetened beverages as a contributor to the metabolic dysregulation that increases risk for nonalcoholic fatty liver disease and type 2 diabetes.
-
3.
Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults.
Sigala, DM, Hieronimus, B, Medici, V, Lee, V, Nunez, MV, Bremer, AA, Cox, CL, Price, CA, Benyam, Y, Chaudhari, AJ, et al
The Journal of clinical endocrinology and metabolism. 2021;(11):3248-3264
-
-
Free full text
-
Abstract
CONTEXT Studies in rodents and humans suggest that high-fructose corn syrup (HFCS)-sweetened diets promote greater metabolic dysfunction than sucrose-sweetened diets. OBJECTIVE To compare the effects of consuming sucrose-sweetened beverage (SB), HFCS-SB, or a control beverage sweetened with aspartame on metabolic outcomes in humans. METHODS A parallel, double-blinded, NIH-funded study. Experimental procedures were conducted during 3.5 days of inpatient residence with controlled feeding at a research clinic before (baseline) and after a 12-day outpatient intervention period. Seventy-five adults (18-40 years) were assigned to beverage groups matched for sex, body mass index (18-35 kg/m2), and fasting triglyceride, lipoprotein and insulin concentrations. The intervention was 3 servings/day of sucrose- or HFCS-SB providing 25% of energy requirement or aspartame-SB, consumed for 16 days. Main outcome measures were %hepatic lipid, Matsuda insulin sensitivity index (ISI), and Predicted M ISI. RESULTS Sucrose-SB increased %hepatic lipid (absolute change: 0.6 ± 0.2%) compared with aspartame-SB (-0.2 ± 0.2%, P < 0.05) and compared with baseline (P < 0.001). HFCS-SB increased %hepatic lipid compared with baseline (0.4 ± 0.2%, P < 0.05). Compared with aspartame-SB, Matsuda ISI decreased after consumption of HFCS- (P < 0.01) and sucrose-SB (P < 0.01), and Predicted M ISI decreased after consumption of HFCS-SB (P < 0.05). Sucrose- and HFCS-SB increased plasma concentrations of lipids, lipoproteins, and uric acid compared with aspartame-SB. No outcomes were differentially affected by sucrose- compared with HFCS-SB. Beverage group effects remained significant when analyses were adjusted for changes in body weight. CONCLUSION Consumption of both sucrose- and HFCS-SB induced detrimental changes in hepatic lipid, insulin sensitivity, and circulating lipids, lipoproteins and uric acid in 2 weeks.
-
4.
A Pilot Study Comparing the Effects of Consuming 100% Orange Juice or Sucrose-Sweetened Beverage on Risk Factors for Cardiometabolic Disease in Women.
Price, CA, Medici, V, Nunez, MV, Lee, V, Sigala, DM, Benyam, Y, Keim, NL, Mason, AE, Chen, SY, Parenti, M, et al
Nutrients. 2021;(3)
Abstract
Overconsumption of sugar-sweetened beverages increases risk factors associated with cardiometabolic disease, in part due to hepatic fructose overload. However, it is not clear whether consumption of beverages containing fructose as naturally occurring sugar produces equivalent metabolic dysregulation as beverages containing added sugars. We compared the effects of consuming naturally-sweetened orange juice (OJ) or sucrose-sweetened beverages (sucrose-SB) for two weeks on risk factors for cardiometabolic disease. Healthy, overweight women (n = 20) were assigned to consume either 3 servings of 100% orange juice or sucrose-SB/day. We conducted 16-hour serial blood collections and 3-h oral glucose tolerance tests during a 30-h inpatient visit at baseline and after the 2-week diet intervention. The 16-h area under the curve (AUC) for uric acid increased in subjects consuming sucrose-SB compared with subjects consuming OJ. Unlike sucrose-SB, OJ did not significantly increase fasting or postprandial lipoproteins. Consumption of both beverages resulted in reductions in the Matsuda insulin sensitivity index (OJ: -0.40 ± 0.18, p = 0.04 within group; sucrose-SB: -1.0 ± 0.38, p = 0.006 within group; p = 0.53 between groups). Findings from this pilot study suggest that consumption of OJ at levels above the current dietary guidelines for sugar intake does not increase plasma uric acid concentrations compared with sucrose-SB, but appears to lead to comparable decreases of insulin sensitivity.
-
5.
An Exploration of the Role of Sugar-Sweetened Beverage in Promoting Obesity and Health Disparities.
Sigala, DM, Stanhope, KL
Current obesity reports. 2021;(1):39-52
-
-
Free full text
-
Abstract
PURPOSE OF REVIEW The mechanistic role of sugar-sweetened beverage (SSB) in the etiology of obesity is undetermined. We address whether, compared to other foods, does consumption of SSB (1) automatically lead to failure to compensate for the energy it contains? (2) fail to elicit homeostatic hormone responses? (3) promote hedonic eating through activation of the brain's reward pathways? We followed the evidence to address: (4) Would restriction of targeted marketing of SSB and other unhealthy foods to vulnerable populations decrease their prevalence of obesity? RECENT FINDINGS The data are lacking to demonstrate that SSB consumption promotes body weight gain compared with isocaloric consumption of other beverages or foods and that this is linked to its failure to elicit adequate homeostatic hormone responses. However, more recent data have linked body weight gain to reward activation in the brain to palatable food cues and suggest that sweet tastes and SSB consumption heightens the reward response to food cues. Studies investigating the specificity of these responses have not been conducted. Nevertheless, the current data provide a biological basis to the body of evidence demonstrating that the targeted marketing (real life palatable food cues) of SSB and other unhealthy foods to vulnerable populations, including children and people of color and low socioeconomic status, is increasing their risk for obesity. While the mechanisms for the association between SSB consumption and body weight gain cannot be identified, current scientific evidence strongly suggests that proactive environmental measures to reduce exposure to palatable food cues in the form of targeting marketing will decrease the risk of obesity in vulnerable populations.
-
6.
Synergistic effects of fructose and glucose on lipoprotein risk factors for cardiovascular disease in young adults.
Hieronimus, B, Medici, V, Bremer, AA, Lee, V, Nunez, MV, Sigala, DM, Keim, NL, Havel, PJ, Stanhope, KL
Metabolism: clinical and experimental. 2020;:154356
Abstract
BACKGROUND Fructose consumption increases risk factors for cardiometabolic disease. It is assumed that the effects of free sugars on risk factors are less potent because they contain less fructose. We compared the effects of consuming fructose, glucose or their combination, high fructose corn syrup (HFCS), on cardiometabolic risk factors. METHODS Adults (18-40 years; BMI 18-35 kg/m2) participated in a parallel, double-blinded dietary intervention during which beverages sweetened with aspartame, glucose (25% of energy requirements (ereq)), fructose or HFCS (25% and 17.5% ereq) were consumed for two weeks. Groups were matched for sex, baseline BMI and plasma lipid/lipoprotein concentrations. 24-h serial blood samples were collected at baseline and at the end of intervention. Primary outcomes were 24-h triglyceride AUC, LDL-cholesterol (C), and apolipoprotein (apo)B. Interactions between fructose and glucose were assessed post hoc. FINDINGS 145 subjects (26.0 ± 5.8 years; body mass index 25.0 ± 3.7 kg/m2) completed the study. As expected, the increase of 24-h triglycerides compared with aspartame was highest during fructose consumption (25%: 6.66 mmol/Lx24h 95% CI [1.90 to 11.63], P = 0.0013 versus aspartame), intermediate during HFCS consumption (25%: 4.68 mmol/Lx24h 95% CI [-0.18 to 9.55], P = 0.066 versus aspartame) and lowest during glucose consumption. In contrast, the increase of LDL-C was highest during HFCS consumption (25%: 0.46 mmol/L 95% CI [0.16 to 0.77], P = 0.0002 versus aspartame) and intermediate during fructose consumption (25%: 0.33 mmol/L 95% CI [0.03 to 0.63], P = 0.023 versus aspartame), as was the increase of apoB (HFCS-25%: 0.108 g/L 95%CI [0.032 to 0.184], P = 0.001; fructose 25%: 0.072 g/L 95%CI [-0.004 to 0.148], P = 0.074 versus aspartame). The post hoc analyses showed significant interactive effects of fructose*glucose on LDL-C and apoB (both P < 0.01), but not on 24-h triglyceride (P = 0.340). CONCLUSION A significant interaction between fructose and glucose contributed to increases of lipoprotein risk factors when the two monosaccharides were co-ingested as HFCS. Thus, the effects of HFCS on lipoprotein risks factors are not solely mediated by the fructose content and it cannot be assumed that glucose is a benign component of HFCS. Our findings suggest that HFCS may be as harmful as isocaloric amounts of pure fructose and provide further support for the urgency to implement strategies to limit free sugar consumption.
-
7.
Effects of Consuming Sugar-Sweetened Beverages for 2 Weeks on 24-h Circulating Leptin Profiles, Ad Libitum Food Intake and Body Weight in Young Adults.
Sigala, DM, Widaman, AM, Hieronimus, B, Nunez, MV, Lee, V, Benyam, Y, Bremer, AA, Medici, V, Havel, PJ, Stanhope, KL, et al
Nutrients. 2020;(12)
Abstract
Sugar-sweetened beverage (sugar-SB) consumption is associated with body weight gain. We investigated whether the changes of (Δ) circulating leptin contribute to weight gain and ad libitum food intake in young adults consuming sugar-SB for two weeks. In a parallel, double-blinded, intervention study, participants (n = 131; BMI 18-35 kg/m2; 18-40 years) consumed three beverages/day containing aspartame or 25% energy requirement as glucose, fructose, high fructose corn syrup (HFCS) or sucrose (n = 23-28/group). Body weight, ad libitum food intake and 24-h leptin area under the curve (AUC) were assessed at Week 0 and at the end of Week 2. The Δbody weight was not different among groups (p = 0.092), but the increases in subjects consuming HFCS- (p = 0.0008) and glucose-SB (p = 0.018) were significant compared with Week 0. Subjects consuming sucrose- (+14%, p < 0.0015), fructose- (+9%, p = 0.015) and HFCS-SB (+8%, p = 0.017) increased energy intake during the ad libitum food intake trial compared with subjects consuming aspartame-SB (-4%, p = 0.0037, effect of SB). Fructose-SB decreased (-14 ng/mL × 24 h, p = 0.0006) and sucrose-SB increased (+25 ng/mL × 24 h, p = 0.025 vs. Week 0; p = 0.0008 vs. fructose-SB) 24-h leptin AUC. The Δad libitum food intake and Δbody weight were not influenced by circulating leptin in young adults consuming sugar-SB for 2 weeks. Studies are needed to determine the mechanisms mediating increased energy intake in subjects consuming sugar-SB.
-
8.
Fructose and hepatic insulin resistance.
Softic, S, Stanhope, KL, Boucher, J, Divanovic, S, Lanaspa, MA, Johnson, RJ, Kahn, CR
Critical reviews in clinical laboratory sciences. 2020;57(5):308-322
-
-
Free full text
-
Abstract
Excessive caloric intake in a form of high-fat diet (HFD) was long thought to be the major risk factor for development of obesity and its complications, such as fatty liver disease and insulin resistance. Recently, there has been a paradigm shift and more attention is attributed to the effects of sugar-sweetened beverages (SSBs) as one of the culprits of the obesity epidemic. In this review, we present the data invoking fructose intake with development of hepatic insulin resistance in human studies and discuss the pathways by which fructose impairs hepatic insulin action in experimental animal models. First, we described well-characterized pathways by which fructose metabolism indirectly leads to hepatic insulin resistance. These include unequivocal effects of fructose to promote de novo lipogenesis (DNL), impair fatty acid oxidation (FAO), induce endoplasmic reticulum (ER) stress and trigger hepatic inflammation. Additionally, we entertained the hypothesis that fructose can directly impede insulin signaling in the liver. This appears to be mediated by reduced insulin receptor and insulin receptor substrate 2 (IRS2) expression, increased protein-tyrosine phosphatase 1B (PTP1b) activity, whereas knockdown of ketohexokinase (KHK), the rate-limiting enzyme of fructose metabolism, increased insulin sensitivity. In summary, dietary fructose intake strongly promotes hepatic insulin resistance via complex interplay of several metabolic pathways, at least some of which are independent of increased weight gain and caloric intake. The current evidence shows that the fructose, but not glucose, component of dietary sugar drives metabolic complications and contradicts the notion that fructose is merely a source of palatable calories that leads to increased weight gain and insulin resistance.
-
9.
Are Fruit Juices Healthier Than Sugar-Sweetened Beverages? A Review.
Pepin, A, Stanhope, KL, Imbeault, P
Nutrients. 2019;11(5)
Abstract
Free sugars overconsumption is associated with an increased prevalence of risk factors for metabolic diseases such as the alteration of the blood lipid levels. Natural fruit juices have a free sugar composition quite similar to that of sugar-sweetened beverages. Thus, could fruit juice consumption lead to the same adverse effects on health as sweetened beverages? We attempted to answer this question by reviewing the available evidence on the health effects of both sugar-sweetened beverages and natural fruit juices. We determined that, despite the similarity of fruits juices to sugar-sweetened beverages in terms of free sugars content, it remains unclear whether they lead to the same metabolic consequences if consumed in equal dose. Important discrepancies between studies, such as type of fruit juice, dose, duration, study design, and measured outcomes, make it impossible to provide evidence-based public recommendations as to whether the consumption of fruit juices alters the blood lipid profile. More randomized controlled trials comparing the metabolic effects of fruit juice and sugar-sweetened beverage consumption are needed to shape accurate public health guidelines on the variety and quantity of free sugars in our diet that would help to prevent the development of obesity and related health problems.
-
10.
Pathways and mechanisms linking dietary components to cardiometabolic disease: thinking beyond calories.
Stanhope, KL, Goran, MI, Bosy-Westphal, A, King, JC, Schmidt, LA, Schwarz, JM, Stice, E, Sylvetsky, AC, Turnbaugh, PJ, Bray, GA, et al
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2018;(9):1205-1235
-
-
Free full text
-
Abstract
Calories from any food have the potential to increase risk for obesity and cardiometabolic disease because all calories can directly contribute to positive energy balance and fat gain. However, various dietary components or patterns may promote obesity and cardiometabolic disease by additional mechanisms that are not mediated solely by caloric content. Researchers explored this topic at the 2017 CrossFit Foundation Academic Conference 'Diet and Cardiometabolic Health - Beyond Calories', and this paper summarizes the presentations and follow-up discussions. Regarding the health effects of dietary fat, sugar and non-nutritive sweeteners, it is concluded that food-specific saturated fatty acids and sugar-sweetened beverages promote cardiometabolic diseases by mechanisms that are additional to their contribution of calories to positive energy balance and that aspartame does not promote weight gain. The challenges involved in conducting and interpreting clinical nutritional research, which preclude more extensive conclusions, are detailed. Emerging research is presented exploring the possibility that responses to certain dietary components/patterns are influenced by the metabolic status, developmental period or genotype of the individual; by the responsiveness of brain regions associated with reward to food cues; or by the microbiome. More research regarding these potential 'beyond calories' mechanisms may lead to new strategies for attenuating the obesity crisis.