Sugars and Sweet Taste: Addictive or Rewarding?

The notion of food "addiction" often focuses on the overconsumption of sweet tasting foods or so-called sugar "addiction". In the extreme, some have suggested that sugar and sweet tastes elicit neural and behavioral responses analogous to those observed with drugs of abuse. These concepts are complicated by the decades long uncertainty surrounding the validity and reproducibility of functional magnetic resonance imaging (fMRI) methodologies used to characterize neurobiological pathways related to sugar and sweet taste stimuli. There are also questions of whether sweet taste or post-ingestion metabolic consequences of sugar intake would lead to addiction or excessive caloric intake. Here, we present a focused narrative review of literature related to the reward value of sweet taste which suggests that reward value can be confounded with the construct of "addictive potential". Our review seeks to clarify some key distinctions between these constructs and questions the applicability of the addiction construct to human over-eating behaviors. To adequately frame this broad discussion requires the flexibility offered by the narrative review paradigm. We present selected literature on: techniques used to link sugar and sweet tastes to addiction neurobiology and behaviors; sugar and sweet taste "addiction"; the relationship of low calorie sweetener (LCS) intake to addictive behaviors and total calorie intake. Finally, we examined the reward value of sweet tastes and contrasted that with the literature describing addiction. The lack of reproducibility of fMRI data remains problematic for attributing a common neurobiological pathway activation of drugs and foods as conclusive evidence for sugar or sweet taste "addiction". Moreover, the complicated hedonics of sweet taste and reward value are suggested by validated population-level data which demonstrate that the consumption of sweet taste in the absence of calories does not increase total caloric intake. We believe the neurobiologies of reward value and addiction to be distinct and disagree with application of the addiction model to sweet food overconsumption. Most hypotheses of sugar "addiction" attribute the hedonics of sweet foods as the equivalent of "addiction". Further, when addictive behaviors and biology are critically examined in totality, they contrast dramatically from those associated with the desire for sweet taste. Finally, the evidence is strong that responses to the palatability of sweets rather than their metabolic consequences are the salient features for reward value. Thus, given the complexity of the controls of food intake in humans, we question the usefulness of the "addiction" model in dissecting the causes and effects of sweet food over-consumption.

Daily Eating Frequency in US Adults: Associations with Low-Calorie Sweeteners, Body Mass Index, and Nutrient Intake (NHANES 2007-2016).

Studies of relationships between eating frequency and/or timing and energy intake have not examined associations with low-calorie sweeteners (LCS). We assessed the frequency of eating behavior related to LCS consumption emphasizing timing, calorie intake, and body mass index (BMI) among United States (US) adults aged ≥19 years. Using the National Health and Nutrition Examination Survey (NHANES) 2007-2016, we defined eating episodes as food and/or beverage intake within 15 min of one another over the first 24-h dietary recall. We coded items ingested during episodes (n = 136,938) and assessed LCS presence using US Department of Agriculture (USDA) food files. Episode analysis found intakes of foods only (27.4%), beverages only (29.5%), and foods with beverages (43.0%). LCS items were consumed without concurrent calories from other sources in fewer than 2.7% of all episodes. Within participants having normal weight (29.4%), overweight (33.6%) and obese (37.1%) BMIs, LCS consumers (35.2% overall) evidenced: more episodes/day; and fewer: calories, carbohydrates, fats, and protein per episode. Per person, those consuming LCS had lower total calories and higher fiber intake per day. LCS consumption was associated with higher BMI. Number of eating episodes/day and longer hours when eating episodes occurred were also consistently associated with higher BMI. Consuming LCS did not modify these relationships. These results did not show that LCS consumption was associated with increased caloric intake from other dietary sources.

Low-Calorie Sweeteners in Foods, Beverages, and Food and Beverage Additions: NHANES 2007-2012.

BACKGROUND: Most publications about low-calorie sweeteners (LCSs) focus on person-level intake prevalence. OBJECTIVE: We assessed LCS distribution in foods, beverages, and food and beverage additions (FBAs), e.g., mayonnaise, in the US adult diet as reported in the NHANES (2007-2012). METHODS: Dietary items reported in the first 24-h recall were coded for LCS and/or nutritive sweeteners (NSs) with the use of USDA What We Eat in America food files. We calculated the number of times items were reported and LCS/NS content. RESULTS: Of reported items, 56.1% were foods, 29.1% were beverages, and 14.8% were FBAs. LCS was contained in 0.7% of foods, 8.1% of beverages, and 10.4% of FBAs. This food-level analysis identified FBAs as a significant source of LCSs in the US diet. CONCLUSION: Identifying the diversity of LCS and NS sources will enhance exposure classification for examining diet and health relations, including body weight management.

Low-Calorie Sweeteners: Exploring Underutilized Database Resources to Understand Dietary Patterns and Obesity.

The use and impact of low-calorie sweeteners (LCS) in relation to the national challenges of overweight and obesity are complex and controversial. Most research on LCS have focused on the prevalence of consumption of LCS in beverages. The 2015 Dietary Guidelines Advisory Committee emphasized dietary patterns and health rather than a focus on specific nutrients or foods. The committee took this approach to shift the national emphasis onto the context of total rather than individual nutrient consumption. A broader research paradigm is needed to elucidate the actual exposure to LCS and how they are consumed within dietary patterns in the US population. National-level databases exist that can be used to broaden scientific understanding of the effects of LCS and health outcomes. These databases are underutilized, and they provide potential tools for grasping a fuller picture of LCS in the US diet.

Reported Consumption of Low-Calorie Sweetener in Foods, Beverages, and Food and Beverage Additions by US Adults: NHANES 2007-2012.

BACKGROUND: Low-calorie sweeteners (LCSs), artificial sweeteners, or high-intensity sweeteners are incorporated into foods, beverages, and food and beverage additions (FBAs). Many prior studies have focused on LCS beverage consumption, but not included LCS consumption from foods or FBAs. OBJECTIVES: We aimed to describe the prevalence of LCS consumption by US adults, and to examine the relation between intake of products containing LCSs and macronutrients. METHODS: Two nonconsecutive 24-h dietary recalls from NHANES 2007-2012 and the National Cancer Institute usual intake method were used to estimate prevalence of LCS intake from foods, beverages, and FBAs, and macronutrients among US adults aged ≥19 y (n = 14,098, weighted n = 218,391,752) in a cross-sectional study. The prevalence of LCS consumption from reported foods, beverages, and FBAs among US adults was examined by sociodemographic characteristics and body mass index (BMI). Logistic regression estimated ORs and 95% CIs for associations between sociodemographic characteristics and LCS use (overall and in foods, beverages, and FBAs). RESULTS: Among adults, 47.8% reported intake of ≥1 food, beverage, or FBA containing LCSs over 2 d. Intake was higher among: women non-Hispanic whites, college graduates or higher, and those with higher income and obese BMIs (P < 0.001). Intake of beverages containing LCSs was higher for ages 51-70 y than 19-30 y and those with overweight and obese BMIs (P < 0.001) than for normal-weight individuals. Calories, carbohydrate, and sugar intake were lower and fiber was higher in LCS-consumers than in nonconsumers. Specifically, calories from beverages were lower in those who reported LCS intake. CONCLUSIONS: Individuals reporting LCS consumption demonstrated lower total energy intake than did individuals without LCS intake. Although the main source of LCSs in the US adult diet was beverages (31.9%), we found that FBAs also present a significant contribution (25.2%), surpassing food (9.3%). This enables targeted understanding of national consumption of these products as well as dietary education and intervention opportunities.

Effects of HIV infection on the metabolic and hormonal status of children with severe acute malnutrition.

BACKGROUND: HIV infection occurs in 30% of children with severe acute malnutrition in sub-Saharan Africa. Effects of HIV on the pathophysiology and recovery from malnutrition are poorly understood. METHODS: We conducted a prospective cohort study of 75 severely malnourished Ugandan children. HIV status/CD4 counts were assessed at baseline; auxologic data and blood samples were obtained at admission and after 14 days of inpatient treatment. We utilized metabolomic profiling to characterize effects of HIV infection on metabolic status and subsequent responses to nutritional therapy. FINDINGS: At admission, patients (mean age 16.3 mo) had growth failure (mean W/H z-score -4.27 in non-edematous patients) that improved with formula feeding (mean increase 1.00). 24% (18/75) were HIV-infected. Nine children died within the first 14 days of hospitalization; mortality was higher for HIV-infected patients (33% v. 5%, OR = 8.83). HIV-infected and HIV-negative children presented with elevated NEFA, ketones, and even-numbered acylcarnitines and reductions in albumin and amino acids. Leptin, adiponectin, insulin, and IGF-1 levels were low while growth hormone, cortisol, and ghrelin levels were high. At baseline, HIV-infected patients had higher triglycerides, ketones, and even-chain acylcarnitines and lower leptin and adiponectin levels than HIV-negative patients. Leptin levels rose in all patients following nutritional intervention, but adiponectin levels remained depressed in HIV-infected children. Baseline hypoleptinemia and hypoadiponectinemia were associated with increased mortality. CONCLUSIONS: Our findings suggest a critical interplay between HIV infection and adipose tissue storage and function in the adaptation to malnutrition. Hypoleptinemia and hypoadiponectinemia may contribute to high mortality rates among malnourished, HIV-infected children.

Severe acute malnutrition in childhood: hormonal and metabolic status at presentation, response to treatment, and predictors of mortality.

OBJECTIVE: Malnutrition is a major cause of childhood morbidity and mortality. To identify and target those at highest risk, there is a critical need to characterize biomarkers that predict complications prior to and during treatment. METHODS: We used targeted and nontargeted metabolomic analysis to characterize changes in a broad array of hormones, cytokines, growth factors, and metabolites during treatment of severe childhood malnutrition. Children aged 6 months to 5 years were studied at presentation to Mulago Hospital and during inpatient therapy with milk-based formulas and outpatient supplementation with ready-to-use food. We assessed the relationship between baseline hormone and metabolite levels and subsequent mortality. RESULTS: Seventy-seven patients were enrolled in the study; a subset was followed up from inpatient treatment to the outpatient clinic. Inpatient and outpatient therapies increased weight/height z scores and induced striking changes in the levels of fatty acids, amino acids, acylcarnitines, inflammatory cytokines, and various hormones including leptin, insulin, GH, ghrelin, cortisol, IGF-I, glucagon-like peptide-1, and peptide YY. A total of 12.2% of the patients died during hospitalization; the major biochemical factor predicting mortality was a low level of leptin (P = .0002), a marker of adipose tissue reserve and a critical modulator of immune function. CONCLUSIONS: We have used metabolomic analysis to provide a comprehensive hormonal and metabolic profile of severely malnourished children at presentation and during nutritional rehabilitation. Our findings suggest that fatty acid metabolism plays a central role in the adaptation to acute malnutrition and that low levels of the adipose tissue hormone leptin associate with, and may predict, mortality prior to and during treatment.

Vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose.

Vitamin D has in vitro and in vivo effects on ß cells and insulin sensitivity. Vitamin D deficiency (VDD) has been associated with the onset and progression of type 2 diabetes mellitus (DM-2). However, studies involving supplementation of vitamin D in subjects with previously established diabetes have demonstrated inconsistent effects on insulin sensitivity. The aim of this open-label study was to assess the effects of high-dose vitamin D3 supplementation on insulin sensitivity in subjects with VDD and impaired fasting glucose. We studied 8 subjects with VDD and prediabetes with the modified, frequently sampled intravenous glucose tolerance (mFSIGT) test before and after vitamin D supplementation. Vitamin D3 was administered as 10,000 IU daily for 4 weeks. The mFSIGT was analyzed with MinMod Millennium (purchased from Dr. Richard Bergman, Keck School of Medicine of USC, Los Angeles, Calif) to obtain estimates of acute insulin response to glucose (AIRg), insulin sensitivity (SI), and disposition index (DI). We found that AIRg decreased (P = 0.011) and SI increased (P = 0.012) after a intervention with vitamin D. If these findings are repeated in a randomized, double-blind study, the results indicate that orally administered high-dose vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose and suggests that high-dose vitamin D3 supplementation might provide an inexpensive public health measure in preventing, or at least delaying, the progression from impaired fasting glucose to diabetes.

The effect of traditional risk factors for stone disease on calcium oxalate crystal adherence in the rat bladder.

Crystal adherence in the urinary tract has been studied using the chemically injured rat bladder and cell cultures. These studies have provided evidence that mucin prevents adherence and have studied various compounds for their ability to promote or inhibit crystal adherence. Little work has been done examining the effect on crystal adherence of traditional risk factors for stone disease. The study reported here examined the effect hypercalciuria, hyperoxaluria and pH on calcium oxalate crystal adherence using the intact rat bladder model. Calcium at levels seen in hypercalciuric stone formers was associated with increased adherence. Oxalate at levels seen in stone formers had no effect on adherence. There was a tendency to increased crystal adherence at higher pH values only when phosphorus was present as the buffer. Hypercalciuria is a risk factor for stone disease by increasing the level of saturation of calcium oxalate and calcium phosphate in the urine and by decreasing inhibitor function. This study suggests that it may also play a role by increasing crystal adherence within the urinary tract.

Integration of an Internet-based medical chart into a pharmacotherapy lecture series.

OBJECTIVES: To integrate an Internet-based medical chart (IMC) system into a pharmacotherapy course to facilitate evaluation and feedback processes, foster development of written documentation skills, and prepare pharmacy students for future changes in electronic medical documentation systems. DESIGN: An IMC system was introduced into a pharmacotherapy course for third-professional year pharmacy students and 4 "finish the SOAP note" activities were added to the curriculum. Students' performance on the SOAP notes were assessed by a team of evaluators. At the end of the semester, students and evaluators completed separate 6-item survey instruments concerning the usefulness of the IMC system in meeting the course objectives. ASSESSMENT: Students' performance on documentation activities improved over the course of the semester: 87% of the students avoided repeating previous mistakes by their final documentation activity. The vast majority of the students and evaluators found the system easy to use and the activities helpful. CONCLUSION: The development, implementation, and initial expansion of the IMC system across both laboratory and pharmacotherapy courses was a success. Continued integration into clinical coursework is planned and will further expand opportunities for applied learning experiences to prepare students for their experiential program and beyond.

Effect of conjugated equine estrogens on oxidative metabolism in middle-aged and elderly postmenopausal women.

The effects of conjugated equine estrogens (CEE) 0.625 mg daily on cytochrome P450 (CYP) were quantified in 12 middle-aged and 13 elderly postmenopausal women at baseline and 6 months later. CYP phenotype was characterized by caffeine (CYP1A2), chlorzoxazone (CYP2E1), dapsone (CYP, N-acetyltransferase 2), dextromethorphan (CYP2D6), and mephenytoin (CYP2C19) metabolism. CEE significantly decreased CYP1A2 (caffeine metabolic ratio: 0.57 +/- 0.20 before, 0.40 +/- 0.20 after, P = .001) and significantly increased CYP2D6 (dextromethorphan/dextrorphan ratio: 0.0116 +/- 0.0143 before, 0.0084 +/- 0.0135 after, P = .022) metabolism. CEE had no overall effect on CYP2C19, CYP2E1, CYP-mediated dapsone metabolism, and N-acetyltransferase 2. The dextromethorphan metabolic ratio decreased only in the seniors. The dapsone recovery ratio decreased in the middle-aged group and increased in the seniors. CEE significantly influenced CYP1A2, CYP2D6, and CYP-mediated dapsone oxidative metabolism but not CYP2C19, CYP2E1, or N-acetyltransferase 2 metabolism in postmenopausal women. Age influenced CYP2D6 metabolism and dapsone hydroxylation.

B-type natriuretic peptide (BNP) and N-terminal pro-BNP in obese patients without heart failure: relationship to body mass index and gastric bypass surgery.

BACKGROUND: Further investigations are warranted to better characterize variables that may confound the clinical interpretation of plasma natriuretic peptide measurements, which are increasingly recognized to have diagnostic and predictive importance. METHODS: Blood samples (EDTA plasma) from patients (n = 206) attending clinics for the medical treatment and follow-up of obesity were analyzed for B-type natriuretic peptide (BNP; Bayer assay) and the N-terminal segment of its prohormone (NT-proBNP; Roche assay). Natriuretic peptide concentration ranges were evaluated in those without diagnosis of congestive heart failure (CHF) or chronic kidney disease (CKD). RESULTS: BNP and NT-proBNP were directly correlated (r = 0.87; P = 0.01), with NT-proBNP concentrations higher relative to BNP. Of obese patients without CHF or CKD, 21.6% (40 of 185) had NT-proBNP concentrations greater than the published assay upper reference limit. Concentrations of both natriuretic peptides were higher in patients currently exposed to beta blockers, patients with the diagnosis of hypertension or type 2 diabetes, and patients with a history of gastric bypass surgery. An inverse relationship between body mass index (BMI) and both BNP and NT-proBNP was evident. According to the National Institutes of Health, National Heart, Lung, and Blood Institute classification, more than 95% of the participants sampled in this study were either obesity class 2 (35 kg/m(2) < BMI < 39.9 kg/m(2)) or class 3 (BMI >or=40 kg/m(2)) CONCLUSIONS: A substantial proportion of obese patients without CHF or CKD have concentrations greater than the upper reference limit for NT-proBNP but not for simultaneously measured BNP. A history of gastric bypass surgery appeared to be a significant predictor of increased natriuretic peptide concentrations when assessed in a population of patients with class 2 or 3 obesity.

A prospective, randomized comparison of the metabolic effects of pioglitazone or rosiglitazone in patients with type 2 diabetes who were previously treated with troglitazone.

OBJECTIVE: To characterize potential differences in glycemic control, plasma lipid level, and weight in a cohort of patients previously treated with troglitazone (TROG) who were switched to either pioglitazone or rosiglitazone. RESEARCH DESIGN AND METHODS: After a 2-week washout from TROG, 186 patients were randomly assigned to receive either pioglitazone (PIO) or rosiglitazone (ROSI). Weight, HbA(1c), and fasting lipid profile were documented before discontinuing TROG and at 4 months after starting either pioglitazone or rosiglitazone. Secondarily, the effect of concurrent medications on study outcomes was assessed. RESULTS: A total of 127 patients completed follow-up: 67 individuals in the PIO group (32 women, 35 men) and 60 individuals in the ROSI group (33 women, 27 men). There were no significant differences in gender mix, age, weight, fasting lipid profile, or HbA(1c) between the ROSI and PIO groups. After 4 months of randomized treatment, no change in HbA(1c) from baseline between or within groups was noted. Both groups experienced an equal and significant increase in weight from baseline of approximately 2.0 kg. Thiazolidinedione and HMG-CoA reductase inhibitor therapy had significant and independent effects on lipid profile (P < 0.005). Significant improvements in lipid profile were noted in the PIO group (P < 0.01), whereas none were detected with conversion to ROSI. Specifically, the PIO group experienced an average decrease in total cholesterol of approximately 20 mg/dl. CONCLUSIONS: Differing effects on lipid profile were apparent after random conversion from TROG to either PIO or ROSI, despite similar weight increase and glycemic control. The clinical significance of these differences remains to be determined, and further comparative research is warranted.

The Effects of Lansoprazole on the Disposition of Antipyrine and Indocyanine Green in Normal Human Subjects.

This study was designed to evaluate the potential effects of acute and chronic daily oral doses of lansoprazole (60 mg) on the disposition of antipyrine, an almost completely metabolized low hepatic extraction compound, and indocyanine green, a hepatically secreted compound with high extraction ratio. The study utilized a randomized, placebo-controlled, double-blind, two-period crossover design. Sixteen of 18 subjects completed all phases of the study. Both antipyrine (10 mg kg(minus sign1)) and indocyanine green (0.5 mg kg(minus sign1)) were administered as single intravenous bolus doses on Days 1 and 7 of lansoprazole or placebo dosing. Acute exposure to lansoprazole had no statistically significant effects on the plasma pharmacokinetics of indocyanine green or antipyrine. After the seventh dose, there was a small but statistically significant reductions in indocyanine green total body clearance (CL), and elimination rate constant of 10.6% and 8%, respectively. Additionally, a small statistically significant reduction (8.6%) in antipyrine volume of distribution was detected. No other plasma antipyrine pharmacokinetic parameters were changed with concomitant lansoprazole administration. About a 12% increase in the recovery of one of the major antipyrine urine metabolites (NORA) was detected. Overall, this study demonstrates little or no effect of lansoprazole on the pharmacokinetics of antipyrine and indocyanine green.

Disposition of Misoprostol and Its Active Metabolite in Impaired Hepatic Function.

The pharmacokinetics of misoprostol and its active metabolite, misoprostol acid, was assessed in 17 healthy subjects and 17 subjects with various degrees of hepatic impairment. Before misoprostol administration, subjects underwent antipyrine and indocyanine green clearance studies to assess hepatic functional capacity. Subjects were administered 400 mcg of oral misoprostol in an open-label design. There was a lower antipyrine clearance in the group with hepatic disease as compared to normal volunteers (0.56 versus 0.80 ml min(minus sign1) kg(minus sign1), respectively, p = 0.022). There was no difference in indocyanine green clearance values between groups. The C(max), t(1/2)&bgr, and [Formula: see text] tended to be larger in the hepatic group; however, there was no statistical difference. Adverse events, mostly gastrointestinal in nature, occurred more often in the subjects with hepatic disease. These data suggest the pharmacokinetics of misoprostol may be altered in the presence of hepatic disease. However, because of significant interpatient variability, definitive dosing recommendations cannot be made. Further study in this area is needed.