Effect of nutritive and non-nutritive sweeteners on hemodynamic responses to acute stress: a randomized crossover trial in healthy women.

BACKGROUND: The mechanisms by which chronic stress increases the risk of non-communicable diseases remain poorly understood. On one hand, chronic stress may increase systemic vascular resistance (SVR) and blood pressure, which may lead to blood vessels injury and altered myocardial perfusion. On the other hand, chronic stress may promote the overconsumption of sugar-containing foods and favor obesity. There is indeed evidence that sweet foods are preferentially consumed to alleviate stress responses. The effects of nutritive and non-nutritive sweeteners (NNS) on hemodynamic stress responses remain however largely unknown. OBJECTIVE/DESIGN: This study aimed at comparing the effects of sucrose-containing and NNS-containing drinks, as compared to unsweetened water, on hemodynamic responses to acute stress in twelve healthy female subjects. Acute stress responses were elicited by a 30-min mental stress (5-min Stroop's test alternated with 5-min mental arithmetic) and a 3-min cold pressure test (CPT), each preceded by a resting baseline period. Hemodynamic stress responses were investigated by the repeated measurement of mean arterial pressure and the continuous monitoring of cardiac output by thoracic electrical bioimpedance measurement. SVR was selected as a primary outcome because it is a sensitive measure of hemodynamic responses to acute stress procedures. RESULTS: With all three drinks, SVR were not changed with mental stress (P = 0.437), but were increased with CPT (P = 0.045). Both mental stress and CPT increased mean arterial pressure and heart rate (all P < 0.001). Cardiac output increased with mental stress (P < 0.001) and remained unchanged with CPT (P = 0.252). No significant differences in hemodynamic responses were observed between water, sucrose and NNS (stress × condition, all P > 0.05). CONCLUSIONS: These results demonstrate that sucrose and NNS do not alter hemodynamic responses to two different standardized acute stress protocols.

Effects of gastric bypass surgery on postprandial gut and systemic lipid handling.

BACKGROUND & OBJECTIVES: Obesity is often associated with increased postprandial triglyceride (TG) concentrations, mainly from chylomicrons- and VLDL-TG. These alterations are usually reverted to normal after gastric bypass surgery (GB), through mechanisms which remain unknown. The objective of this study was therefore to assess the contribution of exogenous labelled fatty acids ingested with a meal to postprandial blood chylomicrons and VLDL-TG concentrations after GB. SUBJECTS/METHODS: 7 GB patients 3-5 years after surgery (GB: 2M/5F, mean BMI 30 ± 2 kg/m2, mean age 40 ± 3 years), 6 overweight non operated subjects (OW: 1M/5F, mean BMI 31 ± 3 kg/m2, mean age 38 ± 2 years) and 8 normal weight healthy subjects (NW: 4M/4F, mean BMI 22 ± 1 kg/m2, mean age 26 ± 4 years) were studied over 7 h following ingestion of a liquid meal containing 18 g fat labelled with 250 mg 13C16 palmitate, 22 g protein, 36 g fructose and 36 g glucose. TG, 13C palmitate (13C-palm) and apoB48 concentrations were measured hourly in whole plasma and/or in chylomicrons and VLDL lipoprotein sub-fractions. RESULTS: OW subjects had higher chylomicron-than NW (chylo-TG 96.5 (23.1) vs 28.8 (11.8) mmol/l*420min (p = 0.02)), but similar total, chylo-13C-palm and apoB48 iAUCs. In GB, chylo- 13C-palm and apoB48 increased earlier after meal ingestion, but then remained lower than in NW and OW throughout the postprandial period. GB also had lower chylo-TG iAUCs than OW (8.9 (11.5) vs 96.5 (23.2) mmol/l*420min, p = 0.003). Their apoB48 iAUCs were not different from NW and OW (509.2 (90.5) vs 710.2 (80.5) and 870.1 (297.6) pg/ml*420min, all p > 0.05). CONCLUSIONS: An accelerated postprandial apoB48 rise, together with unchanged postprandial apoB48 iUAC, suggests that intestinal fat absorption and chylomicron secretion was quantitatively unaltered, but accelerated after gastric bypass. In contrast, the decreased postprandial chylo-TG and 13C-palm iAUCs suggest that plasma chylomicron clearance was enhanced after gastric bypass.

The extra-splanchnic fructose escape after ingestion of a fructose-glucose drink: An exploratory study in healthy humans using a dual fructose isotope method.

BACKGROUND & AIMS: The presence of specific fructose transporters and fructose metabolizing enzymes has now been demonstrated in the skeletal muscle, brain, heart, adipose tissue and many other tissues. This suggests that fructose may be directly metabolized and play physiological or pathophysiological roles in extra-splanchnic tissues. Yet, the proportion of ingested fructose reaching the systemic circulation is generally not measured. This study aimed to assess the amount of oral fructose escaping first-pass splanchnic extraction after ingestion of a fructose-glucose drink using a dual oral-intravenous fructose isotope method. METHODS: Nine healthy volunteers were studied over 2 h before and 4 h after ingestion of a drink containing 30.4 ± 1.0 g of glucose (mean ± SEM) and 30.4 ± 1.0 g of fructose labelled with 1% [U-13C6]-fructose. A 75%-unlabeled fructose and 25%-[6,6-2H2]-fructose solution was continuously infused (100 µg kg-1 min-1) over the 6 h period. Total systemic, oral and endogenous fructose fluxes were calculated from plasma fructose concentrations and isotopic enrichments. The fraction of fructose escaping first-pass splanchnic extraction was calculated assuming a complete intestinal absorption of the fructose drink. RESULTS: Fasting plasma fructose concentration before tracer infusion was 17.9 ± 0.6 µmol.L-1. Fasting endogenous fructose production detected by tracer dilution analysis was 55.3 ± 3.8 µg kg-1min-1. Over the 4 h post drink ingestion, 4.4 ± 0.2 g of ingested fructose (i.e. 14.5 ± 0.8%) escaped first-pass splanchnic extraction and reached the systemic circulation. Endogenous fructose production significantly increased to a maximum of 165.4 ± 10.7 µg kg-1·min-1 60 min after drink ingestion (p < 0.001). CONCLUSIONS: These data indicate that a non-negligible fraction of fructose is able to escape splanchnic extraction and circulate in the periphery. The metabolic effects of direct fructose metabolism in extra-splanchnic tissues, and their relationship with metabolic diseases, remain to be evaluated. Our results also open new research perspectives regarding the physiological role of endogenous fructose production.

The Impact of Caloric and Non-Caloric Sweeteners on Food Intake and Brain Responses to Food: A Randomized Crossover Controlled Trial in Healthy Humans.

Whether non-nutritive sweetener (NNS) consumption impacts food intake behavior in humans is still unclear. Discrepant sensory and metabolic signals are proposed to mislead brain regulatory centers, in turn promoting maladaptive food choices favoring weight gain. We aimed to assess whether ingestion of sucrose- and NNS-sweetened drinks would differently alter brain responses to food viewing and food intake. Eighteen normal-weight men were studied in a fasted condition and after consumption of a standardized meal accompanied by either a NNS-sweetened (NNS), or a sucrose-sweetened (SUC) drink, or water (WAT). Their brain responses to visual food cues were assessed by means of electroencephalography (EEG) before and 45 min after meal ingestion. Four hours after meal ingestion, spontaneous food intake was monitored during an ad libitum buffet. With WAT, meal intake led to increased neural activity in the dorsal prefrontal cortex and the insula, areas linked to cognitive control and interoception. With SUC, neural activity in the insula increased as well, but decreased in temporal regions linked to food categorization, and remained unchanged in dorsal prefrontal areas. The latter modulations were associated with a significantly lower total energy intake at buffet (mean kcal ± SEM; 791 ± 62) as compared to WAT (942 ± 71) and NNS (917 ± 70). In contrast to WAT and SUC, NNS consumption did not impact activity in the insula, but led to increased neural activity in ventrolateral prefrontal regions linked to the inhibition of reward. Total energy intake at the buffet was not significantly different between WAT and NNS. Our findings highlight the differential impact of caloric and non-caloric sweeteners on subsequent brain responses to visual food cues and energy intake. These variations may reflect an initial stage of adaptation to taste-calorie uncoupling, and could be indicative of longer-term consequences of repeated NNS consumption on food intake behavior.

Endurance Training with or without Glucose-Fructose Ingestion: Effects on Lactate Metabolism Assessed in a Randomized Clinical Trial on Sedentary Men.

Glucose-fructose ingestion increases glucose and lactate oxidation during exercise. We hypothesized that training with glucose-fructose would induce key adaptations in lactate metabolism. Two groups of eight sedentary males were endurance-trained for three weeks while ingesting either glucose-fructose (GF) or water (C). Effects of glucose-fructose on lactate appearance, oxidation, and clearance were measured at rest and during exercise, pre-training, and post-training. Pre-training, resting lactate appearance was 3.6 ± 0.5 vs. 3.6 ± 0.4 mg·kg-1·min-1 in GF and C, and was increased to 11.2 ± 1.4 vs. 8.8 ± 0.7 mg·kg-1·min-1 by exercise (Exercise: p < 0.01). Lactate oxidation represented 20.6% ± 1.0% and 17.5% ± 1.7% of lactate appearance at rest, and 86.3% ± 3.8% and 86.8% ± 6.6% during exercise (Exercise: p < 0.01) in GF and C, respectively. Training with GF increased resting lactate appearance and oxidation (Training × Intervention: both p < 0.05), but not during exercise (Training × Intervention: both p > 0.05). Training with GF and C had similar effects to increase lactate clearance during exercise (+15.5 ± 9.2 and +10.1 ± 5.9 mL·kg-1·min-1; Training: p < 0.01; Training × Intervention: p = 0.97). The findings of this study show that in sedentary participants, glucose-fructose ingestion leads to high systemic lactate appearance, most of which is disposed non-oxidatively at rest and is oxidized during exercise. Training with or without glucose-fructose increases lactate clearance, without altering lactate appearance and oxidation during exercise.

Effects of roux-en-Y gastric bypass surgery on postprandial fructose metabolism.

OBJECTIVE: Fructose is partly metabolized in small bowel enterocytes, where it can be converted into glucose or fatty acids. It was therefore hypothesized that Roux-en-Y gastric bypass (RYGB) may significantly alter fructose metabolism. METHODS: We performed a randomized clinical study in eight patients 12-17 months after RYGB and eight control (Ctrl) subjects. Each participant was studied after ingestion of a protein and lipid meal (PL) and after ingestion of a protein+lipid+fructose+glucose meal labeled with (13) C-fructose (PLFG). Postprandial blood glucose, fructose, lactate, apolipoprotein B48 (apoB48), and triglyceride (TG) concentrations, (13) C-palmitate concentrations in chylomicron-TG and VLDL-TG, fructose oxidation ((13) CO2 production), and gluconeogenesis from fructose (GNGf) were measured over 6 hours. RESULTS: After ingestion of PLFG, postprandial plasma fructose, glucose, insulin, and lactate concentrations increased earlier and reached higher peak values in RYGB than in Ctrl. GNGf was 33% lower in RYGB than Ctrl (P = 0.041), while fructose oxidation was unchanged. Postprandial incremental areas under the curves for total TG and chylomicrons-TG were 72% and 91% lower in RYGB than Ctrl (P = 0.064 and P = 0.024, respectively). ApoB48 and (13) C-palmitate concentrations were not significantly different. CONCLUSIONS: Postprandial fructose metabolism was not grossly altered, but postprandial lipid concentrations were markedly decreased in subjects having had RYGB surgery.

Metabolic fate of fructose ingested with and without glucose in a mixed meal.

Ingestion of pure fructose stimulates de novo lipogenesis and gluconeogenesis. This may however not be relevant to typical nutritional situations, where fructose is invariably ingested with glucose. We therefore assessed the metabolic fate of fructose incorporated in a mixed meal without or with glucose in eight healthy volunteers. Each participant was studied over six hours after the ingestion of liquid meals containing either 13C-labelled fructose, unlabeled glucose, lipids and protein (Fr + G) or 13C-labelled fructose, lipids and protein, but without glucose (Fr), or protein and lipids alone (ProLip). After Fr + G, plasma 13C-glucose production accounted for 19.0% ± 1.5% and 13CO2 production for 32.2% ± 1.3% of 13C-fructose carbons. After Fr, 13C-glucose production (26.5% ± 1.4%) and 13CO2 production (36.6% ± 1.9%) were higher (p < 0.05) than with Fr + G. 13C-lactate concentration and very low density lipoprotein VLDL 13C-palmitate concentrations increased to the same extent with Fr + G and Fr, while chylomicron 13C-palmitate tended to increase more with Fr + G. These data indicate that gluconeogenesis, lactic acid production and both intestinal and hepatic de novo lipogenesis contributed to the disposal of fructose carbons ingested together with a mixed meal. Co-ingestion of glucose decreased fructose oxidation and gluconeogenesis and tended to increase 13C-pamitate concentration in gut-derived chylomicrons, but not in hepatic-borne VLDL-triacylglycerol (TG). This trial was approved by clinicaltrial. gov. Identifier is NCT01792089.

High protein intake reduces intrahepatocellular lipid deposition in humans.

BACKGROUND: High sugar and fat intakes are known to increase intrahepatocellular lipids (IHCLs) and to cause insulin resistance. High protein intake may facilitate weight loss and improve glucose homeostasis in insulin-resistant patients, but its effects on IHCLs remain unknown. OBJECTIVE: The aim was to assess the effect of high protein intake on high-fat diet-induced IHCL accumulation and insulin sensitivity in healthy young men. DESIGN: Ten volunteers were studied in a crossover design after 4 d of either a hypercaloric high-fat (HF) diet; a hypercaloric high-fat, high-protein (HFHP) diet; or a control, isocaloric (control) diet. IHCLs were measured by (1)H-magnetic resonance spectroscopy, fasting metabolism was measured by indirect calorimetry, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, and plasma concentrations were measured by enzyme-linked immunosorbent assay and gas chromatography-mass spectrometry; expression of key lipogenic genes was assessed in subcutaneous adipose tissue biopsy specimens. RESULTS: The HF diet increased IHCLs by 90 +/- 26% and plasma tissue-type plasminogen activator inhibitor-1 (tPAI-1) by 54 +/- 11% (P < 0.02 for both) and inhibited plasma free fatty acids by 26 +/- 11% and beta-hydroxybutyrate by 61 +/- 27% (P < 0.05 for both). The HFHP diet blunted the increase in IHCLs and normalized plasma beta-hydroxybutyrate and tPAI-1 concentrations. Insulin sensitivity was not altered, whereas the expression of sterol regulatory element-binding protein-1c and key lipogenic genes increased with the HF and HFHP diets (P < 0.02). Bile acid concentrations remained unchanged after the HF diet but increased by 50 +/- 24% after the HFHP diet (P = 0.14). CONCLUSIONS: Protein intake significantly blunts the effects of an HF diet on IHCLs and tPAI-1 through effects presumably exerted at the level of the liver. Protein-induced increases in bile acid concentrations may be involved. This trial was registered at www.clinicaltrials.gov as NCT00523562.