Effects of intragastric administration of L-tryptophan on the glycaemic response to a nutrient drink in men with type 2 diabetes - impacts on gastric emptying, glucoregulatory hormones and glucose absorption

Published: 05 January 2021BACKGROUND: The rate of gastric emptying and glucoregulatory hormones are key determinants of postprandial glycaemia. Intragastric administration of L-tryptophan slows gastric emptying and reduces the glycaemic response to a nutrient drink in lean individuals and those with obesity. We investigated whether tryptophan decreases postprandial glycaemia and slows gastric emptying in type 2 diabetes (T2D). METHODS: Twelve men with T2D (age: 63 ± 2 years, HbA1c: 49.7 ± 2.5 mmol/mol, BMI: 30 ± 1 kg/m2) received, on three separate occasions, 3 g ('Trp-3') or 1.5 g ('Trp-1.5') tryptophan, or control (0.9% saline), intragastrically, in randomised, double-blind fashion, 30 min before a mixed-nutrient drink (500 kcal, 74 g carbohydrates), containing 3 g 3-O-methyl-D-glucose (3-OMG) to assess glucose absorption. Venous blood samples were obtained at baseline, after tryptophan, and for 2 h post-drink for measurements of plasma glucose, C-peptide, glucagon and 3-OMG. Gastric emptying of the drink was quantified using two-dimensional ultrasound. RESULTS: Tryptophan alone stimulated C-peptide (P = 0.002) and glucagon (P = 0.04), but did not affect fasting glucose. In response to the drink, Trp-3 lowered plasma glucose from t = 15-30 min and from t = 30-45 min compared with control and Trp-1.5, respectively (both P < 0.05), with no differences in peak glucose between treatments. Gastric emptying tended to be slower after Trp-3, but not Trp-1.5, than control (P = 0.06). Plasma C-peptide, glucagon and 3-OMG increased on all days, with no major differences between treatments. CONCLUSIONS: In people with T2D, intragastric administration of 3 g tryptophan modestly slows gastric emptying, associated with a delayed rise, but not an overall lowering of, postprandial glucose.Maryam Hajishafiee, Rachel A. Elovaris, Karen L. Jones, Leonie K. Heilbronn, Michael Horowitz, Sally D. Poppitt and Christine Feinle-Bisse

Effects of intraduodenal infusion of lauric acid and L-tryptophan, alone and combined, on glucoregulatory hormones, gastric emptying and glycaemia in healthy men

Background and aim: In healthy men, intraduodenal administration of the fatty acid, lauric acid (‘C12’) and the amino acid, L-tryptophan (‘TRP’), at loads that individually do not affect energy intake, reduce energy intake sub- stantially when combined. C12 and TRP may also stimulate cholecystokinin and glucagon-like peptide-1 (GLP-1), which both slow gastric emptying, a key determinant of postprandial blood glucose. Accordingly, combination of C12 and TRP has the potential to reduce post-meal glycaemia more than either nutrient alone. Methods: Twelve healthy, lean men (age (mean ± SD): 28 ± 7 years) received, on 4 separate occasions, 45-min intraduodenal infusions of C12 (0.3 kcal/min), TRP (0.1 kcal/min), C12 + TRP (0.4 kcal/min), or 0.9% saline (control), in a randomised, double-blind fashion. 30 min after commencement of the infusion a mixed- nutrient drink was consumed and gastric emptying measured (13C breath-test) for 3 h. Blood samples were obtained at baseline, in response to treatments alone, and for 2 h post-drink for measurements of plasma glucose, cholecystokinin, GLP-1, C-peptide, insulin and glucagon. ‘Early’ (first 30 min) and ‘overall’ glycaemic and hormone responses were evaluated. Results: C12 + TRP and C12 delayed the rise in, but did not affect the overall glycaemic response to the drink, compared with control and TRP (all P < 0.05). C12 + TRP slowed gastric emptying compared with control and TRP (both P < 0.005), and C12 non-significantly slowed gastric emptying compared with control (P = 0.090). C12 + TRP and C12 delayed the rise in C-peptide and insulin, and also stimulated CCK and glucagon, compared with control and TRP (all P < 0.05). Only C12 + TRP stimulated early and overall GLP-1 compared with control (P < 0.05). Conclusions: In healthy men, C12 + TRP and C12, in the loads administered, had comparable effects to delay the rise in glucose following a nutrient drink, probably primarily by slowing of gastric emptying, as a result of CCK and GLP-1 stimulation, while TRP had no effect.M. Hajishafiee, C. McVeay. K. Lange, J.F. Rehfeld, M. Horowitz, C. Feinle-Bisse

The effect of Alpha-lipoic acid supplementation on endothelial function: A systematic review and meta-analysis

There is evidence that alpha-lipoic acid (ALA) supplementation plays an important role in preventing cardiovascular diseases. However, its effect, specifically, on endothelial function (EF) is unclear. Therefore, this systematic review and meta-analysis aimed to evaluate the effects of ALA supplementation on EF. Databases including PubMed/Medline, Scopus, and ISI Web of Science were searched to identify eligible publications from inception up to April 2020. Randomized controlled trials assessing the effect of ALA supplementation on flow-mediated dilation (FMD) levels in adults were included. The pooled results were obtained using the random-effects model and are expressed as weighted mean differences (WMD) with 95 confidence intervals (CI). Five studies including six effect sizes and 300 participants were included. ALA supplementation significantly increased FMD levels by 2.36 (95 CI: 1.21�3.51; p <.001), compared with the control. Subgroup analyses suggested that the effects of ALA on FMD could be changed by age and health status of the participants. Dose�response analysis also showed that ALA dosage had a significant non-linear effect on FMD levels. The results showed that ALA supplementation appears to improve the EF. However, the role of ALA supplementation in improving other biomarkers of EF requires further research. © 2020 John Wiley & Sons, Ltd

Suppression of energy intake by intragastric L-tryptophan in lean and obese men: relations with appetite perceptions and circulating cholecystokinin and tryptophan

Background: L-Tryptophan reduces energy intake in healthy men. The underlying mechanisms, including appetite, plasma cholecystokinin (CCK), tryptophan (Trp), and the ratio of Trp to large neutral amino acids (Trp:LNAAs ratio), and whether responses differ in lean and obese individuals, are uncertain. Objectives: We evaluated the effects of intragastric Trp on energy intake (primary outcome) and their potential mechanisms, pre- and postmeal, in lean men and those with obesity. Methods: Twelve lean men [mean ± SD age: 30 ± 3 y; BMI (in kg/m2): 23 ± 1] and 13 men with obesity (mean ± SD age: 31 ± 3 y; BMI: 33 ± 1) received, on 3 separate occasions, in double-blind, randomized order, 3 g (“Trp-3”) or 1.5 g (“Trp-1.5”) Trp, or control (“C”), intragastrically, 30 min before a buffet-meal. Energy intake from the buffet-meal, hunger, fullness, and plasma CCK and amino acid concentrations were measured in response to Trp alone and for 2 h postmeal. Data were analyzed using maximum likelihood mixed-effects models, with treatment, group, and treatment-by-group interaction as fixed effects. Results: Trp alone increased plasma CCK, Trp, and the Trp:LNAAs ratio (all P < 0.001), with no difference between groups. Trp suppressed energy intake (P < 0.001), with no difference between groups (lean, C: 1085 ± 102 kcal, Trp-1.5: 1009 ± 92 kcal, Trp-3: 868 ± 104 kcal; obese, C: 1249 ± 98 kcal, Trp-1.5: 1217 ± 90 kcal, Trp-3: 1012 ± 100 kcal). Postmeal, fullness was greater after Trp-3 than after C and Trp-1.5 (all P < 0.05), and in men with obesity than in leanmen (P < 0.05). Plasma Trp and the Trp:LNAAs ratio were greater after Trp-3 and Trp-1.5 than after C (all P < 0.001), and tended to be less in men with obesity than in the lean (P = 0.07) (Trp:LNAAs ratio: lean, C: 1.5 ± 0.2, Trp-1.5: 6.9 ± 0.7, Trp-3: 10.7 ± 1.4; obese, C: 1.4 ± 0.1, Trp-1.5: 4.6 ± 0.7, Trp-3: 7.8 ± 1.3). There were inverse correlations of energy intake with plasma Trp and the Trp:LNAAs ratio in both groups (lean, both r = −0.50, P < 0.01; obese, both r = −0.40, P < 0.05). Conclusions: Intragastric Trp has potent energy intake–suppressant effects, in both lean men and those with obesity, apparently related to the Trp:LNAAs ratio.Maryam Hajishafiee, Sina S Ullrich, Penelope CE Fitzgerald, Michael Horowitz, Kylie Lange, Sally D Poppitt, and Christine Feinle-Bisse

Effects of intragastric tryptophan on acute changes in the plasma tryptophan/large neutral amino acids ratio and relationship with subsequent energy intake in lean and obese men

28 Jul 2020Circulating tryptophan/large neutral amino acids (tryptophan/LNAA) ratio, an indicator of brain serotonin levels, may be important in appetite regulation, together with gastrointestinal (gastric emptying, plasma cholecystokinin) mechanisms. We have compared effects of intragastric tryptophan ('Trp') on the plasma tryptophan/LNAA ratio in lean and obese men, and the associations of the tryptophan/LNAA ratio, gastric emptying and CCK concentrations with energy intake. Lean and obese male participants (n = 16 each) received 3 g Trp or volume-matched control intragastrically, 15 min before a mixed-nutrient drink (300 mL, 400 kcal) (t = 0 min) in randomised, double-blind fashion. Plasma amino acid (for calculation of the plasma tryptophan/LNAA ratio) and CCK concentrations were measured from t = -20-60 min. Gastric emptying was assessed from t = 0-60 min, and ad-libitum energy intake from a standardised buffet-style meal from t = 60-90 min. The increase in the plasma tryptophan/LNAA ratio was less in obese, than lean, participants (P 0 kcal) after Trp compared with those who did not (by ≤0 kcal) (P < 0.05). Moreover, in participants who reduced their energy intake, the ratio was lower in obese, than in lean (P < 0.05). There was a trend for an inverse correlation between energy intake with the plasma tryptophan/LNAA ratio in lean (r = -0.4, P = 0.08), but not in obese, participants. There was no significant difference in gastric emptying or CCK between participants who reduced their energy intake and those who did not. In conclusion, the plasma tryptophan/LNAA ratio appears to be a determinant of the suppression of energy intake in response to tryptophan in normal-weight people, but not in those with obesity. The role of the plasma tryptophan/LNAA ratio to regulate energy intake, and potential changes in obesity, warrant evaluation in prospective studies.Maryam Hajishafiee, Sina S. Ullrich, Robert E. Steinert, Sally D. Poppitt, Natalie D. Luscombe-Marsh, Michael Horowitza and Christine Feinle-Bisse

Consumption of spicy foods and the prevalence of irritable bowel syndrome

AimTo explore the association between consumption of spicy foods and prevalence of irritable bowel syndrome (IBS) among Iranian adults.MethodsIn this cross-sectional study, data from 4763 Iranian adult participants were used. Consumption of spicy foods was estimated using a dietary habits questionnaire that included a question on spicy foods consumption: "how frequently do you use spicy foods (pepper, curry, ginger, cinnamon and turmeric) during a week?" Participants could respond to the question by choosing one of these choices: never, 1-3 times, 4-6 times, 7-9 times, or more than 10 times per week. A modified Persian version of the Rome III questionnaire was used to determine the prevalence of IBS.ResultsIBS was prevalent in 21.7% (18.6% of men and 24.1% of women) of the study population. After controlling for potential confounders including dietary behaviors, those consuming spicy foods ≥ 10 times per week were 92% more likely to have IBS compared with those who never consumed spicy foods (OR = 1.92; 95%CI: 1.23-3.01, P trend ConclusionConsumption of spicy foods is directly associated with IBS, particularly in women. Further, prospective studies are warranted to (1) examine this association in other populations; and (2) evaluate whether dietary interventions, for example a reduction in spice consumption, would improve IBS symptoms.Ahmad Esmaillzadeh, Ammar Hassanzadeh Keshteli, Maryam Hajishafiee, Awat Feizi, Christine Feinle-Bisset and Peyman Adib

Intragastric administration of leucine and isoleucine does not reduce the glycaemic response to, or slow gastric emptying of, a carbohydrate-containing drink in type 2 diabetes

AIMS: In healthy individuals, intragastric administration of the branched-chain amino acids, leucine and isoleucine, diminishes the glycaemic response to a mixed-nutrient drink, apparently by stimulating insulin and slowing gastric emptying, respectively. This study aimed to evaluate the effects of leucine and isoleucine on postprandial glycaemia and gastric emptying in type-2 diabetes mellitus (T2D). METHODS: 14 males with T2D received, on 3 separate occasions, in double-blind, randomised fashion, either 10g leucine, 10g isoleucine or control, intragastrically 30 min before a mixed-nutrient drink (500 kcal; 74g carbohydrates, 18g protein, 15g fat). Plasma glucose, insulin and glucagon were measured from 30 min pre- until 120 min post-drink. Gastric emptying of the drink was also measured. RESULTS: Leucine and isoleucine stimulated insulin, both before and after the drink (all P<0.05; peak (mU/L): control: 70±15; leucine: 88±17; isoleucine: 74±15). Isoleucine stimulated (P<0.05), and leucine tended to stimulate (P=0.078), glucagon before the drink, and isoleucine stimulated glucagon post-drink (P=0.031; peak (pg/mL): control: 62±5; leucine: 70±9; isoleucine: 69±6). Neither amino acid affected gastric emptying or plasma glucose (peak (mmol/L): control: 12.0±0.5; leucine: 12.5±0.7; isoleucine: 12.0±0.6). CONCLUSIONS: In contrast to health, in T2D, leucine and isoleucine, administered intragastrically in a dose of 10 g, do not lower the glycaemic response to a mixed-nutrient drink. This finding argues against a role for 'preloads' of either leucine or isoleucine in the management of T2D.Rachel A. Elovaris, Maryam Hajishafiee, Sina S. Ullrich, Penelope C.E. Fitzgerald,Kylie Lange, Michael Horowitz, Christine Feinle-Bisse

Association between healthy lifestyle score and upper gastrointestinal disorders in Iranian adults

Background and Objective: Although lifestyle-related factors have separately been examined in relation to functional gastrointestinal disorders (FGIDs), there is no epidemiologic data on the combined association of lifestyle factors with these conditions. We aimed to examine how combinations of several lifestyle factors were associated with functional dyspepsia (FD), its symptoms and gastro-esophageal reflux disease (GERD) in a large group of Iranian adults. Methods: This descriptive -analytic study was conducted on 3363 Iranian adults (19-70 yr), whom were working in 50 health centers across Isfahan province in Iran during 2012. We used easy non-random sampling to select participants. The “healthy lifestyle score” for each participant was calculated by summing up the binary score given for five lifestyle factors, including dietary habits, dietary intakes, psychological distress, smoking and physical activity. A dish-based 106-item semi-quantitative validated food frequency questionnaire, General Practice Physical Activity Questionnaire, General Health Questionnaire and other pre-tested questionnaires were used to assess the components of healthy lifestyle score. A validated Persian version of ROME III questionnaire was used, to assess functional gastrointestinal disorders. Results: The prevalence of FD and GERD among study participants was 14.5 and 23.6%, respectively. After adjustment for potential confounders, we found that individuals with the highest score of healthy lifestyle had 79 and 74% lower odds of FD (95% CI: 0.05-0.92, OR: 0.21, P=0.03) and GERD (95% CI: 0.09-0.69, OR: 0.26, P=0.01), respectively, compared with those with the lowest score. They were also less likely to have early satiation (95% CI: 0.11-0.73, OR: 0.28, P=0.001), postprandial fullness (95% CI: 0.09-0.50, OR: 0.22, P<0.001) and epigastric pain (95% CI: 0.21-0.92, OR: 0.44, P=0.03). In addition to the combined healthy lifestyle score, low levels of psychological distress, a healthy diet, healthy dietary habits and non-smoking were separately associated with FGIDs (P<0.05). Conclusion: This study showed that adherence to a healthy lifestyle was associated with lower odds of GERD, FD and its symptoms in this group of Iranian adults. Individual lifestyle-related factors were also associated with these conditions