Papers by aahana shrestha
The impact of heat treatment of bovine milk on gastric emptying and nutrient appearance in peripheral circulation in healthy females: a randomized controlled trial comparing pasteurized and ultra-high temperature milk
The American journal of clinical nutrition, Mar 1, 2024

The American Journal of Clinical Nutrition, 2020
Background: Lactose malabsorption (LM) is a major cause of digestive discomfort from dairy produc... more Background: Lactose malabsorption (LM) is a major cause of digestive discomfort from dairy products. Recently, a role for bovine β-casein A1 has been proposed. Objectives: We examined whether there are distinct symptoms of digestive discomfort due to either lactose or differing bovine β-casein types. Methods: Women (n = 40; age: 25.2 ± 0.5 y) with selfreported varying dairy tolerance underwent a 50-g lactose challenge. Based on postchallenge LM and digestive discomfort, participants were classified as either lactose intolerant (LI; n = 10, selfreported intolerant, diagnosed lactose intolerant), nonlactose dairy intolerant (NLDI; n = 20, self-reported intolerant, diagnosed lactose tolerant), or dairy tolerant (DT; n = 10, self-reported tolerant, diagnosed lactose tolerant). In a double-blinded randomized sequence, participants consumed 750 mL conventional milk (CON; containing A1 and A2 β-casein and lactose), a2 Milk (A2M; exclusively containing A2 β-casein with lactose), or lactose-free conventional milk (LF-CON; containing A1 and A2 β-casein without lactose). Subjective digestive symptoms and breath hydrogen (measuring LM) were recorded regularly over 3 h, and further ad hoc digestive symptoms over 12 h. Results: LI subjects experienced prolonged digestive discomfort with CON milk. A2M reduced (P < 0.05) some symptoms (nausea: A2M 8 ± 3 mm compared with CON 15 ± 3mm; fecal urgency: A2M 4 ± 1 compared with CON 10 ± 3 mm), and attenuated the rise in breath hydrogen over 3 h, relative to CON milk (A2M 59 ± 23 compared with CON 98 ± 25 ppm at 150 min; P < 0.01). In contrast, NLDI subjects experienced rapid-onset, transient symptoms (abdominal distension, bloating, and flatulence) without increased breath hydrogen, irrespective of milk type. Conclusions: In LI individuals, LM and digestive comfort with lactose-containing milks was improved with milk containing exclusively A2 β-casein. Furthermore, self-reported dairy intolerance without LM (NLDI) is characterized by early-onset digestive discomfort following milk ingestion, irrespective of lactose content or β-casein type. This trial was registered at www.anzctr.org.au as ACTRN12616001694404.

Metabolic changes in serum metabolome in response to a meal
European journal of nutrition, Dec 10, 2015
The change in serum metabolic response from fasting state to postprandial state provides novel in... more The change in serum metabolic response from fasting state to postprandial state provides novel insights into the impact of a single meal on human metabolism. Therefore, this study explored changes in serum metabolite profile after a single meal. Nineteen healthy postmenopausal women with normal glucose tolerance participated in the study. They received a meal consisting of refined wheat bread (50 g carbohydrates, 9 g protein, 4.2 g fat and 2.7 g dietary fibre), 40 g cucumber and 300 mL noncaloric orange drink. Blood samples were collected at fasting and five postprandial time points. Metabolic profile was measured by nuclear magnetic resonance and targeted liquid chromatography-mass spectrometry. Changes over time were assessed with multivariate models and ANOVA, with baseline as control. The metabolomic analyses demonstrated alterations in phospholipids, amino acids and their breakdown products, glycolytic products, acylcarnitines and ketone bodies after a single meal. More specifically, phosphatidylcholines, lysophosphatidylcholines and citrate displayed an overall declining pattern, while leucine, isoleucine, methionine and succinate increased initially but declined thereafter. A sharp decline in acylcarnitines and ketone bodies and increase in glycolytic products postprandially suggest a switch in the body&amp;amp;#39;s energy source from β-oxidation to glycolysis. Moreover, individuals with relatively high postprandial insulin responses generated a higher postprandial leucine responses compared to participants with lower insulin responses. The study demonstrated complex changes from catabolic to anabolic metabolism after a meal and indicated that the extent of postprandial responses is different between individuals with high and low insulin response.

Journal of Nutrition, Apr 9, 2014
Changes in serum metabolic profile after the intake of different food products (e.g., bread) can ... more Changes in serum metabolic profile after the intake of different food products (e.g., bread) can provide insight into their interaction with human metabolism. Postprandial metabolic responses were compared after the intake of refined wheat (RWB), whole-meal rye (WRB), and refined rye (RRB) breads. In addition, associations between the metabolic profile in fasting serum and the postprandial concentration of insulin in response to different breads were investigated. Nineteen postmenopausal women with normal fasting glucose and normal glucose tolerance participated in a randomized, controlled, crossover meal study. The test breads, RWB (control), RRB, and WRB, providing 50 g of available carbohydrate, were each served as a single meal. The postprandial metabolic profile was measured using nuclear magnetic resonance and targeted LC-mass spectrometry and was compared between different breads using ANOVA and multivariate models. Eight amino acids had a significant treatment effect (P < 0.01) and a significant treatment 3 time effect (P < 0.05). RWB produced higher postprandial concentrations of leucine (geometric mean: 224; 95% CI: 196, 257) and isoleucine (mean 6 SD: 111 6 31.5) compared with RRB (geometric mean: 165;
Current developments in nutrition, Jun 1, 2020

Frontiers in Nutrition, Feb 15, 2021
Background: Sheep milk (SM) is a possible alternate dairy source for those who experience digesti... more Background: Sheep milk (SM) is a possible alternate dairy source for those who experience digestive symptoms with cow milk (CM). While both the milks contain lactose, one of the causes for self-reported intolerance to CM, the composition of SM and CM also differs across proteins and fats, which have been shown to impact digestive processes. Objective: To compare the acute digestive comfort and lactose malabsorption of SM to CM in female dairy avoiders. Method: In a double-blinded, randomized cross over trial, 30 dairy-avoiding females (aged 20-30 years) drank 650 mL of SM or CM (each reconstituted from spray dried powder) following an overnight fast, on two separate occasions at least 1 week apart. Blood samples were collected for glucose and insulin assessment, and single nucleotide polymorphisms of the lactase (LCT) gene (C/T 13910 and G/A 22018 ). Breath H 2 and visual analog scale (VAS) digestive symptom scores were recorded at fasting and regular intervals over 4 h after ingestion. Results: Eighty percentage of study participants were lactase non-persistent (LNP; CC 13910 and GG 22018 genotype). Digestive symptoms, including abdominal cramps, distension, rumbling, bloating, belching, diarrhea, flatulence, vomiting, and nausea, were similar in response to SM and CM ingestion (milk × time, P > 0.05). Breath H 2 was greater after CM than SM (72 ± 10 vs. 43 ± 6 ppm at 240 min, P < 0.001), which may be due to greater lactose content in CM (33 vs. 25 g). Accordingly, when corrected for the lactose content breath H 2 did not differ between the two milks. The response remained similar when analyzed in the LNP subset alone (n = 20). Lactose Digestion in Dairy-Avoiders Conclusions: Despite a higher energy and nutrient content, SM did not increase adverse digestive symptoms after ingestion, relative to CM, although there was a reduced breath H 2 response, which could be attributed to the lower lactose content in SM. The tolerability of SM should be explored in populations without lactose intolerance for whom underlying trigger for intolerance is unknown.

Frontiers in Nutrition, Nov 5, 2020
Background: Intolerances to bovine dairy are a motivating factor in consumers seeking alternate-o... more Background: Intolerances to bovine dairy are a motivating factor in consumers seeking alternate-or replacement-dairy beverages and foods. Sheep milk (SM) is an alternate dairy source, with greater protein, although similar amino acid composition compared to cow milk (CM). Studies are yet to address the appearance of circulating amino acids following consumption of SM, relative to CM, in humans. Objective: To clinically determine the appearance of branched chain amino acids, and other amino acids, in circulation in response to equal servings of SM and CM, in females who avoid dairy products. Design: In a double-blinded, randomized, cross-over trial, 30 self-described dairy avoiding females (20-40 years) drank 650 mL of SM or CM that were reconstituted from the spray dried powders (30 and 25 g in 180 mL water, respectively) on separate occasions, following an overnight fast. After reconstitution, the energy and protein provided by SM was higher than for CM (2,140 vs. 1,649 kJ; 29.9 vs. 19.4 g protein); content of branched chain amino acids (BCAAs) were 10.5 and 6.5 mg•mL -1 , respectively. Blood samples were collected at fasting and at regular intervals over 5 h after milk consumption. Plasma amino acids were measured by HPLC. Results: 80% of subjects self-identified as lactose intolerant, and the majority (47%) "avoided drinking milk" "most of the time". SM resulted in greater plasma appearance of BCAAs at 60 min (641.1 ± 16.3 vs. 563.5 ± 14.4 µmol•L -1 ; p < 0.001) compared with CM. SM similarly resulted in elevated postprandial concentrations of the amino acids lysine, methionine, and proline, particularly at 240 min (time × milk interactions p = 0.011, 0.017, and p = 0.002, respectively). Postprandial increases in plasma alanine concentrations were sustained to 120 min after CM (time × milk interaction p = 0.001) but not after SM, despite greater quantities provided by SM. Milan et al. Conclusions: SM is a rich source of protein, and relative to CM, provides a greater quantity of BCAAs, with a corresponding elevation of the postprandial circulating BCAA response. SM is therefore a possible dairy alternative of benefit to those who need to increase total protein intake or for individuals with heightened protein requirements.

Current Developments in Nutrition, 2019
Objectives Riboflavin, the most abundant and bioavailable B-vitamin present in milk, is highly se... more Objectives Riboflavin, the most abundant and bioavailable B-vitamin present in milk, is highly sensitive to degradation; thus, riboflavin content may vary depending on processing or the type of milk. Milk is one of the richest dietary source of riboflavin, making sufficient intake more challenging for those with dietary restrictions, such as lactose and dairy intolerant populations. Additionally, these individuals experience altered digestive function following dairy intake which may alter the bioavailability of ingested nutrients. Therefore, this study investigated whether B-vitamin bioavailability from milk is altered by milk type or processing, and whether this bioavailability is diminished in individuals with lactose and dairy intolerance. Methods The study recruited self-reported milk tolerant and intolerant young women (n = 40). All participants underwent a lactose challenge (50 g) for classification as dairy tolerant (DT, n = 10), lactose intolerant (LI, n = 10) or non-lactos...
Proceedings, 2019
Background: Lactose intolerance is due to the malabsorption of lactose, the predominant sugarpres... more Background: Lactose intolerance is due to the malabsorption of lactose, the predominant sugarpresent in milk [...]
Proceedings, 2019
Background: Lactase non-persistence, a condition affecting 75% of the world’s population, ischara... more Background: Lactase non-persistence, a condition affecting 75% of the world’s population, ischaracterized by inactivity of the lactase enzyme, resulting in lactose intolerance. [...]

Metabolic changes in serum metabolome in response to a meal
European Journal of Nutrition, 2015
The change in serum metabolic response from fasting state to postprandial state provides novel in... more The change in serum metabolic response from fasting state to postprandial state provides novel insights into the impact of a single meal on human metabolism. Therefore, this study explored changes in serum metabolite profile after a single meal. Nineteen healthy postmenopausal women with normal glucose tolerance participated in the study. They received a meal consisting of refined wheat bread (50 g carbohydrates, 9 g protein, 4.2 g fat and 2.7 g dietary fibre), 40 g cucumber and 300 mL noncaloric orange drink. Blood samples were collected at fasting and five postprandial time points. Metabolic profile was measured by nuclear magnetic resonance and targeted liquid chromatography-mass spectrometry. Changes over time were assessed with multivariate models and ANOVA, with baseline as control. The metabolomic analyses demonstrated alterations in phospholipids, amino acids and their breakdown products, glycolytic products, acylcarnitines and ketone bodies after a single meal. More specifically, phosphatidylcholines, lysophosphatidylcholines and citrate displayed an overall declining pattern, while leucine, isoleucine, methionine and succinate increased initially but declined thereafter. A sharp decline in acylcarnitines and ketone bodies and increase in glycolytic products postprandially suggest a switch in the body&amp;amp;#39;s energy source from β-oxidation to glycolysis. Moreover, individuals with relatively high postprandial insulin responses generated a higher postprandial leucine responses compared to participants with lower insulin responses. The study demonstrated complex changes from catabolic to anabolic metabolism after a meal and indicated that the extent of postprandial responses is different between individuals with high and low insulin response.

Nutrients, 2019
Hydrogen (H2) measurement in exhaled breath is a reliable and non-invasive method to diagnose car... more Hydrogen (H2) measurement in exhaled breath is a reliable and non-invasive method to diagnose carbohydrate malabsorption. Currently, breath H2 measurement is typically limited to clinic-based equipment. A portable breath analyser (AIRE, FoodMarble Digestive Health Limited, Dublin, Ireland) is a personalised device marketed for the detection and self-management of food intolerances, including lactose malabsorption (LM). Currently, the validity of this device for breath H2 analysis is unknown. Individuals self-reporting dairy intolerance (six males and six females) undertook a lactose challenge and a further seven individuals (all females) underwent a milk challenge. Breath samples were collected prior to and at frequent intervals post-challenge for up to 5 h with analysis using both the AIRE and a calibrated breath hydrogen analyser (BreathTracker, QuinTron Instrument Company Inc., Milwaukee, WI, USA). A significant positive correlation (p < 0.001, r > 0.8) was demonstrated bet...

Frontiers in Nutrition, 2020
Background: Intolerances to bovine dairy are a motivating factor in consumers seeking alternate—o... more Background: Intolerances to bovine dairy are a motivating factor in consumers seeking alternate—or replacement—dairy beverages and foods. Sheep milk (SM) is an alternate dairy source, with greater protein, although similar amino acid composition compared to cow milk (CM). Studies are yet to address the appearance of circulating amino acids following consumption of SM, relative to CM, in humans. Objective: To clinically determine the appearance of branched chain amino acids, and other amino acids, in circulation in response to equal servings of SM and CM, in females who avoid dairy products. Design: In a double-blinded, randomized, cross-over trial, 30 self-described dairy avoiding females (20–40 years) drank 650 mL of SM or CM that were reconstituted from the spray dried powders (30 and 25 g in 180 mL water, respectively) on separate occasions, following an overnight fast. After reconstitution, the energy and protein provided by SM was higher than for CM (2,140 vs. 1,649 kJ; 29.9 vs...

Comparison of the impact of bovine milk β-casein variants on digestive comfort in females self-reporting dairy intolerance: a randomized controlled trial
The American journal of clinical nutrition, 2019
BACKGROUND Lactose malabsorption (LM) is a major cause of digestive discomfort from dairy product... more BACKGROUND Lactose malabsorption (LM) is a major cause of digestive discomfort from dairy products. Recently, a role for bovine β-casein A1 has been proposed. OBJECTIVES We examined whether there are distinct symptoms of digestive discomfort due to either lactose or differing bovine β-casein types. METHODS Women (n = 40; age: 25.2 ± 0.5 y) with self-reported varying dairy tolerance underwent a 50-g lactose challenge. Based on postchallenge LM and digestive discomfort, participants were classified as either lactose intolerant (LI; n = 10, self-reported intolerant, diagnosed lactose intolerant), nonlactose dairy intolerant (NLDI; n = 20, self-reported intolerant, diagnosed lactose tolerant), or dairy tolerant (DT; n = 10, self-reported tolerant, diagnosed lactose tolerant). In a double-blinded randomized sequence, participants consumed 750 mL conventional milk (CON; containing A1 and A2 β-casein and lactose), a2 Milk (A2M; exclusively containing A2 β-casein with lactose), or lactose-...

Differences in Postprandial Responses to Breads and Fasting Metabolic Characteristics Associated with Postprandial Insulin Demand in Postmenopausal Women 1 – 3
Changes in serummetabolic profile after the intake of different food products (e.g., bread) can p... more Changes in serummetabolic profile after the intake of different food products (e.g., bread) can provide insight into their interaction with human metabolism. Postprandial metabolic responses were compared after the intake of refined wheat (RWB), whole-meal rye (WRB), and refined rye (RRB) breads. In addition, associations between the metabolic profile in fasting serum and the postprandial concentration of insulin in response to different breads were investigated. Nineteen postmenopausal women with normal fasting glucose and normal glucose tolerance participated in a randomized, controlled, crossover meal study. The test breads, RWB (control), RRB, and WRB, providing 50 g of available carbohydrate, were each served as a single meal. The postprandial metabolic profile was measured using nuclear magnetic resonance and targeted LC–mass spectrometry and was compared between different breads using ANOVA and multivariate models. Eight amino acids had a significant treatment effect (P < ...

Frontiers in Nutrition
Background: Sheep milk (SM) is a possible alternate dairy source for those who experience digesti... more Background: Sheep milk (SM) is a possible alternate dairy source for those who experience digestive symptoms with cow milk (CM). While both the milks contain lactose, one of the causes for self-reported intolerance to CM, the composition of SM and CM also differs across proteins and fats, which have been shown to impact digestive processes.Objective: To compare the acute digestive comfort and lactose malabsorption of SM to CM in female dairy avoiders.Method: In a double-blinded, randomized cross over trial, 30 dairy-avoiding females (aged 20–30 years) drank 650 mL of SM or CM (each reconstituted from spray dried powder) following an overnight fast, on two separate occasions at least 1 week apart. Blood samples were collected for glucose and insulin assessment, and single nucleotide polymorphisms of the lactase (LCT) gene (C/T13910 and G/A22018). Breath H2 and visual analog scale (VAS) digestive symptom scores were recorded at fasting and regular intervals over 4 h after ingestion.Re...

BMC Gastroenterology
Background Adult lactase non-persistence (LNP) is due to low lactase expression, resulting in lac... more Background Adult lactase non-persistence (LNP) is due to low lactase expression, resulting in lactose malabsorption (LM). LNP is a genetic trait, but is typically determined by LM markers including breath H2, blood glucose, and urinary galactose after a lactose tolerance test. Known validity of these markers using milk is limited, despite being common practice. Compositional variation, such as β-casein variants, in milk may impact diagnostic efficacy. This study aimed to evaluate the diagnostic accuracy to detect LNP using these commonly measured LM markers after both lactose and milk challenges. Methods Fourty healthy young women were challenged with 50 g lactose then randomized for separate cross-over visits to ingest 750 mL milk (37.5 g lactose) as conventional (both A1 and A2 β-casein) and A1 β-casein-free (a2 Milk™) milk. Blood, breath and urine were collected prior to and up to 3 h following each challenge. The presence of C/T13910 and G/A22018 polymorphisms, determined by res...
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Papers by aahana shrestha