Effects of A2 Milk on Gastrointestinal Function in Non-lactose Milk Intolerance

NCT03060395 | Completed

• 1 other identifier: A2study
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

There is increasing evidence that a number of people experience moderate milk intolerance characterised by increased gas production, bloating and abdominal cramp, which can neither be attributed to lactose intolerance, nor to milk protein allergy. Milk digestion can lead to the formation of bioactive peptides, one of which derived from a mutated gene variant (A1) coding for milk beta-casein has been associated with increased gastrointestinal inflammation and poor gastrointestinal function. In this study, we hypothesise that consumption of non-mutated A2 milk will improve gastrointestinal symptoms in non-lactose milk intolerant individuals.

Conditions

Milk Intolerance

Outcome Measures

Primary Outcomes (1)

• Change in gastrointestinal inflammation indicated by fecal calprotectin

  Measurement of fecal calprotectin (ug/g feces)

  baseline, 14 days, 28 days, 42 days and 56 days

Secondary Outcomes (18)

• Change in NMR-based urinary metabolic profiles

  baseline, 14 days, 28 days, 42 days and 56 days

• Change in NMR-based plasma metabolic profiles

  baseline, 14 days, 28 days, 42 days and 56 days

• Change in NMR-based fecal metabolic profiles

  baseline, 14 days, 28 days, 42 days and 56 days

• Change in gut microbiota ecosystem assessed by sequencing the 16S rDNA extracted from feces

  baseline, 14 days, 28 days, 42 days and 56 days

• Change in systemic inflammation indicated by circulating levels of high sensitivity C-reactive protein

  baseline, 14 days, 28 days, 42 days and 56 days

Study Arms (2)

A1/A2 milk

SHAM COMPARATOR

Commercial conventional A1/A2 semi-skimmed fresh pasteurised cow milk. Progressive intake of intervention milk as follows: * Days 1 and 2: 100 mL twice a day * Days 3 and 4: 150 mL twice a day * Days 5 and 6: 200 mL twice a day * Days 7 to 14: 250 mL twice a day

Dietary Supplement: A1/A2 milk 100; Dietary Supplement: A1/A2 milk 150; Dietary Supplement: A1/A2 milk 200; Dietary Supplement: A1/A2 milk 250

A2 milk

ACTIVE COMPARATOR

Commercial A2 semi-skimmed fresh pasteurised cow milk. Progressive intake of intervention milk as follows: * Days 1 and 2: 100 mL twice a day * Days 3 and 4: 150 mL twice a day * Days 5 and 6: 200 mL twice a day * Days 7 to 14: 250 mL twice a day

Dietary Supplement: A2 milk 100; Dietary Supplement: A2 milk 150; Dietary Supplement: A2 milk 200; Dietary Supplement: A2 milk 250

Interventions

A2 milk 100 DIETARY_SUPPLEMENT

Days 1 and 2: 100 mL A2 milk twice a day

A2 milk

A2 milk 150 DIETARY_SUPPLEMENT

Days 3 and 4: 150 mL A2 milk twice a day

A2 milk

A2 milk 200 DIETARY_SUPPLEMENT

Days 5 and 6: 200 mL A2 milk twice a day

A2 milk

A2 milk 250 DIETARY_SUPPLEMENT

Days 7 to 14: 250 mL A2 milk twice a day

A2 milk

A1/A2 milk 100 DIETARY_SUPPLEMENT

Days 1 and 2: 100 mL A1/A2 milk twice a day

A1/A2 milk

A1/A2 milk 150 DIETARY_SUPPLEMENT

Days 3 and 4: 150 mL A1/A2 milk twice a day

A1/A2 milk

A1/A2 milk 200 DIETARY_SUPPLEMENT

Days 5 and 6: 200 mL A1/A2 milk twice a day

A1/A2 milk

A1/A2 milk 250 DIETARY_SUPPLEMENT

Days 7 to14: 250 mL A1/A2 milk twice a day

A1/A2 milk

Eligibility Criteria

• Age: 18 Years - 56 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BMI: 20-35kg/m2
• Glucose\<7mmol/l (not diagnosed with diabetes)
• Total cholesterol\<7mmol/l
• Triacylglycerol\<4mmol/l
• Normal liver and kidney function
• Regular milk drinker with self-reported intolerance to commercial milk.
• Suffered from mild to moderate digestive discomfort after milk consumption.
• Have normal blood pressure 120/80 mmHg (BP \<160/90 mmHg can be accepted) during quiet respiration.
• Agree not to take any medication, supplements and other dairy products including acidophilus milk
• Be willing to comply with all the requirements and procedures of the study.
• Agree to sign the informed consent form;
• Agree not to enrol in another interventional clinical research study while participating in this study.
• Fully understand the nature, objective, benefit and the potential risks and side effects of the study.

You may not qualify if:

• Females who are pregnant or planning to be a pregnant and lactating.
• Have known dairy allergy.
• Have stopped drinking milk for the last 6 month.
• Have history of lactose intolerance
• Have history of faecal impaction.
• Received antibiotics in the previous six months
• Smoker
• Anemia
• Trying to lose weight by following a diet or exercise regimen designed for weight loss, or taking any drug influencing appetite and any drug for weight loss for the last three months.
• Have participated in similar dairy or probiotics-containing product's clinical trials within 3 months before the screening.
• Currently taking medicines for cardiovascular or metabolic disease.
• History of alcohol or drug misuse.
• Have history of or be diagnosed of any of the following diseases that may affect the study results: gastrointestinal disorders, hepatopathy, nephropathy, endocrine disease, blood disorders, respiratory, cardiovascular diseases and known on-going allergy such as asthma.
• Currently suffering from any gastrointestinal disorders or gastrointestinal disease, including irritable bowel syndrome, colitis, ulcerative colitis, celiac disease, irritable bowel syndrome (IBS);
• Had hospitalizations within 3 months before screening; Currently drug frequency user of that may affect the gastrointestinal function or immune system. As judged by investigator.

Sponsors & Collaborators

• University of Reading: lead

Study Sites (1)

Department of Food and Nutritional Sciences

Reading, Berkshire, RG6 6AP, United Kingdom

Location

Related Publications (4)

• Ul Haq MR, Kapila R, Sharma R, Saliganti V, Kapila S. Comparative evaluation of cow beta-casein variants (A1/A2) consumption on Th2-mediated inflammatory response in mouse gut. Eur J Nutr. 2014 Jun;53(4):1039-49. doi: 10.1007/s00394-013-0606-7. Epub 2013 Oct 29.

  PMID: 24166511 BACKGROUND

• Ho S, Woodford K, Kukuljan S, Pal S. Comparative effects of A1 versus A2 beta-casein on gastrointestinal measures: a blinded randomised cross-over pilot study. Eur J Clin Nutr. 2014 Sep;68(9):994-1000. doi: 10.1038/ejcn.2014.127. Epub 2014 Jul 2.

  PMID: 24986816 BACKGROUND

• Jianqin S, Leiming X, Lu X, Yelland GW, Ni J, Clarke AJ. Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows' milk. Nutr J. 2016 Apr 2;15:35. doi: 10.1186/s12937-016-0147-z.

  PMID: 27039383 BACKGROUND

• Johnson AO, Semenya JG, Buchowski MS, Enwonwu CO, Scrimshaw NS. Correlation of lactose maldigestion, lactose intolerance, and milk intolerance. Am J Clin Nutr. 1993 Mar;57(3):399-401. doi: 10.1093/ajcn/57.3.399.

  PMID: 8438774 BACKGROUND

MeSH Terms

Conditions

Lactose Intolerance

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Sandrine P Claus, PhD

  University of Reading

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor in Integrative Metabolism

Study Record Dates

• First Submitted: January 17, 2017
• First Posted: February 23, 2017
• Study Start: April 1, 2017
• Primary Completion: April 30, 2018
• Study Completion: March 31, 2019
• Last Updated: April 28, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)