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

NCT ID: NCT03060395

Last Updated: 2020-04-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

37 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-04-01

Study Completion Date

2019-03-31

Brief Summary

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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.

Detailed Description

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Non-lactose milk intolerance is a condition that has not been defined clinically yet but the current literature reports existence of subjects who are moderately milk intolerant and whose intolerance can neither be attributed to a defect in lactose intolerance, nor to milk protein allergy. Yet, they experience at least one or two of the following symptoms following milk consumption: gases, bloating, abdominal cramp. It is known that the A1gene variant coding for beta-casein leads to the production of a bioactive peptide with opioid activity named betacasomorphin 7 (BCM7). This peptide has been associated with several metabolic health disorders including diabetes, elevated cardiovascular risk and stimulation of pro-inflammatory signals. Recently, it was reported that non-lactose milk intolerant subjects did not experience such symptoms when consuming milk containing the non-mutated A2 gene variant coding for beta-casein. In this study, we hypothesise that consumption of A2 milk will improve gastrointestinal symptoms in non-lactose milk intolerant individuals. The primary outcome of this study will be the reduction of gastrointestinal inflammation following a course of A2 milk consumption.

Conditions

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Milk Intolerance

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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A1/A2 milk

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

Group Type SHAM_COMPARATOR

A1/A2 milk 100

Intervention Type DIETARY_SUPPLEMENT

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

A1/A2 milk 150

Intervention Type DIETARY_SUPPLEMENT

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

A1/A2 milk 200

Intervention Type DIETARY_SUPPLEMENT

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

A1/A2 milk 250

Intervention Type DIETARY_SUPPLEMENT

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

A2 milk

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

Group Type ACTIVE_COMPARATOR

A2 milk 100

Intervention Type DIETARY_SUPPLEMENT

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

A2 milk 150

Intervention Type DIETARY_SUPPLEMENT

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

A2 milk 200

Intervention Type DIETARY_SUPPLEMENT

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

A2 milk 250

Intervention Type DIETARY_SUPPLEMENT

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

Interventions

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A2 milk 100

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

Intervention Type DIETARY_SUPPLEMENT

A2 milk 150

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

Intervention Type DIETARY_SUPPLEMENT

A2 milk 200

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

Intervention Type DIETARY_SUPPLEMENT

A2 milk 250

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

Intervention Type DIETARY_SUPPLEMENT

A1/A2 milk 100

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

Intervention Type DIETARY_SUPPLEMENT

A1/A2 milk 150

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

Intervention Type DIETARY_SUPPLEMENT

A1/A2 milk 200

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

Intervention Type DIETARY_SUPPLEMENT

A1/A2 milk 250

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

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
* Who take medication at least the last 6-month.
* Who do excessive exercise not as part of a weight-loss regime, e.g. athletes.
Minimum Eligible Age

18 Years

Maximum Eligible Age

56 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Reading

OTHER

Sponsor Role lead

Responsible Party

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Sandrine Claus

Associate Professor in Integrative Metabolism

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sandrine P Claus, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Reading

Locations

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Department of Food and Nutritional Sciences

Reading, Berkshire, United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 24166511 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24986816 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27039383 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8438774 (View on PubMed)

Other Identifiers

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A2study

Identifier Type: -

Identifier Source: org_study_id

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