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

Milk Intolerance Clinical Trial

Official title:

Effects of A2 Milk on Gastrointestinal Function of Volunteers Affected by Non-lactose Milk Intolerance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03060395
• Other study ID #: A2study
• Status: Completed
• Phase: N/A
• Start date: April 1, 2017
• Est. completion date: March 31, 2019

Study information

• Verified date: April 2020
• Source: University of Reading
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: March 31, 2019
• Est. primary completion date: April 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 56 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lactose Intolerance
• Milk Intolerance

Intervention

Dietary Supplement:
• A2 milk 100
Days 1 and 2: 100 mL A2 milk twice a day
• A2 milk 150
Days 3 and 4: 150 mL A2 milk twice a day
• A2 milk 200
Days 5 and 6: 200 mL A2 milk twice a day
• A2 milk 250
Days 7 to 14: 250 mL A2 milk twice a day
• A1/A2 milk 100
Days 1 and 2: 100 mL A1/A2 milk twice a day
• A1/A2 milk 150
Days 3 and 4: 150 mL A1/A2 milk twice a day
• A1/A2 milk 200
Days 5 and 6: 200 mL A1/A2 milk twice a day
• A1/A2 milk 250
Days 7 to14: 250 mL A1/A2 milk twice a day

Locations

Country	Name	City	State
United Kingdom	Department of Food and Nutritional Sciences	Reading	Berkshire

Sponsors (1)

Lead Sponsor	Collaborator
University of Reading

Country where clinical trial is conducted

United Kingdom, 

References & Publications (4)

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. — View Citation

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. Erratum in: Nutr J. 2016;15(1):45. — View Citation

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. — View Citation

Ul Haq MR, Kapila R, Sharma R, Saliganti V, Kapila S. Comparative evaluation of cow ß-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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in NMR-based urinary metabolic profiles	Measured using High Resolution 700MHz proton NMR spectroscopy (Bruker) (no unit)	baseline, 14 days, 28 days, 42 days and 56 days
Secondary	Change in NMR-based plasma metabolic profiles	Measured using High Resolution 700MHz proton NMR spectroscopy (Bruker) (no unit)	baseline, 14 days, 28 days, 42 days and 56 days
Secondary	Change in NMR-based fecal metabolic profiles	Measured using High Resolution 700MHz proton NMR spectroscopy (Bruker) (no unit)	baseline, 14 days, 28 days, 42 days and 56 days
Secondary	Change in gut microbiota ecosystem assessed by sequencing the 16S rDNA extracted from feces	Measures relative abundance of bacterial taxa	baseline, 14 days, 28 days, 42 days and 56 days
Secondary	Change in systemic inflammation indicated by circulating levels of high sensitivity C-reactive protein	hs-CRP in mg/L	baseline, 14 days, 28 days, 42 days and 56 days
Secondary	Change in gastrointestinal function assessed using visual analogue scale for GI symptoms	Measures gases, bloating, abdominal cramps, diarrhoea, headache, constipation, nausea and rash	14 days
Secondary	Height (in m) used to detect change in BMI (kg/m^2)		baseline
Secondary	Weight (in kg) used to detect change in BMI (kg/m^2)		baseline, 14 days, 28 days, 42 days and 56 days
Secondary	Change in systolic blood pressure in mmHg		baseline, 14 days, 28 days, 42 days and 56 days
Secondary	Change in diastolic blood pressure in mmHg		baseline, 14 days, 28 days, 42 days and 56 days
Secondary	Diagnostic of lactose intolerance by breath hydrogen concentration following ingestion of 25g lactose in 250 mL water		screening visit, 14 days, 42 days and 56 days
Secondary	Diagnostic of lactose intolerance by breath methane concentration following ingestion of 25g lactose in 250 mL water		screening visit, 14 days, 42 days and 56 days
Secondary	Self-reported change in gut transit time		14 days, 42 days and 56 days
Secondary	Monitoring of changes in psychological behaviour assessed by TMT		baseline, 14 days, 28 days, 42 days and 56 days
Secondary	Monitoring of changes in psychological behaviour assessed by Letter Memory Test		baseline, 14 days, 28 days, 42 days and 56 days
Secondary	Monitoring of changes in psychological behaviour assessed by Flanger Test		baseline, 14 days, 28 days, 42 days and 56 days
Secondary	Monitoring of changes in mood measured by PANAS questionnaire		baseline, 14 days, 28 days, 42 days and 56 days
Secondary	Change in stool consistency using the Bristol stool chart		baseline, 14 days, 28 days, 42 days and 56 days