A2 Milk for Lactose Intolerance

Overseen By Tracy Eaton, MSW

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Purdue University

Must not be taking: Antacids, PPIs, Antibiotics, others

Disqualifiers: Diabetes, HIV, IBD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

35 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop using treatments and products for dairy intolerance, like Lactaid® Dietary Supplements, during the study. It also excludes those using certain medications like chronic antacids, PPIs, and recent antibiotics. If you're on these, you may need to stop them to participate.

What data supports the effectiveness of A2 milk for lactose intolerance?

Research shows that milk containing only A2 beta-casein causes fewer symptoms of lactose intolerance, like abdominal pain, compared to regular milk with both A1 and A2 proteins. This suggests that A2 milk might be easier to digest for people with lactose intolerance. ^{1 2 3 4 5}

Is A2 milk safe for people with lactose intolerance?

Research shows that A2 milk causes fewer stomach problems than regular milk in people with lactose intolerance, suggesting it is generally safe for them to consume. ^{4 5 6 7 8}

How does A2 milk differ from other treatments for lactose intolerance?

A2 milk is unique because it contains only A2 beta-casein protein, unlike regular milk which has both A1 and A2 beta-caseins. This difference is important because A1 beta-casein can release a peptide that may cause digestive discomfort, while A2 milk is associated with fewer symptoms of lactose intolerance. ^{1 4 5 6 9}

What is the purpose of this trial?

Cow's milk contains two types of β-casein: A1 and A2. It is evident from human clinical trials that milk with A1 protein produces more hydrogen and symptoms of lactose intolerance. A pro-inflammatory μ-opioid peptide BCM-7 is released from A1 but not from A2. Milk containing A1 β-casein produced more inflammatory markers than A2 β-casein. This is a double-blinded, randomized, controlled trial conducted to determine if A1 beta-casein containing milk causes acute effects on inflammatory markers following a single milk feeding, as compared to milk containing only A2 beta-casein.

Research Team

Dennis Savaiano, PhD

Principal Investigator

Purdue University

Eligibility Criteria

This trial is for adults aged 18-65 who have a history of dairy intolerance and have avoided dairy for at least a month. Participants must be non-smokers, not pregnant or lactating, without recent drug abuse, and free from certain medical conditions like diabetes, heart failure, gastrointestinal surgeries that affect digestion, or any immune disorders.

Inclusion Criteria

You have avoided dairy or had trouble tolerating dairy in the past month.

I am willing to attend all study visits and complete all required procedures.

Able to understand and provide written informed consent in English

Exclusion Criteria

I have a history of digestive system diseases that could affect study results.

I have had a high colonic enema in the last 30 days.

I weigh less than 16.5 kg and my BMI is over 35.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phone screening and 1 in-person visit for HBT

Intervention

Participants undergo two in-person visits to consume randomized milk and provide breath and blood samples

2 weeks

2 in-person visits, at least 6 days apart

Follow-up

Participants are monitored for safety and effectiveness after intervention

1-2 weeks

Treatment Details

Interventions

• A1 beta-casein containing milk
• Milk containing only A2 beta-casein

Trial Overview The study tests whether milk containing A1 beta-casein increases inflammation compared to milk with only A2 beta-casein in people with dairy intolerance. It's a controlled experiment where participants are randomly assigned to receive one type of milk without knowing which one it is (double-blinded).

Who Is Running the Clinical Trial?

Purdue University

Lead Sponsor

Trials

239

Recruited

72,200+

Findings from Research

True lactose intolerance is less common than thought, and A1 beta-casein, a protein found in milk from many European cattle, may also contribute to cows' milk intolerance by affecting gastrointestinal function.

A study showed that consuming A1 beta-casein milk led to worse stool consistency and increased abdominal pain compared to A2 beta-casein milk, suggesting that A1 beta-casein may trigger negative gastrointestinal effects through opioid receptor activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Milk Intolerance, Beta-Casein and Lactose. Pal, S., Woodford, K., Kukuljan, S., et al.[2018]

In a study with 16 lactose-intolerant subjects, low-lactose milk resulted in significantly fewer symptoms compared to regular milk, indicating it is a safer option for those with lactose intolerance.

A second group of 17 subjects showed a clear link between the amount of lactose consumed and the severity of symptoms, suggesting that low-lactose milk allows for greater consumption without adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptom response to lactose-reduced milk in lactose-intolerant adults. Jones, DV., Latham, MC., Kosikowski, FV., et al.[2018]

In a study of 387 toddlers aged 12-36 months, growing-up milk (GUM) containing only A2 β-casein was found to be well-tolerated and associated with lower constipation scores compared to conventional milk after 14 days.

For toddlers with minor gastrointestinal distress at the start of the study, those consuming A2 GUM experienced significant improvements in overall digestive comfort and GI symptoms within just one week.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Growing-Up Milk Containing Only A2 β-Casein on Digestive Comfort in Toddlers: A Randomized Controlled Trial in China. Meng, Y., Zhou, Y., Li, H., et al.[2023]

In a study involving preschoolers with mild-to-moderate milk intolerance, switching from conventional milk to A2 β-casein milk significantly reduced gastrointestinal symptoms, such as stool frequency and consistency.

Consumption of A2 β-casein milk also led to improvements in cognitive performance, as indicated by better scores on the Subtle Cognitive Impairment Test, with no severe adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Conventional Milk Versus Milk Containing Only A2 β-Casein on Digestion in Chinese Children: A Randomized Study. Sheng, X., Li, Z., Ni, J., et al.[2022]

In a study involving 25 lactose intolerant subjects, milk containing only A2 β-casein resulted in significantly lower abdominal pain compared to conventional milk containing both A1 and A2 β-caseins.

Lactose maldigesters also experienced fewer gastrointestinal symptoms and lower hydrogen production after consuming A2 β-casein milk, indicating it may be a better option for those with lactose intolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Milk Containing A2 β-Casein ONLY, as a Single Meal, Causes Fewer Symptoms of Lactose Intolerance than Milk Containing A1 and A2 β-Caseins in Subjects with Lactose Maldigestion and Intolerance: A Randomized, Double-Blind, Crossover Trial. Ramakrishnan, M., Eaton, TK., Sermet, OM., et al.[2023]

In a study involving 600 Chinese adults with self-reported lactose intolerance, consuming milk with A2 β-casein resulted in significantly lower gastrointestinal symptoms compared to conventional milk containing A1 β-casein, especially within the first 3 hours after consumption.

The findings suggest that A1 β-casein may exacerbate gastrointestinal issues, indicating that some individuals may experience milk-related symptoms due to A1 β-casein rather than lactose intolerance itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cow's milk beta-casein variants on symptoms of milk intolerance in Chinese adults: a multicentre, randomised controlled study. He, M., Sun, J., Jiang, ZQ., et al.[2022]

A2 β-casein, a variant of the casein protein in milk, is associated with positive health outcomes and can be used to produce dairy products that are similar in quality to those made from traditional milk, with only slight differences in properties.

While A2 milk products are feasible to manufacture, the presence of the A variant of κ-casein negatively affects milk coagulation, indicating that cheese-making properties are influenced by multiple genetic factors, not just β-casein variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An approach on detection, quantification, technological properties, and trends market of A2 cow milk. Dantas, A., Kumar, H., Prudencio, ES., et al.[2023]

New analytical methods have been developed to accurately measure total and A1-type β-casein in milk and milk-derived ingredients, which is crucial for ensuring the quality of A2-type nutritional products.

The study found that A2-type milk products contained between 0.26% and 5.0% A1-type β-casein, highlighting the importance of monitoring A1-type levels due to potential adverse health effects associated with its digestion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of Total and A1-Type β-Casein in Milk and Milk-Derived Ingredients by Liquid Chromatography-Mass Spectrometry Using Characteristic Tryptic Peptides. Ehling, S., Wang, M., Weber, L.[2021]

In a study involving 45 participants with self-reported lactose intolerance, milk containing A1 β-casein led to significantly worse digestive discomfort, increased inflammation markers, and slower cognitive processing compared to milk containing only A2 β-casein.

Eliminating A1 β-casein from the diet reduced gastrointestinal symptoms and inflammation, suggesting that some issues attributed to lactose intolerance may actually be related to the effects of A1 β-casein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Jianqin, S., Leiming, X., Lu, X., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Milk Intolerance, Beta-Casein and Lactose. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Symptom response to lactose-reduced milk in lactose-intolerant adults. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of Growing-Up Milk Containing Only A2 β-Casein on Digestive Comfort in Toddlers: A Randomized Controlled Trial in China. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of Conventional Milk Versus Milk Containing Only A2 β-Casein on Digestion in Chinese Children: A Randomized Study. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Milk Containing A2 β-Casein ONLY, as a Single Meal, Causes Fewer Symptoms of Lactose Intolerance than Milk Containing A1 and A2 β-Caseins in Subjects with Lactose Maldigestion and Intolerance: A Randomized, Double-Blind, Crossover Trial. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Effects of cow's milk beta-casein variants on symptoms of milk intolerance in Chinese adults: a multicentre, randomised controlled study. [2022]

7. Canada pubmed.ncbi.nlm.nih.gov

An approach on detection, quantification, technological properties, and trends market of A2 cow milk. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Determination of Total and A1-Type β-Casein in Milk and Milk-Derived Ingredients by Liquid Chromatography-Mass Spectrometry Using Characteristic Tryptic Peptides. [2021]

9. England pubmed.ncbi.nlm.nih.gov

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. [2022]