A2 vs Regular 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: Milk allergy, Diabetes, IBD, others

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

Compensation: Varies

Number of Visits: 30

35 Participants Needed

Trial Summary

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 there are changes in inflammatory markers following two weeks of milk feeding, due to milk containing A1 and A2 beta-casein as compared to milk containing only A2 beta-casein.

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. If you are using any other medications, the protocol does not specify, so it's best to discuss with the study staff.

What data supports the effectiveness of A2 milk as a treatment 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 that contains both A1 and A2 beta-caseins. This suggests that A2 milk may be easier to digest for people with lactose intolerance. ^{1 2 3 4 5}

Is A2 milk safe for people with lactose intolerance?

Research suggests that A2 milk is generally safe and may cause fewer stomach problems than regular milk for people with lactose intolerance. Studies show that A2 milk leads to fewer digestive symptoms and less discomfort compared to milk containing both A1 and A2 proteins. ^{1 2 3 5 6}

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 contains both A1 and A2 proteins. This difference may make A2 milk easier to digest for some people with lactose intolerance, as A1 protein is thought to cause digestive discomfort in some individuals. ^{7 8 9 10 11}

Research Team

Dennis Savaiano, PhD

Principal Investigator

Purdue University

Eligibility Criteria

Adults aged 18-65 with a history of lactose intolerance who have avoided dairy for at least a month can join. They must be willing to attend all study visits, avoid other dairy intolerance treatments during the trial, and not have conditions like severe ulcers, diabetes, milk allergies, heart failure or recent drug/alcohol abuse.

Inclusion Criteria

You have avoided or had problems with dairy products for at least one month.

I agree not to use any products for dairy intolerance during the study.

Able to understand and provide written informed consent in English

Exclusion Criteria

Recent bowel preparation for endoscopic or radiologic investigation within four weeks of screening (e.g., colonoscopy prep)

You have used cigarettes, tobacco, or nicotine products within the last 3 months.

I don't have any conditions that could mimic dairy intolerance symptoms.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phone screening and in-person hydrogen breath test

Intervention Phase 1

Participants consume the first randomized milk for 14 days and undergo hydrogen breath test on day 15

2 weeks

Daily milk consumption, in-person visit on day 15 for HBT and blood draw

Intervention Phase 2

Participants consume the second randomized milk for 14 days and undergo hydrogen breath test on day 15

2 weeks

Daily milk consumption, in-person visit on day 15 for HBT and blood draw

Follow-up

Participants are monitored for any delayed symptoms or reactions after the intervention phases

4 weeks

Treatment Details

Interventions

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

Trial Overview This study is testing how two types of milk affect people with lactose intolerance. One has only A2 beta-casein; the other has both A1 and A2. It's double-blinded (neither researchers nor participants know who gets which milk) and randomized to see if there are differences in inflammation after two weeks.

Participant Groups

Group I: Old World milk Experimental Treatment 1 Intervention

Old World milk containing only a2 beta-casein vs. New World milk that includes both a1 and a2 beta-casein

Group II: New World milk Experimental Treatment 1 Intervention

Old World milk containing only a2 beta-casein vs. New World milk that includes both a1 and a2 beta-casein

Milk containing A1 and A2 beta-casein is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Conventional milk for:

• General nutrition
• Dietary supplement

Approved in United States as Conventional milk for:

• General nutrition
• Dietary supplement

Approved in Canada as Conventional milk for:

• General nutrition
• Dietary supplement

Who Is Running the Clinical Trial?

Purdue University

Lead Sponsor

Trials

239

Recruited

72,200+

Findings from Research

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]

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]

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]

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]

In a study of 30 patients with beta-lactam allergies, the most significant allergenic determinant was identified as benzylpenicilloyl (BPO), with specific IgE responses observed primarily in patients with accelerated reactions.

The study highlighted that intradermal skin testing is the preferred method for diagnosing penicillin allergies, as the radioallergosorbent test (RAST) showed unsatisfactory results for detecting minor determinant-specific IgE antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Importance of the benzylpenicillin nucleus and the side chain of the beta-lactams. Demonstration by skin tests and RAST in penicillin allergic patients]. Muiño, JC., Castro, CC., Wolff, EG., et al.[2015]

In a study of 120 children with suspected beta-lactam hypersensitivity, 93% of drug provocation tests (DPTs) were negative, indicating that most children could safely tolerate the suspected antibiotics, particularly penicillins and cephalosporins.

The results suggest that prior skin testing may not be necessary for children with nonsevere reactions, as directly performing DPT is a safe and effective method for evaluating suspected hypersensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of drug provocation testing in children with suspected beta-lactam hypersensitivity. Goh, SH., Chong, KW., Chiang, WC., et al.[2022]

In a study of 1,170 patients with reported immediate reactions to amoxicillin-clavulanate, 32.7% were found to have selective immediate reactions specifically to clavulanate, highlighting its significant role in allergic responses.

Among those with confirmed reactions, over half experienced anaphylaxis, and skin testing showed low sensitivity (below 50%) for diagnosing clavulanate allergies, indicating that drug provocation tests are often necessary for accurate diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clavulanic Acid Is a Leading Culprit Beta-Lactam in Immediate Allergic Reactions to Penicillins. Torres-Rojas, I., Pérez-Alzate, D., Somoza, ML., et al.[2023]

Over 90% of children who report a beta-lactam allergy can actually tolerate these medications after evaluation, suggesting that many allergy labels may be unnecessary and can lead to negative outcomes like longer hospital stays and increased healthcare costs.

Most children with a history of penicillin allergy can safely use penicillin or amoxicillin unless they have a history of severe allergic reactions, and guidelines are provided for assessing allergy risk and managing treatment in both low and high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-lactam allergy in the paediatric population. Wong, T., Atkinson, A., t'Jong, G., et al.[2021]

Over 95% of patients who report a penicillin allergy can actually tolerate the antibiotic after thorough evaluation, highlighting the importance of accurate allergy assessments.

Recent studies suggest that direct drug provocation tests (DPT) can be safely performed without prior skin testing for patients with low-risk historical reactions to beta-lactam antibiotics, although a standardized protocol for this approach is still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct Challenges for the Evaluation of Beta-Lactam Allergy: Evidence and Conditions for Not Performing Skin Testing. Iammatteo, M., Lezmi, G., Confino-Cohen, R., et al.[2021]

References

1. 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]

2. 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]

3. 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]

4. 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]

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

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

6. Canada pubmed.ncbi.nlm.nih.gov

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

7. Argentina pubmed.ncbi.nlm.nih.gov

[Importance of the benzylpenicillin nucleus and the side chain of the beta-lactams. Demonstration by skin tests and RAST in penicillin allergic patients]. [2015]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Outcome of drug provocation testing in children with suspected beta-lactam hypersensitivity. [2022]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Clavulanic Acid Is a Leading Culprit Beta-Lactam in Immediate Allergic Reactions to Penicillins. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Beta-lactam allergy in the paediatric population. [2021]

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

Direct Challenges for the Evaluation of Beta-Lactam Allergy: Evidence and Conditions for Not Performing Skin Testing. [2021]