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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if milk containing only A2 beta-casein causes fewer symptoms and less inflammation in individuals with lactose intolerance. Participants will consume either regular milk, which contains both A1 and A2 proteins, or A2 milk, which contains only A2 protein, for two weeks. The study will assess any differences in how these milk types affect inflammation and symptoms such as gas and bloating. Individuals who avoid dairy due to discomfort, like gas or cramps, might be well-suited for this trial. As an unphased study, this trial provides a unique opportunity to explore potential dietary solutions for those experiencing discomfort from dairy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that milk containing only A2 protein is usually easier to digest. Studies have found that people who drink A2 milk experience fewer symptoms of lactose intolerance compared to those who consume milk with both A1 and A2 proteins. This suggests that A2 milk might be gentler on the stomach. Evidence also indicates that A1 milk can cause more inflammation, which A2 milk does not.

For those seeking to avoid stomach issues, A2 milk could be a better choice. However, A2 milk is not safe for individuals with a milk allergy. It's always important to understand what works best for one's own body. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for lactose intolerance because they explore the potential benefits of A2 beta-casein, a protein found in milk. Unlike regular milk, which contains both A1 and A2 beta-casein, A2 milk is thought to be easier on the digestive system for those who are lactose intolerant. This is because some research suggests that A1 beta-casein may cause digestive discomfort, while A2 beta-casein does not. These treatments could offer a more comfortable alternative to lactose-free milk options, providing a similar taste and nutritional profile without the digestive issues.

What evidence suggests that this trial's treatments could be effective for lactose intolerance?

This trial will compare the effects of milk containing only A2 beta-casein with milk containing both A1 and A2 beta-casein on symptoms of lactose intolerance. Research has shown that milk with only A2 protein causes fewer symptoms of lactose intolerance than milk with both A1 and A2 proteins. Specifically, studies have found that A2 milk leads to less stomach pain, urgent bowel movements, and stomach rumbling. In contrast, milk with A1 protein is linked to more gut inflammation and slower digestion. Several studies confirm that switching to A2 milk can significantly reduce symptoms like bloating and digestive discomfort. Overall, the evidence suggests that A2 milk may be a better choice for those sensitive to regular milk. ^{6 7 8 9 10}

Who Is on the Research Team?

Dennis Savaiano, PhD

Principal Investigator

Purdue University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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 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 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 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 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]

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]

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]

Citations

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The Impact of A1- and A2 β-Casein on Health Outcomes Milk containing A2 β-casein could significantly reduce the proportion of abdominal bloating and bowel movement difficulty, increase bowel movement frequency, ...

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Milk Intolerance, Beta-Casein and Lactose - PMC Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl ...

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Worldwide research on the health effects of bovine milk ... 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 ...

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The Effect of A2 Milk on Gastrointestinal Symptoms in ... Recent studies suggest that A2 milk may be a safer choice than regular milk in terms of gastrointestinal (GI) discomfort after consumption. In ...

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A2 Milk: Is it Good For You?, Health Benefits, Nutrition ... If you have a diagnosed milk allergy, A2 milk is not a healthy alternative, and you should avoid it. In fact, if you have it, you could have the ...