Evidence map›Paper›PMID 27039383›Full record

Trial reportNutrition journal2016

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.

Sun Jianqin, Xu Leiming, Xia Lu, Gregory W Yelland, Jiayi Ni, Andrew J Clarke

Erratum issued 7 registry-linked trialsOpen access · goldAbstract readComparative StudyRandomized Controlled Trial
In one paragraph

Trial report in Nutrition journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 7 registered trials, which are not on this map. Cited by 93 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 2 pooled it
5.2field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02406469 phase4completednot on this map

Comparative Effects of Milk With A2 Type Beta Casein Versus Milk With A1 and A2 Beta Casein Proteins on Gastrointestinal Physiology, Symptoms and Cognitive Behavior for the Health People Who Are Intolerant to Traditional Cow Milk

TypeinterventionalSponsora2 Milk Company Ltd.Ran2014 to 2015Enrolled45ConditionsLactose IntoleranceArmsOral consumption milk Tetra Pak
NCT02911194 nacompletednot on this map

A1 Beta Casein Free Milk (a2 Milk) for Autism and Attention-deficit Hyperactivity Disorder

TypeinterventionalSponsorNorthumbria UniversityRan2016 to 2018Enrolled40ConditionsAutism, Attention Deficit Hyperactivity Disorder, Autism Spectrum DisorderArmsa2 milk, a1 containing milk
NCT03060395 nacompletednot on this mapstarted 2017, after this paper: background citation

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

TypeinterventionalSponsorUniversity of ReadingRan2017 to 2019Enrolled37ConditionsMilk IntoleranceArmsA2 milk 100, A2 milk 150, A2 milk 200, A2 milk 250, A1/A2 milk 100
NCT05658861 nacompletednot on this mapstarted 2021, after this paper: background citation

Comparing the Gastric Transit of Commercial Milk Containing A1 Beta-casein and A2 Milk Containing Only A2 Beta-casein Using Magnetic Resonance Imaging (MRI)

TypeinterventionalSponsorPurdue UniversityRan2021 to 2022Enrolled10ConditionsLactose Intolerance, Adult TypeArmsMilk containing A1 and A2 beta-casein, Milk containing only A2 beta-casein
NCT05660278 naunknown statusnot on this mapstarted 2022, after this paper: background citation

Comparing the Acute Effects of A1 Containing Commercial Milk and A2 Milk on Inflammation, Lactose Intolerance and Lactose Maldigestion in Lactose Maldigesters

TypeinterventionalSponsorPurdue UniversityRan2022 to 2025Enrolled35ConditionsLactose IntoleranceArmsMilk containing A1 and A2 beta-casein, Milk containing only A2 beta-casein
NCT05669274 naunknown statusnot on this mapstarted 2021, after this paper: background citation

Comparing Inflammation, Lactose Intolerance and Lactose Maldigestion in Lactose Maldigesters on Consumption of Commercial Milk Containing A1 and A2 Beta-Casein and A2 Milk Containing Only A2 Beta-Casein for Two Weeks

TypeinterventionalSponsorPurdue UniversityRan2021 to 2025Enrolled35ConditionsLactose IntoleranceArmsMilk containing A1 and A2 beta-casein, Milk containing only A2 beta-casein
NCT05829720 nacompletednot on this mapstarted 2023, after this paper: background citation

A Double-blind, Parallel Designed, Randomized Controlled Trial to Investigate Effects of Conventional Vs A2 Milk on Breastmilk Composition and Subsequent Infant Gut Health, Crying and Sleep Patterns in Healthy, Full-term Infants

TypeinterventionalSponsora2 Milk Company Ltd.Ran2023 to 2023Enrolled100ConditionsDigestive System Disease, Sleepiness, CryingArmsa2 Full Cream Milk, Conventional Milk (Weidendorf)
3 · Its place in the literature

Who cites it

93 citing papers in PubMed, 2 syntheses or guidelines pooled it, 223 citations in OpenAlex.

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  13. Effects ofNutrients · 2019
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33 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 2 countries.

Sun JianqinClinical Nutrition Center, Huadong Hospital affiliated to Fudan University, Shanghai, China.
Xu LeimingDepartment of Gastroenterology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xia LuEndoscopic Center, Shanghai Internal Medicine Center, Shanghai, China. xialu@medmail.com.cn.
Gregory W YellandDepartment of Gastroenterology, Central Clinical School, The Alfred Centre, Monash University, Melbourne, VIC, Australia.
Jiayi NiS.P.R.I.M. China (Shanghai) Consulting Co., Ltd., Shanghai, China.
Andrew J ClarkeThe a2 Milk Company Limited, Auckland, New Zealand.
Fudan University · CNShanghai International Medical Center · CNShanghai Jiao Tong University · CNThe Alfred Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCows' milk generally contains two types of β-casein, A1 and A2 types. Digestion of A1 type can yield the peptide β-casomorphin-7, which is implicated in adverse gastrointestinal effects of milk consumption, some of which resemble those in lactose intolerance. This study aimed to compare the effects of milk containing A1 β-casein with those of milk containing only A2 β-casein on inflammation, symptoms of post-dairy digestive discomfort (PD3), and cognitive processing in subjects with self-reported lactose intolerance.

methodsForty-five Han Chinese subjects participated in this double-blind, randomized, 2 × 2 crossover trial and consumed milk containing both β-casein types or milk containing only A2 β-casein. Each treatment period was 14 days with a 14-day washout period at baseline and between treatment periods. Outcomes included PD3, gastrointestinal function (measured by smart pill), Subtle Cognitive Impairment Test (SCIT), serum/fecal laboratory biomarkers, and adverse events.

resultsCompared with milk containing only A2 β-casein, the consumption of milk containing both β-casein types was associated with significantly greater PD3 symptoms; higher concentrations of inflammation-related biomarkers and β-casomorphin-7; longer gastrointestinal transit times and lower levels of short-chain fatty acids; and increased response time and error rate on the SCIT. Consumption of milk containing both β-casein types was associated with worsening of PD3 symptoms relative to baseline in lactose tolerant and lactose intolerant subjects. Consumption of milk containing only A2 β-casein did not aggravate PD3 symptoms relative to baseline (i.e., after washout of dairy products) in lactose tolerant and intolerant subjects.

conclusionsConsumption of milk containing A1 β-casein was associated with increased gastrointestinal inflammation, worsening of PD3 symptoms, delayed transit, and decreased cognitive processing speed and accuracy. Because elimination of A1 β-casein attenuated these effects, some symptoms of lactose intolerance may stem from inflammation it triggers, and can be avoided by consuming milk containing only the A2 type of beta casein.

trial registrationClinicalTrials.gov/NCT02406469.

Indexed as

CognitionAdultAgedAnimalsAsian PeopleBiomarkersCaseinsCattleCross-Over StudiesDigestionDouble-Blind MethodEndorphinsFecesFemaleGastrointestinal TractHumansbeta-casomorphin 7BiomarkersCaseinsEndorphinsPeptide FragmentsCognitive processingCows’ milkGastrointestinal functionLactose intoleranceβ-casein

Identifiers

PMID27039383
PMCPMC4818854
OpenAlexW2313134415

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

and 1 more above

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.