Clinical Trials Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Feb 6, 2023; 11(4): 797-808
Published online Feb 6, 2023. doi: 10.12998/wjcc.v11.i4.797
Efficacy of incremental loads of cow’s milk as a treatment for lactose malabsorption in Japan
Matsuri Hasegawa, Kazuko Okada, Satoru Nagata, Shigetaka Sugihara
Matsuri Hasegawa, Shigetaka Sugihara, Department of Pediatrics, Tokyo Women’s Medical University Medical Center East, Arakawa-ku 116-8561, Tokyo, Japan
Kazuko Okada, Department of Pediatrics, Okada Pediatric Clinic, Shinjuku-ku 169-0072, Tokyo, Japan
Satoru Nagata, Department of Pediatrics, Tokyo Women’s Medical University, Shinjuku-ku 162-8666, Tokyo, Japan
Author contributions: Okada K and Nagata S conceptualized and designed the study outline; Hasegawa M and Okada K acquired, analyzed, and interpreted the data, as well as drafted the manuscript; Nagata S advised the interpretation of the data and the critical revision of the manuscript for important intellectual content; Sugihara S obtained funding and supervised the critical revision of the manuscript for important intellectual content; all authors have reviewed and approved the final manuscript.
Supported by Grants of J-milk (Japan Dairy Association).
Institutional review board statement: This work was approved by Tokyo Women’s Medical University Hospital Ethics Committee (approval number 160506).
Clinical trial registration statement: The trial described in this work was registered at under trial number: UMIN 000023298.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors declare that they have no conflicts of interest for this article.
Data sharing statement: No additional date are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Matsuri Hasegawa, MD, Doctor, Department of Pediatrics, Tokyo Women’s Medical University Medical Center East, 2-1-10, Nishiogu, Arakawa-ku 116-8561, Tokyo, Japan.
Received: October 17, 2022
Peer-review started: October 17, 2022
First decision: November 11, 2022
Revised: December 2, 2022
Accepted: January 5, 2023
Article in press: January 5, 2023
Published online: February 6, 2023

Lactose intolerance (LI) is commonly seen in East Asian countries. Several studies showed that lactose or milk loading has been used as a treatment for lactose malabsorption (LM) in Western countries, but there have been no reports regarding this type of treatment in Japan. As lactose or milk loading requires ingestion of large amounts of lactose within a short period, this is considered to be too harsh for Japanese people because of their less habitual milk consumption (175 mL per day in average) than Western people. In this study, we demonstrated lactose tolerance acquisition in a suitable way for Japanese.


To examine the efficacy of lactose (cow’s milk) loading treatment in patients with LM.


Individuals with abdominal symptoms induced by milk or dairy products (LI symptoms) were identified with a questionnaire. A 20 g lactose hydrogen breath test (LHBT) was carried out to confirm LM diagnosis and to evaluate co-existence of small intestinal bacterial overgrowth (SIBO). Respondents diagnosed with LM were selected as study subjects and were treated with incremental loads of cow’s milk, starting from 30 mL and increasing up to 200 mL at 4-7 d intervals. After the treatment, changes in symptoms and LM diagnostic value of 20 g LHBT were investigated. Stool samples pre- and post-treatment were examined for changes in intestinal microbiota using 16S rRNA sequencing. Informed consent was obtained prior to each stage of the study.


In 46 subjects with LI symptoms (10-68 years old, mean age 34 years old) identified with the questionnaire, 35 (76.1%) were diagnosed with LM by 20 g LHBT, and 6 had co-existing SIBO. The treatment with incremental cow’s milk was carried out in 32 subjects diagnosed with LM (14-68 years old, median age 38.5 years old). The mean period of the treatment was 41 ± 8.6 d. Improvement of symptoms was observed in 29 (90.6%; 95% confidence interval: 75.0%-98.0 %) subjects. Although 20 g LHBT indicated that 10 (34.5%) subjects had improved diagnostic value of LM, no change was observed in 16 (55.2%) subjects. Analysis of the fecal intestinal microbiota showed a significant increase in Blautia in 7 subjects who became symptom-free after the treatment (P = 0.0313).


LM was diagnosed in approximately 75% of the subjects who had LI. Incremental loads of cow’s milk is regarded as a useful treatment for LM without affecting everyday life.

Keywords: Lactose Intolerance, Lactose Malabsorption, lactose loading treatment, Intestinal bacterial flora, Fecal microbiota

Core Tip: The incidence of lactose malabsorption (LM) is high in East Asians such as Japan. Colonic adaptation by daily consumption of milk or lactose has been known as a method to treat LM, reducing symptoms of lactose intolerance (LI). However, reports regarding such treatment have not been found in Japan. In this study, we clarified the prevalence of LM diagnosed among the Japanese patients who had LI symptoms, and evaluated the efficacy of incremental loads of cow’s milk as a treatment for LM without affecting everyday life.