Effects of Lactoferrin on Sleep Conditions in Children Aged 12–32 Months: A Preliminary, Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Purpose

To investigate preliminarily the effect of lactoferrin (LF)-fortified formula on sleep conditions in children.

Study Design

A preliminary, randomized, double-blind, placebo-controlled trial.

Methods

Healthy children between the ages of 12 and 32 months who attended nursery schools in Japan were divided into two groups and assigned a placebo or LF (48 mg/day)-fortified formula. Children’s sleep conditions were investigated before and after the 13-week intervention using the Japanese Sleep Questionnaire for Preschoolers (JSQ-P).

Results

Altogether, 109 participants were randomized. Eight participants were eliminated due to lost to follow-up, withdrawal of consent, and ineligibility, with 101 participants (placebo, n = 48; LF, n = 53) included in the full analysis set (FAS) and used for analysis. Wake-up time, bedtime, and nighttime sleep were comparable between the two groups before and after intervention. The change in total JSQ-P T scores tended to improve in the LF group (placebo vs LF: 0.5 ± 6.5 vs −1.9 ± 6.1, p = 0.074), in particular, morning symptoms significantly improved (grumpy in the morning, hard to wake-up, and hard to get out of bed) (placebo vs LF: 0.8 ± 6.2 vs −1.9 ± 6.2, p = 0.028). A better trend was also observed in the LF group regarding restless legs syndrome (RLS)-motor (rubs feet at night and touches feet at night) (placebo vs LF: 2.3 ± 10.7 vs −0.6 ± 13.5, p = 0.083) and insufficient sleep (stays up more than one hour later the day before a holiday and wakes up more than one hour later on a holiday) (placebo vs LF: 0.1 ± 9.8 vs −1.7 ± 8.8, p = 0.095). No adverse drug reactions were found.

Conclusion

LF intake may improve sleep condition, especially morning symptoms in children above one year of age.

Keywords:

• lactoferrin
• sleep
• growing-up formula
• children

Data Sharing Statement

The dataset in the current study is available from the corresponding author on reasonable request.

Acknowledgments

Authors deeply appreciate all individuals involved in this study for their valuable help with data collection: Matsumoto City Medical Association, nursery schools in Matsumoto city (Agata, Azusagawa-higashi, Azusagawa-nishi, Fukashi, Futago, Hata-chuo, Hata-higashi, Hirata, Horigome, Imai, Kanda, Kiri, Kotobuki-higashi, Komiya, Kotobuki, Minami-matsumoto, Mitsuba, Miyata, Murai, Nagisa, Nakajo, Nakayama, Nango, Niimura, Nishikibe, Nobara, Nomizo, Ohisama, Okada, Sakura, Satoyamabe, Shimadachi-chuo, Shimauchi, Shiraita, and Uchida), Mr. Shinji Komatsu and Mr. Keigo Takano of the Matsumoto City Commerce and Industry Tourism Department, and Mr. Katsuya Furihata, Mr. Akira Shimamura, and the public health nurses at Matsumoto Health Laboratory. We also sincerely thank parents and children for participating in this study.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

Momoko Miyakawa, Shutaro Kubo, Hirotsugu Oda, Miyuki Tanaka, Koji Yamauchi, and Fumiaki Abe were employed by Morinaga Milk Industry Co., Ltd., report a patent 2019-085091 pending, and report no other potential conflicts of interest for this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest and report they have no conflicts of interest for this work.

Additional information

Funding

Morinaga Milk Industry provided research funds and the test formulas.