Functional Ingredient Research

Lactulose

Continuing to provide new health value to the world with Morinaga Milk well-researched lactulose
Lactulose

History of lactulose
- following the research on infant formula and breast milk

Lactulose is a type of oligosaccharide made from lactose contained in milk. Sterilized milk also produces lactulose, so it can be said that we can consume lactulose regularly through milk consumption in our daily life. Lactulose began to attract attention as far back as the early 20th century.

Three-dimensional structure of lactulose
Three-dimensional structure of lactulose

At that time, the exact cause was unknown, but the color, shape, and softness of stool differed significantly between breastfed infants and non-breastfed infants. Breastfed infants were more likely to grow up healthily.
In 1899, Dr. Henry Tissier of France revealed that the difference was caused by the number of beneficial bacteria, or bifidobacteria, in the stool of breastfed infants. Dr. Friedrich Petuely, an Austrian pediatrician, gave infants a food supplemented with lactulose, which is an oligosaccharide made from lactose. As published in his paper in 1957, he found that the number of bifidobacteria in infants who had taken the lactulose supplement reaching that of the breastfed infants.

Lactulose reaches the intestines without being digested and absorbed by the gut bacteria in the intestinal tract of humans. Lactulose acts as a substrate to nourish the bifidobacteria, and as a result, the number of bifidobacteria in the intestines increases. There are some infants in the world who cannot drink breast milk due to various reasons. With a dedication to create smiles on these infants, we began considering adding lactulose to infant formula. Then, in 1960, three years after the report by Dr. Petuely, we established a technology that allows stable production of lactulose from lactose contained in milk, and launched Morinaga G Dry Milk, our infant formula containing lactulose.

Morinaga G Dry Milk when introduced in 1960
Morinaga G Dry Milk when introduced in 1960

Bifidobacteria thrive on lactulose

A clinical trial revealed that ingestion of 2g/day of lactulose for two weeks increases bifidobacteria in the stools, improves the intestinal environment, and increases bowel movements. Normally, sugars such as glucose are absorbed during the digestive process, and only a small amount reaches the large intestine. On the other hand, lactulose is not digested and absorbed during the digestive process. After entering through the mouth, lactulose passes through the esophagus, stomach, and small intestine and reaches the large intestine. This is a major feature of lactulose. Bifidobacteria in the large intestine metabolize lactulose and proliferate. In other words, lactulose feeds on bifidobacteria.
At this time, bifidobacteria produce vitamins and short-chain fatty acids (= acetic acid) as unnecessary substances (= metabolites). It is known that intestinal bacteria other than bifidobacteria also metabolize lactulose and produce short-chain fatty acids such as butyric acid and propionic acid in addition to acetic acid.

intestinal bacteria Number of bifidobacteria in the intestine

The vitamins produced by the intestinal bacteria are those that are often lacking in the diet alone. In addition, short-chain fatty acids prevent the growth of bad bacteria, which can cause adverse effects on the human body. In addition to the fact that some of these organic acids travel through the body in the bloodstream and exert a variety of effects, many of them also nourish the large intestine before they enter the bloodstream.
Moreover, short-chain fatty acids are also known to transform calcium into a more easily absorbed form and stimulate the intestines to promote peristalsis.

The relationship between bifidobacteria and lactulose has been better understood with the latest technology

It was known that bifidobacteria feed on lactulose, but until recently the details of how bifidobacteria nourish on lactulose had not been identified.
Therefore, with the collaboration with universities, we proceeded with research using the latest technology and elucidated the functions of bifidobacteria. Bifidobacteria can take in/digest lactulose in its normal state. It was found that a protein called LT-SBP is important for its uptake, and that this protein is widely distributed among bifidobacteria species in humans. This feature makes it possible to predict who will have a particularly high increase in bifidobacteria in their large intestine by taking lactulose.
The intestinal environment varies from person to person, but if further research progresses, the time may come when it will be possible to predict and select which types of probiotics, such as bifidobacteria, and prebiotics that feed on intestinal bacteria that are appropriate for the gut microbiota in each individual.

Changes in bifidobacteria before and after ingestion of lactulose and rate of change of no. of bifidobacteria by total number of LT-SBP *

Changes in bifidobacteria before and after ingestion of lactulose and rate of change of no. of  bifidobacteria by total number of LT-SBP
Source: Illustration based on Y. Sakai et al. (Beneficial Microbes)10.6.629-639 (2019)

Creating high quality lactulose that is delicious and accessible

We not only utilize lactulose for general foods such as specified health foods (so-called Food for Specified Health Uses (FOSHU)) and foods with functional claims, but also sell lactulose as a raw material for pharmaceuticals both domestically and internationally. Under strict quality control of pharmaceutical GMP*, we are working daily to ensure stable production of high quality lactulose. Furthermore, in order to have lactulose used in a wider range of applications, we have succeeded in developing not only as a general syrup but also in powder form. It is possible to process lactulose into powdered products, tablets, capsules, etc. that are easy to transport and store.

We will continue striving to develop even more products and applications for lactulose so that many more people, with or without stomach ailments, will have safe and delicious products that support their health starting from the gut.
* GMP: Abbreviation for Good Manufacturing Practice. Manufacturing rules and systems that ensure the safety and consistent quality of a product.

Product photos (as of March 2022)
Product photos (as of March 2022)

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Lactulose – expanding applications

Lactulose has been added to infant formula, and because of its reliable effect and high safety, it has also been used as a laxative and as a therapeutic drug for hepatic encephalopathy associated with hyperammonemia. Lactulose is widely used all over the world. As a food ingredient, Morinaga Milk launched the beverage "Maiasa Soukai" containing lactulose as the Food for Specified Health Uses and Food in 1995.
Lactulose is a functional ingredient in this product, which is recognized by the Commissioner of the Consumer Affairs Agency of Japan as a beverage that appropriately increases the number of bacteria and keeps the stomach in good condition. Furthermore, from 2021, based on the ability of lactulose to increase bifidobacteria for improvement of the intestinal environment and regulation of good bowel movement, Morinaga Milk has been active in the expanding the use of lactulose as a functional ingredient in various product categories such as beverages and ice cream.

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