The art of balancing calcium absorption: From the discovery of CPP peptides to clinical validation of bovine bone marrow as a nutritional ingredient.

2026-04-08

Once an elderly person suffers a fracture, they become immobile, leading to a rapid decline in bodily functions, often resulting in bedridden status. Therefore, the elderly should pay attention to consuming easily absorbed calcium. The so-called state of tension is a defensive reaction of the body. If a dog appears in front of a cat, the cat's fur will immediately stand on end. From the moment it sees a dog, the cat is in a state of tension. Moreover, not only its appearance but also its internal organs undergo significant changes.

In response to an emergency, the cat's heart beats faster and its bronchi dilate to ensure sufficient oxygen and energy are delivered to the muscles; the digestive organs also enter a state of emergency rest, with blood diverted to the muscles. In other words, all of a cat's organs shift from their normal state to a state of readiness. This state of readiness is for handling emergencies, but if maintained for an extended period, the function of the digestive organs will be suppressed. In a human, this would lead to stomach ulcers and even bleeding due to the digestive juices.

While stress is a defense mechanism, prolonged stress can lead to various physical and mental abnormalities. Stressful situations arising from interpersonal relationships in the workplace are often chronic and have a profound impact. To maintain physical and mental health, it is essential to strive to overcome stress. What methods can prevent the harm caused by stress? According to experiments conducted by Professor Fumio Kurihara of the Food Research Institute at Takenokawa Women's University, calcium can help prevent the harm caused by stress.

Professor Fumio Kurihara wrapped rats in metal mesh to immobilize them and placed them on their backs. Because rats strongly dislike this posture, they were in a state of high stress. After being placed in this position for several hours, the rats exhibited thymus shrinkage, adrenal gland hypertrophy, spleen atrophy, and gastric bleeding. However, if the rats were fed calcium beforehand and then wrapped in metal mesh and placed on their backs, although they were in a state of stress, their internal organs showed no changes.

This demonstrates that pre-treatment with calcium is significantly effective in preventing harm caused by stress in mice. Many foods are rich in calcium, but calcium absorption varies depending on the food. Dried sardines and a type of bok choy are rich in calcium, but their absorption rate is very poor, only about 10% to 20%. In contrast, a 200 ml cup of milk contains approximately 200 mg of calcium, with an absorption rate of 60% to 70%, providing one-third of the daily requirement. The daily calcium requirement is 400 mg for infants, 500-900 mg for children whose teeth and bones are developing, and 600 mg for adults.

Pregnant and lactating women have a particularly high daily calcium requirement, needing more than 1000 mg. While small fish are a good source of calcium, about 10%–20% of the calcium is not absorbed, and approximately 30%–40% of the calcium in milk and dairy products is not absorbed. Vitamin D and lactose are known to be food factors that promote calcium absorption. However, the calcium in cheese, which is low in lactose, is also well absorbed, suggesting that there are other factors in dairy products that promote calcium absorption.

Based on the results of a survey of the main proteins in milk, it was found that only casein could promote calcium absorption. In 1947, Melaumut discovered that when casein was broken down by pancreatic digestive enzymes, some phosphorus-rich peptides remained. They named these phosphorus-containing peptides casein phosphopeptides (CPP). Because these peptides readily bind with calcium and iron, it was hypothesized that they were related to calcium and iron absorption. Calcium ions react with phosphate ions to form insoluble calcium phosphate. However, if CPP is added beforehand, even in trace amounts, this insolubility in water will not occur.

It has been established that CPP in the small intestine can separate calcium ions from phosphate ions, thereby maintaining calcium concentration and promoting absorption in the intestine. While most functional substances in food exist in their original active form, CPP differs from other functional substances; it only becomes active after being digested in the digestive tract. CPP is the first food-derived functional peptide discovered in the digestive tract. More and more potential functional substances like this are likely to be discovered in the future.

Foods fortified with CPP include yogurt-flavored calcium tablets made primarily from beef bone meal containing bone marrow. Each 0.5-gram tablet contains 50 milligrams of calcium and CPP, and is marketed by Meiji Confectionery Co., Ltd. Beverages fortified with CPP are also sold by other companies. CPP has wide applicability as a substance that promotes the absorption of various mineral-fortified foods. According to the 1985 National Nutrition Survey by the Ministry of Health, Labour and Welfare, the average daily protein intake of Japanese people is 77 grams, but there is significant individual variation, with 20% of people consuming more than 100 grams per day.

According to research by Jiang Zhilongnian and others from the Adult Nutrition Research Laboratory of the National Nutrition Institute, people with excessive protein intake excrete more calcium in their urine. They selected six male university students and fed them a high-protein diet for 12 days, followed by a standard diet for the next 12 days. They then measured the changes in calcium levels in the students' feces and urine. The standard diet required 1 gram of protein per kilogram of body weight, while the high-protein diet required 2 grams per kilogram of body weight, twice the protein content of the standard diet.

The test results showed that the calcium content in feces remained almost unchanged, while the calcium content in urine differed significantly. The average calcium content in urine from those who ate a standard diet was 104 grams, while that from those who ate a high-protein diet was 189 grams, approximately twice the former. This indicates both insufficient calcium intake and increased calcium excretion due to excessive protein intake, issues that must be addressed in the future. Previous discussions only considered the absolute amount of a single nutrient's intake in relation to excess or deficiency.

However, the balance between calcium and phosphorus, calcium and manganese, sodium and potassium, omega-3 and omega-6 unsaturated fatty acids, and the balance between various amino acids are more important than their absolute amounts. Simmering chicken or beef bones for a long time yields a delicious bone broth. This is because the marrow in the bones dissolves during prolonged cooking. Long ago, some European countries considered bone marrow a delicacy.

Besides its unique umami flavor, bone marrow also contains collagen, mucopolysaccharides, amino acids, proteins, fats, phospholipids, and essential minerals such as calcium, iron, and zinc, making it a high-quality nutritional source. While many have used bones as calcium supplements in the past, these methods typically involved roasting the bones, thus losing the marrow. Mitsubishi Chemical Foods uses fresh beef bones from Japan as its raw material, employing a unique method to micronize the bones and their marrow before freezing and then processing them into a paste.

This new nutritional ingredient, called "BEEFIT," not only contains a balanced amount of essential minerals, but also boasts a calcium-to-phosphorus ratio of 2:1, the ideal ratio for human absorption. Dr. Yoshio Oi and colleagues at the Jichi Medical University Orthopaedic Surgery and Rehabilitation Center in Japan fed osteoporosis patients cookies supplemented with "BEEFIT." Before the trial began and after 26 weeks, the subjects underwent clinical examinations, X-ray imaging, and assessments for lower back pain symptoms.

The results showed that 91% of patients experienced a comprehensive improvement in their symptoms, and no particular side effects were found with "BEEFIT." Furthermore, experiments on rats demonstrated that bovine bone marrow calcium is more easily absorbed than calcium carbonate. Mitsubishi Chemical Foods Co., Ltd. uses 20 kg of frozen bovine bone marrow powder as a food ingredient to make and sell small cookies. The Japan Cooperative Association sells CO.OP (Seikyōin) fried meatballs with added bovine bone marrow. These are all foods that growing children enjoy.

These cookies, produced and sold by Mitsubishi Chemical Foods, are registered as medical food, so patients can have a portion of the cost covered by their health insurance if a doctor deems it necessary and prescribes it.