Winter 2001 Issue — Natural Bioactive Peptides
For stimulation of the immune system and protection against risk factors for cardiovascular disease

DMV International - Nutrition

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Consumers are taking more responsibility for their own health

People are looking for ways to live healthier lives; they continue to take more and more responsibility for their own health. They opt to include more exercise and healthy foods, functional beverages, supplements or medications that offer added health benefits with natural ingredients. The supplement and food industry can provide the health conscious consumers with products having added health benefits for a healthier and longer life. These health benefits can be reached by adding for example milk calcium, Lactoferrin or bioactive peptides. Bioactive peptides are fractions of protein that combine the nutritional benefits of protein with additional health benefits - such as - immune enhancement, improved gut function, and weight management. Consumers are looking for bioactive peptides that can contribute to healthier lives.

The development of new bioactive peptides begins and ends with the consumer. Consumers understand now that their diets have a direct impact on their health. They are now looking for fortified foods and drinks with extra calcium and/or foods/drinks good for the cholesterol level. Also they are buying supplements with anti-oxidant effect or good heart health. These functional foods and supplements often include bioactive peptides as the active ingredient. Examples of currently available peptides are peptides rich in glutamine, that are used to support the immune system and speed up recovery and anti-hypertensive peptides from milk proteins. Calcium Phospho Peptides (CPPs) are well known for enhancement of the bio-availability of calcium and now there are commercially available peptides, which are able to lower blood triglycerides levels, one of the risk factors for cardiovascular diseases (CVD).

Glutamine rich peptides to improve gut function and recover after illness and exercise

The need for exogenous supply of glutamine was first recognised for clinical nutrition. The major issue with glutamine as a free amino acid is its poor solubility in water and its instability during heating. Both limitations can be overcome by using glutamine peptides. Later, commercial products with glutamine peptides became popular in the sports market. Decreased performance, depressed mood and increased incidence of infections are symptoms of the over-training syndrome. This syndrome has been described for runners, cyclists, swimmers, skiers, ballet dancers and even race horses. The use of glutamine peptides in supplements is decreasing fast in this segment and specially designed blends are launched to provide better recover, less muscle soreness, and limit gastric upsets.

Glutamine peptides have two main activities. First, they are a source of glutamine, an amino acid that becomes conditionally essential during exhaustion and illness. Second, glutamine peptides, especially the product called Glutamine Peptide GPX, protect stressed cells against loss of the energy carrier ATP by mechanisms that remain to be fully elucidated. Glutamine is linked to the energy providing citric acid cycle through glutamic acid and alpha-ketoglutarate synthetase. One can estimate that about 60% of all free amino acids in the body are in the form of glutamine. The muscle is the major store of glutamine. During stress, major changes occur in the flux of glutamine. The muscle concentration decreases sharply, whereas immune and gut cells show increased demands. Plasma glutamine levels may drop below physiological levels, resulting in an imbalance and increased vulnerability to infections. In this condition extra supply of glutamine from the diet is required.

Thus glutamine peptides improve gut function, immune status, and recover after illness and exercise (Amores-Sánchez and Medina, 1999; Castell and Newsholme, 1997). They also provide anti-oxidant protection, and increase levels of the energy carrier glycogen. Moreover Glutamine Peptide GPX protects cells when the body is under conditions of severe stress. Glutamine Peptide GPX is a natural glutamine containing peptide produced by a proprietary process starting with wheat protein and food grade enzymes.

The benefits from the use of glutamine peptide, which emerge from the numerous investigations, animal studies as well as human clinical trials, can be summarised as in table 1:

CPPs to increase calcium absorption into the bones

Calcium deficiency is a global health concern. The average calcium intake is still far below the recommended daily intake (RDI), and this, combined with the reduction in physical exercise and poorer eating habits, is affecting calcium levels in a negative way. As a result, the incidence of osteoporosis is expected to more than double in the next 50 years. In the EU this means an increase in hip fractures from 414,000 to 972,000. The current fracture risk resulting from osteoporosis for women is 30-40%, and for men approximately 13%. Calcium intake can be stimulated by fortification of foods or taking calcium supplements. What is important for the consumers is whether the calcium from the additional calcium sources they are taking is being absorbed into their bones. CPPs can increase the absorption of calcium.

Casein Phospho Peptide (CPP) is a casein-derived product developed to increase calcium absorption into the bones. When CPP is used in combination with a calcium source such as milk calcium Lactoval® it increases the uptake of calcium into the bones and reduces the risk of osteoporosis. CPPs are found in the small intestine. Their presence correlates with high calcium solubility. By keeping calcium in the soluble form, CPPs enhance passive calcium absorption.

Human studies (Heaney et al, 1994, Hansen et al., 1996) and various animal studies suggest that addition of CPP in food may help to enhance the availability for absorption of divalent cations like calcium, zinc and iron. Drinks with calcium and iron together with CPP have been developed to enhance availability of these cations. They can be found especially in the Japanese market. Demand for minerals is high during early childhood. Therefore products containing calcium and CPP should be considered for infant nutrition and weaning foods. Products for children incorporating calcium or milk minerals and CPP in sweets and cookies are seen in the South-East Asian market. CPP combined prevention preferably begins by optimising calcium intake throughout childhood and adolescence, to promote peak bone mass, which is achieved in early adulthood (Bachrach, 2001). In addition to its role to prevent osteoporosis, dietary calcium is also beneficial against high blood pressure, obesity, and colorectal cancer (North American Menopausal Society, 2001).

Benefits of BPPs include the ability to solubilise calcium and the ability to enhance the bio-availability for absorption calcium. Heaney et al. (1994) studied the effect of a purified CPP preparation on the calcium absorption in normal postmenopausal women. No effect was seen when the population was analysed as a whole. Limiting the analysis to women with low calcium absorption resulted in a significant increase in calcium absorption of 5.3% as a result of supplementation with CPP. Hansen et al. (1996) studied the calcium and zinc absorption in young men and women from rice-based or whole-grain cereals. The rice-base meal has low phytate concentrations whereas the whole-grain based meal contained much higher phytate. Phytate is a good chelater of multivalent cations like calcium and zinc. CPP increased the actual quantity of absorbed calcium and zinc by approximately 30% when the low phytate meal was ingested. No increase in both calcium and zinc absorption was seen when CPP was added to the whole-grain meal.

Peptides lowering blood triglycerides and regulating dietary fat absorption

Consumers are worried about cholesterol and blood triglycerides in relation to cardiovascular health. More than 60 million Americans are diagnosed with some form of heart disease. In the next few years, the reduction of three risk factors: LDL cholesterol, atherosclerotic plaque and triglycerides will gain popularity. Today, 73% of consumers are very concerned about cholesterol and 65% about triglycerides. High triglyceride levels (.400mg/dl) are a proven risk factor for cardiovascular disease.

Peptide D4 is a commercially available oligopeptide mixture derived from edible proteins and enzymes developed to effectively lower serum triglycerides levels and to regulate dietary fat absorption. In Japan the concept is becoming increasingly popular amongst health conscious consumers. Most supplements with Peptide D4 are positioned to combat hidden obesity and promote heart health. Various applications ranging from supplements to gels are currently available. In Japan it is sold as Napple drink and has a FOSHU status.

The hypolipidemic action of peptide D4 has been extensively investigated in animals (Kagawa et al. 1996) and also in humans (Kagawa et al. 1998). Peptide D4 exerts its hypotriglyceridimic action by having several metabolic regulations. Firstly, it activates the enzymes like lipoprotein lipase and hepatic triglyceride lipase, resulting in removal of triglycerides from the blood. Secondly, Peptide D4 inhibits Fatty Acid Synthetase (FAS) and reduces the conversion of excess dietary carbohydrates to fat. Therefore it is believed that Peptide D4 makes glucose available preferentially as a source of energy compared to triglycerides.

The main benefits of using Peptide D4 in any formulations are:

  • It helps to maintain cardiovascular health by promoting healthy triglyceride levels.
  • It assists in the management of type II diabetes.

Table 2. Overview of application fields and bioactive peptides

The best is yet to come

All of these bioactive products have the ability to significantly improve the lives of consumers. Their message to the consumer is clear. An overview of the various applications and benefits is summarised in table 2. But the best is yet to come. Current research on bioactive peptides that will further improve the lives of consumers, such as peptide that inhibits angiotensin-converting enzyme (ACE) and lowers blood pressure, will offer further opportunities to satisfy consumer demands with natural ingredients. Most of the Research & Development work in the bioactive are will concentrate on delivering products with benefits in the area of immunity and risk factors of cardiovascular disease as these are the areas of main concern of the health conscious consumer. Moreover, the use of natural health products will increase even more in the near future. Bioactive peptides offer opportunities to respond to this demand for healthy supplements for protection of the immune system and risk factors for cardiovascular disease in a natural way.


Amores Sánchez M.I. and Medina, M.A. (1999) Mol. Genet. Metab. 67: 100.

Bachrach, L.K. (2001) Trends Endocrinol. Metab. 12: 22.

Brown L. et al. (2000) JANA 3(2).

Castell L.M. and Newsholme E.A. (1997) Nutrition 7/8, 738.

Heaney, R.P. et al. (1994) J. Bone Miner. Met. 12(1): 77.

Hansen, M. et al. (1996) Pediatr. Res. 40: 547.

Kagawa, K. et al. (1996) Life Sciences 58: 1745.

Kagawa, K. et al. (1998) J. Nutr. 128: 56.

North American Menopausal Society (2001) Menopause 8: 84.

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