Unlocking the physiological benefits of milk proteins

The challenge to product developers is to advance food products beyond taste, convenience, safety and nutrition to include food ingredients such as milk proteins, which deliver documented health benefits.

Authors' note: On May 7, 2003, at the American Oil Chemists' Society annual meeting, experts in the area of dairy protein nutrition and processing techniques participated in a symposium entitled: The Emerging Role of Dairy Proteins and Bioactive Peptides in Nutrition and Health. This symposium focused on the latest research related to the biological role of milk-derived peptides and amino acids in weight management and regulation of food intake, hypertension, muscle metabolism and genomics, as well as the anticariogenic properties of milk bioactive proteins. New processing techniques used in the manufacture and application of protein concentrates, isolates and other bioactive fractions were also presented. A detailed report of this symposium has been submitted for publication as a supplement in the Journal of Nutrition.

BBovine milk represents a unique source of nutrients and bioactive components that act in synergy as well as independently. Emerging research indicates that milk is a storehouse of structure-specific proteins, lipids and carbohydrates, which confer benefits beyond the content of essential vitamins, minerals and macronutrients. The protein component of milk represents a variety of bioactive amino acids and peptides that function as growth factors, antihypertensive agents, antimicrobial factors, food intake modifiers and immune regulatory factors. New and improved fractionation methods now provide a means to isolate the healthful components in milk and incorporate them in new products.

Bruce German, professor of food science and technology at the University of California, Davis, provides insight into the future use of genomics as a tool for understanding the role of dairy proteins in human health. The challenges to food research are to advance food products beyond the successes of taste, convenience, safety and the provision of essential nutrients, and to build the knowledge base necessary for developing foods that deliver documented health benefits. How then, can scientific and biological principles be developed to assemble this knowledge?

The evolutionary success of milk is a compelling example of a food material designed by selective pressure to provide optimal health to mammalian offspring. Milk contains components that are more than an assembly of essential amino acids. Milk also provides bioactive molecules to improve the competitive success of offspring that consume them. Many of these molecules are proteins that protect offspring from environmental stresses, toxins and pathogens; encourage optimal growth and development; and promote physical and intellectual performance.

These bioactive proteins are the basis of nutritional benefits not previously recognized when essential amino acid composition was the sole criterion of protein quality. The rapidly expanding tools of biotechnology and genomic analysis are enabling new insight into ingested proteins and their specific functions.

Now with human genome sequencing complete, the expression of genes and their protein products impacted by milk components can be identified and quantified, and their effect on nutrition and health evaluated. Another compelling reason to approach milk as a model food fit for structure-function assessment of bioactive proteins is that the gene coding for milk proteins has also been sequenced. Genomic tools, such as proteomics, metabolomics, etc., offer enormous potential for identifying bioactive components of dairy proteins as effective dietary strategies for the management of key risk factors related to chronic disease conditions including hypertension, diabetes, obesity and dental health issues.

Dairy foods are the ideal carrier for functional dairy proteins.

What's the skinny?

Donald Layman, a professor of nutrition at the University of Illinois, Urbana-Champaign, reviews current research on the role of dietary protein on weight control and obesity, as obesity is a major public health concern in the United States. In recent years, a condition termed the Metabolic Syndrome has become increasingly common. A hallmark of this condition is obesity, particularly abdominal obesity, as well as high blood glucose, high blood pressure and low high-density lipoprotein cholesterol. Layman points out that although the general agreement among scientists is that the most critical factor in weight management is total energy intake, the ideal balance of carbohydrates, protein and fat for weight loss is widely disputed.

There is increasing evidence that diets with reduced levels of carbohydrates and increased levels of protein may be beneficial for weight loss. Recent studies indicate that diets lower in carbohydrate and higher in protein appear to improve body weight and body fat loss while preserving lean body mass. Just how these diets work is still unclear but some theories include increased satiety (reduced food intake), increased thermogenesis (fat burning), reduced muscle protein loss, and improved regulation of blood glucose and insulin.

Weight control studies using high protein diets that are high in branched chain amino acids (BCAA), especially leucine, are of particular interest to the dairy industry, as dairy foods and whey proteins are exceptionally rich sources (see table on page 49).

In one study, overweight and obese women were placed on a high-protein (dairy-based), low-carbohydrate, reduced-calorie diet for 16 weeks. These subjects lost 21.6 lbs compared to the 14.8 lbs lost by women on a high-carbohydrate, reduced-calorie, control diet. The high-protein group also lost more body fat (19.4 lbs vs. 12.3 lbs.) and less lean body mass (-0.9 lbs vs. -2.4 lbs) than the carbohydrate group. These data are consistent with other high-protein, low-carbohydrate diet studies and suggest that a diet with increased protein/BCAA and reduced carbohydrates partitions weight loss toward body fat while sparing body protein.

In addition to the weight control and lean body mass sparing attributes, there may be additional benefits associated with high-protein, low-carbohydrate dietary approaches including stabilizing blood glucose and insulin during periods of energy-restriction encountered during weight management. This may be particularly important for management of the Metabolic Syndrome, which is recognized as a pre-diabetic condition.

Layman notes in his research that overweight women with abnormally high insulin levels achieved a three-fold greater reduction in plasma insulin on a high-protein, low-carbohydrate diet compared to the high-carbohydrate control diet. These data suggest that diets with reduced carbohydrates and increased protein, with emphasis on total BCAA and leucine, appear to stabilize blood glucose and insulin during weight loss.

Taken together, application of these findings to dietary strategies for weight management may provide competitive advantages to food products developed with dairy protein sources such as whey protein concentrates or isolates high in total BCAA and leucine.

Lowering pressure

Richard Fitzgerald, a senior lecturer with University Limerick, Ireland, reviews how milk-derived peptides might be exploited as blood pressure lowering food components. Hypertension (high blood pressure) is a primary risk factor for heart disease, which affects 25% of the U.S. population and is a major contributor to stroke and heart failure. Americans spend about $15 billion annually on antihypertensive medications including calcium channel blockers, vasodilators, diuretics and angiotension-I-converting enzyme (ACE) inhibitors.

Blood pressure is controlled in the blood vessels of the body by a number of metabolic systems including the major pathway called the renin-angiotensin system (RAS). The RAS system is important in controlling blood pressure because it generates a highly potent chemical termed angiotensin II, which is controlled by ACE. This results in blood vessel constriction and elevated blood pressure. Inhibitors of the ACE enzyme in blood vessels is a major class of antihypertensive medications that are prescribed to control high blood pressure.

However, several adverse side effects such as hypotension, reduced kidney function, cough and skin rashes have been associated with synthetic ACE inhibitors. Natural inhibitors of ACE have been identified in a variety of food proteins. In particular, milk proteins contain ACE inhibitory peptides (ACE-IP) that can be released by enzymatic hydrolysis either during gastrointestinal digestion or during food processing. It is well established that in vitro incubation of milk proteins with the gastrointestinal proteases pepsin, trypsin and chymotrypsin results in the release of ACE-IP. Hence, it is likely that ACE-IP is generated during normal gastrointestinal digestion. Bacterial and plant proteinases can also be used to release ACE-IP. Therefore, hydrolysates of milk protein, caseinates, whey proteins and fractions enriched in individual milk proteins are potentially good sources of ACE-IP.

The proteinases in various bacterial strains including Lactobacillus lactis and Lactobacillus helveticus, many of which are used in fermented dairy products such as yogurt and fermented milk drinks, have been shown to produce ACE-IP. A number of studies have also shown that ACE-IP can be produced during cheesemaking.

Numerous rat studies demonstrate the hypotensive effects of milk-derived ACE-IP. However, only a limited number of human studies have been conducted to date. Initially it was demonstrated that 20g/day of a tryptic hydrolysate of casein resulted in significant reductions in both systolic (SBP) and diastolic (DBP) in hypertensive subjects. More recently, a tryptic hydrolysate of casein containing specific residues of as1-casein peptide could also reduce blood pressure in hypertensive subjects. Others have demonstrated that 95ml/day of a fermented sour milk could markedly reduce both SBP and DBP in hypertensive adults.

Newer data also suggests that consumption of whey protein hydrolysates result in significant reductions in SBP and DBP blood pressure. It is important to note that the blood pressure-lowering effects of specific hydrolysates or fermented dairy products have no effect in rats and humans with normal blood pressure and that no adverse side effects have been reported following oral ingestion of these materials.

These studies provide impressive optimism about the beneficial role of dairy protein peptides in the management of hypertension. There is a need for high-quality, peer-reviewed evidence that document the hypotensive effects of consuming specific milk protein-based ingredients and products. These data will be required by food processors and government regulatory authorities in order to move forward with food products in the marketplace.

Smile! Say cheese

William Aimutis, group mgr., food chemistry, Cargill Inc., Wayzata, Minn., reviews the role of milk bioactive peptides on the prevention of dental caries. Dental caries, better known as tooth decay, is a major health problem in the United States. In fact, it is sometimes called the "silent epidemic," as it results in health care costs greater than that of either heart disease, cancer or hypertension.

A major emphasis by researchers and product developers has been placed on developing products to offer protection from the causative agents of tooth decay. Milk, in addition to being an excellent source of protein, vitamins and minerals, also contains factors that have anticariogenic properties including calcium, phosphate, casein and lipids. It has been known for some time that dairy products such as cheese and milk are effective in preventing dental caries. Specifically, research has shown cheeses such as Cheddar, Monterey jack, mozzarella and Swiss have anticariogenic properties due to their ability to inhibit plaque acid production from oral bacteria and fermentable carbohydrates. They also stimulate remineralization and inhibit demineralization of the tooth enamel minerals calcium and phosphate.

Recently, researchers have focused on isolating protective factors from milk to use as food additives or in personal hygiene products for dental protection. A number of bioactive milk-based components have been identified as having a potential role in prevention of dental caries based on their potential to inhibit oral pathogenic bacteria such as Streptococcus mutans and/or bind minerals.

The bioactive peptides from milk with antibacterial activity include lactoferrin, lactoferricin (proteolyzed lactoferrin peptide), lysozyme, lactoperoxidase, glycomacropeptide (GMP) and caseinophosphopeptides (CPP). In general, anticariogenic milk-derived bioactive peptides prevent dental lesions by multiple routes including bacterial inhibition, improved buffering capacity in the pellicle surrounding teeth, reduced enamel demineralization and increased enamel remineralization.

Much work has been done with CPP colloidal amorphous calcium (CPP-ACP). CPPs are phosphorylated casein-derived peptides produced by enzymatic digestion of casein with high capacities to solubilize minerals, especially calcium and phosphorus. Clinical studies have shown that two daily exposures of CPP-ACP reduced enamel mineral loss by 51% and resulted in 2.5 times more calcium and phosphorus in the plaque than controls. The anticariogenic mechanism of CPP-ACP suggests that CPP increases the level of calcium phosphate in dental plaque thereby depressing enamel demineralization and enhancing remineralization. Commercialization of dairy-derived bioactive peptides has focused on application in oral products such as toothpaste, gel, mouth rinse and chewing gum.

In summary, research continues to support the role of dairy proteins and peptides in nutrition and health. Presentations by highly respected researchers focus specifically on the role of dairy proteins, peptides and amino acids on regulation of muscle metabolism, weight management and food intake, as well as their potential impact on reducing hypertension and promoting dental health. The challenge to the food industry will be to advance food products beyond taste, convenience, safety and providing essential nutrients, and build knowledge in partnership with scientists, health professionals and regulatory agencies to develop foods that deliver documented health benefits.

Leucine BCAA
Whey Protein Isolate 14% 26%
Milk Protein 10% 21%
Egg Protein 8.5% 20%
Muscle Protein 8% 18%
Soy Protein Isolate 8% 18%
Wheat Protein 7% 15%