Introduction

Whey is a by-product of cheese industry. Approximately 9 L of whey is produced from 10 L of milk during cheese making (Manso and Lopez, 2004). In India whey is also a by-product of chhana/ paneer manufacture. It is very good and inexpensive source of high quality protein for use as a functional food ingredient. The components of whey include whey proteins, enzymes, glycomacropeptides, lactose and minerals. Milk contains two primary sources of protein, the caseins and the proteins from whey. After processing, the casein is responsible for making curd, while whey proteins remain in an aqueous solution. Whey proteins are the group of milk proteins that remain soluble in milk serum or whey after precipitation of casein at pH 4.6 and 20°C. This group includes β-Lactoglobulin, -Lactalbumin, serum albumin, immunoglobulins, lactoferrin and proteose-peptone fractions (Farrell et al., 2004). Broader classifications assign lactoferrins, lactoperoxidase, β-microglobulin, lysozyme, insulin-like growth factor, -globulins and several other small proteins to minor whey proteins (Yalcin, 2006).

Cow milk contains about 20 per cent whey proteins of its total protein content. Whey protein is a complete, high quality protein with a rich amino acid (AA) profile. It contains the full spectrum of AAs including essential AAs (EAAs) and branched-chain AAs (BCAAs) which are important in tissue growth and repair. Leucine is a key BCAA in protein synthesis and has been identified as playing a critical role in insulin and glucose metabolism. The EAAs and BCAAs in whey protein are not only present in higher concentrations than in other protein sources such as soy, corn and wheat, but they are also efficiently absorbed and utilized (Dairy Council, 2004). The biological components of whey, including lactoferrin, betalactoglobulin, alpha-lactalbumin, glycomacropeptide and immunoglobulins demonstrate a range of immune-enhancing properties. In addition, whey has the ability to act as an antioxidant, antihypertensive, antitumor, hypolipidemic, antiviral, antibacterial and chelating agent (Keri, 2004).

Whey proteins posses wide range of functional properties as shown in following Table 1. They can modify some or all of the organoleptic, visual, hydration, surfactant, structural, textural and rheological properties of food, resulting in improved consumer acceptance of the food products (Mehra et al., 2006).

Table 1: Typical functional properties of whey protein in food system (Alfaifi and Stathopoulos, 2010)

Whey is prefered for use as a dietary supplement compared to casein, due to differences in the amino acid composition and absorption kinetics between the two proteins (Bendtsen et al., 2013). Whey protein has a higher proportion of branched chain amino acids than casein (Hall et al., 2003) and is more soluble in the acidic environment of the stomach, leading to more rapid digestion (Boirie et al., 1997), hence it is called as a “fast” protein (Petersen et al., 2009), while casein as a “slow” protein (Bendtsen et al., 2013; Mahe et al., 1996). Using 13C-leucine-labelled whey and casein protein, Boirie et al. (1997) demonstrated that in healthy subjects whey protein results in more rapid appearance, and higher peak plasma concentrations of amino acid, when compared with casein, while Stanstrup et al. (2014) reported that levels of amino acids after a fat rich meal containing whey were substantially higher when compared to the same meal containing casein. As a result of greater solubility, more rapid digestion and resultant higher plasma concentrations of amino acids, whey appears to be the more favourable protein to provide nutritional and functional benefits (Linda et al., 2015).

Commercial Status

Fairly wide range of whey protein products is available in the market. The most common forms available are the concentrate (WPC) or the isolate (WPI). Some producers of infant formulas are increasing the amount of whey protein as a proportion of total protein (and increasing lactoferrin and alpha-lactalbumin) to more closely approximate the properties and benefits of mothers’ milk. Following are various types of whey protein and its uses (Dairy Council, 2013)

Table 2: Various types of whey protein and its uses (Dairy Council, 2013) (Percentages are by weight)

Health Benefits of the Whey

Healthy Aging

With growing age, muscle loss and its negative health implications is a growing concern, both in terms of volume and medical costs. Good nutrition and adequate amounts of high quality whey protein may help in maintaining strong muscles during aging, especially when combined with an exercise and resistance training program (Marcelo and Ritzvi, 2008). Whey protein helps to maintain muscle tissue due to its high concentration of EAAs and BCAAs. This can be particularly important for seniors, active individuals and those trying to maintain or lose weight. By preserving or increasing lean body mass, older adults can protect themselves against undesirable changes in body composition as well as many ailments that are usually associated with aging such as heart disease, stroke, diabetes and other conditions (Dairy Council, 2004). Mehra et al. (2006) found that after consumption of whey protein the older men showed greater protein synthesis, or growth, which helped to limit muscle loss.

Sarcopenia

Sarcopenia is the unexplainable, age-related loss of muscle mass which has a negative impact on strength, power, functional ability and daily living (Nair, 2005). Research indicates its onset around 40 years with profound repercussions after approximately 75 years of age. Since many of its causes appear to be uncontrollable, treatments to decelerate its effects include resistance exercise and consumption of whey proteins. Whey proteins not only appear to be biochemically tailored to preserve valuable muscle mass and maintain immune competence, but also they have very favorable affect on protein metabolism and have a capacity to promote the mechanisms that preserve muscle mass and improve body composition. Research in older adults suggests that whey protein may minimize sarcopenia by stimulating postprandial protein synthesis and limiting body protein loss (Dangin et al., 2002; Miller et al., 2003). Physical activity, specifically resistance training, combined with consumption of whey protein has additional benefits on muscle protein synthesis. Ingesting 10-20 grams of whey protein after activity can improve protein synthesis in seniors, presumably due to the high levels and efficient absorption of EAAs and leucine (Miller et al., 2003; Borsheim et al., 2002).

Bone Health

Another benefit of whey protein for seniors is the ability to help prevent bone loss. A study conducted at Boston University showed that elderly individuals who consumed low levels of protein had a significant loss of bone density four years after the start of the study, especially in the hip and spine areas (Thom et al., (2006). In vitro and animal studies determined milk basic protein (MBP), a component of whey, has the ability to stimulate proliferation and differentiation of osteoblastic cells as well as suppress bone resorption (Toba et al., 2000; Takada et al., 1996; Takada et al., 1997). MBP is prepared from fractionated whey through cation exchange resin. The total protein concentration of MBP is 98 percent, containing lactoferrin, lactoperoxidase and other minor components. Several in vivo studies on rats determined that both whey protein and fractionated whey protein had the ability to increase femoral bone strength in young ovariectomized rats (Takada et al., 1997; Kato et al., 2000).

Physical Performance

Whey protein has long been considered as the “Gold Standard” of proteins for athletes who work hard to develop and sustain a lean, strong and well-defined physique (Gupta et al., 2012). Athletes need more protein in their diet, often as much as twice the recommended daily allowance. The protein they choose makes a difference and here are several reasons why whey protein is a preferred choice for athletes of all types (Solak and Akin, 2012).

• Whey protein is a naturally complete protein, meaning that it contains all of the essential amino acids required in the daily diet. It has the ideal combination of amino acids to help improve body composition and enhance athletic performance.
• Whey protein is a rich source of BCAAs, containing the highest known levels of any natural food source. BCAAs are important for athletes since unlike the other essential amino acids; they are metabolized directly into muscle tissue and are the first ones used during periods of exercise and resistance training. Whey protein provides the body with BCAAs to replenish depleted levels and start repairing and rebuilding lean muscle tissue.
• Whey protein is an excellent source of the essential amino acid, leucine. Leucine is important for athletes as it plays a key role in promoting muscle protein synthesis and muscle growth. Research has shown that individuals who exercise benefit from diets high in leucine and have more lean muscle tissue and less body fat compared to individuals whose diet contains lower levels of leucine. Whey protein isolate has approximately 50% more leucine than soy protein isolate.
• Whey protein is a soluble, easy to digest protein and is efficiently absorbed into the body. It is often referred to as a “fast” protein for its ability to quickly provide nourishment to muscles.
• Whey protein helps athletes maintain a healthy immune system by increasing the levels of glutathione in the body. Glutathione is an anti-oxidant required for a healthy immune system and exercise and resistance training may reduce glutathione levels. Whey protein helps keep athletes healthy and strong to perform their best.

Huang et al. (2017) investigated the effect of whey protein on physiological adaptations and exercise performance of track runners. During 5 weeks supplementation 12 elite male track runners were randomly assigned to whey and maltodextrin groups. Three time points (pre-, post-, and end-test) were used to evaluate related biochemical parameters, body composition and performance. The post-test was set 1 day after a marathon for injury status evaluation and the end-test was also assessed after 1-week recovery from endurance test. The results showed that the whey group exhibited significantly lower aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and creatine kinase indicators after the marathon (post-test), as well as at the end-test.

Sports Nutrition

During exercise, whole body protein synthesis is decreased, and proteins are mobilized into free amino acids. Skeletal muscles take up BCAAs from the blood and break them down into glucose for energy. Therefore BCAAs are unique among amino acids in their ability to provide an energy source during endurance exercise (Pasin and Miller, 2015). Many athletes consume whey protein for its rich BCAA content. Because the demand for BCAAs increases with endurance exercise, whey protein is an ideal way to replace these BCAAs to enhance protein synthesis and muscle growth during the recovery period. Whey proteins are particularly effective at stimulating muscle protein synthesis rates because the AA profile in whey is almost identical to that of skeletal muscle (Wolfe, 2000).  In addition, relatively high levels of EAAs in whey proteins are effective at stimulating protein synthesis in adult muscle (Volpi et al., 2003). Many studies suggest that whey proteins can help in improving lean body mass and performance in athletes on a resistance training regimen-

• In the study conducted by Lands et al, (1999) it was observed that 20 grams of whey protein per day for 12 weeks enhanced glutathione status (an antioxidant), improved athletic performance and decreased body fat percentage in healthy young adults.
• Dernling and DeShanti, (2000) shown that 60 grams of whey protein per day for 12 weeks was effective at decreasing fat mass and increasing lean body mass in overweight men following a calorie restricted diet and resistance training program.
• Dernling and DeShanti, (2000) observed that resistance-trained men when given whey protein supplements (1.5 g/kg body wt/day) for 11 weeks showed improvements in strength and doubled the gain in lean body mass compared to groups supplemented with carbohydrate, creatine or a combination of creatine and whey protein supplement

Weight Management

Maintaining a healthy weight can add years to the individual’s life and help in preventing weight related complications such as diabetes, cancer, and heart disease. Whey protein can play an important role in weight management (Solak and Akin, 2012). Specific factors in whey protein are being investigated for their ability to promote weight loss by increasing satiety, influencing glucose homeostasis, and maintaining lean body mass (Dairy council, 2004). Diet plays a key role in any weight management program and adding whey protein often helps make a positive difference (Solak and Akin, 2012). Following are some of the reasons (Gupta et al., 2012).

• The body requires more energy to digest protein than other foods (thermic effect) and as a result more calories are busnt after a protein meal.
• Whey protein isolate is pure protein with little to no fat or carbohydrates. It is a perfect complement to any low carbohydrate or low glycemic index diet plan.
• Protein has been shown effective in increasing satiety and modulating energy intakes (Halton and Hu, 2004), which may result in a loss of body fat and weight. Several studies have shown whey protein to be more effective than soy, egg and meat proteins in suppressing food intake (Anderson et al, 2004 and Belobrajdic et al., 2004).
• Branched-chain amino acids – specifically leucine – play a unique role in metabolic regulation by increasing fat loss and promoting lean muscle tissue in conjunction with an exercise program (Layman, 2003). Whey protein contains more leucine than milk protein, egg protein and soy protein.
• Whey protein contains bioactive components that help stimulate the release of two appetite-suppressing hormones: cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). In support of this Marcelo and Ritzvi, (2008) showed that whey protein had a greater impact on satiety than casein, the other protein in milk.
• Lactose, the primary sugar in whey has a low glycemic index which assists in controlling hunger and promoting weight loss. It has minimal effect on blood sugar levels and insulin response, making it ideal for people with type 2 diabetes (Dairy council, 2004).
• Calcium may protect against excess adiposity and assist in weight loss efforts (Zemel et al., 2004; Davis et al., 2000). Epidemiological studies link low calcium intakes to an increased risk of obesity (Jacqmain et al., 2003).

Infant Nutrition

Creating a substitute for mother’s milk has proved to be challenging. It is estimated that a nursing infant ingests about 3 g lactoferrin daily during the first week of life, whereas a calf drinking two liters of milk a day ingests about 2 g lactoferrin daily. Whey protein contains many of the same components found in human breast milk and for this reason, is a key ingredient in a wide variety of infant formulas, including those for premature infants (Keri, 2004). Certain types of whey protein based infant formulas have also been shown to help reduce crying in colicky infants (Thoma et al., 2006). While breast-feeding is preferred, infant formulas containing whey protein are the next best thing when breast-feeding is not an option. In addition, whey protein is an excellent protein choice for the expectant mother who needs increased amounts of protein. Pregnancy can increase the body’s protein needs by up to 33% (Gupta et al., 2012).

It is well accepted that nursing infants have a much richer gut flora than do bottle-fed infants, particularly with Bifidobacteria and Lactobacilli (Walzem, 2002). Such flora is normally associated with an increased resistance to colonization of the digestive tract with pathogenic bacteria (Van et al., 2000). In a study by Roberts et al. (1992) it was determined that the addition of lactoferrin to a feeding formula increased levels of Bifidobacteria in bottlefed babies. The levels of Bifidobacteria in formula fed babies that were supplemented with lactoferrin were not as high as those found in breast-fed babies. In addition, Bifidobacteria in formula-fed babies took up to three months to develop, while Bifidobacteria developed more rapidly in nursing infants.

Immunity

Immunoglobulins constitute approximately 10-15 percent of whey proteins (Gupta et al., 2012). Whey contains bioactive components that may offer protection, against infections and viruses, enhance immunity, protect against some cancers. Three whey peptides (α-Lactalbumin, β-Lactoglobulin and Lactoferrin) are known to boost the immune system by increasing production of glutathione. Growth factors known as IgF-I and IgF-II promote gut health and wound healing (Solak and Akin, 2012). Whey proteins optimize a number of aspects of the immune system, primarily by boosting glutathione (GSH) levels in various tissues. GSH protects the cells against free radical damage, pollution, toxins, infection and UV exposure and hence is the centerpiece of the body’s antioxidant defense system. It has been observed that GSH levels are typically depressed in individuals with immune-compromising conditions such as HIV, cancer, chronic fatigue syndrome and others. It also decreases with age and may be partially responsible for conditions such as Alzheimer’s disease, cataracts, Parkinson’s disease and arteriosclerosis (Dairy Council, 2004). Specific components in whey thought to play a role in enhancing the immune system include:

BCAAs

These are metabolized in the muscle to manufacture glutamine, a precursor to GSH and another important component of the immune system (Puddu et al., 2009).

Lactoferrin

It has been shown to exhibit immune-modulating activity through both antimicrobial and antitoxin activity (Harper, 2004). It may also provide protection against viruses such as hepatitis, cytomegalovirus and influenza (Hoerr and Bostwick, 2000).

Cysteine

An amino acid found in high levels in whey proteins, is involved in the intracellular production of GSH (Mehra et al., 2006).

Immunoglobulins

They may confer disease protection to infants through passive immunity and to adults by promoting the activity level of the immune system (Harper, 2004).

Cardiovascular Health

Heart disease is the leading cause of death all over world. With the average life expectancy rising each year, it becomes increasingly important to adopt a nutritious diet and regular exercise program to help maintain a healthy cardiovascular system. Studies have linked a high fat diet to an increased risk of cardiovascular disease (CVD). Because CVD is linked to a number of other factors, including increased age, genetics, obesity, sedentary lifestyle, alcohol intake, and quality of dietary fat. Kawase et al. (2000) conducted a study on a group of 20 healthy adult males to investigate whether a fermented milk supplement with an added whey protein concentrate would affect serum lipids and blood pressure. The fermented milk contained both Lactobacillus casei and Streptococcus thermophilus. During the course of eight weeks, volunteers consumed 200 mL of fermented milk with whey protein concentrate or a placebo in the morning and evening. The placebo consisted of a non-fermented milk product without the addition of whey protein concentrate. After eight weeks, the fermented-milk group showed significantly higher HDLs and lower triglycerides and systolic blood pressure than did the placebo group. While total cholesterol and LDL levels were lower in the fermented-milk group, the difference was not statistically significant.

Research has shown that whey proteins may work against hypertension. Human clinical trials and animal studies have shown that hydrolyzed whey protein isolate assists in reducing the blood pressure of borderline hypertensive individuals (Mehra et al., 2006). An elevated cholesterol level is another factor associated with the heart disease (Mehra et al., 2006). It has been observed that whey proteins may reduce the cholesterol level in individuals however additional research is needed for confirmation of the fact. Fekete et al. (2016) conducted a double-blinded, randomized, 3-way–crossover, controlled intervention study. Forty-two participants were randomly assigned to consume 2 × 28 g whey protein/day, 2 × 28 g Ca caseinate/day, or 2 × 27 g maltodextrin (control)/day for 8 wk separated by a 4 week washout. Significant reductions in 24-h BP [for systolic blood pressure (SBP): −3.9 mm Hg; for diastolic blood pressure (DBP): −2.5 mm Hg were observed after whey-protein consumption compared with control intake. After whey-protein supplementation compared with control intake, peripheral and central systolic pressures (−5.7 mm Hg and −5.4 mm Hg respectively) and mean pressures (−3.7 mm Hg and −4.0 mm Hg respectively) were also lowered. Although both whey protein and calcium caseinate significantly lowered total cholesterol (−0.26 mmol/L and −0.20 mmol/L), only whey protein decreased triacylglycerol (−0.23 mmol/L) compared with the effect of the control.

Cancer

Whey protein concentrates have been researched extensively in the prevention and treatment of cancer. Glutathione stimulation is thought to be the primary immune-modulating mechanism (Kawase et al., 2000). In a review of whey protein concentrates in the treatment of cancer, Bounous (2000) discusses the antitumor and anticarcinogenic potential. The amino acid precursors to glutathione available in whey might-

• increase glutathione concentration in relevant tissues,
• stimulate immunity, and
• detoxify potential carcinogens.

Other authors conclude the iron-binding capacity of whey may also contribute to anticancer potential, as iron may act as a mutagenic agent causing oxidative damage to tissues (Weinberg, 1996). A in vitro study by Kent et al. (2003) demonstrated that an isolate of whey protein, when compared to a casein-based protein, increased glutathione synthesis and protected human prostate cells against oxidant-induced cell death. An in vitro study on a human hepatoma cell line was conducted using a high lactoferrin whey concentrate (Immunocal®), a baicalein medium, or a combination of the two (Tsai et al., 2000). Baicalein, a potential anticancer drug, is a flavonoid extracted from Scutellaria revularis that is thought to have antitumor activity. Immunocal alone did not have a significant impact on the hepatoma cell line. However, when Immunocal was combined with baicalein, cytotoxicity was enhanced by inducing a higher rate of apoptosis than in the group treated with baicalein alone.

Cancer patients undergoing radiation or chemotherapy often have difficulty in meeting their daily nutritional requirements due to nausea and lack of appetite (Solak and Akin, 2012). This may lead to weight loss, muscle loss and protein calorie malnutrition. Whey protein is an excellent protein choice for cancer patients as it is very easy to digest and very gentle to the system (Bounous et al., 1991; Akin, 2006). Whey protein may be added to a wide variety of foods and beverages to increase the protein content without affecting taste. As with serious athletes, cancer patients often have reduced glutathione levels and a weakened immune system. Whey protein, rich in the amino acid cysteine, provides an extra boost to the immune system by raising glutathione levels (Marcelo and Ritzvi, 2008). This may help reduce the risk of infection and improve the responsiveness of the immune system. A research was presented in Annual Meeting of the American Cancer Society in 2003, showing that women with the highest levels of plasma cysteine had a 56% reduction in the risk of breast cancer compared to individuals with the lowest levels of plasma cysteine (Thoma et al., 2006).

Whey protein has been shown to inhibit the growth of several types of cancer tumors. Dr. Thomas Badger, head of the Arkansas Children’s Nutrition Center in Little Rock, found that feeding rats whey protein resulted in their developing 50% fewer tumors than rats fed casein. The rats fed whey protein also developed fewer tumors than rats fed soy protein and the tumors took longer to develop. Whey protein concentrate renders tumor cells more vulnerable to chemotherapy by depleting glutathione (Yalcin, 2006; Tsai et al., 2000). Whey proteins have also been reported to protect against chemically induced carcinogenesis in animal models (Yalcin, 2006; Bounous, 1991; Bounous, 2000).

Diabetes
Type 2 diabetes is a growing health problem, largely in part to the continued rise in obesity. It is not unique to adults and is becoming more of a concern for children and teenagers. Healthy nutrition practices have been shown to play a role in helping to manage, and possibly prevent, the onset of type-2 diabetes. Whey protein is a good choice for diabetics who need to carefully manage food intake. It provides more value than equal amounts of lower quality proteins that are often higher in fat and cholesterol. In addition, whey protein helps control blood glucose levels and has been shown to be beneficial for weight management, both of which are often a concern for type-2 diabetics (Frid et al., 2005; Mehra et al., 2006; Jangale and Bansal, 2013). Frid et al. (2005) evaluated the effect of adding whey protein to high glycaemic index meals taken at breakfast and lunch in patients with type 2 diabetes. Plasma insulin responses were higher after both breakfast (31%) and lunch (57%) with whey (27.6 g) when compared to lean ham or lactose. There was a reduction in blood glucose excursions after lunch but not breakfast, which might be related to either the differing meal content, or to higher insulin resistance seen in the fasting state affecting responses after breakfast (Linda et al., 2015).

Alpha glucosidase is an enzyme that hydrolyzes starch and disaccharides to enable absorption of glucose at the small intestinal brush border. In vitro studies have shown that whey protein hydrolysate has a modest effect to inhibit alpha-glucosidase (Lacroix and Li-Chan, 2013), which may be clinically relevant given that alpha-glucosidase inhibitors, such as acarbose, are used widely in the management of type 2 diabetes to improve postprandial glycaemia. Human studies are required to further evaluate this mechanism and the magnitude of the glucose lowering effect attributable to it (Linda et al., 2015). The capacity for whey preload to stimulate incretin hormone secretion and slow gastric emptying has also been established in subjects with type 2 diabetes by Ma et al. (2009). They reported that in type 2 diabetes patients 55 g whey protein preload, given 30 min before a meal, slowed gastric emptying when compared to either a nutrient free preload or ingestion of whey with the meal. Whey protein markedly reduced postprandial glucose excursions (iAUC after whey preload about half that of control) and stimulated insulin and CCK, as well as GIP and GLP-1. Both the GLP-1 response and the reduction in postprandial glycaemia were greater when whey was given as a preload, when compared to ingestion with the meal. Accordingly, this study not only established that whey can slow gastric emptying substantially in type 2 diabetes, but that the timing of supplementation is pivotal to the stimulation of incretins and other gut hormones. These acute effects of whey preloads to improve postprandial glycaemia were confirmed by Jakubowich et al. (2014) in another study in type 2 patients. While whey has been shown to slow gastric emptying acutely, it remains to be seen whether this effect is sustained with long term administration (Linda et al., 2015). Gunnerud et al. (2013), found that a drink containing 25 g glucose and either 4.5 g, 9 g or 18 g whey protein, reduced postprandial glycaemia (iAUC) by 25%, 37% and 46% respectively, compared to 25 g glucose alone; the reductions with 9 g and 18 g whey were statistically significant. There was also a dose-dependent increase in insulin (iAUC 0 – 120 min), which reached statistical significance with the highest dose of whey. While whey has convincing dose-dependent effects on glucose, insulin and appetite, the optimal dose for improving long-term glycaemic control in people with type 2 diabetes is yet to be determined (Linda et al., 2015).

Mohamed et al. (2016) demonstrated the protective role of dietary camel whey protein (CWP) in decreasing the tendency of the offspring of diabetic mothers to develop diabetes and related complications. CWP was administered as a supplement to streptozotocin (STZ)-induced diabetic pregnant mice. Three groups of female mice (n = 10) were used: non-diabetic control mice, diabetic mice and diabetic mice orally administered CWP during the pregnancy and lactation periods. Immune response of B and T cells in adult male offspring (n = 15 in each group) was tested by using flow cytometry, western blotting, and ELISAs. Offspring of diabetic dams exhibited several postpartum complications, such as significant aberrant overexpression of activating transcription factor-3 (ATF-3), significant elevation of the plasma levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and reactive oxygen species (ROS), marked decreases in the plasma levels of IL-2 and IL-7, significant inhibition of CCL21- and CXCL12-mediated chemotaxis of B- and T-lymphocytes, and a marked decrease in the proliferative capacity of antigen-stimulated B- and T-lymphocytes. Administration of CWP to diabetic dams substantially restored the expression of ATF-3 and the levels of ROS, pro-inflammatory cytokines, IL-2, and IL-7 in the offspring. Furthermore, the chemotaxis of B- and T-lymphocytes toward CCL21 and CXCL12 and the proliferative capacities of these lymphocytes were restored in the male offspring of diabetic mice administered CWP.

Wound Healing

When the body is working to heal wounds and surgical incisions it requires increased amounts of protein. Amino acids are the building blocks that initiate the growth of new skin during the healing process. Inadequate amounts of protein or diets high in poor quality proteins, such as gelatin, may delay the healing process. Whey protein is a very high quality protein and is often the preferred choice for high protein products recommended by physicians following surgery or burn therapy (Kargi and Ozmihci, 2006). Whey protein also contains components with protective anti-microbial properties, such as lactoferrin. In recent years companies have introduced mouthwashes and oral care products containing these protective whey protein components. The companies are taking advantage of the unique features of whey protein to create new products for diabetics and others sensitive to oral irritations (Lonnerdal, 2009). Abdel-Salam et al. (2016), investigated the impact of a diet containing whey protein (WP) on wound healing in malnourished mice. Diets comprised either 5 g/kg protein malnourished (MAL) or 150 g/kg protein (control) for 3 weeks. WP-supplemented animals received the MAL diet for 3 weeks, followed by a 1-week treatment with a WP supplemented diet. Thereafter, full thickness skin wounds were punched below the shoulder blades of each mouse. Results demonstrated that MAL mice showed a very sharp increment in their malondialdehyde (MDA) level and a significant decrease in glutathione (GSH) level compared to the control during the first 24 h. In contrast, WP supplemented MAL-mice showed a significant decrease in MDA level and displayed an improvement in GSH level compared to the MAL-mice. mRNA levels of IGF-1 and CCL22 (wound healing macrophages (WHM) were significantly down-regulated in MAL-mice, while regulatory macrophage marker (RM) CCL-1 and the classically activated macrophages (CAM) marker, CCLX10, were higher than the control. WP was found to significantly restore the phagocytic activity in MAL mice closer to that of the control mice. Histological investigation of the skin revealed that epidermal cell proliferation and migration, and dermal reorganization was gradually improved in WP animals. Thus, the time required for wound healing was shorter in MAL-mice supplemented with a WP diet than in MAL-mice.

Hepatitis

Whey protein supplementation demonstrates variable effects in patients infected with Hepatitis B or C. Initially it was found that bovine lactoferrin prevented hepatitis C virus (HCV) infection in vitro in a human hepatocyte line (Ikeda et al., 1998). These results prompted further clinical trials. A pilot study was conducted on 11 patients with chronic HCV. Each patient received either 1.8 or 3.6 g bovine lactoferrin daily for eight weeks. In patients with low pretreatment viral loads of HCV, decreases in HCV RNA and serum alanine transaminase were observed. In patients with higher pretreatment HCV viral loads, levels did not change significantly (Tanaka et al., 1999).

In an open study on 25 patients with either Hepatitis B or C, patients were given 12 g whey (Immunocal) twice daily for 12 weeks (Watanabe et al., 1999). Prior to the start of treatment with whey, patients were given 12 g casein protein daily for two weeks. Patients were also given casein following Immunocal for a four-week period. In the 17 patients with HCV, no significant changes were noted. In the group with hepatitis B virus (HBV), serum lipid peroxidase levels decreased, while IL-2 and NK activity increased. In six of eight HBV patients serum alanine transferase levels were reduced, while plasma glutathione levels increased in five of the same eight. This trial shows promise for the use of whey protein in the treatment of HBV.

Human Immunodeficiency Virus (HIV)

Glutathione deficiency is a common problem for individuals infected with HIV. In an effort to increase cysteine, and ultimately glutathione; several studies have been conducted on the use of whey proteins in HIV-positive individuals (Micke et al., 2002; Micke et al., 2001). In a study 30 subjects with HIV were randomized to receive a daily dose of 45 g whey protein from one of two sources – Protectamin® or Immunocal. The two products have different amino acid profiles and Immunocal is produced at a lower isolation temperature (<72 degrees C). After two weeks of oral supplementation, the Protectamin-supplemented group demonstrated significantly elevated glutathione levels, while the Immunocal group had statistically non-significant elevations.

The same researchers conducted a subsequent six-month study, using the same dose and products (Micke et al., 2002). Similarly, in the Protectamin group glutathione levels increased within a two-week period, while levels in the Immunocal group did not. All participants were then crossed over to receive Protectamin. After six months, all patients had a significantly increased glutathione level when compared to baseline numbers. Two small studies have been conducted on HIV-positive women examining exercise, whey supplementation, and body composition (Agin et al., 2000; Agin et al., 2001). There was increase in body mass composition with whey supplementation in former study whereas; in later there was no effect. Both studies note an improvement in quality of life with increased exercise and whey protein intake. Treatment groups received 1.0 g/kg daily of undenatured bovine-derived whey protein powder.

Gastrointestinal Support

A small, randomized, double-blind, crossover study was conducted on 10 children with short bowel syndrome to examine the effect of a hydrolyzed versus a non-hydrolyzed whey protein on growth and development (Ksiazyk et al., 2002). Energy intake, nitrogen balance, intestinal permeability, and weight gain were similar among all children, indicating the particular form of whey was not an essential component. In children experiencing bowel resection, food introduction and promotion of normal growth and development is of utmost importance. The increased transit time of whey proteins in the small intestine makes it an ideal protein source for this small subset of children.

Whey protein has demonstrated a protective effect on the gastric mucosa. This effect is thought to be related to the sulfhydryl component, particularly cysteine and its link with glutamic acid in the production of glutathione (Hiraishi et al., 1999; Hiraishi et al., 1994). Several animal studies have demonstrated this protective effect.  In a study by Rosaneli et al. (2002), rats fed a whey protein concentrate showed a 41 percent reduction in ulcerative lesions caused by ethanol ingestion, while a 73 percent reduction rate was observed following repeat doses of whey. A study by Matsumoto et al. (2001) demonstrated an isolated alpha-lactalbumin formula had a four-fold effect on reducing ulcerative lesions compared to a whey protein formula containing only 25 percent alpha-lactalbumin.

Conclusion

The whey, previously considered as a potent pollutant with high BOD has evolved into most sought-after product because of the lactose, minerals and proteins as well as the functional properties that it imparts to food. The ingredients of whey such as lactose, lactoferrin, lactoperoxidase, immunoglobulins, glycomacropeptides, transforming groth factors, spingolipids and calcium can be used as bioactive ingredients for promotion of health. These ingredients also have broad spectrum antimicrobial, anticancer and immunepotentiating properties, which provide added benefits over traditional fibre-based probiotics. Thus whey can serve as an attractive ecofriendly, cost effective bioceutical alternate to other nutraceuticals.

In the past few years, effects of whey protein on the heart, cardiovascular system and glucose metabolism have been identified that are promising but require additional research. It is not clear whether these potential beneficial health effects are due to whey protein itself, bioactive compounds, BCAA or other component(s) in milk and dairy foods. By staying abreast of the research and being informed of the specific types of whey protein products, health professionals will be in a strong position to make the most appropriate recommendations to meet the needs and goals of clients and patients.

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