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The use of a whey protein concentrate in the treatment of patients with metastatic carcinoma: A phase I-II clinical study
Abstract
Glutathione (GSH) concentration is high in most tumour cells and this may be an important factor in resistance to chemotherapy. Previous in-vitro and animal experiments have shown a differential response of tumour versus normal cells to various cysteine delivery systems. More specifically, an in-vitro assay showed that at concentrations that induce GSH synthesis in normal human cells, a specially prepared whey protein concentrate, Immunocal, caused GSH depletion and inhibition of proliferation in human breast cancer cells. On the basis of this information five patients with metastatic carcinoma of the breast, one of the pancreas and one of the liver were fed 30 grams of this whey protein concentrate daily for six months. In six patients the blood lymphocyte GSH levels were substantially above normal at the outset, reflecting high tumour GSH levels. Two patients (#1, #3) exhibited signs of tumour regression, normalization of haemoglobin and peripheral lymphocyte counts and a sustained drop of lymphocyte GSH levels towards normal. Two patients (#2, #7) showed stabilisation of the tumour, increased haemoglobin levels. In three patients (#4, #5, #6,) the disease progressed with a trend toward higher lymphocyte GSH levels. These results indicate that whey protein concentrate might deplete tumour cells of GSH and render them more vulnerable to chemotherapy.
... The findings of the effect of WPC supplementation investigated by three authors reported a similar efficacy to WPIS on clinical outcomes (Kennedy et al. 1995;Gillis et al. 2016;Perrone et al. 2017). The trial by Kennedy et al. 1995 in patients with metastatic carcinoma undergoing CT provided mixed study effects in terms of tumor growth and indicated that WPC appears to ameliorate GSH in normal cells but deplete GSH in tumor cells, making them more sensitive to chemotherapy. ...
... The findings of the effect of WPC supplementation investigated by three authors reported a similar efficacy to WPIS on clinical outcomes (Kennedy et al. 1995;Gillis et al. 2016;Perrone et al. 2017). The trial by Kennedy et al. 1995 in patients with metastatic carcinoma undergoing CT provided mixed study effects in terms of tumor growth and indicated that WPC appears to ameliorate GSH in normal cells but deplete GSH in tumor cells, making them more sensitive to chemotherapy. However, the study suffered from the lack of a true control group and small sample size (Kennedy et al. 1995). ...
... The trial by Kennedy et al. 1995 in patients with metastatic carcinoma undergoing CT provided mixed study effects in terms of tumor growth and indicated that WPC appears to ameliorate GSH in normal cells but deplete GSH in tumor cells, making them more sensitive to chemotherapy. However, the study suffered from the lack of a true control group and small sample size (Kennedy et al. 1995). The clinically significant improvements in functional walking capability in patients undergoing colorectal resection for cancer with WPC prior to surgery was highlighted by Gillis et al. 2016. ...
Cancer prevalence is rising rapidly around the globe, contributing immensely to the burden on health systems, hence the search for more effective and selective treatments still remains enticing. Whey, as a natural source, has received extensive focus in recent years because of its intriguing applications to health benefits. Growing consumer appreciation of the nutraceutical effects of whey components makes them an attractive field within cancer research. Whey is a valuable source of superior-quality proteins, lactose, vitamins, and minerals that contribute to proper nutrition as well as help hamper illness and even complement certain disease-related therapy prognosis. As a result, industry leaders and dairy producers are devising new ways to valorize it. Great emphasis on cancer prevention and treatment has been given to whey protein (WP) by the scientific community. WP intake has been proven to induce anti-cancer effects in various in vitro and in vivo studies. Nutritionists and dietitians are now enormously endorsing the role of WP in the therapeutic field, notably for cancer cachexia management. However, human intervention studies with WP are in their infancy and remain to be established with different tumor entities to provide valid proof of its ability to act as a coadjuvant in cancer treatment.
... It is clear that aflatoxin plays a significant role in liver cancer in developing countries, but not in the developed world where other risk factors such as cirrhosis are more important. Whey proteins (WP), by-products of the manufacture of cheese and curd, were shown to be tumor protective in animal models (Eason et al., 2004), and in limited clinical trials of cancer patients (Kennedy et al., 1995;Marshall 2004). In addition, whey has the ability to act as an antioxidant (Bounous, 2000), antihypertensive, antitumor (Yoo et al., 1998), hypolipidemic, antiviral (Low et al. 2003), antibacterial (Ajello et al. 2002), and chelating agent (Weinberg, 1996). ...
... WPC was mixed with water; the mixture was stirring with a magnetic stirrer and left in refrigerator over night to fully hydrate (Kennedy et al., 1995). However, Korean ginseng was extracted with 10 volumes of distilled water at 85 O C for 8 hours five times. ...
... 10,14 Non-denatured whey protein concentrates and isolates have been shown to increase glutathione levels in many diseases and disorders such as acquired immune deficiency syndrome (AIDS), cystic fibrosis, lung disease, chronic fatigue syndrome, hepatitis B, and cancer (e.g., colon, liver, breast, pancreas), without any toxicity or adverse events. 10,[14][15][16][17][18][19][20][21][22][23][24][25][26] There have been only occasional cases of gastrointestinal upset reported. 14 Non-denatured whey protein isolate use has not been examined in autism; and although reports are conflicting, some anecdotal reports suggest that some children with autism may have problems with ingestion of cysteine-rich or any sulfur-rich compound, such as whey protein. ...
... As mentioned in the Introduction, non-denatured whey protein isolate has been shown to increase glutathione levels and improve the healing process in many diseases and disorders, such as cystic fibrosis, lung disease, AIDS and other types of immune deficiencies, chronic fatigue, hepatitis B, and cancer, with no toxicity or adverse events. [14][15][16][17][18][19][20][21][22][23][24][25][26] Immunocal ® , a non-denatured whey protein isolate, has been shown to augment GSH levels and to improve clinical parameters. ...
Purpose: To examine the tolerability of non-denatured whey protein isolate (NWPI) in children with autism. Many children with autism are low in glutathione and have higher levels of oxidative stress. NWPI can raise glutathione levels and reduce oxidative stress. However, anecdotal reports suggest that NWPI may be problematic in children with autism because it contains cysteine and other sulfurated amino acids.
Methods: A 6-week open-label trial was conducted, supplementing 10 children with autism or autism spectrum disorder (ASD), 3-15 years of age, with NWPI (Immunocal®). To measure possible side effects, procedures that examined the frequency, intensity, and types of side effects, as well as behavioral measures, were completed at baseline, and at days 3, 14, 30, and 45.
* Correspondence:
Janet K. Kern, PhD
Autism Treatment Center
10503 Metric Drive
Dallas, Texas 75243
Phone: 972-644-2076 Fax: 972-644-5650 E-mail: jkern@atcoftexas.org
Results: Seven of the ten children took the supplement over the six-week trial and tolerated it well. Two children discontinued after two weeks due to possible side effects: one due to gastrointestinal disturbance and one due to being less responsive to parents. Another child discontinued due to difficulty of administering the product.
Conclusion: This study suggests that NWPI can be used as a supplement for this small population of children with autism without high rates of side effects, which means that further studies to determine its safety and efficacy in larger populations might yield the same promising result. Larger studies are planned to determine its efficacy in raising glutathione levels.
... It is clear that aflatoxin plays a significant role in liver cancer in developing countries, but not in the developed world where other risk factors such as cirrhosis are more important. Whey proteins (WP), by-products of the manufacture of cheese and curd, were shown to be tumor protective in animal models (Eason et al., 2004), and in limited clinical trials of cancer patients (Kennedy et al., 1995;Marshall 2004). In addition, whey has the ability to act as an antioxidant (Bounous, 2000), antihypertensive, antitumor (Yoo et al., 1998), hypolipidemic, antiviral (Low et al. 2003), antibacterial (Ajello et al. 2002), and chelating agent (Weinberg, 1996). ...
... WPC was mixed with water; the mixture was stirring with a magnetic stirrer and left in refrigerator over night to fully hydrate (Kennedy et al., 1995). However, Korean ginseng was extracted with 10 volumes of distilled water at 85 O C for 8 hours five times. ...
Aflatoxins the major toxic metabolites of fungi which are able to induce chronic liver damages. The
antioxidant and hepatoprotective effects of whey protein concentrate (WPC) and/or Korean ginseng extract (KGE) were evaluated in vitro in in vivo. In the in vitro study, five concentrations (e.g. 20, 40, 60, 80 and 100 mg/100 ml) of WPC and/or KGE were tested for their antioxidant activity using ABTS and thiobarbituric acid reactive substances (TBARS) assays. In the in vivo study, male Sprague-Dawley rats were divided into eight groups including the control group, the group fed AFs-contaminated diet (2.5 mg/kg diet) and the groups treated with WPC (500 mg/kg b.w) and/or KGE (20 mg/kg b.w) with or without aflatoxins for 30 days. The results indicated that both WPC and KGE exhibit antioxidant activity in vitro and the combined treatment showed the potential effect. Both agents showed a potential hepatoprotective effects against aflatoxins-induced liver damage and oxidative stress. They succeeded to restore the biochemical parameters and improve the histological and histochemical picture of the liver. This improvement was pronounced in the group received the combined treatment of WPC and KGE. It could be concluded that WPC should be incorporated with KGE when used as functional foods for people suffering from liver diseases.
... Scientific data indicates that whey-derived peptides possess a range of valuable biological properties for human health. Whole whey proteins and protein subfractions (α-lactalbumin, bovine serum albumin, lactoferrin) have anticancer activity, what was proven using different cancer cell line models, from both human and animals (Kennedy et al., 1995;See et al., 2002;Gillis et al., 2016;Madzima et al., 2017;Bumrungpert et al., 2018;Sternhagen & Allen, 2001;Laursen et al., 1990;Cheng et al., 2017;Attaallah et al., 2012;Xiao et al., 2006). Various in vitro methods were used to evaluate antioxidant potential of whey proteins-DPPH radical assay, ABTS assay, ferric-reducing antioxidant power, and oxygen radical absorbance capacity. ...
The potential of whey from Italian cheese productions to support skin health and anti-ageing mechanism was studied. The effect of whey on dermal and epidermal cells was evaluated. Whey inhibited the activity of elastase and tyrosinase enzymes by 60% and 32%, respectively. Whey cytotoxicity against tested skin cell lines, human fibroblasts (HDFa) and keratinocytes (HaCaT) was not observed. Moreover, the antioxidant activity of the samples was noted, after treatment with whey intracellular ROS level was decreased by 87% in comparison with the hydrogen peroxide-treated cells. Fibroblasts produced a significant amount of extracellular matrix molecules, collagen I, elastin and glycosaminoglycans as a result of treatment with tested whey. In addition, the ability of samples to improve the cell barrier integrity of keratinocytes was proven. The obtained results indicate that pure whey supports skin health and shows potential to be used by the cosmetic industry.
... Whey proteins can increase cellular glutathione content in normal tissue cells but reduce the content in tumour cells that are more vulnerable to chemotherapy (Kennedy, Konok, Bounous, Baruchel, & Lee, 1995). Glutathione directly participates in the destruction of ROS through glutathione peroxidase, and maintains vitamin C and E in the reducing form (Pasquier, Olivier, Auclair, & Packer, 1994). ...
Continuing studies show that whey components, notably proteins, have valuable nutritional and techno-functional properties supporting their applications in foods and drinks. Complementing these features is the increasing evidence of the health-promoting characteristics of whey proteins and peptides. This paper reviews whey production, composition, and the physico-chemical characteristics of whey proteins and peptides, and critically reviews the health-promoting traits of these components. The role that whey proteins and peptides may play in the prevention and/or adjunctive treatment of various lifestyle and ageing diseases (e.g., diabetes, cancer, liver disease, sarcopenia, cardiovascular disease) are covered. Where possible, the mechanisms of action for the various bioactivities are reviewed, as is the usefulness of whey proteins and peptides in protecting, stabilising and delivering functional food components, notably nano-based systems. This paper highlights the bright future for whey proteins and peptides based on their valuable nutritional, techno-functional and bioactive characteristics, but particularly their health-promoting functions.
... Kennedy et al. 1995 [106] Breast, pancreatic, liver Whey protein supplementation significantly increased albumin (2.9%) and immunoglobulin G (4.8%) levels compared to the control group at week 12. Controls showed a significantly lower percent change in glutathione levels (6.0%), whereas there was a significant time-dependent increase in the intervention group (11.7%). Whey protein supplementation improved nutrition status scores in the intervention group compared to the control. ...
... 21 We defined the period of time of 42 days as a chronic alcohol treatment (1-14 days-acute toxicity, 21-28-subacute toxicity and after 28 days-chronic toxicity). 22,23 The whey was administered with a rat gavage tube, every day during the experiment, once daily, always at 9 am, continuously for 6 weeks, as follows: cow whey powder product administration, dissolved in 0.5 g/mL of distilled water, (ingredients: carbohydrates-61 g/100 g, proteins-11 g/100 g and lipids-2 g/100 g) was ordered based on the average daily intake of whey from previous human studies [24][25][26] (recommended doses-5-50 g of whey per day) and the dose is extrapolated from humans to rat, [27][28][29] through the metabolic body size or food intake rather than body weight as a criterion (the dose amounted 0.4g/200 g of animal weight). Ethanol (12%) was administered (Ethanol absolute 99% "Merck") diluted with distilled water, daily ad libitum for 6 weeks. ...
In 2012, alcohol liver disease (ALD) resulted in 3.3 million - 5.9% of global
deaths. This study introduced whey protection capacity against chronic
alcohol-induced liver injury.
Rats were orally administered to 12% ethanol solution in water (ad libitum,
average 8.14 g of ethanol/kg b.w./day) alone or combined with whey (per os, 2g/kg
b.w./day). After 6-week treatment, chronic ethanol consumption induced significant
histopathological liver changes: congestion, central vein dilation, hepatic portal vein
branch dilation, Kupffer cells hyperplasia, fatty liver changes, and hepatocytes focal
necrosis. Ethanol significantly increased liver catalase activity and glutathione
reductase protein expression without significant effects on anti-oxidative enzymes:
glutathione peroxidase (GPx), copper-zinc-containing superoxide dismutase and
manganese-containing superoxide dismutase. Co-treatment with whey significantly
attenuated pathohistological changes induced by ethanol ingestion and increased
GSH-Px and NFkB protein expression.
Our results showed positive effects of whey on liver chronically exposed to
ethanol, which seem to be associated with NFkB-GPx signaling.
... Whey protein is naturally bioactive which basically contains high concentrations of cysteine and consequently glutathione-an antioxidant that is essential for improving human health. Whey protein concentrate increased the preventive factors and reduce the oxidative stress factors and rise the resistance factors in human cells (Konok et al. 1995;Baruchel and Viaux 1996). ...
Abstract Background Manipulation of functional dairy products and natural phytochemicals may be a good source of micronutrients for traditional therapies and improve the hypoglycemia. The objective of this study to find out the protective effects of whey protein (WP) mixed with Garcinia kola seeds (GK) and extract of olive leaves (OL) against alloxan-induced oxidative stress and diabetes in rats. Methods The 42 male Sprague-Dawley rats (120-150 g) were housed individually and randomly allocated to two main groups; normal group (n = 6) and six equal alloxan-induced diabetic groups (n = 36). Normal (first) and diabetic control (second) groups received basal diet only during the experiment, while groups (third, fourth, fifth, sixth, and seventh) received basal diet and an oral extract from WB (300 mg/day); OL (200 mg/day); WP and OL mixture (300 + 200 mg/day); GK (15 mg/day); and WP and GK mixture (300 + 15 mg/day) respectively. Biochemical markers including hematological parameters, glucose, BUN, creatinine, albumin, total protein, and liver enzymes were determined. Brain sample were taken for histopathological examination. Results In comparison with second group, the administration of WP, GK, OL, WP and GK mixture, and WP and OL extracts respectively resulted in significant decrease in blood glucose (61.0 ± 10.8, 68.5 ± 6.6, 64.8 ± 14.6, 82.2 ± 8.4, and 91.7 ± 20 vs. 135.6 mg/dl ± 12.3 respectively). Liver enzymes were improved with administration of WP, GK, and OL extracts compared with positive control. Brain histopathological investigation showed reduction in tissue changes among rats received the suggested interventions. Conclusions The obtained data can be concluded that administration of WP, GK, and OL extracts had evident favorable effects on blood glucose, major hematological, and biochemical parameters as well as the histological picture of brain.
... Remarkably, total dairy and cheese consumption, but not necessarily milk intake, is one of the main correlates of prostate cancer in the present study, which is also highlighted by Factor 1 and Factor 3. The positive and negative role of dairy foods is often explained by the content of calcium (50,51,53), but the paradoxical relationships between cancer and various dairy products may better reflect the content of whey. Whey proteins have remarkable anti-cancerogenic properties (54,55) and are present in milk and fermented whole milk (yogurt), but not in cheese, curd, butter or cream. A recent metaanalysis of 11 cohort studies by Lu et al. (56) gives some support to this hypothesis. ...
The aim of this work was to offer an ecological alternative to conventional observational studies and identify factors potentially associated with cancer incidence in Europe. The incidence of 24 types of cancer in 39 European countries (2012) was compared with a long-term mean supply of 68 food items from the FAOSTAT database (1993–2011) and some other variables such as smoking, body mass index, raised cholesterol, and socioeconomic indicators. In addition to simple Pearson linear correlations, the data were analyzed via factor analyses and penalized regression methods. This comparison identified two main groups of cancers that are characteristically associated with the same variables. The first group consists of cancers of the prostate, breast, white blood cells, and melanoma. Their incidence increases with rising gross domestic product (GDP) per capita, a prevalence of raised cholesterol and a high intake of animal products. The second group includes primarily cancers of the digestive tract and is most consistently correlated with alcoholic beverages, lard, and eggs. In addition, we found specific correlations between certain variables and some other types of cancer (smoking—lung and larynx cancer; low GDP per capita and high carbohydrate consumption—stomach and cervical cancer; tea drinking—esophageal cancer; maize consumption and wine drinking—liver cancer). The documented findings often remarkably agree with the current scientific consensus, and when combined with evidence based on different methodologies, they can further extend our knowledge of the etiology of cancer. In addition, our study also identifies several foods with possible preventive effects and indicates that various dairy products may markedly differ in their relationship to cancer incidence. All these data can potentially be of fundamental importance for clinical practice and the survival of cancer patients.
... Subsequently, studies have been performed on patients with metastatic carcinoma, who were given this specially prepared whey protein isolate for six months. Although it did not cure the cancer, a significant proportion showed either tumor regression/stabilization or normalization of hemoglobin and white blood cell counts [18]. The same researchers have demonstrated that elevated GSH levels may enhance certain chemotherapeutic agents. ...
The majority of cancer patients receiving conventional medical therapy receive chemotherapy, radiotherapy, surgery or palliative support. Nutritional support is increasingly recognized as vital to successful treatment. Glutathione (GSH) is a naturally-occurring tripeptide in human cells that serves many important functions, including antioxidant regulation, detoxification, protein synthesis and repair, immune modulation, and redox signaling. Altering glutathione levels has been demonstrated to have significant effects in chemotherapy/radiotherapy outcomes as well as influence on retarding cachexia. This review article summarizes some of the most notable findings, suggesting that up-regulation of glutathione through nutritional intervention has a potential to be integrated into a holistic approach to cancer treatment.
... Immunocal is a high lactoferrin whey concentrate, which alone does not have a significant effect on the hepatoma cell line. But, when this was combined with baicalein ( Fig. 16.1), the cytotoxicity was enhanced by inducing a higher rate of apoptosis than in the group treated with baicalein alone (Kennedy et al., 1995;Tsai et al., 2000). ...
Whey (also known as lactoserum) is a liquid obtained after the separation of milk fat and casein from the whole milk. The dairy industries are facing challenges for its disposal and always looking for simple and economical solutions. The best approach is to convert whey into some useful value added products. The combined knowledge based on bioorganic chemistry and biotechnological techniques helped in transforming whey to value added products. Whey in different forms has been used in breads, bakery, snack items, beverages, confectionary products and other nutritional food products. Whey has also been used as a substrate for the growth of different microorganisms which further helps in the development of useful products like lactic acid, citric acid, biogas etc. In this chapter, a comprehensive coverage of literature is discussed for the effective utilization of whey for the production of value added products.
... Supplementing formula-fed piglets with a low-molecular weight fraction of bovine colostrum whey resulted in improved intestinal barrier function (De Vos et al., 2014). It has been reported that the colostrum whey proteins can be administered at 30 g/d for 6 mo without inducing side effects in humans (Kennedy et al., 1995). ...
Inflammatory bowel disease (IBD) is a poorly understood chronic immune disorder for which there is no medical cure. Milk and colostrum are rich sources of bioactives with immunomodulatory properties. Here we compared the therapeutic effects of oral delivery of bovine milk-derived iron-saturated lactoferrin (Fe-bLF), angiogenin, osteopontin (OPN), colostrum whey protein, Modulen IBD (Nestle Healthsciences, Rhodes, Australia), and cis-9,trans-11 conjugated linoleic acid (CLA)-enriched milk fat in a mouse model of dextran sulfate-induced colitis. The CLA-enriched milk fat significantly increased mouse body weights after 24 d of treatment, reduced epithelium damage, and downregulated the expression of proinflammatory cytokines and nitrous oxide. Modulen IBD most effectively decreased the clinical score at d 12, and Modulen IBD and OPN most effectively lowered the inflammatory score. Myeloperoxidase activity that denotes neutrophil infiltration was significantly lower in mice fed Modulen IBD, OPN, angiogenin, and Fe-bLF. A significant decrease in the numbers of T cells, natural killer cells, dendritic cells, and a significant decrease in cytokine expression were observed in mice fed the treatment diets compared with dextran sulfate administered mice. The Fe-bLF, CLA-enriched milk fat, and Modulen IBD inhibited intestinal angiogenesis. In summary, each of the milk components attenuated IBD in mice, but with differing effectiveness against specific disease parameters.
... WPC powder contains 80% proteins was obtained from Davisco Foods International, Inc., Eden Prairie, Minnesota, USA. The WPC was prepared according the method of Kennedy et al. [26] by mixing with water and stirring with a magnetic stirrer and left in refrigerator overnight to fully hydrate. ...
This study evaluated the effect of whey protein concentrate (WPC) or fennel seed extract (FSE) on paraoxonase-1 activity (PON1) and oxidative stress in liver of tienilic acid (TA) treated rats. Six groups of rats were treated for six weeks as follows: control; WPC (0.5 g/kg/day); FSE (200 mg/ kg/day); TA (1 g/kg/twice a week); TA (1 g/kg/twice a week) plus WPC (0.5 g / kg/day); TA (1 g/kg/twice a week) plus FSE (200 mg/kg/day). TA administration significantly increased ALT and AST besides to total- and direct bilirubin levels. Also, serum tumor necrosis factor-α and nitric oxide levels were significantly increased. Furthermore, serum PON1, and hepatic reduced glutathione, glutathione-S-transferase and Na+/ K+-ATPase values were diminished matched with a significant rise in the level of hepatic lipid peroxidation. Also, triglycerides, total- and LDL-cholesterol levels were significantly elevated while HDL-cholesterol was unchanged. The administration of either WPC or FSE to TA–treated animals significantly protected the liver against the injurious effects of tienilic acid. This appeared from the improvement of hepatic functions, atherogenic markers, Na+/ K+ ATPase activity, endogenous antioxidants and hepatic lipid peroxidation level; where WPC showed the strongest protection effect. In conclusion, the present study indicated that WPC and FSE improve PON1 activity and attenuate liver dysfunction induced by TA. This may be attributed to the high content of antioxidant compounds in WPC and fennel extract.
... Health benefits to humans of whey consumption have drawn increased attention, because whey is rich not only in nutrients but also in bioactive components such as proteins [15]. It has been reported that whey proteins exert several therapeutic effects on humans in a number of clinical trials as they are potential antioxidants, protect cells from ethanol damage and ROS-induced cell damage this protection includes their capacity to stimulate GSH synthesis as whey proteins are a cystine-rich protein source which is the rate-limiting step in GSH synthesis [16][17][18].The major proteins contained in whey are beta-lactglobulin (BLG), a-lactalbumin, immunoglobulin, and protease peptone 3 [19]. ...
effect of Beta-lactglobulin (β-LG), Lacprodan®alpha-10(LAC) and L-methionine as hepatoprotective agents against thioacetamide (TAA) rats' model was studied. Method: Group 1 control negative; Group2 control positive(TAA only) , the treated 3-9 groups received TAA (100mg/kg, i.p.) twice weekly ,group3,4 received daily β-LG (100mg/kg and 200 mg/kg), respectively. Group 5 received a combination of β-LG (50 mg/kg) and L-methionine (40 mg/kg).Groups 6,7 and 8 received the same as groups 3,4 and 5 except we use LAC instead of β-LG ,while group 9 received L-methionine (40 mg/kg) only .Results: TAA induced elevation in serum levels of alanine aminotransferase (ALT), Aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin(TB) .Moreover, TAA induced oxidative stress indicated in elevation of malondialdehyde (MDA) and nitric oxide content(NO) as well as reduction in antioxidant enzymes(hepatic reduced glutathione concentration (GSH) and superoxide dismutase (SOD) activity). Administration of whey proteins and L-methionine concurrently with TAA attenuated hepatic fibrosis induced by TAA. WPs and L-methionine caused decline in serum AST, ALT, ALP and TB levels besides reduction of MDA and NO free radicals while increased GSH concentration, SOD activity. Conc.: whey proteins useful as pharmacological agent that suppress hepatic fibrosis.
... Table III shows the main human clinical studies of some commercial bioactive peptides. Kennedy, 1995Rosaneli, 2002Frid, 2005Pins, 2006Lee, 2007Xu, 2008 de Leeuw, 2009 α-La and its hydrolysates *Stress relief and reduced depressive mood *Improves cognitive functions in stress -vulnerable subjects by increased brain tryptophan and serotonin activity *Increases plasma tryptophan levels and its ratio to neutral amino acids *Inhibits the growth of skin papillomas in humans when topically applied Ingredient for infant formulae -Vivinal alpha‖ Markus, 2000Gustafsson, 2004Scrutton, 2007 Kayser, 1996Iwasa, 2002Ajello, 2002Tamura, 2004Mader, 2005Zimecki, 2005Hayes, 2006Zimecki, 2007Petitclerc, 2007McBride, 2007Lyons, 2007 ...
Whey is an important surplus product of food industry. Based on the point of view, huge quantities of whey produced worldwide can represent an environmental problem with its disposal, or, due to the fact that whey is rich in fermentable nutrients, it can be considered as an attractive substrate for biotechnological production of various industrially interesting products. Therefore, this chapter is intended to summarize possible up-stream processing methods, general principles and fermentation strategies for the microbial productions using whey as a substrate. Further, among huge amount of potential products, this chapter focuses on the production of high value substances and materials which find applications especially in the fields of health care, medicine and pharmacy. At first, many biologically active substances such as vitamins, carotenoids, antibiotics etc. can be produced from whey employing various microorganisms and cultivation strategies. Moreover, also number of biopolymers which can be used in the form of drug carriers, scaffolds, sutures, adhesives etc. can be produced by using whey as a cheap complex substrate. Apart from poly (lactic acid), these materials include polyhydroxyalkanoates - bacterial polyesters and also several polysaccharides such as xanthan, alginate, hyaluronic acid, gellan, pullulan, dextran or chitosan. In addition, the aim of this review is also to provide basic economical consideration of fermentation processes. In conclusion, utilization of whey as a substrate for microbial productions of high value products could result in a very promising process meeting both economic and ecological requirements.
... In cancer patients, intake of whey proteins has been reported to increase the number of blood leucocytes (Kennedy et al., 1995). Feeding diets containing milk proteins has also been shown to delay thymic involution. ...
6.1 Introduction The population of elderly persons is growing rapidly in all countries. According to latest WHO estimates there are about 600 million people aged 60 years or older in the world and this figure is expected to rise to over 2 billion (20% of the world population) by the year 2050 (United Nations, 1999; WHO, 1999). Furthermore, the number of people over the age of 80 is expected to more than triple, and the number of centenarians is projected to increase by 15-fold within the next 50 years. This increase in life expectancy has been the result of improvements in diet, health-care and living conditions. Ageing is associated with a decline or deterioration in many physiological functions including the immune system (Wick and Grubeck-Loebenstein, 1997). Decline in immune function with age is termed as immunosenescence and is found in all mammalian species. Immunosenescence is deemed to be responsible for enhanced morbidity and mortality in the aged. Epidemiological and clinical studies have revealed that elderly persons suffer more often from infectious diseases (respiratory tract and urinary tract infections, gastroenteritis, tuberculosis, endo-carditis and septicaemia), cancers and autoimmune and atopic reactions than their younger counterparts (Kelley and Bendich, 1996). As a result, the care of elderly accounts for a significantly higher percentage of health-care costs relative to their population. For example, 11% of the elderly population use over 40% of health-care resources in the US (Chandra, 1989). The effective means to correct this age-related immune dysfunction are highly sought and the years since 1980 have seen enormous interest in both fundamental and applied research that is aimed at improving geriatric health. It has been Dairy products and the immune function in the elderly 133 suggested that dietary supplementation could be used to improve and maintain immune health in the elderly. Being a non-invasive, cost-effective and practical means of health improvement, it is of special interest to both consumers and the health-care providers. The challenge, therefore, is to identify nutrients/food components or develop products that are able to improve immune health. This chapter will outline scientific evidence for immunological changes associated with ageing and then discuss evidence, both scientific and clinical, regarding the use of milk or milk products (including fermented products) for optimizing immune health in the elderly.
... Few clinical studies correlate antineoplastic effect on milk protein, but the results are very promising. It is believed that, contrary to what occurs in normal cells, the glutathione concentration is high in tumor cells making them resistant to chemotherapeutic drugs [33]. In some cases, a 6 month administration of 30g/day dose of whey protein concentrate led to a decrease or stabilization of glutathione levels, resulting in stabilization or regression of the tumor. ...
The colostrum serum in the human milk has a variety of proteins that characterize and contribute exclusively to the quality of nutrition. In addition to being an important source of special amino acids required for rapid growth of the baby, many of these proteins have specific functions; such as assisting in the absorption of the fluids, defending against viral and bacterial infections, and stimulating the development of the intestinal mucosa by increasing the immunocompetence of the neonate. Some proteins such as the bile, a salt-stimulated lipase, the α-amylase and α1-antitrypsin, exert their function in the gastrointestinal tract, helping the absorption of the micronutrients and macronutrients milk, because they are relatively resistant to digestive enzymes. Furthermore, other proteins such as lactoferrin, secretory immunoglobulin A, lactoperoxidase, haptocorrin, and lactaderina bioactive peptides are formed during digestion, human milk proteins may inhibit the growth of pathogens such as bacteria and viruses, or promote probiotic activity, favoring the growth of beneficial bacteria such as strains of the genera Lactobacillus and Bifidobacterium. There are proteins, such as cytokines, that modulate the immune response, regulate the inflammatory response and the development and growth of the newborn. Currently it is possible to reproduce the recombinant proteins of human milk in transgenic plants and animals on a large scale at a low cost. Thus, some components found in human milk can be added to other diets, substituting some qualities of the food, however it is unlikely that all original components in human milk can be reproduced and used, by employing the available technology.
... 16 A small number of clinical trials have been undertaken, proposing that high levels of GSH in tumour cells confer resistance to chemotherapeutic agents 1 . Of these, one study of 5 patients produced conflicting results, highlighting the need for larger trials 17 . In another, 20 patients with stage IV malignancies were treated daily with 40g whey in combination with supplements such as ascorbic acid and a multi-vitamin/mineral formulation 18 . ...
... [1] Moreover, they possess specific physiological actions. [2,3] Beta-lactoglobulin (β-LG), the main constituent of whey proteins, accounting for about half of the protein in bovine whey isolate [4] is a rich source of cysteine, [5] one of the most essential amino acids. ...
The production of whey protein thickeners by drying protein gels to produce instant thickening powders has been previously investigated. The use of native whey proteins as a food thickener, however, has not been studied earlier. In this work, we characterized thermally treated whey protein solutions with improved thickening properties. Viscosity contour maps were constructed to outline the viscosity values at different protein and salt concentrations. Huggins-Kraemer constants revealed that at low ionic strengths, polymerized protein molecules behave as flexible coils, while at higher ionic strengths, molecules appear to be aggregated in a spherical like shape.
... In addition, protective action in human prostate cells (KENT;HARPER;BOMSER, 2003), inhibitory action in mammary cells and in a rat mammary carcinoma model (BARUCHEL;VIAUX, 1996), inhibition of growth and metastasis of murine melanoma (BEZAULT et al., 1994), inhibition of hepatocellular carcinoma caused by Hepatitis C Virus (HCV) (IKEDA et al., 1998), inhibition of tumors in animal model systems (BOUNOUS; KONGSHAVN;GOLD, 1988;McINTOSH et al., 1995;McINTOSH;LE LEU, 2001;DIAS et al., 2006) have also been tested. Whey proteins have been used in treatments of metastatic mammal and liver carcinoma (KENNEDY et al., 1995), skin papiloma (GUSTAFSSON et al., 2004), and humans submitted to neck and head cancer surgery (CHMIEL, 1997) as well as on treatments for human glioblastoma transplanted to rats (FISCHER, 2004). ...
Whey protein samples (S-1 to S-5) were tested invivo and invitro for nutritional properties and selected bioactivities. Weanling male Wistar rats fed modified AIN-93G (12gprotein.100g-1) diets for 21 days were used the invivo studies. The nutritional parameters did not differ among the protein diets tested. Erythrocyte glutathione content was considered high and was higher for S-3, but liver glutathione was the same for all dietary groups. For S-3, cytokine secretion (IL-10 and TNF-α) by human peripheral blood mononuclear cells (in RPMI-1640 medium) was higher in the absence of antigen than in the presence of BCG antigen. Interleukin-4 secretion was repressed in all treatments. The IC50, whey protein concentration required to inhibit 50% of the melanoma cell proliferation, was 2.68mg.mL-1 of culture medium for the S-3 sample and 3.66mg.mL-1 for the S-2 sample. Based on these results, it was concluded that S-3 (whey protein concentrate enriched with TGF-β and lactoferrin) produced better nutritional and immunological responses than the other products tested.
... 16 Despite the availability of new symptomatic therapies, there are still patients who do not achieve adequate response or develop side effects requiring discontinuation of the medicine. Therefore, a preliminary study was performed on a small group of patients with moderate-to-severe PV, using a nondenatured bioactive whey protein isolate, clinically proven in previous trials [17][18][19][20][21] to increase GSH levels. ...
Background:
Psoriasis is a common autoimmune disease with enhanced systemic inflammation and heightened levels of oxidative stress. Glutathione is the major antioxidant in human cells.
Objectives:
To determine if a nondenatured bioactive whey protein isolate previously demonstrated to increase glutathione levels can clinically improve patients with psoriasis vulgaris.
Methods:
A single site, prospective, non-blinded trial. Seven patients with psoriasis were recruited to take a nondenatured bioactive whey protein isolate, 20g orally per day, in addition to their current treatments, if any. Psoriasis Area and Severity Index scores and photographs were taken at baseline and monthly for three months.
Results:
Patients with psoriasis were found to have a beneficial clinical improvement, whether they were on existing topical therapy, narrowband ultraviolet B, or no other treatment.
Conclusion:
The positive preliminary outcomes from this pilot study suggest a randomized, double-blind, clinical trial would be worthwhile in evaluating whether this protein isolate would result in statistically significant improvement for patients with psoriasis.
... The ability of the PPP methanolic extract to scavenge 1,1-di- phenyl-2-picrylhydrazyl radical (DPPH) free radicals were determined by the method described by Singh et al. (2002). While, the free radical scavenging activity of the whey powder aqueous extract was determined according to the method of Kennedy et al. (1995) ...
The antioxidant activity of pomegranate peel powder (PPP) and whey powder (WP) was evaluated, their hepatoprotective effect of each alone or in combination (PPWP) at equal levels was also evaluated in Wistar rats against carbon tetrachloride (CCL4) induced liver injury. The hepatoprotective activity was assessed using various biochemical parameters and histopathological studies. The results indicated that both PPP and WP exhibited antioxidant activity. Also, rats fed on diets supplemented with 10% PPP, 10% WP or 10% of their mixture (PPWP) for 28 days showed a potential hepatoprotective effects compared to liver injury control group (IC). They succeeded to restore the biochemical parameters and improved the histological alteration of the liver. This improvement was pronounced in the group received PPWP. It could be concluded that whey powder should be incorporated with pomegranate peel powder when used as ingredients in functional foods for people suffering from liver diseases.
... Whey proteins are important source of balanced amino acids (Mcintosh, Regester, Le Leu, Royle, & Smithers, 1995;Regester, Mcintosh, Lee, & Smithers, 1996). In addition, they possess specific physiological properties (Bounous, Gervais, Amer, Batist, & Gold, 1989;Kennedy, Konok, Bounous, Baruchel, & Lee, 1995) and important functional properties (Jost, 1995). b-lactoglobulin (b-LG) is the main constituent of whey proteins, and is responsible for most of their functional properties (Fox, 1989). ...
Dilute solution Newtonian viscosity of whey protein polymers at different temperatures has not been assessed in literature. In this work, a thermally-treated whey protein solution at 8% w/w and pH 6.8 was prepared. Dilute solution viscometry was investigated at different temperatures from 30 °C to 65 °C. Intrinsic viscosity and voluminosity data indicate slight shrinkage in molecular size upon temperature increase. The temperature dependence of viscosities was expressed by the Arrhenius–Frenkel–Eyring equation and the thermodynamic parameters of viscous flow of polymer solutions were calculated. Results show a positive entropy change of viscous flow, indicating ordered structures. Chromatographic separation results prove that although disulphide bonds form the polymer backbone chain, both hydrophobic associations and hydrogen bonding still play a role in molecular structuring, even at very low protein concentrations. The calculated shape factor indicates spherical polymer molecules over the entire investigated temperature range.
... Few studies on humans have been carried out, although the results have been satisfactory. According to the statement that, unlike in normal cells, whey proteins could reduce glutathione concentrations in cancerous cells 28 , there is a suggestion that providing these proteins might reduce glutathione concentrations. Therefore, chemotherapy would be more effective against cancerous cells. ...
Milk protein fraction contains many biologically active compounds. Besides milk proteins, caseins, and milk whey proteins, it also contains low amounts of other proteins and peptides. These peptides, which are inactive within the sequence of the native protein, can be released by enzymatic hydrolysis, for example during gastrointestinal digestion, or during food processing. These bioactive peptides from milk proteins are potential modulators of several metabolic processes in the body. Moreover, milk whey proteins are a varied mixture of secreted proteins, such as ?-lactalbumin, ?-lactoglubulin, lactoferrin, lactoperoxidase, immunoglobulins, glycomacropeptides and a large amount of growth factors. These proteins have some biological effects, ranging from an anticarcinogenic effect to effects on the digestive function.
... Several studies evaluated whey protein in the prevention and/or treatment of cancers (reviewed in Refs. [12][13][14]). Dietary whey protein concentrate (WPC) inhibited colon tumor incidence, reduced tumor burden and extended life span [relative to casein (CAS) diet] in dimethylhydrazine (DMH)-treated A/J mice [12,15,16]. ...
We evaluated partially hydrolyzed whey protein (WPH) for inhibitory effects on the development of colon aberrant crypt foci (ACF) and intestinal tumors in azoxymethane (AOM)-treated rats. Pregnant Sprague-Dawley rats and their progeny were fed AIN-93G diets containing casein (CAS, control diet) or WPH as the sole protein source. Colons and small intestines from the male progeny were obtained at 6, 12, 20 and 23 weeks after AOM treatment. At 6 and 23 weeks, post-AOM, WPH-fed rats had fewer ACF than did CAS-fed rats. Intestinal tumors were most frequent at 23 weeks, post-AOM. At this time point, differences in colon tumor incidence with diet were not observed; however, WPH-fed rats had fewer tumors in the small intestine (7.6% vs. 26% incidence, P=.004). Partially hydrolized whey protein suppressed circulating C-peptide concentration (a stable indicator of steady-state insulin secretion) at all four time points relative to the corresponding CAS-fed animals. The relative mRNA abundance for the insulin-responsive, transcription factor gene, SREBP-1c, was reduced by WPH in the duodenum but not colon. Results indicate potential physiological linkages of dietary protein type with circulating C-peptide (and by inference insulin), local expression of SREBP-1c gene and propensity for small intestine tumorigenesis.
... WPC80 powder was weighed in a beaker and 100 mL of water was added to obtain the previous concentrations. The mixture was stirred with a magnetic stirrer and left in a refrigerator overnight to fully hydrate [33]. ...
The aims of the present study were to evaluate the antioxidant, radical scavenging, and metal-chelating activity of whey protein concentrate (WPC) and Spirulina alone or in combination in vitro and to evaluate their hepatoprotective effects against CCl(4) in vivo.
Five concentrations (20, 40, 60, 80, and 100 mg/100 mL) of WPC, Spirulina, and their combination were tested in vitro. In the in vivo study, eight groups of male rats comprised the control group and the groups treated with WPC, Spirulina alone, or in combination with or without CCl(4) were used.
The in vitro study showed that WPC and Spirulina showed antioxidant, radical scavenging, and metal-chelating activities in dose-dependent manner. The in vivo study showed that both agents succeeded in preventing liver damage induced by CCl(4). This prevention was more pronounced in rats receiving the combination of WPC and Spirulina.
Whey protein concentrate and Spirulina have free radical scavenging properties and antioxidant activity.
... Whey proteins not only play an important role in nutrition as an exceptionally rich and balanced source of amino acids (Regester et al., 1996), but in a number of instances also appear to have specific physiological actions, in vivo. Many of the bioactive whey proteins, notably α-lactalbumin, β-lactoglobulin, lactoferin, lactoperoxidase, immunoglobulins, glycomacropeptide and a variety of growth factors have been implicated in a number of biological effects like anticancer activity, immunostimulatory effects, influence on digestive function, organism longevity etc. (Bounous et al., 1989; Bounous et al., 1993; Kennedy et al., 1995; Perez et al., 1992). β-lactoglobulin is a globular protein with a monomer molecular weight of 18.4 kDa and account for about 50% of the protein in bovine whey isolate (Fox, 1989). ...
Nutritional value in addition to diverse physico-chemical and functional properties make whey proteins highly suitable for food purpose. One of important functional demand of whey proteins is their capability to induce and stabilize aerated food products. The aim of this work was to obtain whey protein isolate and β-lactoglobulin with improved foaming properties, what will in addition to its high nutritional value, make them more acceptable for use in whipped dairy products. For these purpose, whey protein isolate and β-lactoglobulin were treated with high hydrostatic pressure of 400, 500 and 600 MPa, for holding period of 10 minutes. Solubility changes were expressed as nitrogen solubility. Turbidity measurements of diluted protein solutions were used to obtain information about protein aggregation in addition to scanning electron microscopic pictures. Assessment of foaming properties has been based on the foam volume and foam stability. All analysis were carried out on whey protein isolate and β-lactoglobulin before and after high pressure treatment. The results obtained showed pressure-induced structural changes together with partial denaturation in both samples proportional to the intensity of applied pressure. The observed effects of pressure treatments on foaming properties clearly indicate that the extent of pressure-induced changes in the physicochemical properties of whey protein isolate and β-lactoglobulin positively affected foamability and foam stability, respectively.
... Whey proteins not only play an important role in nutrition as an exceptionally rich and balanced source of amino acids (Regester et al., 1996), but in a number of instances also appear to have specific physiological actions, in vivo. Many of the bioactive whey proteins, notably α-lactalbumin, β-lactoglobulin, lactoferin, lactoperoxidase, immunoglobulins, glycomacropeptide and a variety of growth factors have been implicated in a number of biological effects like anticancer activity, immunostimulatory effects, influence on digestive function, organism longevity etc. (Bounous et al., 1989;Bounous et al., 1993;Kennedy et al., 1995;Perez et al., 1992). ...
Nutritional value in addition to diverse physico-chemical and functional properties make whey proteins highly suitable for food purpose. One of important functional demand of whey proteins is their capability to induce and stabilize aerated food products.The aim of this work was to obtain whey protein isolate and β-lactoglobulin with improved foaming properties, what will in addition to its high nutritional value, make them more acceptable for use in whipped dairy products. For these purpose, whey protein isolate and β-lactoglobulin were treated with high hydrostatic pressure of 400, 500 and 600 MPa, for holding period of 10 minutes. Solubility changes were expressed as nitrogen solubility. Turbidity measurements of diluted protein solutions were used to obtain information about protein aggregation in addition to scanning electron microscopicpictures. Assessment of foaming properties has been based on the foam volume and foam stability. All analysis were carried out on whey protein isolate and β-lactoglobulin before and after high pressure treatment. The results obtained showed pressure-induced structural changes together with partial denaturation in both samples proportional to the intensity of applied pressure. The observed effects of pressure treatments on foaming properties clearly indicate that the extent of pressure-induced changes in the physicochemical properties of whey protein isolate and β-lactoglobulin positively affected foamability and foam stability, respectively.
Native and chemically modified whey proteins and their peptide derivatives are encountering the interest of nutraceutical and pharmaceutical industries, due to the numerous properties, ranging from antimicrobial to immunological and antitumorigenic, that result in the possibility to employ milk and its protein components in a wide range of treatment and prevention strategies. Importantly, whey proteins were found to exert antiviral actions against different enveloped and non-enveloped viruses. Recently, the scientific community is focusing on these proteins, especially lactoferrin, since in vitro studies have demonstrated that they exert an important antiviral activity also against SARS-CoV-2. Up-to date, several studies are investigating the efficacy of lactoferrin and other whey proteins in vivo. Aim of this review is to shed light on the most relevant findings concerning the antiviral properties of whey proteins and their potential applications in human health, focussing on their application in prevention and treatment of SARS-CoV-2 infection.
Diethylnitrosamine (DEN), a natural carcinogen, is widely used in basic research to develop hepatocellular carcinoma in the experimental animals. The present study evaluated/compared the modulatory activities of bovine whey protein concentrate (WPC, 300 and 600 mg kg⁻¹ body weight) and lactoferrin (30 and 60 mg kg⁻¹ body weight), given orally/daily and concurrently for 14 weeks with DEN, in a mouse model of early hepatocarcinogenesis. The results showed that both WPC and lactoferrin (especially at the higher doses) improved the body weight, lymphoid organs cellularity, blood cell counts, and serum proteins, as well as alleviated significantly (P < 0.001) the elevation in clotting time, serum aminotransferases activities, serum α-fetoprotein and tumour necrosis factor-α concentrations, and hepatic malondialdehyde and nitric oxide concentrations in the DEN-treated mice. In conclusion, WPC and lactoferrin were effective under the experimental conditions in decreasing the markers of liver injury/carcinoma, anaemia, and immunotoxicity in DEN-induced hepatocarcinogenic mice.
Changes in immunological pathways are involved in all stages of cancer. The immune system is composed of cells which are extremely sensitive to environmental changes. Antitumor immune response involves several pathways. The innate immune response is carried out by neutrophils, macrophages, eosinophils, mast cells, and natural killer (NK) cells, while the adaptive immune response is carried out by B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Overall, lymphocytes act through the recognition of specific antigens circulating in the blood or on the cell surface. Connections between the innate and adaptive immune systems are made either by direct cell contact or by release of cytokines. Under normal conditions, inflammatory response is self-limiting because the production of pro-inflammatory cytokines (TH1 cytokines) is followed by generation of anti-inflammatory (TH2) cytokines such as interleukin (IL)-1, IL-10, or IL-13. Under special circumstances and defects in the resolution process or if its underlying factors continue, then inflammation will turn into chronic inflammation linked to increased risk of cancer. Chronic inflammation can increase the risk of cancer through promoting tumor initiation, the rate and extent of cell division, neovascularization, and angiogenesis. In addition, chronic inflammation results in an overload of reactive oxygen species (ROS), which, in turn, may lead to the development and progression of chronic diseases like cancer. Upregulation of cyclooxygenase (COX)-2, which is not expressed in most cells, may contribute to cancer development and progression through the release of prostaglandins (PGs). Signal transduction pathways like nuclear factor-kappa B (NF-κB) promote inducible expression of several proteins, such as cytokines, chemokines, acute-phase response proteins, cell adhesion molecules, antimicrobial peptides, inducible nitric oxide synthase (iNOS), and COX-2. Antitumoral immune response is mainly produced by T-cells to destroy tumor cells. However, immune escape mechanisms are a hallmark of tumor progression. Recent efforts have been devoted to develop small-molecule drugs that stimulate antitumoral immunity. While immunotherapy alone seems not to be sufficient to eradicate tumors, results of adjuvant immunotherapy are becoming ever more convincing. Bioactive dietary components that antagonize immune escape mechanisms would have potential to prevent tumor development or enhance tumor regression.
Whey protein is one of the two major protein types of bovine milk, accounting for 20 percent of milk protein, while casein accounts for the remaining 80 percent. Human breast milk contains less methionine, phenylalanine, and lysine compared to bovine milk and more cysteine and tryptophan. Branched chain amino acids (BCAAs) are highly valued amino acids due to their high solubility in the digestive tract and therefore, faster rate of absorption compared to other proteins that require pre‐digestion to remain soluble in the gut. The protein digestibility corrected amino acid score (PDCAAS) is currently the most accepted and widely used method for measurement of the protein value in human nutrition as it takes into account true fecal digestibility of proteins. Clinical trials have shown that whey protein has beneficial effects in the treatment of cancer, human immunodeficiency virus (HIV), hepatitis B, cardiovascular disease, osteoporosis and serves well as an antimicrobial agent.
Milk is an important component of a balanced diet and contains numerous valuable constituents. Considerable acclaimed health benefits of milk are related to its proteins, not only for their nutritive value but also for their biological properties. Scientific evidence suggests that anticarcinogenic activities, antihypertensive properties, immune system modulation, and other metabolic features of milk, are affiliated with its proteins (intact proteins or its derivatives). In this article, the main health-related aspects of milk proteins, such as anticarcinogenic, immunomodulatory, antimicrobial, anticariogenic, antihypertensive, and hypocholesterolemic effects are reviewed. Collectively, the findings indicate the effectiveness of milk proteins on reduction of risk factors for cancer, cardiovascular diseases and overall improvement of health aspects.
Milk is an important component of a balanced diet and contains numerous valuable constituents. Considerable acclaimed health benefits of milk are related to its proteins, not only for their nutritive value but also for their biological properties. Scientific evidence suggests that anticarcinogenic activities, antihypertensive properties, immune system modulation, and other metabolic features of milk, are affiliated with its proteins (intact proteins or its derivatives). In this article, the main health-related aspects of milk proteins, such as anticarcinogenic, immunomodulatory, antimicrobial, anticariogenic, antihypertensive, and hypocholesterolemic effects are reviewed. Collectively, the findings indicate the effectiveness of milk proteins on reduction of risk factors for cancer, cardiovascular diseases and overall improvement of health aspects.
In the treatment of neoplastic patients many toxicities caused by chemo or radiotherapy are related to the formation of free radicals and to the oxidative stress and have been treated with antioxidants products. Besides some vitamins (A, E, C, carotenoids, etc) few specific antioxidants are used in the supportive treatment in medical oncology: amifostine, dexrazoxane, sodium 2-sulfanylethanesulfonate (MESNA), glutathione (GSH). The aminoacids included in the milk whey proteins (cysteine and glutamic acid) as precursors of GSH can increase the tissue concentration of GSH, stimulate the immunologic system, detoxify potential carcinogens and neutralize the Reactive Oxygen Species (ROS). The milk proteins are used in the supportive treatment of the neoplastic patient especially for the antioxidants properties of GSH. A whey protein concentrate supplemented with a high content of cysteine and glutamic acid, as precursors of GSH, given to breast cancer patients under chemo or radiotherapy, has led to an increase of BAP test (plasma anti-oxidant capacity) and of d-ROMs test (plasma oxidant capacity). Cysteine as precursor of milk proteins as well as of GSH may also be considered an important agent in the supportive treatment of neoplastic cachexia. We still need controlled clinical trials and reliable guide lines in order to use natural or pharmaceutical supplements in medical oncology.
Whey proteins, due to their documented biological properties that are exerted by their complex or due to the singular characteristics of their single fractions, have been and continue to be used with success in numerous pathological (e.g. metabolic, cardiovascular, degenerative and infective disorders etc.) and physiological conditions (e.g. sports activities). The purpose of this second section is in fact the presentation of a series of experimental and clinical studies carried out both on animals and in humans, in which the efficacy of whey protein formulations was evaluated in comparison to certain outcomes. Despite what has been done to date, further studies are needed in order to identify a more defined role - in terms of type, dose, administration modality, and pharmacokinetics etc. - of whey proteins in nutritional supplementation or, more precisely, as nutraceutics, especially in pathological situations, in association or in synergy with conventional medical or surgical treatments. Please note that in this section were not taken into account the clinical applications of whey proteins, respectively, in oncology, in asthenic syndrome of autoimmune diseases, in neurology and in cystic fibrosis at which is dedicated the Section III of this issue.
The purpose of this study is to investigate the possible antimutagenic effects of whey proteins against genotoxic effects induced by aflatoxins in the mammalian cell system. The micronuclei, chromosomal abnormalities in both somatic and germ cells as well as DNA titrations in male rats were assayed. Whey proteins was added to the diet containing aflatoxins (2.5 mg AFs kg-1) and fed to mature male rats for 9 weeks. The results indicated that aflatoxin significantly (p<0.001) increased chomosomal abnormalities in somatic and germ cells, DNA titration and micronuclei of bone marrow cells. Addition of whey proteins to the aflatoxins contaminated diet resulted a significant decrease in chromosomal aberrations in somatic cells (62.8%, p<0.001), in germ cells (57.9%, p<0.01) and in micronuclei polychromatic erythrocytes (62.8%, p<0.001). It could be concluded that whey protein reduced the mutagenesis and clastogenesis effects of AFs. Although the mechanism of antimutagenecity is unknown, it seems plausible that the whey protein acts as a blocking agent by chemical or physical interaction with the mutagens. Furthermore, this study revealed that the addition of whey proteins to aflatoxin contaminated diet diminished most of the genotoxic effects of the Aflatoxin.
Putative anti-cancer activity of whey proteins has been investigated in an animal model to evaluate their potential role in disease prevention, and to contribute to a basis for their inclusion as ingredients in functional foods. Animal feeding trials have compared the efficacy of dietary whey proteins in retarding chemically induced colon cancer in a rat model of the disease. Dairy proteins, in particular whey protein, were found to be efficacious in retardation of colon cancer in young rats compared with other dietary proteins (meat, soy). The influence of dietary whey protein on development of colon cancer in mature rats has also been examined. Results similar to those with younger animals have been demonstrated, a finding that suggests age does not significantly alter the outcome. Efficacy of whey protein fractions has also been assessed. Preliminary results suggest that diets supplemented with lactoferrin or with β-lactoglobulin enhance protection against the development of putative tumor precursors (aberrant crypts) in the hind gut wall. The mechanism behind the apparent anti-cancer activity of dietary whey proteins in these studies may be related to their sulfur amino acid content, for which there is a high requirement in the rat, and hypothesised role in protecting DNA in methylated form. In a parallel study, a number of potential functional foods containing whey protein (flavored milk, pasta, ice cream, dessert pudding, muesli, and savory dip) have been developed in preparation for human clinical trials. The foods containing whey protein were generally highly acceptable in taste trials. These products are expected to be suitable as delivery vehicles for dietary whey protein in studies aimed at substantiating the human health benefits of this protein source.
The effect of dietary bovine whey protein concentrate (WPC) on gut mucosal antibody responses to orally-administered antigens was investigated in BALB/c mice. Test mice were fed a diet containing 20% (w/w) total protein of a novel WPC (ALACEN 472) for 12 weeks. Test and control (chow-fed) mice were immunized orally with cholera toxin (CT) and ovalbumin (OVA) at different times throughout the dietary regime, and gut mucosal antibody responses were assessed at the end of the experiment. Both groups of mice produced mucosal antibodies against CT and OVA, although responses were significantly higher among WPC-fed mice, regardless of the time-point at which immunizations were administered throughout the study. WPC had no significant effect on blood lymphocyte phenotype expression or splenic T or B cell mitogenesis, suggesting that the immunomodulatory action was not due to systemic lymphocyte activation. This study confirms previous reports that dietary WPC can potentiate humoral immunity in mice, and provides the first evidence that WPC can enhance mucosal antibody responses to orally-administered antigens.
Fully protected natural and unnatural N-acetylcysteine, dipeptide Cys–Gly, glutathione, and homoglutathione derivatives were synthesized by the Ugi four-component reaction using various benzylthio aldehydes and ketones as carbonyl building blocks. The scope and limitations of the method were investigated. Formation of imidazoline by-products in the Ugi reaction was discussed. 2,2,2-Trifluoroethanol was shown to be a superior reaction media than methanol in some reactions. Also, the 4-methyl-2,6,7-trioxabicyclo[2.2.2]octyl derivative (OBO-ester) of isocyanoacetic acid was shown to be superior to use than ethyl isocyanoacetate as a peptide synthesis precursor in cases when higher reactivity of an isocyanide is required.
Some whey protein concentrates (WPCs) can act as immunostimulatory and anticancer dietary components when delivered as a major protein source to animals and human beings. In this study, we have investigated the effects of a known immunostimulatory WPC (IMUCARE) when delivered to mice in a modified milk powder (MMP), nutritionally balanced for young children (aged 1-3 years). Groups of BALB/c mice were fed with MMP-based diets with or without IMUCARE WPC supplemented at 10.5 g/100 g of diet for periods of 4 weeks. Ex vivo immunologic assays indicated that splenic lymphoproliferative responses, as well as blood and peritoneal leukocyte phagocytic activity, were elevated in mice fed MMP supplemented with IMUCARE WPC, in comparison either to mice fed with MMP alone or to control mice that did not receive milk proteins. In contrast, both IMUCARE WPC–supplemented MMP and MMP alone were shown to stimulate enhanced humoral immunity, with significantly elevated serum and intestinal tract antibody responses to orally administered antigens being recorded in these mice compared with animals fed with nonmilk protein. These results confirm that IMUCARE WPC retains immunoenhancing efficacy when delivered in a nutritionally balanced milk product and additionally identifies nutritionally balanced MMP as a potential immunostimulatory dietary food product.
The variety, availability, sales and use of dietary supplements (DS) remain poorly understood by the mainstream medical community, but the potential for use and abuse of DS cannot be taken lightly by undersea medical officers (UMO). Despite the indisputable pharmacologic effects many of these over-the-counter (OTC) products exert, the use of DS is generally overlooked by clinicians. DS information is not covered in much depth, if at all, in medical education, and physicians are not trained in this area. As such, many may feel uncomfortable with their lack of familiarity regarding the ever-increasing supplement pharmacopoeia. Peer-reviewed scientific research and evidenced-based information are often limited. Moreover, because the general public and active duty community perceive these natural substances as harmless, the products often do not come to the attention of physicians at all. Less than half of all users of DS consult a physician or a practitioner about alternative products (Aeromed) Whereas the literature on DS use is limited, research specific to use of DS under extreme environments is even sparser: virtually no studies have been conducted in hyperbaric/ undersea environments. Due to the physiologic and psychological challenges of these extreme environments, military and civilian restrictions on the use of most medications in aviation and diving are quite specific and very strict. Because DS are not regulated by the Food and Drug Administration (FDA) as drugs, specifics regarding their use have not been addressed in diving regulations. To date, US Navy divers are not required to disclose their use of supplements, nor has it been common practice for UMOs or civilian equivalents to inquire about such use. However, considerable risks are expected with the use of many DS that are currently marketed. The safety and efficacy of most DS are not known for environments encountered routinely by the military diver.
An investigation carried out in 11 dairies in Serbia has shows that 78.75 % of whey, a by-product of cheese industry, is emitted into river systems, thus contributing to the organic pollution of the environment. This pollution can be avoided by processing of whey into food and pharmaceuticals. It is shown that low-temperature regime of whey concentration and fractionation, based on vacuum concentration and diafiltration, preserves whey proteins undenaturated, as proved by differential scanning calorimetry method. Functional native whey proteins based food products, with potentially high immunomodulatory activity, are obtained.
Lactoferrin (Lf) is a glycoprotein found in milk and other body fluids. Supplements of Lf are isolated from cow’s milk. Lf
possesses immune-modulating, antioxidant and anti-inflammatory properties which together support its anticancer activity.
Lf also possesses strong antimicrobial activity against a diverse range of bacteria, fungi, parasites and viruses.
Key WordsAntibacterial-anticancer-antifungal-antiparasitic-antiviral-immunomodulation-lactoferrin
The effect of two whey protein concentrates (WPCs) and three whey protein isolates (WPIs) on the growth and intracellular glutathione concentration of Jurkat T cells was determined. Standard RPMI 1640 media containing foetal calf serum with no WPC or WPI supplementation was used as the control, while supplementation with N-acetyl cysteine—a known glutathione promoter—was included as a positive control. Both WPCs lowered the cell count-adjusted glutathione concentration following a 24 h incubation period and one significantly (p<0.05) increased cell proliferation. Only one of the three WPIs significantly (p<0.05) inhibited cell proliferation although its composition with respect to β-lactoglobulin, glycomacropeptide, α-lactalbumin, IgG, proteose peptone and BSA content was almost identical to another WPI, as determined by HPLC. Based on co-migration with standards under two different modes of chromatography, lactoferrin was detected in the WPI showing the inhibitory effect at a level of 0.4 mg mL−1, but not in any of the other concentrated whey protein products. None of the whey protein products tested increased cell-adjusted intracellular glutathione concentration.
The synthesis and characterization of ruthenium(II) arene complexes of the general formula [(eta(6)-arene)Ru(XY)Z](+), where arene = p-cymene (p-cym), hexamethylbenzene (hmb), or biphenyl (bip), XY = o-phenylenediamine (o-pda), o-benzoquinonediimine (o-bqdi), or 4,5-dimethyl-o-phenylenediamine (dmpda), and Z = Cl, Br, or I, are reported (complexes 1-6). In addition, the X-ray crystal structures of [(eta(6)-p-cym)Ru(o-pda)Cl]PF(6) (1) and [(eta(6)-hmb)Ru(o-bqdi)Cl]PF(6) (3PF(6)) are described. The Ru-N distances in 3PF(6) are significantly shorter [2.033(4) and 2.025(4) A] compared to those in 1 [2.141(2) and 2.156(2) A]. All of the imine complexes (3-5) exhibit a characteristic broad (1)H NMR NH resonance at ca. delta 14-15. Complex 1 undergoes concomitant ligand-based oxidation and hydrolysis (38% after 24 h) in water. The oxidation also occurs in methanol. The iodido complex [(eta(6)-p-cym)Ru(o-bqdi)I]I (4) did not undergo hydrolysis, whereas the chlorido complex 3 showed relatively fast hydrolysis (t(1/2) = 7.5 min). Density functional theory calculations showed that the total bonding energy of 9-EtG in [(eta(6)-p-cym)Ru(o-pda)(9-EtG-N7)](2+) (1EtG) is 23.8 kJ/mol lower than that in [(eta(6)-p-cym)Ru(o-bqdi)(9-EtG-N7)](2+) (3EtG). The greater bonding energy is related to the contribution from strong hydrogen bonding between the NH proton of the chelating ligand and O6 of 9-EtG (1.69 A). A loss of cytotoxic activity was observed upon oxidation of the amine ligand to an imine (e.g., IC(50) = 11 microM for 1 and IC(50) > 100 microM for 3, against A2780 ovarian cancer cells). The relationship between the cytotoxic activity and the solution and solid state structures of the imine and amine complexes is discussed.
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