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Table of Contents > Interactions & Depletions > Whey protein Print

Whey protein



Interactions

Whey protein/Drug Interactions:
  • GeneralGeneral: One study reported the binding of nine drugs to human milk whey proteins (455). No drug bound to alpha-lactalbumin. Four drugs, diclofenac, phenytoin, prednisolone, and warfarin, bound to albumin. Five drugs, atenolol, diclofenac, prednisolone, propranolol, and warfarin, bound to lactoferrin. The clinical relevance of this for whey proteins is not clear.
  • AlbendazoleAlbendazole: In in vitro research, a whey/concentrate diet vs. pasture grazing altered the pharmacokinetics of albendazole (ABZ) metabolites (456). Noted changes were a decrease in peak concentration for ABZ sulfoxide (ABZSO) and ABZ sulfone (ABZSO2), and shorter elimination half-lives and mean residence times for these metabolites.
  • AlcoholAlcohol: In an animal study, whey protein concentrate protected against ethanol-induced gastric mucosal ulcerative lesions (457).
  • AlendronateAlendronate: According to secondary sources, whey protein can decrease alendronate absorption and potentially decrease its effectiveness.
  • AnalgesicsAnalgesics: According to secondary sources, whey protein has pain-killing effects.
  • Antiallergy agentsAntiallergy agents: According to various meta-analyses, use of hydrolyzed whey protein-based formulas may decrease the risk of cow's milk allergy in at-risk infants vs. whole cow's milk-based formulas (458; 459; 460). In an animal study, feeding a growth factor-enriched fraction from milk whey to suckling pups reduced immune activation to the food antigen ovalbumin (461). In animal research, feeding whey protein concentrate resulted in elevated levels of antigen-specific intestinal tract and serum antibodies against all tested antigens (462).
  • AntibioticsAntibiotics: In in vitro research, bovine and camel whey protein hydrolysates had antimicrobial effects (463). The antibacterial effects of whey proteins have been shown in various in vitro and animal studies (464; 465). According to secondary sources, whey might decrease how much antibiotic the body absorbs. According to secondary sources, the calcium in whey protein may attach to tetracyclines in the stomach, decreasing absorption.
  • Antidiabetic agentsAntidiabetic agents: In human studies, whey protein decreased postprandial glucose in patients with type 2 diabetes (93; 94; 95), and insulin responses were higher (96; 97; 95). In human studies, the high amino acids in whey protein and whey protein hydrolysates induced increased insulin and glucagon responses (466; 467; 468; 469). In animal research, a malleable protein matrix (MPM), composed of whey fermented by a proprietary Lactobacillus kefiranofaciens strain, was found to reestablish the fasting glucose insulin ratio index to normal levels, and the plasma glucose level area under the curve was lowered (470). In animal research, whey protein improved glycemic homeostasis over casein (101). In animal research, whey protein increased the insulin response to glucose, associated with enhanced oral glucose tolerance, increased the slope of the glucose-insulin curve vs. glucose alone, increased glucagon-like peptide-1 (GLP-1) secretion, and increased levels of both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) (471).
  • AntihypertensivesAntihypertensives: In human research, hydrolyzed and nonhydrolyzed whey protein reduced blood pressure (108; 109). In animal research, whey protein reduced blood pressure and increased life span in a hypertensive model (472). In animal study, a malleable protein matrix (MPM), composed of whey fermented by a proprietary Lactobacillus kefiranofaciens strain, was found to reduce systolic blood pressure in spontaneously hypertensive rats (470). Antihypertensive activity was also found for peptides produced from digestion of whey protein in animal research (473; 474), as was inhibitory activity against angiotensin I-converting enzyme in animal and in vitro research (474; 475; 476; 477; 478; 479; 480; 481; 482; 483; 484; 485; 486).
  • Anti-inflammatory agentsAnti-inflammatory agents: In animal research, whey supplementation decreased subepidermal inflammation following burn injury (487). In animal research, a novel ingredient (malleable protein matrix) containing whey protein was found to reduce inflammation by reducing the number of recruited cells and cytokine and chemokine production (tumor necrosis factor-alpha, IL-1beta, and IL-6) (488). This product has shown anti-inflammatory effects in other animal models (489).
  • Antilipemic agentsAntilipemic agents: In human studies, whey protein reduced postprandial triglyceride levels (98; 93), as well as fasting triglyceride and total and LDL cholesterol levels (99; 100). The plasma and liver lipid-lowering effects of whey protein (on total and VLDL cholesterol and triglycerides) have been shown in animal studies (101; 102; 103; 104; 105).
  • Antinematodal agentsAntinematodal agents: In in vitro research, bovine whey proteins (or components associated with the proteins) reduced the motility of both sheathed and exsheathed nematode L3 Ostertagia circumcincta (490).
  • AntineoplasticsAntineoplastics: In a human study, whey protein resulted in tumor stabilization or regression in four of seven patients (92). In an animal study, a whey protein-containing product reduced methotrexate-induced mucositis (491; 492; 493; 494). In an animal study, dietary whey protein concentrate had antitumor effects (495; 496; 497; 498; 499; 500; 501; 502; 503; 194; 504) and reduced the number of aberrant crypt foci (clusters of abnormal glands in the gastrointestinal system) (505; 502). According to in vitro research, whey protein may increase the cytotoxic effects of anti-cancer agents to cancer cells (506).
  • Antithrombotic agentsAntithrombotic agents: In in vitro research, unheated and heat-denatured alpha-lactalbumin and denatured beta-lactoglobulin stimulated plasminogen activator activity (106).
  • Antiulcer agentsAntiulcer agents: In animal research, whey protein protected against gastric mucosal injury due to ulcers (507; 508). In animal research, whey protein concentrate protected against ethanol-induced gastric mucosal ulcerative lesions (457) and indomethacin-induced injury (509). A whey-derived growth factor extract also protected against mucosal damage in animal research (510). In in vitro research, gelation of whey proteins protected cells against acidic conditions (511).
  • AntiviralsAntivirals: In animal research, a bovine whey protein concentrate had antiviral effects against diarrhea-causing rotaviruses (512; 513). In separate research, a bovine macromolecular whey protein fraction had antiviral effects against rotavirus in vitro (514; 515).
  • Bone agentsBone agents: In human research, milk basic protein, a whey protein, increased bone density (142; 140; 141). In human research, milk basic protein decreased urinary cross-linked N-telopeptides of type 1 collagen/creatinine and deoxypyridinoline/creatinine (142). In men, milk basic protein increased serum osteocalcin and decreased urinary cross-linked N-telopeptides of type-I collagen (516). In animal research, the whey protein milk basic protein suppressed osteoclast-mediated bone resorption by directly suppressing the number of pits on the osteoclasts (517). In animal research, whey protein increased bone proteins, such as collagen, enhanced bone-breaking energy (518), increased bone mineral density, potentially due to increased calcium absorption (519; 520), and increased alkaline phosphatase activity and insulin-like growth factor (521).
  • Cardiovascular agentsCardiovascular agents: In animal research, whey protein reduced blood pressure and increased life span in a hypertensive model (472). In animal research, whey protein decreased concentrations of cytotoxic aldehydes and increased cardiac levels of glutathione peroxidase and glutathione in mice treated with chronic iron overload (522).
  • Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: In animal research, the level of CYP1A2 mRNA was reduced when animals were fed whey vs. casein (107). This was accompanied by a reduction in constitutive levels of the aryl hydrocarbon receptor (Ah receptor) (transcription factor) in liver cytosol.
  • Dental agentsDental agents: In human research, a bovine immune whey had antibacterial effects and thus beneficial effects on dental plaque (523). In animal research, casein-free milk fractions, including whey protein, reduced the cariogenicity of sucrose-containing foods (524). In rats, high-dose milk basic protein aided in the recovery of alveolar bone loss in periodontitis (525).
  • Dermatological agentsDermatological agents: In human research, XP-828L (a protein extract of bovine whey) decreased psoriasis severity scores (178). In animal research, whey protein hydrolysates decreased development of atopic dermatitis-like skin lesions (526). Serum soluble E-selectin levels were significantly lower. In vitro, beta-lactoglobulin exhibited a depigmenting effect and suppressed the activity of tyrosinase; retinol binding activity may have played a role in this action (527).
  • Fertility agentsFertility agents: Whey semen extenders were examined in in vitro research but were without effect in cryopreservation (528). Specific whey proteins were examined for protective effects of equine sperm in storage; some (e.g., alpha-lactalbumin) were detrimental and others (beta-lactoglobulin) were protective (529). In in vitro research, soluble whey protein fractions enhanced the lipase activity of BUSgp60 lipase, known to promote degradation of sperm (530).
  • GalactagoguesGalactagogues: In in vitro research on tissue cultures of the bovine mammary gland, a whey fraction of bovine milk altered milk constituents, synthesis, and secretion (531). In animal research, a 6-30kDa fraction of phase 3 whey was found to inhibit milk constituent synthesis and secretion in vitro (532). The expression of this gene may be altered by changes in the suckling pattern of the young (533).
  • Gastrointestinal agentsGastrointestinal agents: In human research, ingestion of a cell-free concentrated milk whey was found to alter fecal bacteria (534). In animal research, cheese whey protein protected against induced gut inflammation; stimulation of mucin and modification of microflora composition were implicated as mechanisms of action (535).
  • Hepatoprotective agentsHepatoprotective agents: In human research, whey protein isolate improved the liver attenuation index and hepatic macrovesicular steatosis, with reductions in levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (116). In animal research, whey protein had hepatoprotective effects in animals given injections of D-galactosamine (536). The whey protein suppressed an increase in plasma alanine and aspartate aminotransferase activity, lactate dehydrogenase, bilirubin, and hyaluronic acid, as well as histopathological signs of portal fibrosis, bile duct proliferation, and perivenular sclerosis.
  • Hormonal agentsHormonal agents: In human research, a whey blend decreased levels of estradiol (537). In human research, whey protein decreased serum testosterone (538) and blunted exercise-induced increases in testosterone (539).
  • Immunomodulating agentsImmunomodulating agents: In human research, serum response to a vaccine was higher with whey protein vs. soy protein (110). In human research, feeding a whey concentrate made from the milk of cows immunized with Clostridium difficile and its toxins reduced the recurrence of associated diarrhea by about 50% (540). In animal research, the effect of whey protein following immunization with two different adjuvants, complete Freund's adjuvant (CFA) and alum, was investigated (541). The whey protein mixture was found to induce divergent responses following immunization with the two adjuvants, suggesting that the choice of adjuvant is important. In animal research, whey protein increased biliary levels of s-IgA (111). In animal research, subcutaneous injection in the flank fold of whey protein preparations of various purities resulted in a decline of efferent lymphocyte output, and no changes were observed in interferon-gamma levels in lymph plasma (542). Two bovine milk whey fractions (lactoperoxidase and lactoferrin) resulted in an initial transient decline in efferent lymphocyte output and lymph flow rate, with a significant difference between the two fractions in interferon-gamma levels. No significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Both fractions showed an inhibitory effect on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, but not in animal research. These effects may be inhibited when these whey proteins are provided in whole whey protein (543).
  • IndomethacinIndomethacin: In an animal study, pretreatment with indomethacin reduced the gastroprotective effects of alpha-lactalbumin (507).
  • Iron saltsIron salts: In in vitro research, the percentage of iron absorption was reduced by substitution of whey protein for egg white (544). In an animal study, whey protein decreased concentrations of cytotoxic aldehydes and increased cardiac levels of glutathione peroxidase and glutathione in mice treated with chronic iron overload (522). In vitro, hydrolysis of whey proteins appeared promising for iron absorption (545).
  • LevodopaLevodopa: According to secondary sources, whey protein might decrease levodopa absorption and therefore decrease its effectiveness.
  • Mood-altering agentsMood-altering agents: In a human study, alpha-lactalbumin increased plasma tryptophan (TRP) and the ratio of TRP to neutral amino acids, with no effect on salivary cortisol secretion or tasks of emotional processing (19).
  • Performance enhancement agentsPerformance enhancement agents: In human research, whey protein increased muscle mass and/or strength (156; 159; 546). In animal research, exercise training resulted in an increase in the skeletal muscle glycogen content, and this further increased when animals were fed whey protein; glycogen content in the liver also increased (547). Increased skeletal muscle synthesis was observed following exercise in animals that were fed whey protein (548). In human research, ingestion of whey protein increased myofibrillar protein synthesis (549). The ability of whey protein to build muscle and aid in exercise recovery has been discussed in secondary sources.
  • Renal agentsRenal agents: In human research, urinary glycolate excretion was 5.3-fold higher on a gelatin diet vs. a whey diet, and urinary oxalate excretion was 43% higher; hyperoxaluria was associated with calcium stone formation (550).
  • Respiratory agentsRespiratory agents: In human research, whey protein increased FEV1 in patients with severe chronic obstructive pulmonary disease (COPD) (147).
  • Satiety agentsSatiety agents: In some human studies, whey protein suppressed appetite (127; 91; 133; 134; 126). In one human study, a test meal higher in whey (48g) increased subjective satiety, as well as plasma amino acids, CKK, GIP, and GLP-1 (551). In another human study, a liquid preload containing 55g of whey decreased later energy intake vs. a glucose preload, potentially due to increased CCK; whey also increased branched-chain amino acid levels (552).
  • Weight loss agentsWeight loss agents: In a human study, whey protein resulted in weight loss (181). The weight loss effects of whey protein may be due to increased satiety and decreased energy intake at the next meal, as shown in human studies (551; 552). Weight loss or decreased weight gain have been shown in animal studies, compared with other protein sources or lower-protein diets (553; 554; 555).
  • Wound-healing agentsWound-healing agents: In animal research, post-Cesarean treatment with intragastrically administered whey protein promoted wound healing (556).

Whey protein/Herb/Supplement Interactions:
  • Amino acidsAmino acids: The enhancement of the biological value of whey protein by covalent addition into peptide linkage of limiting essential amino acids has been discussed (557). Further details are not available. In human research, a mixture of maltodextrin plus hydrolyzed whey protein enriched with glutamine dipeptide prevented the loss of cell membrane integrity induced by exercise (558). In animal research, addition of arginine to whey protein decreased glutamine body stores, and the addition of glutamine had no effect on glutamine levels (559). However, addition of glutamine increased muscle synthesis in animal research (560).
  • AnalgesicsAnalgesics: According to secondary sources, whey protein has pain killing effects.
  • Antiallergy agentsAntiallergy agents: According to various meta-analyses, use of hydrolyzed whey protein-based formulas may decrease risk of cow's milk allergy in at-risk infants vs. whole cow's milk-based formulas (458; 459; 460). In animal research, feeding a growth factor-enriched fraction from milk whey to suckling pups reduced immune activation to the food antigen ovalbumin (461). In animal research, whey protein concentrate resulted in elevated levels of antigen-specific intestinal tract and serum antibodies against all tested antigens (462).
  • AntibacterialsAntibacterials: In in vitro research, bovine and camel whey protein hydrolysates have antimicrobial effects (463). The antibacterial effects of whey proteins have been shown in various in vitro and animal studies (464; 465).
  • Anti-inflammatory herbsAnti-inflammatory herbs: In animal research, whey supplementation decreased subepidermal inflammation following burn injury (487). In animal research, a novel ingredient (malleable protein matrix), containing whey protein, was found to reduce inflammation by reducing the number of recruited cells and cytokine and chemokine production (tumor necrosis factor-alpha, IL-1beta, and IL-6) (488). This product has shown anti-inflammatory effects in other animal models (489).
  • AntilipemicsAntilipemics: In human research, whey protein reduced postprandial triglyceride levels (98; 93), as well as fasting triglyceride and total and LDL cholesterol levels (99; 100). The plasma and liver lipid-lowering effects of whey protein (on total and VLDL cholesterol and triglycerides) have been shown in animal research (101; 102; 103; 104; 105).
  • Antinematodal agentsAntinematodal agents: In in vitro research, bovine whey proteins (or components associated with the proteins) reduced the motility of both sheathed and exsheathed nematode L3 Ostertagia circumcincta (490).
  • AntineoplasticsAntineoplastics: In human research, whey protein resulted in tumor stabilization or regression in four of seven patients (92). In animal research, dietary whey protein concentrate had antitumor effects (495; 496; 497; 498; 499; 500; 501; 502; 503; 194) and reduced the number of aberrant crypt foci (clusters of abnormal glands in the gastrointestinal system) (505; 502).
  • AntioxidantsAntioxidants: In human research, whey protein resulted in increases in glutathione levels in patients with HIV (117; 189; 170). In cystic fibrosis patients, whey protein decreased peripheral lymphocyte GSH levels (150). In in vitro research, whey protein concentrate showed antioxidant, radical-scavenging, and metal-chelating activities (561). In animal research, whey protein was able to prevent oxidative stress at rest or during exercise (562). The antioxidant effects of whey protein concentrate and its peptides have been shown in other in vitro studies (563; 564; 565; 566; 567) and animal studies (487). Whey protein isolate solutions incorporating antioxidants (ascorbyl palmitate and alpha-tocopherol) have been used to make films (568).
  • Antithrombotic agentsAntithrombotic agents: In in vitro research, unheated and heat-denatured alpha-lactalbumin and denatured beta-lactoglobulin stimulated plasminogen activator activity (106).
  • Antiulcer herbs and supplementsAntiulcer herbs and supplements: In animal research, whey protein protected against gastric mucosal injury due to ulcers (507; 508). In animal research, whey protein concentrate protected against ethanol-induced gastric mucosal ulcerative lesions (457) and indomethacin-induced injury (509). A whey-derived growth factor extract also protected against mucosal damage in animal research (510). In in vitro research, gelation of whey proteins protected cells against acidic conditions (511).
  • AntiviralsAntivirals: In animal research, a bovine whey protein concentrate had antiviral effects against diarrhea-causing rotaviruses (512; 513). In separate research, a bovine macromolecular whey protein fraction had antiviral effects against rotavirus in vitro (514; 515).
  • Bone agentsBone agents: In human research, milk basic protein, a whey protein, increased bone density (142; 140; 141). In human research, milk basic protein decreased urinary cross-linked N-telopeptides of type 1 collagen/creatinine and deoxypyridinoline/creatinine (142). In men, milk basic protein increased serum osteocalcin and decreased urinary cross-linked N-telopeptides of type-I collagen (516). In animal research, the whey protein milk basic protein suppressed osteoclast-mediated bone resorption by directly suppressing the number of pits on the osteoclasts (517). In animal research, whey protein increased bone proteins, such as collagen, enhanced bone-breaking energy (518), increased bone mineral density, potentially due to increased calcium absorption (519; 520), and increased alkaline phosphatase activity and insulin-like growth factor (521).
  • CalciumCalcium: The bioavailability of calcium was increased when provided as a micellar calcium phosphate-phosphopeptide (MCP-PP) complex vs. a commercial whey calcium (569). In animal research, a high-calcium/whey diet increased fat excretion over a low-calcium/casein diet (570). In vitro, a cheese whey digest increased calcium uptake into cells (571).
  • Cardiovascular herbs and supplementsCardiovascular herbs and supplements: In animal research, whey protein reduced blood pressure and increased life span in a hypertensive model (472). In animal research, whey protein decreased concentrations of cytotoxic aldehydes and increased cardiac levels of glutathione peroxidase and glutathione in mice treated with chronic iron overload (522).
  • ColostrumColostrum: The addition of whey protein concentrate to colostrum (first milk) had no effect on plasma IgG (572).
  • CopperCopper: According to a review, when bovine milk was stored for six hours in indigenous brass vessels, copper levels increased in the milk, and the copper was associated with the whey proteins (7%) vs. casein (67%) (573).
  • CreatineCreatine: A case of acute cholestatic liver injury was associated with the combination of whey protein and creatine supplements (191).
  • Cytochrome P450-metabolized herbs and supplementsCytochrome P450-metabolized herbs and supplements: In animal research, the level of CYP1A2 mRNA was reduced when animals were fed whey vs. casein (107). This was accompanied by a reduction in constitutive levels of the Ah receptor in liver cytosol.
  • Dental agentsDental agents: In human research, a bovine immune whey had antibacterial effects and thus beneficial effects on dental plaque (523). In animal research, casein-free milk fractions, including whey protein, reduced the cariogenicity of sucrose-containing foods (524). In rats, high-dose milk basic protein aided in the recovery of alveolar bone loss in periodontitis (525).
  • Dermatological herbs and supplementsDermatological herbs and supplements: In human research, XP-828L (a protein extract of bovine whey) decreased psoriasis severity scores (178). In animal research, whey protein hydrolysates decreased development of atopic dermatitis-like skin lesions (526). Serum soluble E-selectin levels were significantly lower. In vitro, beta-lactoglobulin exhibited a depigmenting effect and suppressed the activity of tyrosinase; retinol binding activity may have played a role in this action (527).
  • Fertility herbs and supplementsFertility herbs and supplements: Whey semen extenders were examined in in vitro research but were without effect in cell preservation (528). Specific whey proteins were examined for protective effects of equine sperm in storage; some (e.g., alpha-lactalbumin) were detrimental and others (beta-lactoglobulin) were protective (529). In in vitro research, soluble whey protein fractions enhanced the lipase activity of BUSgp60 lipase, known to promote degradation of sperm (530).
  • Folic acidFolic acid: In in vitro research, beta-lactoglobulin bound to folic acid, meaning it could potentially be used as a folic acid carrier in foods (574).
  • FructooligosaccharidesFructooligosaccharides: In animal research, a mixture of whey peptide, omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids), and fructooligosaccharides protected against induced inflammation (575).
  • GalactagoguesGalactagogues: In in vitro research in tissue cultures of the bovine mammary gland, a whey fraction of bovine milk altered milk constituents, synthesis, and secretion (531). In animal research, a 6-30kDa fraction of phase 3 whey was found to inhibit milk constituent synthesis and secretion in vitro (532). The expression of this gene may be altered by changes in the suckling pattern of the young (533).
  • Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: In human research, ingestion of a cell-free concentrated milk whey was found to alter fecal bacteria; it was determined that live cells were not required (534). In animal research, cheese whey protein protected against induced gut inflammation; stimulation of mucin and modification of microflora composition were implicated as mechanisms of action (535).
  • Hepatoprotective herbs and supplementsHepatoprotective herbs and supplements: In human research, whey protein isolate improved the liver attenuation index and hepatic macrovesicular steatosis, with reductions in levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (116). In animal research, whey protein had hepatoprotective effects in animals given injections of D-galactosamine (536). The whey protein suppressed an increase in plasma alanine and aspartate aminotransferase activity, lactate dehydrogenase, bilirubin, and hyaluronic acid, as well as histopathological signs of portal fibrosis, bile duct proliferation, and perivenular sclerosis.
  • Hormonal herbs and supplementsHormonal herbs and supplements: In human research, a whey blend decreased levels of estradiol (537). In human research, whey protein decreased serum testosterone (538) and blunted exercise-induced increases in testosterone (539).
  • HypoglycemicsHypoglycemics: In human research, whey protein decreased postprandial glucose in patients with type 2 diabetes (93; 94; 95), and insulin responses were higher (96; 97; 95). In human research, the high amino acids in whey protein and whey protein hydrolysates induced increased insulin and glucagon responses (466; 467; 468; 469). In animal research, a malleable protein matrix (MPM), composed of whey fermented by a proprietary Lactobacillus kefiranofaciens strain was found to reestablish the fasting glucose insulin ratio index to normal levels, and the plasma glucose level area under the curve was lowered (470). In animal research, whey protein improved glycemic homeostasis over casein (101). In animal research, whey protein increased the insulin response to glucose, associated with enhanced oral glucose tolerance, increased the slope of the glucose-insulin curve vs. glucose alone, increased glucagon-like peptide-1 (GLP-1) secretion, and increased levels of both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) (471).
  • HypotensivesHypotensives: In human research, hydrolyzed and nonhydrolyzed whey protein reduced blood pressure (108; 109). In animal research, whey protein reduced blood pressure and increased life span in a hypertensive model (472). In animal research, a malleable protein matrix (MPM), composed of whey fermented by a proprietary Lactobacillus kefiranofaciens strain, was found to reduce systolic blood pressure in spontaneously hypertensive rats (470). Antihypertensive activity was also found for peptides produced from digestion of whey protein in animal research (473; 474), as was inhibitory activity against angiotensin I-converting enzyme in animal and in vitro research (474; 475; 476; 477; 478; 479; 480; 481; 482; 483).
  • Immunomodulating agentsImmunomodulating agents: In human research, serum response to a vaccine was higher with whey protein vs. soy protein (110). In human research, a whey concentrate made from the milk of cows immunized with Clostridium difficile and its toxins reduced the recurrence of associated diarrhea by about 50% (540). In animal research, the effect of whey protein following immunization with two different adjuvants, complete Freund's adjuvant (CFA) and alum, was investigated (541). The whey protein mixture was found to induce divergent responses following immunization with the two adjuvants, suggesting that the choice of adjuvant is important. In animal research, whey protein increased biliary levels of s-IgA (111). In animal research, subcutaneous injection in the flank fold of whey protein preparations of various purities resulted in a decline of efferent lymphocyte output, and no changes were observed in interferon-gamma levels in lymph plasma (542). Two bovine milk whey fractions (lactoperoxidase and lactoferrin) resulted in an initial transient decline in efferent lymphocyte output and lymph flow rate, with a significant difference between the two fractions in interferon-gamma levels. No significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Both fractions showed an inhibitory effect on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, but not in animal research. These effects may be inhibited when these whey proteins are provided in whole whey protein (543).
  • IronIron: In in vitro research, the percentage of iron absorption was reduced by substitution of whey protein for egg white (544). In animal research, whey protein decreased concentrations of cytotoxic aldehydes and increased cardiac levels of glutathione peroxidase and glutathione in mice treated with chronic iron overload (522). In vitro, hydrolysis of whey proteins appeared promising for iron absorption (545). The use of ferripolyphosphate-whey protein and iron-whey protein complexes for iron fortification of dairy products was shown in animal research (576).
  • LeucineLeucine: In human research, whey protein plus leucine had no greater effect on the anabolic response of muscle than whey protein alone (577).
  • LimoneneLimonene: In in vitro research, whey protein isolate resulted in less degradation of limonene and formation of limonene oxidation products, limonene oxide, and carvone.
  • MaltodextrinMaltodextrin: In human research, a mixture of maltodextrin plus hydrolyzed whey protein enriched with glutamine dipeptide prevented the loss of cell membrane integrity induced by exercise (558).
  • Minerals (general)Minerals (general): In a review, the effects of various components in breast milk, cow's milk, and infant formula (e.g., whey proteins) on facilitation or inhibition of the absorption of minerals and trace elements in infants was discussed (578). Further details are lacking at this time. Zorin discussed the potential for new food sources of essential trace elements (zinc, copper, manganese, chromium), such as cow's milk whey (579). In in vitro research, whey-dominant formulas are not likely to hamper mineral availability (580).
  • Mood altering agentsMood altering agents: In human research, alpha-lactalbumin increased plasma tryptophan (TRP) and the ratio of TRP to neutral amino acids, with no effect on salivary cortisol secretion or tasks of emotional processing (19).
  • Omega-3 fatty acidsOmega-3 fatty acids: In animal research, a mixture of whey peptide, omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids), and fructooligosaccharides protected against induced inflammation (575).
  • Performance enhancement herbs and supplementsPerformance enhancement herbs and supplements: In human research, whey protein increased muscle mass and/or strength (156; 159; 546). In animal research, exercise training resulted in an increase in the skeletal muscle glycogen content, and this further increased when animals were fed whey protein; glycogen content in the liver also increased (547). Increased skeletal muscle synthesis was observed following exercise in animals that were fed whey protein (548). In human research, ingestion of whey protein increased myofibrillar protein synthesis (549). The ability of whey protein to build muscle and aid in exercise recovery has been discussed in secondary sources.
  • ProbioticsProbiotics: Addition of probiotic bacteria to hydrolyzed whey formula may promote endogenous barrier mechanisms in patients with atopy over hydrolyzed whey alone (581; 582) and alter stool consistency and bacterial colonization (583). In vitro, probiotics may be able to produce bioactive peptides from whey proteins (584; 585). In animal research, addition of probiotic bacteria had no effect over a conventional dry feed and antibiotics for diarrhea-reduction in weanling pigs (586). The effects of probiotics, administered with hydrolyzed whey formula, have been examined in various animal studies (587). The probiotics restored aberrant macromolecular transport in the gastrointestinal system.
  • Renal agentsRenal agents: In human research, urinary glycolate excretion was 5.3-fold higher on a gelatin diet vs. a whey diet and urinary oxalate excretion was 43% higher; hyperoxaluria is associated with calcium stone formation (550).
  • Respiratory agentsRespiratory agents: In human research, whey protein increased FEV1 in patients with severe chronic obstructive pulmonary disease (COPD) (147).
  • Satiety agentsSatiety agents: In some human studies, whey protein suppressed appetite (127; 91; 133; 134; 126). In human research, a test meal higher in whey (48g) increased subjective satiety, as well as plasma amino acids, CKK, GIP, and GLP-1 (551). In human research, a liquid preload containing 55g of whey decreased later energy intake vs. a glucose preload, potentially due to increased CCK; whey also increased branched-chain amino acid levels (552).
  • SeleniumSelenium: In animal research, selenium decreased bacterial growth in whey fractions of the milk (588).
  • SpirulinaSpirulina: In animal research, whey protein concentrate and spirulina prevented liver damage induced by CCl(4) to a greater extent than whey protein concentrate alone (561).
  • VitaminsVitamins: In human research, the sympatho-adrenal system was stimulated using a vitamin mixture and whey protein (1).
  • Weight loss herbs and supplementsWeight loss herbs and supplements: In human research, whey protein resulted in weight loss (181). Weight loss effects of whey protein may be due to increased satiety and decreased energy intake at the next meal, as shown in human research (551; 552). Weight loss or decreased weight gain have been shown in animal studies, compared with other protein sources or lower protein diets (553; 554; 555).
  • Wound-healing agentsWound-healing agents: In animal research, post-Cesarean treatment with intragastrically administered whey protein promoted wound healing (556).
  • ZincZinc: In human research, zinc supplementation of an amino acid/whey supplement accelerated serum IGF-1 response to the protein supplement (589). In a human research, source of protein, such as whey, casein, or egg, had no effect on zinc absorption (590). In animal research, zinc retention was higher from a casein-based vs. a whey-based diet (591). However, in a separate animal study, the availability of zinc was greater in a diet consisting of whey protein compared to casein as the protein component (592).

Whey protein/Food Interactions:
  • BreadBread: In Argentina, the nutritional value of French bread was increased by adding whey proteins (593).
  • CarbohydratesCarbohydrates: The type of carbohydrate ingested with whey protein (sucrose, maltodextrin, honey) did not induce differences in whey protein-induced changes in glucose and insulin concentrations (594).
  • Fortified blended foodsFortified blended foods: Hoppe et al. reviewed the evidence of adding whey to fortified blended foods (FBF) for malnourished infants and young children or people living with HIV or AIDS (595). Adding whey improved the protein quality, allowing a reduction in the total amount of protein needed. Improved flavor was also discussed, as was the decreased need for plant sources of protein. Price was increased.
  • GlucoseGlucose: Postexercise ingestion of glucose plus whey protein hydrolysates increased skeletal muscle glycogen vs. glucose alone in animal research (596).
  • High-protein dietsHigh-protein diets: In human research, protein gain following a single whey protein meal was found to result from an increase in protein synthesis, with no effect on protein breakdown (597; 598).
  • Low-protein dietsLow-protein diets: In animal research, additional whey protein to animals on a low-protein diet was unable to prevent impaired bone status (599).
  • Milk fatMilk fat: In animal research, whey protein isolate increased lipid uptake from milk fat (600).
  • Salomat Uzbek diabetic press cakesSalomat Uzbek diabetic press cakes: Medical and biologic assessments were made of Salomat Uzbek diabetic press cakes, made of category II wheat flour with addition of rice flour and whey (601). Protein levels and essential amino acids were increased and carbohydrates were decreased.

Whey protein/Lab Interactions:
  • Amino acidsAmino acids: In human research, alpha-lactalbumin increased plasma tryptophan (TRP) and the ratio of TRP to neutral amino acids (19). Compared with casein, whey protein induced a short, quick increase in plasma amino acids, whereas amino acids from casein were absorbed moderately in a plateau-like manner (598). In humans, whey protein hydrolysates increased Val-Leu and Ile-Leu concentrations vs. nonhydrolyzed protein and increased indispensable amino acids and branched-chain amino acids over soy protein (469). In humans, whey protein increased plasma leucine, and amino acids in general (175; 176; 97).
  • AntibodiesAntibodies: In an animal study, feeding a growth factor-enriched fraction from milk whey to suckling pups reduced immune activation to the food antigen ovalbumin (461). In an animal study, whey protein concentrate resulted in elevated levels of antigen-specific intestinal tract and serum antibodies against all tested antigens (462). In in vitro research, use of whey protein in culture medium induced various effects in the cells, including increased antibody production (602).
  • Beta-lactoglobulinBeta-lactoglobulin: Based on ELISA, human milk proteins (lactoferrin, beta-casein, and alpha-lactalbumin) may cross-react during determination of bovine beta-lactoglobulin, giving false positive results (603).
  • Blood pressureBlood pressure: In human research, hydrolyzed and nonhydrolyzed whey protein reduced blood pressure (108; 109).
  • Bone metabolism markersBone metabolism markers: In human research, milk basic protein decreased urinary cross-linked N-telopeptides of type 1 collagen/creatinine and deoxypyridinoline/creatinine (142). In men, milk basic protein increased serum osteocalcin and decreased urinary cross-linked N-telopeptides of type-I collagen (516). Whey protein with low levels of minerals increased serum osteocalcin (sOC), whereas whey protein with high levels of minerals decreased levels of sOC (604). In healthy adult women, milk basic protein resulted in decreased urinary cross-linked N-telopeptides of type-I collagen/creatinine and deoxypyridinoline/creatinine, with no significant differences in serum osteocalcin or bone-specific alkaline phosphatase concentrations (142). Decreased serum NTx (139) and urinary NTx (140; 141) and increased sOC (141), have been shown in other human studies. In animal research, whey protein increased alkaline phosphatase activity and insulin-like growth factor (521).
  • Cell countsCell counts: In human research, whey protein resulted in increased CD4 lymphocytes (100). A decrease in CD8 cell count was noted between baseline and 16 weeks (189). In animal research, in mice infected with Eimeria vermiformis, the alpha whey fraction increased white cell, CD4+, and CD8+ lymphocyte counts, as well as Con A-stimulated interferon (IFN)-gamma production by spleen cells (605). In animal research, whey protein enhanced innate immunity by increasing the natural killer cell proportion in the epithelial and lamina propria compartments, and increased intestinal CD8-alpha+ intraepithelial lymphocytes (606).
  • C-peptideC-peptide: In human research, whey protein increased C-peptide (97). In an animal study, hydrolyzed whey protein decreased levels of circulating C-peptide (502).
  • CreatinineCreatinine: In human research, whey protein dominant formulas increased creatinine excretion (607).
  • CytokinesCytokines: In animal research, whey protein isolate reduced ischemia/reperfusion-induced IL-6 release; alpha-lactalbumin and beta-lactoglobulin were active proteins, and the nitric oxide-mediated mechanism was implicated (608). In animal research, a novel ingredient (malleable protein matrix) containing whey protein was found to reduce inflammation by reducing the number of recruited cells and cytokine and chemokine production (tumor necrosis factor-alpha, IL-1beta, and IL-6) (488). In animal research, whey protein extract, likely via beta-lactoglobulin and alpha-lactalbumin, stimulated the accumulation of interleukin (IL)-1beta, IL-8, IL-6, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and tumor necrosis factor-alpha (609). Neutrophils incubated with whey protein extract, and the individual whey proteins, produced IL-1 receptor (Ra) in excess of IL-1beta, and the ratio of IL-1Ra to IL-1beta increased linearly.
  • EicosanoidsEicosanoids: According to information from an aging rate study, feeding whey protein isolate inhibited leukotriene B4 production of the spleen (610).
  • E-selectinE-selectin: In animal research, whey protein hydrolysates reduced serum soluble E-selectin levels (526).
  • Fecal bacteriaFecal bacteria: In a human study, ingestion of a cell-free concentrated milk whey was found to alter fecal bacteria; it was determined that live cells were not required (534). Whey retentate from Bifidobacteria fermented milk altered fecal bacteria in an animal study (611). This topic has been reviewed (612).
  • Free fatty acidsFree fatty acids: In a human study, whey protein decreased plasma free fatty acids (93).
  • GlucagonGlucagon: In a human study, the high amino acids in whey protein and whey protein hydrolysates induced increased insulin and glucagon responses (466; 467; 468; 469).
  • GlucoseGlucose: In a human study, whey protein decreased postprandial glucose in patients with type 2 diabetes (93; 94; 95) and in healthy patients (130). In an animal study, a malleable protein matrix (MPM), composed of whey fermented by a proprietary Lactobacillus kefiranofaciens strain, was found to reestablish the fasting glucose insulin ratio index to normal levels, and the plasma glucose level area under the curve was lowered (470). In animal research, whey protein improved glycemic homeostasis over casein (101).
  • Glucose-modulating hormonesGlucose-modulating hormones: In a human study, whey protein increased glucagon-like peptide-1 (GLP-1) (136). In an animal study, whey protein increased the insulin response to glucose, associated with enhanced oral glucose tolerance, increased the slope of the glucose-insulin curve vs. glucose alone, increased GLP-1 secretion, and increased levels of both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) (471). In an animal study, whey protein stimulated glucagon-like peptide (GLP)-2 secretion (613).
  • GlutathioneGlutathione: In a human study, whey protein resulted in increases in glutathione levels in patients with HIV (117; 189; 170; 190). In human research, whey protein resulted in a reduction in glutathione observed following exercise (614) and increased glutathione levels in lymphocytes (615).
  • GlycogenGlycogen: In an animal study, liver glycogen increased (547; 616). In an animal study, branched-chain amino acid-containing dipeptides from whey protein hydrolysates increased glucose uptake into skeletal muscle, resulting in increased glycogen content (617).
  • GSHGSH: In cystic fibrosis patients, whey protein decreased peripheral lymphocyte GSH levels (150).
  • HbA1cHbA1c: In a human research, use of a tooth powder containing whey protein reduced HbA1c levels, although this was not statistically significant (183).
  • Hematological parametersHematological parameters: In human research, whey protein had no effect on hematological parameters (618).
  • HemoglobinHemoglobin: In human research, whey protein had no effect on hemoglobin (619).
  • HormonesHormones: In human research, a whey blend decreased levels of estradiol (537).
  • ImmunoglobulinsImmunoglobulins: In allergic individuals, whey protein decreased IgE levels (112). In ovalbumin-sensitized mice, oral administration of the PP fraction decreased total and ovalbumin (OVA)-specific IgE in the serum, by decreasing mRNA expression of IgE in splenocytes; other Ig classes were not affected. Also, the B cell population in the spleen was decreased, while the T cell population was increased. In in vitro research, an extract from bovine colostral whey stimulated growth of cells and growth factors; IgE antibody responses were suppressed in mice (113). Decreased IgE production has been shown in various other animal studies (114; 115). In animal research, whey protein increased biliary levels of s-IgA (111).
  • InsulinInsulin: In human research, whey protein caused increased insulin responses (96; 97; 95; 134; 130; 94; 620; 136; 135). In a human study, the high amino acids in whey protein and whey protein hydrolysates increased insulin and glucagon responses (466; 467; 468; 469).
  • Insulin-like growth factor (IGF-1)Insulin-like growth factor (IGF-1): In a human study, whey increased (621) or had no effect on IGF-1 (622). According to secondary sources, whey protein may stimulate IGF-1.
  • LeptinLeptin: In animal research, beta-lactoglobulin improved hormone levels of leptin (623). In human research, whey protein decreased leptin levels (181).
  • Liver enzymesLiver enzymes: In human research, whey protein decreased AST and ALT (116; 168). In animal research, whey protein suppressed plasma alanine, aspartate aminotransferase activity, lactate dehydrogenase, bilirubin, and hyaluronic acid, as well as histopathological signs of portal fibrosis, bile duct proliferation, and perivenular sclerosis.
  • Plasma lipidsPlasma lipids: In human research, whey protein reduced postprandial triglyceride levels (98; 93), as well as fasting triglyceride and total and LDL cholesterol levels (99; 100), and HDL cholesterol and apo B levels (181). Lipid-lowering effects of whey protein (on total and VLDL cholesterol and triglycerides) have been shown in animal studies (101; 102; 103; 104; 105).
  • Plasma ureaPlasma urea: In human research, whey protein increased plasma urea (624).
  • Plasminogen activatorPlasminogen activator: In in vitro research, unheated and heat-denatured alpha-lactalbumin and denatured beta-lactoglobulin stimulated plasminogen activator activity (106).
  • Satiety hormonesSatiety hormones: In human research, whey protein increased CKK, GIP, GLP-1, and peptide YY (551; 127; 91; 126; 128; 94; 135). In human research, a liquid preload containing 55g of whey decreased later energy intake vs. a glucose preload, potentially due to increased CCK; whey also increased branched-chain amino acid levels (552). In in vitro research, whey protein hydrolysates (and all protein sources measured) increased cholecystokinin (CCK) release but had no direct effect on CCK-1 receptor-expressing cells (625). In human research, ghrelin levels stayed lower in the whey group (91; 135).
  • TestosteroneTestosterone: In human research, whey protein decreased serum testosterone (538) and blunted exercise-induced increases in testosterone (539).
  • Urinary glycolateUrinary glycolate: In human research, urinary glycolate excretion was 5.3-fold higher on a gelatin diet vs. a whey diet and urinary oxalate excretion was 43% higher (550).
  • Urinary inorganic sulfate (iSO4)Urinary inorganic sulfate (iSO4): In human research, whey protein-based formulas may increase urinary iSO4 (626).
  • Urinary nitrogenUrinary nitrogen: Consumption of whey protein increased urinary nitrogen after exercise in healthy human subjects (627) and in the elderly (172).

Copyright © 2011 Natural Standard (www.naturalstandard.com)

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.
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