Should You Add Whey Protein to Your Daily Routine?

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Using whey protein has the potential to enhance your overall health and longevity

Whey is a protein complex made from milk that has healing properties including immune-boosting, antioxidant, antihypertensive, antitumor, hypolipidemic, chemoprotective and anti-inflammatory.[i] Clinical research shows whey protein''s benefits in fighting cancer, age-related diseases, obesity, cardiovascular disease risks and cognitive disorders while enhancing exercise performance and muscle recovery.

Cancer Prevention and Treatment

Great emphasis on cancer prevention and treatment has been given to whey protein (WP) by the scientific community, validating whey''s anticancer and chemotherapy toxicity-fighting effects through in vitro, in vivo and human studies.[ii] For example, through in vitro study of mice, whey protein isolate (WPI), bovine collagen hydrolysate (BCH) or its fractions all inhibited melanoma cell growth.[iii]

Similarly, the best combination for decreasing proliferation of mice melanoma cells was combining one of the collagen hydrolysates (BCH or BCH-P1) with WPI, along with paclitaxel -- a chemotherapy treatment.[iv]

In an animal study, researchers found that dietary exposure to whey proteins alters rat mammary gland proliferation, apoptosis and gene expression during postnatal development and reduced breast tumor incidence compared to those fed a casein diet. The whey protein hydrolysate''s (WPH''s) protective effects against breast cancer were associated with altered mammary gland differentiation and increased expression of a tumor suppressor.[v] In another rat study, both soy and whey proteins changed mammary differentiation, which protected the protein-fed rats from developing induced-mammary cancer.[vi]

Advanced cancer patients (lung, stomach, esophagus, pancreas, colon, blood, breast and head‐neck cancers) who are undergoing chemotherapy often become malnourished. In 166 of these patients, those who received both nutritional counseling and 20 grams (g) of WPI supplementation for three months experienced improved body composition, muscle strength, body weight and reduced chemotherapy toxicity compared to the control group of counseling only.[vii]

In another study of 42 cancer patients undergoing chemotherapy, those who took 40 g of WPI plus zinc and selenium outperformed the control group on increased glutathione (GSH) levels -- super antioxidants in the body -- and improved nutritional status and immunity.[viii]

Chemotherapy can also cause cachexia -- muscle wasting. To fight this, an immune-modulating diet (IMD) -- including immunonutrition elements such as vitamins A, C, E, zinc and selenium -- in combination with WP and chemotherapy prevented colon cancer cachexia without suppressing chemotherapeutic effectiveness.[ix] In an in-vitro study of mice, curcumin by nanoencapsulation with WP was highly effective in preventing colon and prostate cancers.[x]

Age-Related Diseases: Sarcopenia, Dynapenia and Osteoporosis

Sarcopenia -- age-related loss of muscle mass -- dynapenia -- age-related loss of muscle strength and power (also called muscle atrophy) -- and osteoporosis -- age-related bone loss -- are prevalent in older people and associated with increased falls, functional decline and higher mortality.[xi],[xii] WP supplementation either immediately pre- or post-resistance training (RT) had a significant effect on skeletal muscle mass, muscular strength and functional capacity in a study of 70 older women compared to a placebo group.[xiii]

In a comparison study, 22 healthy older women with an average age of 69 were randomly assigned to consume either a 30 g supplement of WP or collagen peptide (CP) twice daily along with RT twice daily for six days. WP was found to be more effective than CP in skeletal muscle retention in older women.[xiv]

Elderly individuals who use both resistance training and WP ingestion -- particularly for its amino acid leucine -- close to the hours they exercise have shown marked improvement in maintaining their skeletal muscle mass, which is believed to decrease their overall disease burden and improve their quality of life.[xv]

Bone loss has been induced by ovariectomy in rats verified in vivo studies and a new report shows that a WP fraction isolated from milk may support the recovery of bone loss.[xvi] In a similar animal study, after six weeks, feeding rats dietary WPH or WP prevented loss of bone, physical properties, mineral density and mineral content and improved breaking strength of femurs, demonstrating that both WPH and WP supplementation prevent bone loss induced by ovariectomy in rats.[xvii]

In vitro, WP was found to stimulate the proliferation and differentiation of osteoblasts cultured in different concentrations, which highlights its important role in bone formation and as a therapy to prevent osteoporosis by activating osteoblasts.[xviii]

Cardiovascular Disease and Obesity-Related Disease Risks

According to the Centers for Disease Control and Prevention (CDC), common risk factors and diseases associated with cardiovascular disease (CVD) (including heart disease and stroke) and obesity or being overweight are high blood pressure, high low-density lipoprotein (LDL) cholesterol, diabetes, unhealthy diet and physical inactivity.[xix],[xx]

In their meta-analysis of nine trials of overweight or obese patients, researchers found that WP significantly reduced body weight and fat mass and improved multiple CVD risk markers including systolic blood pressure, diastolic blood pressure, glucose, high-density lipoprotein and total cholesterol.[xxi]

In 48 obese patients with insulin resistance, groups were randomly assigned to three 45-day very-low-calorie ketogenic diet regimens of less than 800 calories per day containing whey, plant or animal protein. Body weight, body mass index, blood pressure, waist circumference, insulin resistance index, insulin and total and low-density lipoprotein cholesterol decreased in all patient groups, but the WP group had the most pronounced improvements in muscle strength.[xxii]

In 84 mice fed a high-fat diet, WP was more effective than soy protein in preventing obesity by significantly lowering body mass index, body weight, weight gain and the expression of lipogenesis-related genes -- which potentially could lead to dyslipidemia, Type 2 diabetes, fatty liver, autoimmune diseases, neurodegenerative diseases and cancers.[xxiii]

In two obesity-induced high-fat diet fed mice experiments, WP reduced whole body weight, adipose tissues and increased serum and brain glucagon-like peptide levels -- which are satiety-inducing hormones that suppressed the appetite and led to a significant decrease in food intake.[xxiv],[xxv]

In a study of 70 obese and overweight subjects, supplementation with WP, casein or glucose for 12 weeks resulted in the WP group having significant decreases in total cholesterol and LDL cholesterol, fasting insulin levels and homeostasis model assessment of insulin resistance compared to the casein or glucose groups.[xxvi]

In a 12-week experiment, caloric intake was reduced 500 calories per day and subjects consumed either WP Prolibra -- a protein mix high in leucine, bioactive peptides and milk calcium -- or an isocaloric ready-to-mix beverage 20 minutes before breakfast and 20 minutes before dinner. Subjects in both groups lost a significant amount of weight but those in the WP group lost significantly more body fat and preserved more lean muscle compared to the other group and those reductions led to reduced risks for obesity-related diseases.[xxvii]

Neurological Disorders and Cognitive Decline

WP intake protected against memory loss or impairment and aging in a mouse model. Researchers showed that WP intervention alleviated neuronal damage and altered a gut microbe related to Alzheimer's Disease.[xxviii]

The milk fat globule membrane found in WP regulated the neuroinflammatory pathology of AD in a mouse model. The cognitive decline/dysfunction of Alzheimer''s-induced mice was significantly improved with WP treatment for three months.[xxix]

In a crossover study of 23 high stress-vulnerable subjects and 29 low stress-vulnerable subjects with intake of either alpha-lactalbumin (WP diet) or sodium caseinate (control diet), the results suggested that the WP diet improved cognitive performance in subjects experiencing high stress and anxiety via increased brain tryptophan and serotonin activities when compared to the control treatment.[xxx]

Athletic Performance and Exercise-Induced Muscle Damage

Thirty-two men were assigned to either a WP or control treatment group. Participants were also fed three meals per day and did a supervised resistance exercise program for 60 minutes per day, six days per week over four weeks. WP increased muscle and peak torque of the dominant knee flexors, dominant shoulder extensors and non-dominant shoulder extensors and the total work of the dominant knee and shoulder extensors compared to the control group.

Overall, WP enhanced muscle mass, overall muscular strength and endurance.[xxxi] Nine males completed four conditions randomly:

1. A control condition of a typical mixed diet containing 10% protein, 65% carbohydrate and 25% fat
2. A placebo condition diet with the same calories of the WP conditions
3. A low-dose condition of WP at 0.8 gram per kilogram of body mass per day (g/kg/day) in addition to the typical mixed diet
4. A high-dose condition of 1.6 g/kg/day of WP with the typical mixed diet

Following the final meal, significant increases in total amino acids, essential amino acids, branched-chain amino acids and leucine were observed in plasma with WP groups relative to their dosage but not in the control and placebo groups.[xxxii]

In a double-blind review study, 12 healthy trained men were tested after various conditions 10 hours and 24 hours after resistance exercises or no exercise as control group and either took 25 g WP or an energy-matched placebo treatment. The WP group significantly increased the whole-body protein metabolism and athletic performance recovery resulting from acute resistance exercises compared to the control or placebo groups.[xxxiii]

Twenty physically active females who did repeated sprint exercises were assigned to consume two doses of 70 milliliters (mL) of WPH or placebo of isoenergetic carbohydrate for four days post exercise-induced muscle damage (EIMD). Compared to the placebo, the WPH treatment was highly beneficial for reducing symptoms of EIMD and improving recovery of muscle function for females doing sprints.[xxxiv]

Researchers studied 92 nonathletic non-obese males, ages 18 to 55 years, for five days treating them with either 0.9 g/kg weight divided into three doses per day of WP or pea protein or a water supplement as a control group. In comparison to the control group of water, high intake of whey protein for five days significantly mitigated the increased muscle damage biomarkers over the long haul while the intake of pea protein had only an intermediate effect on muscle damage caused by eccentric exercises.[xxxv]

In a study of eight male and female participants resistance-trained for 12 weeks, between the ages of 18 and 30 years old, who took either WP or placebo, the WP with resistance trained group increased muscle mass with no effects on their muscle strength in comparison to the placebo.[xxxvi]

The Power of Whey Protein

Using its antioxidant, anticancer, neuroprotective, cardiotherapeutic, chemopreventive and anti-inflammation superpowers, WP can be a masterful weapon against cancer, obesity, age-related diseases, cardiovascular risks and brain dysfunction as well as a booster to athletic performance and muscle recovery in both the young and the old. Please see more research at GreenMedInfo.com under the topic of whey.


References

[i] Keri Marshall. Therapeutic applications of whey protein. Altern Med Rev. 2004 Jun;9(2):136-56. PMID: 15253675

[ii] Anjana Thampy, Meena Kumari Palani Kumar, Muthukumar Serva Peddha, Madhavi Reddy. The effectiveness of whey proteins in prevention and treatment of cancer: a review. Crit Rev Food Sci Nutr. 2022 Sep 15:1-17. Epub 2022 Sep 15. PMID: 36111369

[iii] G A Castro, D A Maria, S Bouhallab, V C Sgarbieri. In vitro impact of a whey protein isolate (WPI) and collagen hydrolysates (CHs) on B16F10 melanoma cells proliferation. J Dermatol Sci. 2009 Oct;56(1):51-7. Epub 2009 Aug 19. PMID: 19695839

[iv] Georgia A Castro, Durvanei A Maria, Consuelo J Rodrigues, Valdemiro C Sgarbieri. Analysis of cell cycle phases and proliferative capacity in mice bearing melanoma maintained on different dietary proteins. J Cutan Pathol. 2009 Oct;36(10):1053-62. Epub 2009 Jan 27. PMID: 19187112

[v] Renea R Eason, Michael C Velarde, Leon Chatman, S Reneé Till, Yan Geng, Matthew Ferguson, Thomas M Badger, Rosalia C M Simmen. Dietary exposure to whey proteins alters rat mammary gland proliferation, apoptosis, and gene expression during postnatal development. J Nutr. 2004 Dec;134(12):3370-7. PMID: 15570039

[vi] J Craig Rowlands, Reza Hakkak, Martin J Ronis, Thomas M Badger. Altered mammary gland differentiation and progesterone receptor expression in rats fed soy and whey proteins. Toxicol Sci. 2002 Nov;70(1):40-5. PMID: 12388833

[vii] Emanuele Cereda, Annalisa Turri, Catherine Klersy, Silvia Cappello, Alessandra Ferrari, Andrea Riccardo Filippi, Silvia Brugnatelli, Marilisa Caraccia, Silvia Chiellino, Valeria Borioli, Teresa Monaco, Giulia Maria Stella, Luca Arcaini, Marco Benazzo, Giuseppina Grugnetti, Paolo Pedrazzoli, Riccardo Caccialanza. Whey protein isolate supplementation improves body composition, muscle strength, and treatment tolerance in malnourished advanced cancer patients undergoing chemotherapy. Cancer Med. 2019 Nov ;8(16):6923-6932. Epub 2019 Sep 30. PMID: 31568698

[viii] Akkarach Bumrungpert, Patcharanee Pavadhgul, Pornpimon Nunthanawanich, Anchalee Sirikanchanarod, Araya Adulbhan. Whey Protein Supplementation Improves Nutritional Status, Glutathione Levels, and Immune Function in Cancer Patients: A Randomized, Double-Blind Controlled Trial. J Med Food. 2018 Jun ;21(6):612-616. Epub 2018 Mar 12. PMID: 29565716

[ix] Kentaro Nakamura, Akina Sasayama, Takeshi Takahashi, Taketo Yamaji. An Immune-Modulating Diet in Combination with Chemotherapy Prevents Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice. Nutr Cancer. 2015 Jul 2:1-9. Epub 2015 Jul 2. PMID: 26133950

[x] Guddadarangavvanahally K Jayaprakasha, Kotamballi N Chidambara Murthy, Bhimanagouda S Patil. Enhanced colon cancer chemoprevention of curcumin by nanoencapsulation with whey protein. Eur J Pharmacol. 2016 Jul 9. Epub 2016 Jul 9. PMID: 27404761

[xi] Manini TM, Clark BC. Dynapenia and aging: an update. J Gerontol A Biol Sci Med Sci. 2012 Jan;67(1):28-40. doi: 10.1093/gerona/glr010. Epub 2011 Mar 28. PMID: 21444359; PMCID: PMC3260480.

[xii] Ailsa A Welch, Eirini Kelaiditi, Amy Jennings, Claire J Steves, Tim D Spector, Alexander MacGregor. Dietary Magnesium Is Positively Associated With Skeletal Muscle Power and Indices of Muscle Mass and May Attenuate the Association Between Circulating C-Reactive Protein and Muscle Mass in Women. J Bone Miner Res. 2015 Aug 19. Epub 2015 Aug 19. PMID: 26288012

[xiii] Nabuco HCG, Tomeleri CM, Sugihara Junior P, Fernandes RR, Cavalcante EF, Antunes M, Ribeiro AS, Teixeira DC, Silva AM, Sardinha LB, Cyrino ES. Effects of Whey Protein Supplementation Pre- or Post-Resistance Training on Muscle Mass, Muscular Strength, and Functional Capacity in Pre-Conditioned Older Women: A Randomized Clinical Trial. Nutrients. 2018 May 3;10(5):563. doi: 10.3390/nu10050563. PMID: 29751507; PMCID: PMC5986443.

[xiv] Oikawa SY, Kamal MJ, Webb EK, McGlory C, Baker SK, Phillips SM. Whey protein but not collagen peptides stimulate acute and longer-term muscle protein synthesis with and without resistance exercise in healthy older women: a randomized controlled trial. Am J Clin Nutr. 2020 Mar 1;111(3):708-718. doi: 10.1093/ajcn/nqz332. Erratum in: Am J Clin Nutr. 2020 Dec 10;112(6):1656. PMID: 31919527; PMCID: PMC7049534.

[xv] Alan Hayes, Paul J Cribb. Effect of whey protein isolate on strength, body composition and muscle hypertrophy during resistance training. Curr Opin Clin Nutr Metab Care. 2008 Jan;11(1):40-4. PMID: 18090657

[xvi] Marlena C Kruger, Gabrielle G Plimmer, Linda M Schollum, Neill Haggarty, Satyendra Ram, Kate Palmano. The effect of whey acidic protein fractions on bone loss in the ovariectomised rat. Br J Nutr. 2005 Aug;94(2):244-52. PMID: 16115359

[xvii] Jonggun Kim, Hyung Kwan Kim, Saehun Kim, Ji-Young Imm, Kwang-Youn Whang. Whey Protein Concentrate Hydrolysate Prevents Bone Loss in Ovariectomized Rats. J Med Food. 2015 Dec ;18(12):1349-56. Epub 2015 Sep 14. PMID: 26367331

[xviii] R Xu. Effect of whey protein on the proliferation and differentiation of osteoblasts. J Dairy Sci. 2009 Jul;92(7):3014-8. PMID: 19528578

[xix] CDC. Chronic Disease. Resources. Publications. Factsheets. Heart Disease and Stroke Risk Factors. https://www.cdc.gov/chronicdisease/resources/publications/factsheets/heart-disease-stroke.htm#:~:text=The%20Nation's%20Risk%20Factors%20and,unhealthy%20diet%2C%20and%20physical%20inactivity

[xx] CDC. Healthy Weight. Effects. https://www.cdc.gov/healthyweight/effects/index.html

[xxi] Kamonkiat Wirunsawanya, Sikarin Upala, Veeravich Jaruvongvanich, Anawin Sanguankeo. Whey Protein Supplementation Improves Body Composition and Cardiovascular Risk Factors in Overweight and Obese Patients: A Systematic Review and Meta-Analysis. J Am Coll Nutr. 2018 01 ;37(1):60-70. Epub 2017 Oct 31. PMID: 29087242

[xxii] Sabrina Basciani, Elisabetta Camajani, Savina Contini, Agnese Persichetti, Renata Risi, Loris Bertoldi, Lidia Strigari, Giancarlo Prossomariti, Mikiko Watanabe, Stefania Mariani, Carla Lubrano, Alfredo Genco, Giovanni Spera, Lucio Gnessi. Very-Low-Calorie Ketogenic Diets With Whey, Vegetable, or Animal Protein in Patients With Obesity: A Randomized Pilot Study. J Clin Endocrinol Metab. 2020 09 1 ;105(9). PMID: 32484877

[xxiii] Jeon, Y.G., Kim, Y.Y., Lee, G. et al. Physiological and pathological roles of lipogenesis. Nat Metab 5, 735–759 (2023). doi:10.1038/s42255-023-00786-y

[xxiv] Chaitra Rai, Poornima Priyadarshini. Whey protein hydrolysates improve high-fat-diet-induced obesity by modulating the brain-peripheral axis of GLP-1 through inhibition of DPP-4 function in mice. Eur J Nutr. 2023 Sep ;62(6):2489-2507. Epub 2023 May 8. PMID: 37154934

[xxv] Andong Ji, Wei Chen, Tianyu Zhang, Runjia Shi, Xinqi Wang, Yan Wang, Huina Xu, Duo Li. Whey protein and soy protein prevent obesity by upregulating uncoupling protein 1 to activate brown adipose tissue and promote white adipose tissue browning in high-fat diet-fed mice. Food Funct. 2022 Nov 28. Epub 2022 Nov 28. PMID: 36440964

[xxvi] Sebely Pal, Vanessa Ellis, Satvinder Dhaliwal. Effects of whey protein isolate on body composition, lipids, insulin and glucose in overweight and obese individuals. Br J Nutr. 2010 Sep;104(5):716-23. Epub 2010 Apr 9. PMID: 20377924

[xxvii] Joy L Frestedt, John L Zenk, Michael A Kuskowski, Loren S Ward, Eric D Bastian. A whey-protein supplement increases fat loss and spares lean muscle in obese subjects: a randomized human clinical study. Nutr Metab (Lond). 2008;5:8. Epub 2008 Mar 27. PMID: 18371214

[xxviii] Ning Ding, Hanxiu Meng, Chao Wu, Wallace Yokoyama, Hui Hong, Yongkang Luo, Yuqing Tan. Whey Protein Hydrolysate Renovates Age-Related and Scopolamine-Induced Cognitive Impairment. Nutrients. 2023 Feb 28 ;15(5). Epub 2023 Feb 28. PMID: 36904228

[xxix] Yu Li, Zhong-Hao Zhang, Shao-Ling Huang, Zhong-Bao Yue, Xue-Song Yin, Zi-Qi Feng, Xu-Guang Zhang, Guo-Li Song. Whey protein powder with milk fat globule membrane attenuates Alzheimer's disease pathology in 3×Tg-AD mice by modulating neuroinflammation through the peroxisome proliferator-activated receptorγsignaling pathway. J Dairy Sci. 2023 Aug ;106(8):5253-5265. Epub 2023 Jul 4. PMID: 37414601

[xxx]Markus CR, Olivier B, de Haan EH. Whey protein rich in alpha-lactalbumin increases the ratio of plasma tryptophan to the sum of the other large neutral amino acids and improves cognitive performance in stress-vulnerable subjects. Am J Clin Nutr. 2002 Jun;75(6):1051-6. doi: 10.1093/ajcn/75.6.1051. PMID: 12036812

[xxxi] Chae-Been Kim, Jong-Hoon Park, Hyoung-Su Park, Hye-Jin Kim, Jung-Jun Park. Effects of Whey Protein Supplement on 4-Week Resistance Exercise-Induced Improvements in Muscle Mass and Isokinetic Muscular Function under Dietary Control. Nutrients. 2023 Feb 16 ;15(4). Epub 2023 Feb 16. PMID: 36839361

[xxxii] Forbes SC, McCargar L, Jelen P, Bell GJ. Dose response of whey protein isolate in addition to a typical mixed meal on blood amino acids and hormonal concentrations. Int J Sport Nutr Exerc Metab. 2014 Apr;24(2):188-95. doi: 10.1123/ijsnem.2013-0136. Epub 2013 Nov 13. PMID: 24225595.

[xxxiii] West DWD, Abou Sawan S, Mazzulla M, Williamson E, Moore DR. Whey Protein Supplementation Enhances Whole Body Protein Metabolism and Performance Recovery after Resistance Exercise: A Double-Blind Crossover Study. Nutrients. 2017 Jul 11;9(7):735. doi: 10.3390/nu9070735. PMID: 28696380; PMCID: PMC5537849

[xxxiv] Meghan A Brown, Emma J Stevenson, Glyn Howatson. Whey protein hydrolysate supplementation accelerates recovery from exercise-induced muscle damage in females. Appl Physiol Nutr Metab. 2018 Apr ;43(4):324-330. Epub 2017 Nov 6. PMID: 29106812

[xxxv] David C Nieman, Kevin A Zwetsloot, Andrew J Simonson, Andrew T Hoyle, Xintang Wang, Heather K Nelson, Catherine Lefranc-Millot, Laetitia Guérin-Deremaux. Effects of Whey and Pea Protein Supplementation on Post-Eccentric Exercise Muscle Damage: A Randomized Trial. Nutrients. 2020 Aug 9 ;12(8). Epub 2020 Aug 9. PMID: 32784847

[xxxvi] Duarte NM, Cruz AL, Silva DC, Cruz GM. Intake of whey isolate supplement and muscle mass gains in young healthy adults when combined with resistance training: a blinded randomized clinical trial (pilot study). J Sports Med Phys Fitness. 2020 Jan;60(1):75-84. doi: 10.23736/S0022-4707.19.09741-X. Epub 2019 Sep 23. PMID: 31565912

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