Whey protein (WP), commonly consumed for muscle building and weight loss, has been associated with various health concerns. Significant findings were revealed, such as WP’s potential link to liver and kidney damage, alterations in gut microbiota, increased acne incidence, impacts on bone mass, and emotional and behavioural changes. These findings underscore the complexity of WP’s effects on human health, indicating both beneficial and detrimental outcomes in relation to different posologies in a variety of settings. Be cautious for protein intaking in situations of hepatic and renal compromised functions, as well as in acne susceptibility, while possible beneficial effects can be achieved for the intestinal microbiota, humoral and behavioural level, and finally bone and muscle mass in elderly. The importance of balanced WP consumption and call for more in-depth research to understand its long-term health effects were emphasized. Health professionals and individuals considering WP supplementation should be aware of these potential risks and approach its use with informed caution.
WHEY PROTEIN (WP) Type | Concentration |
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WHEY PROTEIN Constituents | % Concentration |
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WP Isolate | 90–95% |
Beta Lactoglobulin (β-LG) | 50–55 |
Details of studies on health and side effects from WP supplementation are presented in Table 3 for human studies and Table 4 for preclinical studies.
First Author | Year | Study Design | Participants | N. of Patients | Age | Dose (per day) | Follow-Up Period | Outcomes | Ref. |
---|---|---|---|---|---|---|---|---|---|
Chitapanarux | 2009 | open labeled pilot study | Male and female with NASH | 38 | 15–60 | 20 g WP | 12 weeks | ↓ Hepatic steatosis ↓ Oxidative stress ↑ GSH |
|
Amanzadeh | 2003 | Male Sprague Dawley rats, (8 weeks old, Weight 232 g) | 3.34 g/kg/day: | 59 days | [ | ↓ urinary pH, ↑ ammonia and calcium concentration in urine in the ↑ protein group ↓ bone density at the femur level in the ↑ protein group | 26 | ] | [ |
WP Concentrated | 25–99% | ||||||||
38 | ] | Zhu | 2011 | RCT | Healthy menopausal women | 210 | 70–80 | ||
Orosco | 2004 | 30 g of WP vs. 2.1 g of protein | Male Wistar rats (Weight 200–250 g) | 190 g/Kg alpha-lactalbumin | 6 days | 2 years | ↔ hip BMD | Hydrolysed WP | Variable |
Undenatured WP | |||||||||
Alfa-Lactoalbumin (α-LA) | Variable, common range 25–99% |
15–20 | |||||||||||
↑ Serotonin production | ↓ Anxiety after alpha-lactalbumin consumption | [ | 39 | ↔ femoral neck strength | ↑ IGF-1 in WP group | [27] | Immunoglobulin A (IgA) | <15 | |||
Immunoglobulin G1 (IgG1) | |||||||||||
] | |||||||||||
Aparicio | 2011 | Immunoglobulin G2 (IgG2) | |||||||||
Albino male Wistar rats (Young, Weight 150 g) undergoing endurance training | Immunoglobulin M (IgM) | ||||||||||
Not specified | Bovin Serum Albumin (BSA) | 5–10 | |||||||||
LActoferrin (Lf) | <1–2% | ||||||||||
3 months | Lysozyme (Ly) | <1% | |||||||||
Lactoperoxidase (Lp) | |||||||||||
Santos | 2011 | Cross-sectional study<1% | |||||||||
Male bodybuilders | Casein Macropeptides | <10% | |||||||||
Sulphydryl oxidase | <1% | ||||||||||
Superoxide Dysmutase | <1% |
127 | ||||||||||||||
17–44 | ||||||||||||||
Not specified, but included regular diet and supplements | N/A | ↑ Renal volume; ↑ Calcium excretion with high protein intake | ↓ Effects of high protein with endurance exercise | ↑ Anger scores and anger expression above average | [40 | ↓ Anger management and inward anger below average Association between ↑ weekly protein intake and ↑ anger expression |
[28] | |||||||
] | Simonart | 2012 | Case series | Healthy male adult bodybuilders | 5 | 19–35 | Not specified | 6 months | ↑ Development of moderate to severe acne after whey protein consumption ↑ Acne severity according to GAGS ↔ No change with standard acne treatments for some; complete clearance for one after discontinuing whey protein and initiating topical treatment | |||||
Delamaire | 2012 | Male Sprague Dawley Rats | ↔ Partial regression with topical treatments for others | 8.7–13 g/dL | 15 days | ↔ Presence of mesenteric fat ↓ Low neonatal weight ↑ Weight gain in puberty/adulthood ↑ Food intake ↑ Serum insulin, leptin, triglycerides | [ | 29 | ] | |||||
↑ Pancreatic β-cell number; ↑ Adipocyte size | [ | 41 | ] | Silverberg | 2012 | Case series | Athletes and adolescents | 5 | 14–18 | Not specified | N/A | ↑ cystic acne, papules, pustules, and a few comedones on bilateral cheeks WP discontinuation led to acne improvement |
[30] | |
Nunes | 2013 | Sedentary Wistar rats (250 to 300 g; 90 days old) undergoing endurance training |
1.8 g/kg post-training | 8 weeks | ↑ Plasma ALT/AST; ↑ Liver/kidney toxicity with protein supplements, no training ↓ Liver/kidney toxicity with protein + resistance training |
[42] | Pontes | 2013 | prospective observational study | |||||
Deminice | Men and women | 30 | 18–30 | Not specified | 60 days | ↑ Comedones, papules, pustules counts over time | ↔ No significant change in scar count ↑ Severity of acne according to Leeds Acne Grading System over time ↔ No influence of sex or family history on lesion increase |
[31] | ||||||
2015 | Wistar rats | (weight 120 g) |
Not specified | 4 weeks | ↑ Hepatic oxidative stress markers in protein-supplemented vs. control | [43] | Cengiz | 2017 | Retrospective analysis of case series | Male adolescent users of protein-calorie supplements | 6 | |||
Gürgen | 2015 | Young male Wistar albino rats (Weight 170 g) Untrained mice | 16–18 | Not specified | 3 months | ↑ Acne lesions post protein supplement initiation | Acne localization to the trunk, sparing the face ↓ Acne severity with discontinuation of supplements and treatment |
Not specified↔ No other health anomalies detected in blood tests | 5 days and 4 weeks | ↑ Inflammatory interleukins/TNF-alpha with 4 weeks protein supplementation [32] |
||||
↑ Liver toxicity; ↑ Apoptotic signals | [ | 44 | ] | Hattori | 2017 | Interventional study | Men and women | 18 | 21–38 | |||||
Sanchez-Moya | 2017 | 27 g WP vs. Albumin | In vitro (donor faeces) | Variable | 24 h | 3 days with a 1-week washout period between supplements | ↑ mean protein equivalent of nitrogen appearance | ↔ in lithogenic parameters ↑ Urinary calcium in 39% of subjects ↓ Urinary pH in 44% of subjects ↔ other urinary elements |
↑ Bifidobacterium and Lactobacillus with whey supplementation. ↑ Production of short-chain fatty acids.[33] |
|||||
[ | 45 | ] | Moreno- Pérez | 2018 | Randomized pilot study | Cross-country runners | 24 | 18–45 | 1.8–3 g/kg | Ten weeks. | ||||
Zhou | 2022 | Female Kunming mice (age 6 weeks, weight 25–30 g) | Variable | 7 weeks | ↑ SOD concentrations; ↓ Oxidative stress with protein supplementation. ↑ Lactobacillus; ↓ Helicobacter; positive intestinal effects. | ↔ Fecal pH | ↔ Fecal water content ↔ Fecal ammonia ↔ Fecal SCFA concentrations ↔ Plasma malondialdehyde levels ↑ Bacteroidetes phylum ↓ Roseburia ↓ Blautia ↓ Bifidobacterium longu |
[34] | ||||||
Bauer | 2020 | RCT | Sarcopenic older adults | 380 | >65 | 21 g protein, 3 g leucine, 10 µg vitD and 500 mg calcium per serving | 26 weeks in total (13-week RCT followed by 13-week OLE) | ↑ eGFR in test group during RCT; no change during OLE Plateau of serum calcidiol and calcium levels after 13 weeks ↓ PTH levels in the test group during RCT and in former control groups during OLE Overall good tolerability of the WP-MND over the 6-month intervention period |
[35] | |||||
Schlickmann | 2021 | Cross-sectional study | Gym users | 594 | 37 | Not specified | N/A | ↑ Slight alterations in AST ↑ Slight alterations in urea levels |
[36] | |||||
Nhean | 2023 | prospective, cross-sectional survey with retrospective, observational cohorts | High- risk HIV subjects consuming APES while under PrEP | 50 | >18 (median 32) | survey on regular usage | 34 | ↑ grade 3–4 ALT/AST elevations ↑ serum creatinine |
[37] |
First Author | Year | Model | WP Dose | Follow-Up Period | Outcome | Ref. |
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[ | ||||||
46 | ||||||
] | ||||||