Protein supplements: the performance gains came with extra calories

In a Bayesian meta-analysis of 75 studies in 1,206 athletes, protein supplements improved performance only in trials where the control group got fewer calories. Pure protein against placebo gave a standardized effect of 0.37 on endurance (0.02 to 0.71) and 0.72 on strength (0.18 to 1.27). Every significant effect came from trials that did not match energy intake, so part of the gain may come from the extra energy. For body composition the numbers are small. In 13 trials in women, whey protein added 0.82 lb (0.37 kg) of lean mass (95% CI 0.06 to 0.67) without changing fat mass, and the gain disappeared in trials that used resistance training alone. In older adults with sarcopenia or frailty, 13 trials with 1,057 people found protein plus exercise added 5.8 lb (2.64 kg) of grip strength over exercise alone (0.75 to 4.53), with very low certainty. Across 15 trials, whey with exercise raised muscle protein synthesis 1.3 to 1.6 fold right after training and up to 2.5 fold when taken 45 minutes before. Synthesis rate is a marker measured in a muscle biopsy, and it does not tell you how much muscle you end up with.

The numbers, per 3.5 oz (100 g)

What your body absorbs

• In a crossover RCT in 10 young men, about 10 g of leucine-rich beta-lactoglobulin and 10 g of whey isolate raised muscle protein synthesis by about 52% alike. — Ten healthy young men (26 years), randomized double-blind crossover (n = 10) Evidence B source
  MPS +~52% fed and +~58% fed plus exercise, no difference between supplements; plasma EAA/BCAA/leucine higher after BLG
• A meta-analysis of 15 RCTs found whey protein with exercise raised muscle protein synthesis 1.3 to 1.6 fold when taken right after training and up to 2.5 fold when taken 45 minutes before. — healthy adults, 21 RCTs (15 in meta-analysis), muscle biopsy studies (n = 15 trials) Evidence A source
  Myofibrillar FSR Hedges g 1.24 (95% CI 0.71-1.77); dose-dependent across 10-60 g

What it does to your health

• In a Cochrane review, balanced energy and protein supplements cut stillbirth risk by 40% across 5 trials with 3408 women and raised mean birthweight by about 41 g across 11 trials with 5385 women. — Pregnant women given balanced energy and protein supplementation, mostly in low-income settings (n = 3408 (stillbirth); 5385 (birthweight)) Evidence A source
  Stillbirth RR 0.60 (95% CI 0.39 to 0.94), 5 trials, 3408 women; birthweight MD +40.96 g (95% CI 4.66 to 77.26), 11 trials, 5385 women; moderate-quality evidence
• A 2026 individual-data meta-analysis of 8 trials with 10,252 women in low- and middle-income countries found balanced energy-protein supplements lowered preterm small-baby risk by 31%. — Pregnant women in low- and middle-income countries, 8 RCTs of prenatal BEP supplements (n = 10252) Evidence A source
  Preterm-SGA RR 0.69 (95% CI 0.52 to 0.91); term-SGA RR 0.88 (95% CI 0.81 to 0.96)
• A 2025 meta-analysis of 24 trials and observational studies found balanced protein-energy supplements added about 63 g to birthweight, with no effect on preterm birth. — Pregnant women receiving balanced protein-energy supplementation, 24 studies (n = 24 studies) Evidence C source
  Birthweight MD 62.67 g (CI 27.92 to 97.43); LBW RR 0.73 (0.57 to 0.95); SGA RR 0.74 (0.59 to 0.93); preterm birth RR 0.86 (0.68 to 1.08)
• A meta-analysis of 13 RCTs in women found whey protein added 0.82 lb (0.37 kg) of lean mass without changing fat mass. — women, 13 RCTs with 28 groups (n = 13 trials) Evidence A source
  Lean mass WMD +0.82 lb (95% CI 0.13 to 1.5; metric: 0.37 kg, 0.06 to 0.67); fat mass -0.44 lb (-1.5 to 0.6; metric: -0.20 kg, -0.67 to 0.27); with energy restriction +2 lb (0.90 kg)
• A meta-analysis of 65 RCTs found milk protein supplements lowered systolic blood pressure by 2 mmHg and total cholesterol by 4 mg/dL. — adults in 65 RCTs of casein, whey or milk protein (n = 65 trials) Evidence A source
  SBP WMD -1.99 mmHg (95% CI -3.16 to -0.82); TC -4.03 mg/dL (-7.91 to -0.16); TG -6.11 mg/dL; no effect on LDL or DBP
• In 13 RCTs with 1,057 older adults with sarcopenia or frailty, protein plus exercise added 5.7 lb (2.6 kg) of grip strength over exercise alone, with very low certainty. — adults aged 65 years or older with sarcopenia or physical frailty, 13 RCTs (n = 1057) Evidence A source
  Skeletal muscle index MD +0.89 kg/m2 (0.45 to 1.33); handgrip MD +5.8 lb (1.7 to 10; metric: 2.64 kg, 0.75 to 4.53) vs exercise alone

Safety, limits and interactions

• In the same Cochrane review, high-protein supplements in one trial of 505 women raised the risk of a small-for-gestational-age baby by 58%. — Pregnant women given high-protein supplementation, one trial (n = 505) Evidence A source
  Small for gestational age RR 1.58 (95% CI 1.03 to 2.41), moderate-quality evidence; no effect on stillbirth, preterm birth or birthweight
• In a meta-analysis of observational studies, the highest total and animal protein intakes were linked with about 80% higher risk of gestational diabetes than the lowest, and plant protein showed no link. — Women before and during pregnancy, 13 observational studies, 3451 GDM cases (n = 31005) Evidence C source
  Highest vs lowest: total protein RR 1.82 (1.42 to 2.33); animal protein RR 1.79 (1.50 to 2.14); plant protein RR 0.98 (0.81 to 1.20)
• A 2026 review of 25 prospective studies with 115,496 pregnant women linked higher animal-sourced protein intake with 62% higher gestational diabetes risk. — Pregnant women, 25 prospective observational studies (n = 115496) Evidence C source
  Animal-sourced protein highest vs lowest RR 1.62 (95% CI 1.20 to 2.18), I2 82%, dose-response, moderate certainty
• Lab tests of 30 sports protein powders in China found at least one toxic metal in every sample, with plant-based powders carrying about three times the lead of dairy ones. — 30 commercial sports protein supplements sold in China (n = 30 products) Evidence D source
  Mean Pb 0.18 mg/kg plant vs 0.06 mg/kg dairy; Cd 0.05 vs 0.01 mg/kg
• A European test of 56 plant-based protein powders found that at 30 g a day, exposure to essential and potentially toxic elements stayed within reference intake limits. — 56 plant-based protein supplement samples from European sources (n = 56 samples) Evidence D source
  At 30 g/day no reference intake limit exceeded
• A case report described a 60-year-old patient whose valproic acid blood levels fell when taken with a protein supplement and recovered once doses were spaced apart. — one 60-year-old patient on valproic acid (n = 1) Evidence C source
  VPA concentrations decreased with co-administration; returned to therapeutic range when intake was spaced out

What people believe that the data does not support

• WHO does not recommend high-protein supplementation for pregnant women in undernourished populations to improve maternal and perinatal outcomes. — Pregnant women in undernourished populations Evidence E source
  Recommendation against high-protein supplementation (WHO ANC guideline 2016)
• A Bayesian meta-analysis of 75 studies in 1,206 athletes found protein supplements helped performance only in trials where the control group got fewer calories. — 75 studies, 1,206 athletes (n = 1206) Evidence A source
  Pure protein vs placebo: endurance SMD 0.37 (0.02 to 0.71), strength SMD 0.72 (0.18 to 1.27); all significant effects from trials with unmatched energy intake
• A meta-analysis of RCTs found milk-derived protein supplements did not change bone mineral density at the spine or hip, against the claim that dairy protein leaches calcium. — adults in RCTs; whole-body BMD 7 RCTs, lumbar spine 10, hip 8 (n = 7-10 trials per site) Evidence A source
  No significant effect on BMD or bone turnover markers; IGF-1 increased (13 RCTs)
• The EU did not authorize a claim that a milk and soy protein supplement gives a fast increase of energy, strength and muscular development. — EU market (n = -) Evidence E source
  -

Who this works differently for

• A 2023 modular systematic review of randomized trials concluded that balanced protein and energy supplements reduce low birth weight, small babies and stillbirth in women with undernutrition. — Pregnant women with undernutrition, RCTs and reviews of RCTs Evidence A source
  BPE reduced risk of LBW, SGA and stillbirth in undernourished women (pooled numbers not in the abstract)
• The US protein RDA in pregnancy is 71 g a day, which FDA adopted as the label reference for pregnant and lactating women. — Pregnant and lactating women, US labeling Evidence E source
  RDA 71 g/day protein in pregnancy (IOM), RDI 71 g on labels for pregnant and lactating women
• The AHRQ 2024 review notes a higher protein RDA in pregnancy and lactation, of 1.1 to 1.3 g per kg a day. — Pregnant and lactating women, DRI reference values Evidence E source
  EAR 0.88 to 1.05 g/kg/d; RDA 1.1 to 1.3 g/kg/d in pregnancy and lactation
• An individual-data meta-analysis of 11 RCTs with 12,549 pregnant women in low- and middle-income countries found balanced energy-protein supplements added 1.3 lb (0.59 kg) of pregnancy weight gain. — 11 RCTs, 12,549 pregnant women in low- and middle-income countries (n = 12549) Evidence A source
  GWG adequacy +6% (2.18 to 9.56); total GWG +1.3 lb (0.26 to 2.3; metric: 0.59 kg, 0.12 to 1.05); inadequate GWG RR 0.93 (0.89 to 0.97)

What is still unknown

• The Cochrane authors called for large, well-designed randomized trials of raising energy and protein intake in pregnant women whose intake is below recommended levels. — Pregnant women in trials of energy and protein supplementation, 17 trials (n = 9030) Evidence A source
  Call for large randomized trials in women with intake below recommended levels
• A meta-analysis of RCTs in children aged 6 to 23 months found extra protein of at least 5 g a day did not shift weight-for-length, and long-term effects are unknown. — children aged 6-23 months, 19 trials (12 in meta-analysis) (n = 12 trials) Evidence A source
  WLZ SMD 0.0 (-0.09 to 0.09) in low- and middle-income countries; 0.17 (-0.12 to 0.47) in high-income countries
• In advanced chronic kidney disease, a meta-analysis of 17 RCTs found protein or amino acid supplements raised serum albumin by 1.76 g/L, but effects on quality of life could not be pooled. — adults with eGFR <30 mL/min or on dialysis, 17 RCTs, supplements >5 g/day (n = 17 trials) Evidence A source
  Serum albumin MD +1.76 g/L (0.67 to 2.84), I2 88%; BMI +0.29 kg/m2; HRQOL not meta-analysable

The bottom line

Milk proteins moved heart numbers a little. Across 65 randomized trials of casein, whey or milk protein, systolic pressure fell by 1.99 mmHg (95% CI -3.16 to -0.82) and total cholesterol by 4.03 mg/dL (-7.91 to -0.16), while LDL and diastolic pressure did not change. In a crossover trial in 10 young men, a leucine-rich beta-lactoglobulin supplement and whey isolate each raised muscle protein synthesis by about 52 percent, with no difference between them, an acute result in a very small sample. The fear that dairy protein leaches calcium from bone was tested. In a meta-analysis of randomized trials, 7 to 10 per bone site, milk-derived protein supplements did not change bone mineral density or bone turnover markers. IGF-1 rose across 13 of those trials, and what that means is unknown. The EU register snapshot holds 3 claims for protein supplements and authorizes none. One refused product promised a fast increase of energy, strength and muscular development. Some groups respond differently. In an individual-data meta-analysis of 11 trials with 12,549 pregnant women in low- and middle-income countries, balanced energy-protein supplements added 1.3 lb (0.59 kg) of pregnancy weight gain (0.12 to 1.05). Those were food supplements for undernourished women, a different product from a sports powder. In children aged 6 to 23 months, at least 5 g of extra protein a day did not shift weight-for-length across 12 trials, and long-term effects are unknown. In advanced kidney disease, 17 trials found protein or amino acid supplements raised serum albumin by 1.76 g/L (0.67 to 2.84), with high heterogeneity and high risk of bias, and effects on quality of life could not be pooled. People with kidney disease should take them only under a doctor's supervision. One case report describes a 60-year-old patient whose valproic acid levels fell when the drug was taken together with a protein supplement and returned to the therapeutic range once the two were spaced apart. It is a single case and the proposed mechanism is a guess. If you take valproate, mention the powder to whoever checks your levels. We found no peer-reviewed study of heavy metals in protein powders, so this page cannot say whether they are a problem. Whey and casein are milk proteins, and we have no card on allergy or on other medicines.

Sources

1. prsp-daily-r1-04 · RCT (crossover)
   MPS increased significantly in both FED (~52%) and FED-EX (~58%) states, with no significant differences between supplements.
   Nutrients, 2025 · checked 2026-09-29
2. prsp-daily-r1-05 · meta-analysis
   The combination of whey protein supplementation and exercise has been shown to significantly enhance FSR (Hedge's g = 1.24, 95% CI: 0.71-1.77; p < 0.001), with increases ranging from 1.3 to 1.6 folds when consumed immediately after exercise and up to 2.5 folds when given 45 min prior to multiple-set resistance exercise.
   Nutrients, 2025 · checked 2026-09-29
3. ev-ppreg-01 · Cochrane systematic review
   Risk of stillbirth was significantly reduced for women given balanced energy and protein supplementation (RR 0.60, 95% CI 0.39 to 0.94, five trials, 3408 women, moderate-quality evidence), and the mean birthweight was significantly increased (random-effects MD +40.96 g, 95% CI 4.66 to 77.26, Tau² = 1744, I² = 44%, 11 trials, 5385 women, moderate-quality evidence).
   Cochrane Database Syst Rev, 2015 · checked 2026-10-06
4. ev-ppreg-04 · IPD meta-analysis of RCTs
   In the four-group categorization, prenatal BEP supplementation led to a 31% lower risk of preterm-SGA (RR: 0.69; 95% CI [0.52, 0.91]; P = 0.008) and a 12% lower risk of term-SGA (RR: 0.88; 95% CI [0.81, 0.96]; P = 0.005).
   PLoS Med, 2026 · checked 2026-10-06
5. ev-ppreg-06 · meta-analysis of mixed designs
   Meta-analysis of pooled studies revealed that balanced protein supplementation had a significant effect on birthweight (g) (MD: 62.67, CI: 27.92-97.43), low birth weight (LBW) (RR: 0.73, CI: 0.57-0.95), birth length (MD: 0.20, CI: 0.10-0.30), and small-for-gestational-age (SGA) babies (RR: 0.74, CI: 0.59-0.93) and had no significant effect on the birth head circumference (MD: 0.05, CI: -0.09 to 0.20), perinatal death (RR: 0.83, CI: 0.50-1.37), and preterm birth (RR: 0.86, CI: 0.68-1.08).
   Womens Health (Lond), 2025 · checked 2026-10-06
6. prsp-daily-r1-02 · meta-analysis
   Globally, WP supplementation increased lean mass (WMD, 0.37 kg; 95% confidence interval [CI], 0.06 to 0.67) while not influencing changes in fat mass (-0.20 kg; 95%CI, -0.67 to 0.27) relative to non-WP control.
   Nutr Rev, 2018 · checked 2026-09-29
7. prsp-daily-r1-03 · meta-analysis
   The pooled analysis of 65 RCTs revealed that MP supplementation significantly reduced levels of total cholesterol (TC) (weighted mean difference [WMD]: -4.03 mg/dL; 95% CI: -7.91, -0.16; P = .042), systolic blood pressure (SBP) (WMD: -1.99 mmHg; 95% CI: -3.16, -0.82; P < .001), and triglycerides (TG) (WMD: -6.11 mg/dL; 95% CI: -9.78, -2.44; P = .001) in the MP group compared with the untreated group.
   Nutr Rev, 2026 · checked 2026-09-29
8. prsp-daily-r1-08 · meta-analysis
   Combined protein and exercise interventions demonstrated significant improvements in skeletal muscle index (MD = 0.89 kg/m², 95 % CI: 0.45 to 1.33) and handgrip strength (MD: +2.64 kg, 95 % CI: +0.75 to +4.53) compared to exercise alone.
   Arch Gerontol Geriatr, 2025 · checked 2026-09-29
9. ev-ppreg-02 · Cochrane systematic review
   High-protein supplementation (one trial, 505 women), was associated with a significantly increased risk of small-for-gestational age babies (RR 1.58, 95% CI 1.03 to 2.41, moderate-quality evidence).
   Cochrane Database Syst Rev, 2015 · checked 2026-10-06
10. ev-ppreg-07 · meta-analysis of observational studies
    Comparing the highest and lowest intakes of total, animal, and plant proteins revealed the summary RRs of 1.82 (95% CI: 1.42, 2.33), 1.79 (95% CI: 1.50, 2.14), and 0.98 (95% CI: 0.81, 1.20), respectively, indicating a significant positive association between total and animal protein intake and GDM.
    Clin Nutr, 2024 · checked 2026-10-06
11. ev-ppreg-08 · meta-analysis of cohort studies
    There was moderate certainty evidence that animal-sourced protein (HvL: RR 1.62 (95% CI 1.20 to 2.18) I2 82%) and animal-sourced fat (HvL: RR 1.59 (95% CI 1.34 to 1.88) I2 0%) intakes were associated with higher GDM in a dose-response manner.
    BMC Med, 2026 · checked 2026-10-06
12. ev-ppreg-12 · laboratory product analysis
    While all samples contained at least one target metal, plant-derived products exhibited higher mean Pb (0.18 mg/kg) and Cd (0.05 mg/kg) levels compared to dairy-derived products (0.06 and 0.01 mg/kg, respectively; P < 0.01).
    Environmental Research, 2026 · checked 2026-10-06
13. ev-ppreg-13 · laboratory product analysis
    At the recommended consumption level of 30 g/day, exposure to both essential and PTEs did not exceed reference intake limits.
    Journal of Trace Elements in Medicine and Biology, 2025 · checked 2026-10-06
14. prsp-daily-r1-07 · case report
    When the intake was spaced out, VPA serum concentrations returned to the therapeutic range.
    Nutr Hosp, 2025 · checked 2026-09-29
15. ev-ppreg-09 · Agency recommendation
    In undernourished populations, high-protein supplementation is not recommended for pregnant women to improve maternal and perinatal outcomes
    WHO, 2016, WHO recommendations on antenatal care for a positive pregnancy experience (eLENA summary) · checked 2026-10-06
16. prsp-daily-r1-01 · meta-analysis
    However, the results indicated that all significant effects were observed in randomized controlled trials where the energy intake between the intervention and control groups was not matched.
    J Int Soc Sports Nutr, 2026 · checked 2026-09-29
17. prsp-daily-r1-06 · meta-analysis
    Our findings do not support the claim that proteins of dairy origin are detrimental to bone health.
    Osteoporos Int, 2023 · checked 2026-09-29
18. prsp-daily-r1-12 · EU claim register
    POL-HC-7138 Fructose, Glucose, Maltodextrine, Milk protein concentrate, 5.Soy protein concentrate, Creatine, Vitamin C, Magnezium Oxide, Zinc Oxide,Alimentary flavors energizer and proteic food supplement / recomended for fast increase of energy, strenght and muscular development / recovery musular energy after physical and mental effort Non-authorised
    EU Register on nutrition and health claims, claim POL-HC-7138, snapshot 2026-09-21 · checked 2026-09-29
19. ev-ppreg-05 · systematic review of RCTs
    Evidence suggests that balanced protein and energy (BPE) supplementation for pregnant women with undernutrition can reduce the risk of LBW, SGA and SB.
    Am J Clin Nutr, 2023 · checked 2026-10-06
20. ev-ppreg-10 · Regulatory reference value
    In the preamble to the proposed rule (79 FR 11879 at 11943), we noted that the IOM established 71 grams/day protein as the RDA for pregnant and lactating women based on the needs for maternal and fetal development and human milk production.
    FDA, 2016, Food Labeling: Revision of the Nutrition and Supplement Facts Labels, final rule (FR Doc. 2016-11867) · checked 2026-10-06
21. ev-ppreg-11 · Agency report
    A higher EAR and RDA is also observed during pregnancy and lactation (EAR: 0.88-1.05 g/kg/d, RDA: 1.1-1.3 g/kg/d).
    AHRQ, 2024, Evaluation of Dietary Protein and Amino Acid Requirements: A Systematic Review · checked 2026-10-06
22. prsp-daily-r1-09 · IPD meta-analysis
    Compared to the comparison group, prenatal BEP led to a 6% greater GWG percent adequacy (95% CI: 2.18, 9.56; p = 0.002), a 0.59 kg greater estimated total GWG at delivery (95% CI, 0.12, 1.05; p = 0.014), a 10% lower risk of severely inadequate GWG (RR: 0.90; 95% CI: 0.83, 0.99; p = 0.025), and a 7% lower risk of inadequate GWG (RR: 0.93; 95% CI: 0.89, 0.97; p = 0.001).
    PLoS Med, 2025 · checked 2026-09-29
23. ev-ppreg-03 · Cochrane systematic review
    Large, well-designed randomised trials are needed to assess the effects of increasing energy and protein intake during pregnancy in women whose intake is below recommended levels.
    Cochrane Database Syst Rev, 2015 · checked 2026-10-06
24. prsp-daily-r1-10 · meta-analysis
    Diets with higher protein content did not substantially affect WLZ.
    Am J Clin Nutr, 2025 · checked 2026-09-29
25. prsp-daily-r1-11 · meta-analysis
    Protein and/or amino acid supplementation was associated with an improvement in serum albumin (mean difference (MD) = 1.76 g/L, 95% confidence interval (CI) [0.67, 2.84], P = .002, I2 = 88%)
    J Ren Nutr, 2026 · checked 2026-09-29