Casein Protein

Bos taurus (bovine milk-derived)
Evidence Level
Moderate
6 Clinical Trials
4 Documented Benefits
3/5 Evidence Score

Casein is the main protein in cow's milk. It clots in the stomach and is digested slowly, so blood amino acids rise less sharply than after whey but stay raised for longer. It supplies all the essential amino acids. In young men who trained in the evening, 40 g of casein taken before sleep was digested and absorbed overnight and raised whole-body protein synthesis, and in a 12-week training trial a nightly protein drink before sleep led to larger gains in strength and thigh muscle size than a placebo drink. A meta-analysis of 49 resistance-training trials found that protein supplements in general add modest gains in lean mass and strength. In the hours right after exercise, casein raised muscle protein synthesis less than whey or soy in a small study. People with a milk allergy should avoid casein.

Studied Dose Overnight studies gave 30 g or 40 g of casein about 30 minutes before sleep. A 12-week training trial gave a nightly drink with 27.5 g of protein, 15 g of carbohydrate and 0.1 g of fat before sleep.
Active Compound Casein, the main protein in cow's milk, sold as micellar casein or as caseinates; it is made up of alpha-s1, alpha-s2, beta and kappa casein.

Benefits

Muscle size and strength with resistance training

In a 12-week randomized trial in 44 young men, a nightly protein drink (27.5 g of protein) before sleep led to larger gains in one-rep max strength, thigh muscle cross-sectional area and type II muscle fiber size than a placebo drink. The abstract describes a protein supplement without naming the protein type, and this is the only long-term pre-sleep trial cited here.

Overnight muscle protein synthesis after evening exercise

In 16 young men who lifted weights in the evening, 40 g of casein taken 30 minutes before sleep was digested and absorbed overnight, raised whole-body protein synthesis and made net protein balance positive compared with placebo. Muscle protein synthesis was about 22 percent higher, a borderline result (p=0.05). In another study, evening exercise raised overnight synthesis from 30 g of casein by 37 percent.

Slow, sustained amino acid release

In a tracer study in healthy adults, casein gave a slower, longer, moderate rise in blood amino acids than whey, probably because it leaves the stomach more slowly. Casein lowered whole-body protein breakdown by 34 percent while whey did not, and net leucine balance over 7 hours was more positive with casein. These were whole-body measures after one meal, not muscle growth.

Short-term muscle response compared with whey and soy

In young men given drinks matched for 10 g of essential amino acids, micellar casein raised muscle protein synthesis less than whey hydrolysate or soy, both at rest and after leg exercise. The groups were small (6 men each) and synthesis was measured for a few hours, so the result shows a slower response rather than less muscle gained over time.

Mechanism of action

1

Clotting in the stomach

Casein forms clumps in acidic stomach contents, which slows how fast it leaves the stomach. In the tracer study cited here, this was the likely reason casein produced a slower, longer rise in blood amino acids than whey, which gave a sharp but short rise.

2

Leucine and the mTOR pathway

Like other complete proteins, casein supplies leucine, which switches on the mTOR signal that starts muscle protein synthesis; this pathway is worked out mainly in laboratory research. In the comparison study cited here, casein raised blood leucine less than whey and gave a smaller short-term synthesis response.

3

Less whole-body protein breakdown

After a single meal in healthy adults, casein lowered whole-body protein breakdown by 34 percent while whey did not. This was measured across the whole body, not in muscle specifically, and over 7 hours after one meal.

Clinical trials

1
Pre-Sleep Protein During 12 Weeks of Resistance Training: Randomized Trial
PubMed

Randomized placebo-controlled trial of a nightly pre-sleep drink with 27.5 g of protein, 15 g of carbohydrate and 0.1 g of fat versus a noncaloric placebo during a 12-week progressive resistance training program. (Snijders et al. 2015, J Nutr)

44 healthy young men aged about 22.

Strength rose more with protein than placebo (+164 vs +130 kg in summed one-rep max, p<0.001). Quadriceps cross-sectional area grew more with protein (+8.4 vs +4.8 cm2, p<0.05), as did type II muscle fiber size. The abstract describes a protein supplement and does not name the protein type. One co-author worked at DSM.

2
Pre-Sleep Casein and Overnight Recovery After Evening Exercise
PubMed

Trial in which young men did evening resistance exercise, had a recovery drink, and then took 40 g of labelled casein or a placebo drink 30 minutes before sleep, with overnight tracer measurements. (Res et al. 2012, Med Sci Sports Exerc)

16 healthy young men.

Casein was digested and absorbed during sleep and kept blood amino acids raised through the night. Whole-body protein synthesis (311 vs 246 micromol/kg over 7.5 h) and net protein balance (+61 vs -11) improved versus placebo (p<0.01). Muscle protein synthesis was about 22 percent higher, a borderline result (p=0.05).

3
Evening Exercise and Overnight Use of Pre-Sleep Casein
PubMed

Randomized study of 30 g of labelled casein before sleep, with or without resistance exercise earlier in the evening; there was no casein-free group. (Trommelen et al. 2016, Med Sci Sports Exerc)

24 healthy young men (12 per group).

About 57 percent of the casein-derived phenylalanine appeared in the blood overnight. Overnight myofibrillar protein synthesis was 37 percent higher with prior exercise (0.055 vs 0.040 percent per hour, p<0.001), and more casein-derived amino acids were built into new muscle protein. It compared exercise with no exercise, not casein with placebo.

4
Slow Casein Versus Fast Whey After a Single Meal
PubMed

Tracer study in which healthy adults ate one meal of labelled casein or whey with the same leucine content, with whole-body leucine kinetics measured for 7 hours. (Boirie et al. 1997, Proc Natl Acad Sci U S A)

Healthy adults (group sizes are not given in the abstract).

Whey caused a sharp but short rise in blood amino acids, while casein caused a longer, moderate rise. Whey raised whole-body protein synthesis by 68 percent and casein by 31 percent; casein lowered protein breakdown by 34 percent and whey did not. Net leucine balance over 7 hours was more positive with casein. Whole-body measures only.

5
Whey, Casein or Soy and Muscle Protein Synthesis in Young Men
PubMed

Acute study of three groups given a drink with 10 g of essential amino acids as whey hydrolysate, micellar casein or soy protein isolate, at rest and after one-leg resistance exercise. (Tang et al. 2009, J Appl Physiol)

18 healthy young men (6 per group).

Whey raised blood leucine and essential amino acids more than casein or soy. At rest, muscle protein synthesis was about 93 percent higher after whey than casein; after exercise it was about 122 percent higher than casein and 31 percent higher than soy. Soy raised synthesis more than casein at rest (64 percent) and after exercise (69 percent). Casein gave the smallest response. Small groups and a few hours of measurement.

6
Protein Supplements and Resistance Training Gains: Meta-Analysis of 49 Trials
PubMed

Systematic review, meta-analysis and meta-regression of randomized controlled trials lasting at least 6 weeks that combined resistance training with dietary protein supplements. (Morton et al. 2018, Br J Sports Med)

1863 healthy adults across 49 trials.

Protein supplements increased one-rep max strength by 2.49 kg, fat-free mass by 0.30 kg and muscle fiber size versus control. The effect on fat-free mass shrank with age and was larger in people already resistance trained, and there was no further gain above about 1.62 g/kg/day of total protein. Protein supplements in general, not one protein type. The senior author has received support from the US National Dairy Council.

Side effects and drug interactions

Common Potential side effects

Milk allergy: casein is a milk protein, so people with a cow's milk protein allergy should not use it.
Lactose: casein powders can contain some lactose, which may cause bloating, gas or diarrhea in people who are lactose intolerant.
Kidney or liver disease: people with kidney or liver disease should ask their doctor before raising their protein intake with supplements.

Important Drug interactions

Levodopa: dietary protein, including casein, competes with levodopa for transport into the brain; ask the prescriber how to time protein shakes around doses.
Tetracycline and quinolone antibiotics, and levothyroxine: calcium in dairy proteins can reduce their absorption; take them apart from casein shakes as the label or pharmacist advises.
No other clinically significant drug interactions are documented at usual protein supplement doses.

Frequently asked questions about Casein Protein

What is casein protein, and how is it different from whey?

Casein is the main protein in milk. Unlike fast-digesting whey, it clots in the stomach and releases amino acids slowly over several hours, so many people use it at night or between meals.

Should I take casein before bed?

In studies of young men, 30 to 40 grams of casein before sleep was digested overnight and supported overnight protein synthesis, and a nightly protein drink during 12 weeks of training led to larger strength and muscle gains than placebo. Total daily protein also matters: in a large meta-analysis, extra gains stopped at about 1.6 grams per kilogram a day.

How much casein should I take?

The pre-sleep studies used 30 to 40 grams. Follow product labeling and count casein toward your total daily protein from all foods.

Whey or casein, which is better?

They differ in speed. In small studies, whey raised muscle protein synthesis more than casein in the hours after exercise, while casein has been studied before sleep for overnight use. Many people use whey after workouts and casein at night, or whichever fits their diet.

What is Casein Protein?

Casein is the main protein in cow's milk. It clots in the stomach and is digested slowly, so blood amino acids rise less sharply than after whey but stay raised for longer. It supplies all the essential amino acids.

What is Casein Protein used for?

Casein Protein is researched primarily for Athletic Performance and Muscle & Recovery. In a 12-week randomized trial in 44 young men, a nightly protein drink (27.5 g of protein) before sleep led to larger gains in one-rep max strength, thigh muscle cross-sectional area and type II muscle fiber size than a placebo drink.

Is Casein Protein safe, and does it have side effects?

Side effects and cautions reported for Casein Protein include: Milk allergy: casein is a milk protein, so people with a cow's milk protein allergy should not use it. Lactose: casein powders can contain some lactose, which may cause bloating, gas or diarrhea in people who are lactose intolerant. It may also interact with some medications. Casein Protein is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Casein Protein interact with any medications?

Possible interactions include: Levodopa: dietary protein, including casein, competes with levodopa for transport into the brain; ask the prescriber how to time protein shakes around doses. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Casein Protein?

NutraSmarts rates the evidence for Casein Protein as Moderate (3 out of 5). It is backed by 6 study summaries and 6 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(6 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Snijders T, Res PT, Smeets JS, van Vliet S, van Kranenburg J, Maase K, Kies AK, Verdijk LB, van Loon LJ. Protein Ingestion before Sleep Increases Muscle Mass and Strength Gains during Prolonged Resistance-Type Exercise Training in Healthy Young Men. J Nutr. 2015;145(6):1178-84. doi: 10.3945/jn.114.208371.PubMedUsed to support: Randomized trial in 44 young men during 12 weeks of resistance training: a nightly pre-sleep drink with 27.5 g of protein led to larger gains in one-rep max strength, quadriceps cross-sectional area and type II muscle fiber size than a noncaloric placebo. The abstract does not name the protein type. One co-author worked at DSM.
  2. Res PT, Groen B, Pennings B, Beelen M, Wallis GA, Gijsen AP, Senden JM, van Loon LJ. Protein ingestion before sleep improves postexercise overnight recovery. Med Sci Sports Exerc. 2012;44(8):1560-9. doi: 10.1249/MSS.0b013e31824cc363.PubMedUsed to support: In 16 young men after evening resistance exercise, 40 g of casein taken before sleep was digested and absorbed overnight, raised whole-body protein synthesis and net protein balance versus placebo, and gave about 22 percent higher muscle protein synthesis, a borderline result (p=0.05).
  3. Tang JE, Moore DR, Kujbida GW, Tarnopolsky MA, Phillips SM. Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol (1985). 2009;107(3):987-92. doi: 10.1152/japplphysiol.00076.2009.PubMedUsed to support: Acute study in 18 young men (6 per group) given drinks matched for 10 g of essential amino acids: whey hydrolysate raised blood leucine the most; muscle protein synthesis after whey was about 93 percent higher than after micellar casein at rest, and about 122 percent higher than casein and 31 percent higher than soy after resistance exercise. Soy also beat casein (64 percent at rest, 69 percent after exercise). Shows casein's slower digestion gives a smaller short-term synthesis response than faster proteins. Small groups.
  4. Boirie Y, Dangin M, Gachon P, Vasson MP, Maubois JL, Beaufrère B. Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci U S A. 1997;94(26):14930-5. doi: 10.1073/pnas.94.26.14930.PubMedUsed to support: Tracer study in healthy adults after a single meal: casein gave a slower, longer, moderate rise in blood amino acids than whey, lowered whole-body protein breakdown by 34 percent (whey did not), and gave a more positive net leucine balance over 7 hours, while whey raised protein synthesis more. Whole-body measures only.
  5. Trommelen J, Holwerda AM, Kouw IW, Langer H, Halson SL, Rollo I, Verdijk LB, van Loon LJ. Resistance Exercise Augments Postprandial Overnight Muscle Protein Synthesis Rates. Med Sci Sports Exerc. 2016;48(12):2517-2525. doi: 10.1249/MSS.0000000000001045.PubMedUsed to support: In 24 young men given 30 g of casein before sleep, prior evening resistance exercise raised overnight myofibrillar protein synthesis by 37 percent (0.055 vs 0.040 percent per hour, p<0.001) and let more casein-derived amino acids be built into muscle; about 57 percent of the casein-derived phenylalanine appeared in the blood overnight. No casein-free group.
  6. Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, Aragon AA, Devries MC, Banfield L, Krieger JW, Phillips SM. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med. 2018;52(6):376-384. doi: 10.1136/bjsports-2017-097608.PubMedUsed to support: Meta-analysis of 49 randomized trials (1863 participants) lasting at least 6 weeks: protein supplements during resistance training increased one-rep max strength by 2.49 kg and fat-free mass by 0.30 kg; the effect shrank with age, was larger in trained people, and stopped rising above about 1.62 g/kg/day of total protein. Protein supplements in general, not casein alone. The senior author has received US National Dairy Council support.