Casein Protein | Supplementopedia

Overview

Casein is the predominant phosphoprotein found in mammalian milk.

It comprises roughly 80% of the total protein in cow’s milk and 40% of human milk.
Casein forms a micellar complex that slows gastric emptying.
This provides a prolonged release of amino acids, sustaining muscle protein synthesis for up to 7 hours after ingestion.
It is a favored “slow-digest” protein for recovery and overnight nutrition.

Muscle-protein synthesis & recovery: The sustained amino-acid delivery from casein supports net protein balance during periods of fasting, improving lean-mass retention in resistance-trained adults (e.g., 0.4 g kg⁻¹ day⁻¹ of casein improves overnight protein balance).
Weight-management: The prolonged satiety signal (via ghrelin suppression and increased peptide YY) helps reduce caloric intake, supporting modest weight loss in overweight adults.
Bone health: Rich in calcium, phosphate, and bioactive peptides (e.g., casein phosphopeptides) that enhance intestinal calcium absorption, contributing to higher bone mineral density.
Immune modulation: Casein-derived bioactive peptides (e.g., β-casomorphin-7, lactoferrin-derived fragments) exhibit antimicrobial and anti-inflammatory effects, supporting immune function.
Cognitive support: Certain casein peptides cross the blood-brain barrier and may improve cognition and sleep quality, likely via modulation of neurotransmitters (e.g., increased serotonin precursors).

Casein’s high pro-line content stabilizes the α-helical and β-sheet structures that resist gastric proteolysis, forming micelles (≈1 µm) that slowly dissolve in the acidic stomach.
This slow hydrolysis delivers a steady stream of essential amino acids, especially leucine, to the bloodstream.
This maintains mTORC1 (mechanistic target of rapamycin complex 1) signaling for up to 7 hours post-dose.
Simultaneously, casein phosphopeptides bind calcium and phosphate, forming soluble complexes that enhance intestinal calcium uptake via the TRPV6 channel.
Bioactive peptides released by intestinal proteases act on the gut–brain axis (e.g., via opioid-like receptors) and modulate immune cell cytokine production (e.g., reduced IL-6, increased IL-10).
The combined effect supports anabolic, bone-protective, and immunoregulatory pathways.

General adult supplementation: 20–40 g of isolate or micellar casein (≈0.3–0.5 g kg⁻¹ body weight) taken once daily, preferably before sleep to maximize overnight protein synthesis.
Post-exercise recovery: 20 g within 30 min after training + 20 g of whey, providing both rapid and sustained amino-acid supply.
Weight-loss/ satiety: 30 g mixed with water or low-fat milk 30 min before a meal; the slow digestion prolongs satiety.
Special populations: Elderly or sarcopenic individuals may benefit from 30–40 g split into two doses (evening + mid-day) to counter age-related anabolic resistance.
Special considerations: Athletes requiring >2 g kg⁻¹ day⁻¹ total protein may allocate 40 g of casein as part of total intake. For those with low lactose tolerance, use a hydrolyzed or micellar casein with ≤0.5 % lactose.

Casein is generally safe.
Adverse effects are mainly allergic (IgE-mediated cow-milk allergy) or intolerance (lactose, milk-protein intolerance).
Symptoms include urticaria, gastrointestinal distress, or anaphylaxis in severe cases.
Contraindications: known cow-milk protein allergy, severe renal impairment (high protein load may exacerbate uremia).
Potential drug interactions: casein may reduce absorption of certain antibiotics (e.g., tetracyclines) and iron supplements due to calcium binding; separate dosing by ≥2 h.
Pregnant and lactating women can safely consume 20–30 g/day, but individuals with milk-protein hypersensitivity should avoid.
Chronic high intake (>2 g kg⁻¹ day⁻¹) may increase calcium excretion; monitor renal function in at-risk individuals.

Casein is a family of phosphoproteins (α-S1, α-S2, β, κ) with molecular weights ranging 19–25 kDa for each subunit.
The overall empirical formula for a typical casein protein (average) can be approximated as C₁₁₇H₁₈₇N₃₁O₁₉S₁ (e.g., α-S1-casein).
It contains ~3 % phosphorus (as phosphoserine residues) and ~1 % calcium bound in phosphoserine clusters, conferring high water-binding capacity.
The protein is rich in proline, glutamine, and leucine, with a high proportion of hydrophobic residues that promote micelle formation.
Casein’s isoelectric point (pI) is ≈4.6, allowing precipitation at acidic pH (used in cheese making).
The tertiary structure is predominantly α-helical with β-sheet content, lacking a defined tertiary fold, which contributes to its resistance to gastric proteases.

Commercial casein is most commonly derived from bovine milk.
It is obtained through acid precipitation (pH ≈ 4.6) or ultrafiltration of skim milk.
This is followed by spray-drying to produce micellar casein or whey-casein blends.
Alternative sources include goat, sheep, and camel milk, though bovine remains >90 % of market supply.
Extraction methods aim to preserve the native micellar structure (micellar casein) or produce hydrolyzed forms (casein hydrolysate) for faster absorption.
Quality considerations: protein purity ≥90 % (Nitrogen-to-protein conversion factor 6.38), low residual lactose (<0.5 %), and minimal heavy-metal contamination (<0.2 ppm arsenic, lead).
Certifications such as GMP, ISO-22000, and third-party testing (e.g., NSF, Informed-Choice) are recommended to assure purity and safety for athletes and health-conscious consumers.