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Cah4.0
Casein Hydrolysate Research
Mostly mechanism / observationalHigh safety
11 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most Casein Hydrolysate studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from mixed-quality randomised trials published 2001–2024 with a typical study size of 63 participants.
Based on 11 studies · 7 RCTs · 458 total participants
Confidence
Moderate
By outcome
Anxiety & stressModest reduction in stress-related symptoms and state anxiety in small RCTs (stressed women, healthy volunteers under lab stress); effects small and several trials industry-linked · Acute effects within hours; symptom changes over 2-4 weeks · Blunted blood-pressure and cortisol response to acute stressors in a small healthy-volunteer trial; lowered serum cortisol and perceived-stress scores in a stress/acne RCT · Acute (single dose) to 4 weeks
Mostly mechanism / observational8 studies
Sleep & insomniaMixed — one crossover RCT in poor sleepers improved sleep-diary latency and efficiency, but two combination-product RCTs were null on their primary sleep endpoints · 2-4 weeks of nightly use · Some reduction in wake-after-sleep-onset and increased total sleep time on sleep diaries in Lactium trials; objective polysomnography largely unchanged · 2-4 weeks of nightly use
Mostly mechanism / observational5 studies
Active research area
4 studies in the last 5 years
200120122024
1RCTn=171 · medium study2017
There were no significant between group differences between baseline and endpoint on the primary outcome... It currently cannot be concluded that administration of LZComplex3 for 2 weeks improves sleep quality.
Scholey A, Benson S, Gibbs A, Perry N, Sarris J, Murray G. · Nutrients (2017)
Placebo-controlled double-blind trial in 171 healthy adults with mild insomnia; LZComplex3 (Lactium + Zizyphus + hops + magnesium + B6) for 2 weeks
No significant between-group difference on the primary outcome (change in Pittsburgh Sleep Quality Index)
Secondary outcomes (daytime functioning, fatigue, mood, anxiety, cognition, stress reactivity) also improved similarly in both groups
The 30-day treatment by alpha(s1)-casein hydrolysate in females with stress-related symptoms reduced their symptoms, particularly in digestion, cardiovascular, intellectual, emotional and social problems.
Kim JH, Desor D, Kim YT, Yoon WJ, Kim KS, Jun JS, Pyun KH, Shim I. · Eur J Clin Nutr (2007)
Double-blind, randomized, crossover, placebo-controlled trial in 63 women with stress-related symptoms (anxiety, sleep problems, fatigue)
150 mg/day of αs1-casein hydrolysate for 30 days vs placebo, with a 3-week washout
Significant reductions in stress-symptom domains: digestion (P<0.01), cardiovascular (P<0.05), intellectual (P<0.01), emotional (P<0.05), social (P<0.05)
Overall perceived sleep profiles in sleep diaries were significantly improved during the ACH phase... actigraphy demonstrated significantly increased sleep efficiency after continuous use of ACH for four weeks.
Kim HJ, Kim J, Lee S, Kim B, Kwon E, Lee JE, Chun MY, Lee CY, Boulier A, Oh S, Lee HW. · Nutrients (2019)
Double-blind randomized crossover trial in 48 community-based Koreans with mild-to-moderate sleep disturbance; ACH (Lactium) vs placebo for 4 weeks each
Sleep-disturbance scales improved similarly in both phases with no significant group difference (notable placebo response)
Sleep diaries showed significantly improved total sleep time, sleep efficiency, sleep latency, and wake-after-sleep-onset during the ACH phase
No significant differences were observed in sleep quality and insomnia scale characteristics between the two groups... significant differences were observed in the increase in TST, decrease in SOL, increase in SE, decrease in WASO counts.
Lim SE, Kim HS, Lee S, Kang EY, Lim JH, Kim BY, Shin SM, Baek Y. · Front Nutr (2024)
Double-blind randomized controlled trial in 40 adults with sleep discomfort; LTC-022 (Lactium + L-theanine) vs placebo for 8 weeks
NULL on the primary endpoints — no significant group differences on Pittsburgh Sleep Quality Index or Insomnia Severity Index
Within-group sleep-diary improvements in the active group: increased total sleep time and sleep efficiency, decreased sleep-onset latency and wake-after-sleep-onset, earlier bedtime
Administrations of αs1-casein, its 91-100 (α-casozepine)... fragments... have been reported to increase open arm exploration... Some effects appear to be mediated by the GABAA receptor complex.
Lalonde R. · Pharmacol Biochem Behav (2024)
Review of anxiolytic-like actions of milk proteins and their peptides in rodent models (elevated plus-maze, open-field)
αs1-casein and its α-casozepine (91-100) and shorter fragments increase anxiolytic-like behavior
Effects partly mediated by the GABA-A receptor complex (antagonists blocked the action), with possible serotonin, dopamine, and neurotensin involvement
PSG data revealed a significant decrease in sleep onset latency from baseline in the ACH group compared to the placebo group (p = 0.012; -7.7 ± 16.0 min vs. 6.1 ± 17.7 min for ACH and placebo groups, respectively).
Chang CM, Tsai IJ, Yang CC, Liu WC, Yang CP. · Clin Nutr (2024)
4-week randomized, double-blind, placebo-controlled trial in 36 Taiwanese patients with chronic insomnia; ACH (Lactium) monotherapy 600 mg/day for 2 weeks then 300 mg/day vs maltodextrin placebo
Objective polysomnography showed a significant reduction in sleep-onset latency vs placebo (p=0.012) — a positive objective sleep signal for ACH alone, not a combination product
Within-group improvements in ISI, GSDS, PSQI, ESS, and HADS scores; the between-group difference reached significance for GSDS (p=0.045)
A fragment, corresponding to the sequence 91-97 and found in all the hydrolysis media in significant amount, possessed an anxiolytic activity in three behavioral tests measuring this parameter.
Cakir-Kiefer C, Le Roux Y, Balandras F, Trabalon M, Dary A, Laurent F, Gaillard JL, Miclo L. · J Agric Food Chem (2011)
Assessed gastric/pancreatic-protease stability of α-casozepine in vitro
α-Casozepine was slowly degraded; the 91-95 region was fully resistant to all proteases tested
A surviving 91-97 fragment retained anxiolytic activity in three behavioral tests
At 12 weeks, stress levels were significantly lower in [the Lactium] group... as measured by the change in serum cortisol levels... the mean change in PSS scores and HAM-A scores was significant.
Kerure AS, Udare S, Vispute C. · Dermatol Res Pract (2022)
Randomized, controlled, multicenter, open-label trial in 100 patients with moderate-to-severe acne vulgaris; Lactium plus standard care vs standard care alone
Significantly greater reduction in serum cortisol with Lactium over 12 weeks
Significant improvements in Perceived Stress Scale and Hamilton Anxiety Rating Scale scores vs standard care alone