According to time-honoured advice, drinking a glass of warm milk before bedtime promotes a good night's sleep. Milk's sleep-enhancing properties are commonly attributed to tryptophan, but scientists have also discovered a mixture of milk peptides called casein-tryptic hydrolyzate (CTH), which relieves stress and improves sleep. Now researchers have identified specific peptides in CTH that could one day be used in new, natural sleep remedies.
Not all adults get enough sleep. Sedatives, such as benzodiazepines and zolpidem, are commonly prescribed for insomnia, but they can cause side effects and people can become addicted to them. Many sedatives work by activating the GABA receptor, a protein in the brain that suppresses nerve signaling. Scientists have also discovered several natural peptides, or small pieces of proteins, that bind the GABA receptor and have anxiety- and sleep-increasing effects. For example, treating a protein in cow's milk called casein with the digestive enzyme trypsin produces the mixture of sleep-enhancing peptides known as CTH. Within this mixture, a specific peptide known as -casozepine (α-CZP) has been identified that may be responsible for some of these effects. Lin Zheng, Mouming Zhao and colleagues wondered if they could find other, perhaps more potent, sleep-enhancing peptides in CTH.
The researchers first compared the effects of CTH and -CZP in sleep tests in mice, finding that CTH showed better sleep-increasing properties than -CZP alone. This result suggested that other sleep-promoting peptides exist in CTH in addition to α-CZP. The team then used mass spectrometry to identify bioactive peptides released from CTH during simulated gastric digestion, and they virtually screened these peptides for binding to the GABA receptor and ability to cross the blood-brain barrier. When the strongest candidates were tested on mice, the best (called YPVEPF) increased the number of mice falling asleep quickly by about 25% and sleep duration by more than 400% compared to a control group. In addition to this promising peptide, other CTH species that could improve sleep through other pathways should be explored, the researchers said.
