What is DSIP? Delta sleep-inducing peptide in published research

Where does DSIP come from?

DSIP was isolated in 1977 by the group of Marcel Monnier and Guido Schoenenberger in Basel. They electrically stimulated an area of the thalamus in rabbits to induce sleep, collected their cerebral venous blood by dialysis and isolated a peptide that, when infused into the brain ventricles of other rabbits, increased slow-wave (delta) and spindle EEG activity. They named it delta sleep-inducing peptide.

Its sequence is Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, nine amino acids with a calculated molecular weight of about 849 g/mol. In the founding studies the group also made shorter fragments and analogues and tested all nine synthetic peptides in 58 rabbits under double-blind conditions. A 2006 review noted that the DSIP structure differs from every other known peptide family.

How is it described at the molecular level?

There is no agreed mechanism. A 2006 review titled DSIP a still unresolved riddle explained that the link to sleep was never characterised further, partly because no DSIP gene, precursor protein or receptor was ever found. The authors proposed that a still unidentified DSIP-like peptide may be responsible for DSIP-like immunoreactivity and some of the biological activity attributed to DSIP. They also noted that certain synthetic analogues, but not DSIP itself, promoted slow-wave sleep in their own rabbit and rat studies.

Physiological studies point to effects on neuroendocrine systems. In rats, DSIP reduced corticosterone release triggered by corticotropin releasing factor, and the authors located the effect at the pituitary. In brain stem slices it stimulated release of met-enkephalin. In perfused sheep choroid plexus, DSIP crossed into cerebrospinal fluid with low to moderate permeability and a saturable transport component, and a study in dogs reported that it crossed the blood-brain barrier.

What has been observed in published research?

• Sleep EEG (rabbit): infusion into the brain ventricles increased slow-wave and spindle EEG activity in the founding studies.
• Insomnia (human, small studies): in six middle-aged insomniacs without a control group, longer and less interrupted sleep was reported. In a 1992 double-blind study of 16 patients, sleep efficiency and sleep latency improved slightly against placebo, but the authors judged the effects weak and concluded that short-term use was not likely to be of major benefit.
• Stress hormones (rat): DSIP reduced corticotropin releasing factor induced corticosterone release, without changing the response to ACTH.
• Seizures (rat): DSIP and its analogue DSIP-12 reduced the severity of audiogenic seizures provoked by metaphit, and DSIP strengthened the anticonvulsant effect of valproate in the same model.
• Stroke (rat): after middle cerebral artery occlusion, intranasal DSIP over eight days was associated with faster recovery of motor coordination in the rotarod test. The reduction in infarct size was not statistically significant.
• Stability (human and rat blood): DSIP was broken down in blood at rates that depended on temperature and species, while a phosphorylated analogue lasted longer.

What the evidence does not establish

DSIP has a misleading name. Its effect on sleep was not confirmed in the only double-blind human study found, and leading researchers in the field have described the sleep hypothesis as poorly documented. Without an identified gene, precursor or receptor, it is unclear whether DSIP is a natural signalling molecule at all or a fragment detected by cross-reacting antibodies.

Most animal findings are single studies, many decades old, using routes such as infusion into the brain ventricles that are specific to the experimental setting. The human studies were very small and are now more than 30 years old. None of these results establish an effect in people.

How does DSIP compare with related compounds?

Researchers also tested modified forms of DSIP. A phosphorylated version, P-DSIP, was degraded more slowly in blood, and DSIP-12, in which alanine at position 2 is replaced by beta-alanine, was studied alongside DSIP in the rat seizure model. The 2006 review reported that some synthetic analogues promoted slow-wave sleep in rabbits and rats while DSIP itself did not, which is one reason the authors suspected a related natural peptide.

Among peptides studied for stress and behaviour, DSIP is often listed next to Selank. The two have different origins: Selank is a stabilised analogue of the immune peptide tuftsin with small comparative clinical studies behind it, while DSIP was isolated from rabbit blood and has only very small, older human studies. Neither has been compared directly with the other in a published study.

Which formats does Vitality Peps supply?

Vitality Peps supplies DSIP as a 10 mg lyophilised vial and as a 10 mg nasal spray format for laboratory research, each documented by a batch certificate of analysis. Bacteriostatic water is listed separately for reconstituting the vial.

How is it handled in the laboratory?

Because DSIP was broken down readily in blood studies, careful handling matters. Lyophilised powder is stored cold and protected from light and brought to room temperature before opening. It is reconstituted with bacteriostatic water added slowly down the side of the vial, and the working concentration is calculated from the actual vial mass on the batch certificate. Reconstituted solution is refrigerated, labelled and dated. The nasal spray format contains a prepared solution: it is kept refrigerated and dated on opening.

Research use only

DSIP supplied by Vitality Peps is for in vitro laboratory research only. Not a medicine, not a supplement, not for human or veterinary consumption. Nothing above is instructions for use.