Dihexa

An angiotensin IV derived peptide that promoted synapse formation in rodent models of cognitive impairment, with no human data at all.

What it is

Dihexa is a chemically modified fragment of angiotensin IV, engineered to survive in the bloodstream and cross into the brain, which the parent fragment does poorly.

Its proposed mechanism runs through hepatocyte growth factor and its receptor Met, a pathway involved in forming and stabilizing synapses. In rodent work it increased dendritic spine density and improved performance on learning tasks after a cholinergic lesion.

What is unknown

Everything clinical. There are no published human trials of dihexa, no established dose, no safety data, and no pharmacokinetics in people.

The Met pathway it targets is also a growth signaling pathway that features in oncology, where the therapeutic goal is usually to inhibit it rather than to stimulate it. That does not prove harm, but it is the specific unanswered question a sensible person would want answered before taking a Met agonist for months.

The honest position

Dihexa is a research compound with a promising rodent cognition dataset and a completely empty human record. Anything sold as dihexa is unregulated chemical supply.

If cognitive change is the concern, the measurable and modifiable inputs are sleep, vascular risk markers, hearing, activity and metabolic health. None of them are exciting and all of them have outcome data.

Baseline does not dispense this. It is here because people ask about it, and because an honest read of the evidence is more useful than a sales page.

References

  1. Benoist CC, et al. Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs. J Pharmacol Exp Ther. 2011.
  2. McCoy AT, et al. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 2013.