Clinical trials and publications

Effects of N-PEP-12 on Memory among Older Adults

T.H. Crook et al./ Int Clin Psychopharmacol 2005, 20:97-100


This study was undertaken to determine whether N-PEP-12 is effective in improving memory and other cognitive abilities among healthy older adults who have experienced ‘normal’ age-related memory loss. Subjects were 54 males and females, aged 50 years and older, who presented both subjective and objective evidence of memory loss since early adulthood. The study was a fully randomized, double-blind comparison of N- PEP-12 and placebo. Cognitive assessments were performed at baseline and following 30 days of treatment. The primary outcome measure was the Alzheimer’s Disease Assessment Scale–Cognitive (ADAS-cog) Memory score, with the Syndrom Kurz Test (SKT), tests, digit cancellation, digit span, verbal fluency and clinical ratings as secondary outcomes. N-PEP-12 treated subjects performed better than placebo-treated subjects on the ADAS-cog Memory score, the SKT, clinical ratings and some, but not other tests. N-PEP-12 may be an effective treatment for memory loss in healthy older adults

Keywords: Age-related memory loss, memory, neuropeptides, N-PEP-12

Neuropeptide Dietary Supplement N-PEP-12 Enhances Cognitive Function and Activates Brain Biolectrical Activity in Healthy Elderly Subjects

X.A. Álvarez et al./Methods Find Exp Clin Pharmacol 2005, 27(7):483-487


N-PEP-12 is a dietary supplement consisting of neuropeptides and amino acids. In animal experiments, the compound has been shown to enhance cognitive function and reduce neurodegenerative events associated with aging. In this study, we investigated the effects of a single oral dose of N-PEP-12 (180 mg) on brain bioelectrical activity and cognitive performance in healthy elderly subjects. N-PEP-12 induced a significant (p < 0.05) increase in relative α-activity power 6 h after administration. This enhancement was accompanied by a generalized decrease in slow Δ-activity. Significant improvement in memory performance subtests was also seen 6 h after N-PEP-12 administration in some but not in all tests. Taken together, these data suggest that N-PEP-12 might be a reliable dietary supplement to be investigated for improving and perhaps, maintaining brain function among healthy older adults.

Keywords: aging – brain bioelectrical activity – Cognition – Memory – N-PEP-12

Cognitive Effects of the Novel Neuroprotective Dietary Supplement N-PEP-12: Evidence from a Self-Assessment Study

D. Volc et al./Jatros Neurologie & Psychiatrie 2005


The results indicate that N-PEP-12 improves the self-perception of cognitive performance in healthy volunteers. N-PEP-12 seems to constitute a safe and useful dietary supplement to support cognitive performance in elderly subjects.

Long-term Treatment of Aged Long Evans Rats with a Dietary Supplement Containing Neuroprotective Peptides (N-PEP-12) to Prevent Brain Aging: Effects of Three Months Daily

Hutter-Paier B. et al./Journal of Medicine and Life Vol. 8, Issue 2, April-June 2015


A novel dietary supplement produced from purified nerve cell proteins, N-PEP-12, has shown to share properties with naturally occurring peptide growth factors by stimulating neurite outgrowth and beneficial effects on neuronal survival and protection against metabolic stress in cell cultures. The current study investigates the effects of long-term intake on age-dependent memory decline by assessing cognitive performance and synaptic density. All the experiments were performed in aged Long Evans rats randomly assigned to saline or N-PEP-12 once daily by gavage over a period of three months. Behavioral tests were performed in the Morris Water Maze after one, two and three months of treatment. Histological examinations were performed in the hippocampal formation and in the entorhinal cortex by measuring the synaptic density. This study shows that the oral intake of N-PEP-12 has beneficial effects on the cognitive performance of aged animals and that these effects go along with an increase in the synaptic density. Thus, N-PEP-12 may help maintain memory and learning performance during the aging process.

Keywords: N-PEP-12, brain aging, oral gavage, hippocampus

N-PEP-12 – A Novel Peptide Compound that Protects Cortical Neurons in Culture against Different Age and Disease Associated Lesions

M. Windisch, B. Hutter-Paier, E. Grygar and H. Moessler


The neuroprotective potency of N-PEP-12, a novel, proprietary compound consisting of biopeptides and amino acids was investigated. Lesion models have been applied in neuronal cell cultures of embryonic chicken cortex, pre-treated with N-PEP-12 from the first day onwards. On day 8 in vitro neurons were lesioned and cell viability was measured 24 and 48 hours later. To simulate acute brain ischemia, cytotoxic hypoxia was induced by sodium cyanide or by iodoacetate and excitotoxicity by L-glutamate. Ionomycin for up to 48 hours induced calcium overload. The cytoskeleton was disrupted by addition of colchicine. N-PEP-12 shows dose-dependent neuroprotection in all different models. The effect size depends on the recovery time but also on the extent of the lesion. In cases of mild to moderate lesion pronounced dose-dependent effects could be demonstrated. This indicates that chronic exposure to N-PEP-12 is able to prevent neuronal cell death associated to conditions occurring during normal aging and neurological disorders like ischemic stroke, hypoxia, brain trauma, or AD.

Keywords: Peptides, growth factors, neuroprotection, brain lesion

The Neuropeptide-12 Improves Recognition Memory and Neuronal Plasticity of the Limbic System in Old Rats

E.M. Hernández-Hernández, K.C. Hernandez, R.A. Vásquez-Roque, A.Díaz, F. de la Cruz, B. Florán and G.Flores


Aging is a stage of life where cognitive and motor functions are impaired. This is because oxidative and inflammatory processes exacerbate neurodegeneration, which affects dendritic morphology and neuronal communication of limbic regions with memory loss. Recently, the use of trophic substances has been proposed to prevent neuronal deterioration. The neuropeptide-12 (N-PEP-12) has been evaluated in elderly people with dementia, showing improvements in cognitive tasks due to acts as a neurotrophic factor. In the present work, we evaluated the effect of N-PEP-12 on motor activity and recognition memory, as well as its effects on dendritic morphology and the immunoreactivity of GFAP, Synaptophysin (SYP), and BDNF in neurons of the prefrontal cortex (PFC), dorsal hippocampus (DH) and nucleus accumbens (NAcc) of aged rats. The results show that N-PEP-12 improved the recognition memory, but the motor activity was not modified compared to the control animals. N-PEP-12 increases the density of dendritic spines and the total dendritic length in neurons of the PFC (layers 3 and 5) and in DH (CA1 and CA3). Interestingly NAcc neurons showed a reduction in the number of dendritic spines. In the N-PEP-12 animals, when evaluating the immunoreactivity for SYP and BDNF, there was an increase in the three brain regions, while the mark for GFAP decreased significantly. Our results suggest that N-PEP-12 promotes neuronal plasticity in the limbic system of aged animals, which contributes to improving recognition memory. In this sense, N-PEP-12 can be considered as a pharmacological alternative to prevent or delay brain aging and control senile dementias.

Keywords: golgi–cox staining, hippocampus, N-PEP-12, novel object recognition test, nucleus accumbens, pre-frontal cortex