Pancragen

Human studies

Older adults with type 2 diabetes, 2011 (PMID: 22448364)

Who: the Institute of Gerontology of the National Academy of Medical Sciences of Ukraine in Kyiv, with Khavinson as co-author. Design and size: 63 older people were examined, 30 healthy and 33 with type 2 diabetes; some of the diabetic patients received Pancragen and the others did not. The abstract does not give the number in each group, how patients were assigned, or the dose, route or length of treatment, and it describes no randomization, blinding or placebo. Findings: night-time melatonin production was 70 percent lower in the diabetic patients than in healthy people of the same age. In the diabetic patients given Pancragen, fasting glucose and glucose during a standard glucose tolerance test fell significantly, as did plasma insulin and the insulin resistance index; patients not given Pancragen showed no change in these measures. The abstract does not mention adverse events.

Older adults with impaired glucose tolerance, 2013, Russian language (PMID: 28976155)

Who: the D. F. Chebotarev Institute of Gerontology in Kyiv, with Khavinson as co-author. Design and size: 150 healthy people were screened, 39 aged 20 to 39, 42 aged 40 to 59 and 69 aged 60 or older. The study gave the 12 older adults found to have impaired glucose tolerance a product the authors call Pankragen forte, described as the tetrapeptide, at 500 micrograms twice a day for 4 weeks (PMID: 28976155); the abstract does not state the route. No control group is described. Measures: glycated hemoglobin, a 75 g oral glucose tolerance test with glucose and insulin at 30, 60 and 120 minutes, proinsulin, HOMA-IR, the Matsuda index and HOMA beta-cell function. Findings: glucose during the tolerance test fell significantly in half of the 12 patients, and the authors also report better serum lipids and endothelial function and lower platelet aggregation. The abstract does not mention adverse events.

Monkey studies

Old female rhesus monkeys, 2014, Russian language (PMID: 25946840)

Design: the study ran glucose tolerance tests in old and young female rhesus monkeys and repeated them in the old monkeys after giving Pancragen at 50 micrograms per animal per day by intramuscular injection for 10 days (PMID: 25946840). The abstract does not give the number of animals. Findings: at baseline, old monkeys cleared glucose more slowly and had higher insulin and C-peptide peaks than young monkeys. After Pancragen, the old monkeys cleared glucose faster and their insulin and C-peptide responses normalized, and the effect partly persisted 3 weeks after the injections stopped.

Old female rhesus monkeys compared with glimepiride, 2015, Russian language (PMID: 28509500)

Who: the Research Institute of Medical Primatology in Sochi, with Khavinson as co-author. Design and size: the study used 9 old female rhesus monkeys aged 20 to 25 years, giving 5 of them Pancragen at 0.05 mg per animal per day by intramuscular injection for 10 days and 4 of them the diabetes drug glimepiride at 4 mg per animal per day by mouth for 10 days (PMID: 28509500). Blood glucose, insulin and C-peptide were measured before, during and after treatment and during glucose tolerance tests. Findings: both treatments lowered basal glucose. Pancragen normalized insulin and C-peptide levels, while glimepiride produced a stronger, delayed fall in glucose and raised C-peptide without changing insulin. The authors concluded that Pancragen was effective and safe.

Rat studies

Streptozotocin-induced diabetes, 2007 (PMID: 18642713)

Design: Wistar rats made diabetic with streptozotocin, given Pancragen by mouth or by intramuscular injection. The abstract does not give the number of animals. Findings: oral Pancragen produced a pronounced fall in blood glucose during treatment. Intramuscular Pancragen normalized the adhesion of the mesenteric capillary lining (endothelium) but did not change capillary permeability.

Ageing and streptozotocin-induced diabetes, 2010 (PMID: 21246099)

Design: rats of different ages and rats with streptozotocin-induced diabetes, assessed with metabolic measures related to apoptosis (programmed cell death). The abstract reports no results.

Rat tissue explants, 2006, Russian language (PMID: 17152728)

Design: the study treated explants of heart, lung, prostate and pancreas from young (3-week-old) and aged (18-month-old) rats with Pancragen and three other short peptides at 0.05 ng/ml (PMID: 17152728). Findings: each peptide stimulated growth in the matching tissue culture compared with untreated explants, including Pancragen in pancreatic explants.

Pancreatic cells in culture

• 2012 (PMID: 22808515): expression of the differentiation factors CXCL12 and Hoxa3 fell in late-passage (aged) cultures of human embryonic pancreatic cells, and Pancragen raised it, more so in aged cultures.
• 2012, Russian language (PMID: 23734516): in aged human pancreatic cell cultures, H-Lys-Glu-Asp-Trp-NH2 raised MMP2, MMP9, serotonin, CD79alpha, Mcl1, PCNA and Ki67 and lowered p53.
• 2013 (PMID: 23486591): in young and aged pancreatic cell cultures, Pancragen raised the acinar cell factors Pdx1 and Ptf1a and the islet cell factors Pdx1, Pax6, Pax4, Foxa2 and Nkx2.2.
• 2015 (PMID: 25761685): a study of ageing human pancreatic cell cultures from Moscow State University, with Khavinson as co-author, linked age-related changes in PDX1, PAX6 and NGN3 expression to promoter methylation; KEDW changed methylation at a few sites in the FOXA2 promoter without any link to FOXA2 expression.

Binding and modeling studies

KEDW bound wheat histones in a test-tube fluorescence study (PMID: 23581987). Computer models placed the tetrapeptide at the DNA sequence GGCAG in 2014 (PMID: 24770759) and at the sequence acct in 2016 (PMID: 27909961), and a 2022 review docked Pancragen against the amino-acid transporter LAT1 (PMID: 35887081). These are predictions and test-tube measurements, not evidence of effects in the body.

Who did the research

All but one of the indexed primary studies of Pancragen list Khavinson as an author. Collaborators include the Institute of Gerontology in Kyiv, the Research Institute of Medical Primatology in Sochi and a Moscow State University laboratory. Most of the primary studies appeared in Bulletin of Experimental Biology and Medicine, the English edition of a Russian journal, and in the Russian-language journal Advances in Gerontology (Uspekhi gerontologii), as their NLM Catalog records describe them. No replication by an independent group is indexed in PubMed.

Human data

The two human studies of Pancragen do not mention adverse events in their abstracts (PMID: 22448364; PMID: 28976155). No study designed to measure the safety of Pancragen in people is indexed in PubMed.

Animal data

In old female rhesus monkeys, Pancragen lowered basal blood glucose, as did the comparison drug glimepiride (PMID: 28509500). The authors of that study called Pancragen safe, a conclusion drawn from five treated animals over 10 days. In rats with streptozotocin-induced diabetes, oral Pancragen produced a pronounced fall in blood glucose during treatment (PMID: 18642713). No toxicology study of Pancragen is indexed in PubMed.

What the data show

Glucose lowering is the measured effect of Pancragen most relevant to safety. Neither human abstract reports episodes of low blood sugar, and both human studies were small.