What is the current evidence for the use of human placental hydrolysate (HPH) in adult males, particularly in human randomized controlled trials (RCTs)?

Evidence for Human Placental Hydrolysate (HPH) in Adult Males: Randomized Controlled Trials

Human placental hydrolysate (HPH) has shown promising results in randomized controlled trials for liver diseases in adult males, with efficacy comparable to standard treatments for alcoholic and nonalcoholic steatohepatitis, though evidence remains limited for other applications.

Clinical Evidence in Liver Disease

• HPH has demonstrated efficacy in treating alcoholic and nonalcoholic steatohepatitis (ASH/NASH) in adult males, with improvement rates in alanine aminotransferase (ALT) levels comparable to liver extract and flavin adenine dinucleotide combinations 1
• In a multicenter, open-label, randomized comparative study, 62.9% of patients receiving HPH achieved the primary goal of ≥20% improvement in ALT levels compared to 48.8% in the control group 1
• Adverse drug reactions were minimal to moderate and occurred in only 3.1% of patients, with similar treatment compliance rates between HPH and control groups 1

Mechanism of Action in Liver Protection

• HPH exhibits protective effects against hepatocyte apoptosis through multiple mechanisms:
  • Reduction of liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) 2
  • Inhibition of inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α 2
  • Activation of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, and catalase 2
  • Upregulation of the Kelch-like ECH2-associated protein 1-p62-nuclear factor-erythroid 2-related factor 2 pathway, a component of oxidative stress defense 2

Route of Administration Considerations

• Intravenous administration of HPH appears more effective than subcutaneous injection for liver regeneration, as demonstrated in animal studies 3
• Intravenous HPH showed superior effects on:
  • Enhancing liver regeneration rate after partial hepatectomy 3
  • Inhibiting decreases in liver total protein 3
  • Reducing serum transaminase levels 3
  • Minimizing pathological changes such as vacuolation and necrosis in hepatocytes 3

Anti-Stress Effects

• HPH has demonstrated anti-stress effects in male Sprague-Dawley rats, which may be relevant for stress-related conditions in adult males 4
• Treatment with HPH significantly decreased immobility time in the forced swimming test compared to controls 4
• The anti-stress mechanism appears to involve:
  • Increased glutathione peroxidase (GPx) protein levels in the hippocampus 4
  • Decreased expression of NADPH-diaphorase in the paraventricular nucleus 4
  • Regulation of nitric oxide synthase and antioxidant activity in the brain 4

Molecular Mechanisms

• Recent proteomic analysis has identified 41 peptides in HPH that affect mitochondrial function 5
• These peptides regulate multiple targets relevant to cellular health:
  • Caspases (CASP1, CASP3, CASP4) and other apoptosis-regulating proteins (BCL2, CANPL1, PPARA) 5
  • MAP kinases (MAPK1, MAPK3, MAPK4, MAPK8, MAPK9, MAPK10, MAPK14) 5
  • AKT1/GSK3B/MTOR cascade kinases 5
  • HPH peptides inhibit mitochondrial pore formation, apoptosis, and excessive mitochondrial autophagy under conditions of oxidative/toxic stress 5

Limitations and Research Gaps

• Most robust evidence for HPH in adult males is limited to liver diseases, particularly ASH and NASH 1
• While animal studies suggest broader applications, human RCT data for other conditions remains sparse 3, 2, 4
• The available human RCT (Biological & Pharmaceutical Bulletin, 2014) was open-label rather than double-blind, which may introduce bias 1
• Long-term safety and efficacy data from large-scale RCTs are lacking 1

Clinical Application Considerations

• HPH may be considered as an alternative treatment for adult males with alcoholic or nonalcoholic steatohepatitis who have elevated liver enzymes 1
• The safety profile appears favorable with minimal to moderate adverse reactions 1
• For optimal effects in liver disease, intravenous administration may be preferable to subcutaneous injection based on preclinical evidence 3
• The anti-stress effects suggest potential applications for stress-related conditions in adult males, though more human RCT data is needed 4