Supplementation of Blackcurrant Anthocyanins Increased Cyclic Glycine-Proline in the Cerebrospinal Fluid of Parkinson Patients: Potential Treatment to Improve Insulin-Like Growth Factor-1 Function

Nutrients. 2018 Jun 2;10(6):714. doi: 10.3390/nu10060714.


Background: Insulin-like growth factor-1 (IGF-1) function is impaired in Parkinson disease. Cyclic glycine-proline (cGP), a metabolite of IGF-1, is neuroprotective through improving IGF-1 function. Parkinson disease patients score lower on Hospital-associated Anxiety and Depression Scale after supplementing blackcurrant anthocyanins (BCA), which may be associated with IGF-1 function. We evaluated the changes of cGP and IGF-1 before and after the supplementation.

Methods: Plasma and cerebrospinal fluid (CSF) were collected from 11 male patients before and after 28 day supplementation of BCA. The concentrations of IGF-1, IGF binding protein (IGFBP)-3, and cGP were measured using ELISA and HPLC-MS assays. The presence of cGP in the BCA was evaluated.

Results: cGP presented in the BCA. BCA supplementation increased the concentration of cGP (p < 0.01), but not IGF-1 and IGFBP-3 in the CSF. CSF concentration of cGP was correlated with plasma concentration of cGP (R = 0.68, p = 0.01) and cGP/IGF-1 molar ratio (R = 0.66, p = 0.01). The CSF/plasma ratio was high in cGP and low in IGF-1 and IGFBP-3.

Conclusion: cGP is a natural nutrient to the BCA. The increased CSF cGP in Parkinson disease patients may result from the central uptake of plasma cGP. Given neurotrophic function, oral availability, and effective central uptake of cGP, the BCA has the potential to be developed to treat neurological conditions with IGF-1 deficiency.

Keywords: Parkinson disease; autocrine regulation; bioavailability of insulin-like growth factor-1 (IGF-1); blackcurrant anthocyanins; central uptake; cerebrospinal fluid; cyclic Glycine-Proline (cGP).

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anthocyanins / isolation & purification
  • Anthocyanins / therapeutic use*
  • Antiparkinson Agents / isolation & purification
  • Antiparkinson Agents / therapeutic use*
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Fruit / chemistry
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / cerebrospinal fluid
  • Insulin-Like Growth Factor I / cerebrospinal fluid*
  • Insulin-Like Growth Factor I / deficiency
  • Male
  • Middle Aged
  • New Zealand
  • Parkinson Disease / blood
  • Parkinson Disease / cerebrospinal fluid
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / physiopathology
  • Peptides, Cyclic / blood
  • Peptides, Cyclic / cerebrospinal fluid*
  • Ribes / chemistry*
  • Time Factors
  • Treatment Outcome


  • Anthocyanins
  • Antiparkinson Agents
  • Biomarkers
  • IGF1 protein, human
  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Peptides, Cyclic
  • cyclic glycine-proline
  • Insulin-Like Growth Factor I