title: Effects of D-003, a mixture of very long chain fatty acids purified from sugar cane wax, at 5 and 10 mg/day on platelet aggregation in healthy volunteers.
abstract: D-003 is a mixture of high molecular weight aliphatic primary acids purified from sugar cane wax with antiplatelet and cholesterol-lowering effects. Previous studies showed that D-003 (10-20 mg/day) administered for a short time inhibits platelet aggregation, 14 days being the longest duration investigated. This study was conducted to investigate the effects of D-003 (5 and 10 mg/day) for 30 days on platelet aggregation in normocholesterolemic subjects. This report shows the effects of D-003 on platelet aggregation to arachidonic acid (AA) (1.5 mM), collagen (2 microg/ml) and adenosine 5'-diphosphate ADP (2 microM) assessed at baseline and at treatment completion. Fifty-four subjects were randomized to placebo or D-003 (5 or 10 mg/day) for 30 days. Platelet aggregation to AA, collagen and ADP were assessed. D-003 at the lowest dose (5 mg/day) significantly but modestly inhibited (p < 0.01) platelet aggregation to AA (5.0%) and (p < 0.01) to collagen (7.5%). D-003 at 10 mg/day inhibited (p < 0.001) platelet aggregation to AA and collagen (p < 0.01) by 20.3% and 14.7%, respectively. ADP-induced aggregation, however, was unchanged. D-003 at 10 mg/day, but not at 5 mg/day, lowered (p < 0.01) plasma fibrinogen. D-003 (5 and 10 mg/day) reduced low-density lipoprotein cholesterol (LDL-C) by 17.7% and 26.4%, respectively, and total cholesterol (TC) by 14.5% and 18.5%, while at 10 mg/day, but not at 5 mg/day, it increased high-density lipoprotein cholesterol (HDL-C) by 9.6%. Triglycerides, however, were unchanged with D-003. No disturbances in safety indicators were induced with D-003. One subject (D-003 5 mg/day) discontinued the study and four patients (three taking D-003 and one taking placebo) reported adverse effects (AE) (headache in two patients taking D-003 and one patient taking placebo, and polyphagia in one patient taking D-003). In conclusion, D-003 (5-10 mg/day) for 30 days inhibited platelet aggregation to AA and collagen but not to ADP Therefore, the antiplatelet effect was present with the longer treatment, even at a dose of 5 mg/day. The cholesterol-lowering effects of D-003 were consistent with those expected for such a short treatment. In addition, D-003 at 10 mg/day significantly lowered plasma fibrinogen. The treatment was well tolerated.
authors.affiliation: Center for Natural Products of the National Center for Scientific Research, Havana City, Cuba. clinica@enet.cu
authors.forename: M L
authors.initials: ML
authors.lastname: Arruzazabala
authors.forename: V
authors.initials: V
authors.lastname: Molina
authors.forename: D
authors.initials: D
authors.lastname: Carbajal
authors.forename: L
authors.initials: L
authors.lastname: Fernández
authors.forename: R
authors.initials: R
authors.lastname: Mas
authors.forename: G
authors.initials: G
authors.lastname: Castaño
authors.forename: J
authors.initials: J
authors.lastname: Illnait
authors.forename: S
authors.initials: S
authors.lastname: Mendoza
authors.forename: J
authors.initials: J
authors.lastname: Fernańdez
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001772:Blood Cell Count; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005227:Fatty Acids / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: C418063:D-003 sugarcane wax acid mixture; D005227:Fatty Acids; D010975:Platelet Aggregation Inhibitors; D014280:Triglycerides; D002784:Cholesterol