Oben J, Enonchong E, Kothari S, Chambliss W, Garrison R, Dolnick D.. Phellodendron and citrus extracts benefit cardiovascular health in osteoarthritis patients: a double-blind, placebo-controlled pilot study. Nutr J., May 20, 2008;7(1): 16.

NP06-1 (Flavoxine™, Citrofen™, Next Pharmaceuticals, Salinas, California) is a proprietary blend of corktree (Phellodendron amurense) bark and orange (Citrus sinensis) peel. This placebo-controlled, randomized, double-blind clinical trial, conducted at the University of Yaounde I, in Yaounde, Cameroon, included overweight and normal weight subjects with osteoarthritis of the knee. Results regarding NP06-1's effect on osteoarthritis will be reported in future publications. In this article, the authors have examined the effects of NP06-1 on body weight, body mass index (BMI), and cardiovascular health biomarkers.

Overweight (BMI: 25-40 kg/m2) and normal weight (BMI: 18.9-24.9 kg/m2) subjects were randomized into 4 groups using a random number table: overweight treatment (OT), overweight placebo (OP), normal weight treatment (NT), and normal weight placebo (NP). The subjects in the treatment groups received 4 capsules daily of NP06-1 (370 mg) for 8 weeks, and the placebo groups took 4 identical placebo capsules daily. NP06-1 is a proprietary blend of corktree bark extract standardized to contain a minimum of 50% berberine and orange peel extract standardized to contain a minimum of 30% polymethoxylated flavones (PMFs). Out of 80 subjects at the start of the trial, 45 subjects completed it. No serious adverse events were reported as reasons for discontinuation. Reasons given included no improvement, relocation, and nausea. Several drop-outs did not state a reason.

The OT group experienced significant reductions in average weight and BMI at 4 and 8 weeks (P<0.001 for all). At 8 weeks, the weight loss was significantly greater in the OT group (average: -9.2 pounds) compared to the OP group (average: -2.5 pounds) (P<0.001). At 8 weeks, significant reductions in average BMI and weight compared to baseline levels were also observed in the NT group (P<0.05 for both), as well as the NP group (P<0.01 for both). The NT group lost significantly more weight (average: -2.6 pounds), compared to the NP group (average: -1.7 pounds) (P<0.01). There were no significant differences in BMI changes between the overweight or normal treatment and placebo groups. The OT group experienced significant decreases in serum total cholesterol and low-density lipoprotein (LDL) cholesterol levels from baseline to 4 and 8 weeks (P<0.001 for all). There was no significant difference total cholesterol decreases between the OT and OP groups. The OT group's decrease in LDL cholesterol at 8 weeks was significantly greater than that of the OP group (P<0.01). The NT group showed significant decreases in total serum cholesterol levels at 4 and 8 weeks, compared to baseline levels (P<0.01 for both). The NT group also showed significant decreases in LDL cholesterol at 4 and 8 weeks compared to baseline levels (P<0.05 and P<0.01, respectively). The decrease in LDL cholesterol was significantly greater in the NT group compared to the NP group at 8 weeks (P<0.01).

The OT and the NT groups showed significant increases in high-density lipoprotein (HDL) cholesterol at 8 weeks, compared to baseline levels (P<0.05 for both). The increases in the OT group were significantly greater than those in the OP group at 8 weeks (P<0.001), and they were significantly greater in NT group compared to the NP group at 4 and 8 weeks (P<0.05 for both). The OT group also experienced significant decreases in triglyceride levels at 4 and 8 weeks (P<0.05 for both), as did the NT group (P<0.001 for both). The decrease in triglycerides was significantly greater in the OT group compared to the OP group at 8 weeks (P<0.001) and significantly greater in the NT group compared to the NP group at 4 and 8 weeks (P<0.01 for both).

At 4 and 8 weeks, the OT group experienced significant reductions compared to baseline values in systolic blood pressure (P<0.05 for both) and diastolic blood pressure (P<0.01 and P<0.001, respectively). The blood pressure decreases were significantly greater in the OT group compared to the OP group at 4 and 8 weeks for diastolic blood pressure (P<0.05 and P<0.001, respectively) and at 8 weeks for systolic blood pressure (P<0.05). The NT group did not show any significant changes in systolic blood pressure, but there were significant decreases in diastolic blood pressure at 4 and 8 weeks compared to baseline (P<0.05 and P<0.01). The NT group experienced a significantly greater decrease in diastolic blood pressure than the NP group at 4 weeks (P<0.05), but the NP group showed a greater decrease at 8 weeks (P<0.001). Fasting blood glucose levels were significantly decreased compared to baseline levels in the OT group at 4 and 8 weeks (P<0.05 and P<0.001, respectively), and decreases were significantly greater in the OT group compared to the OP group at 4 and 8 weeks (P<0.001). There were no significant changes in the fasting blood glucose levels of the normal weight groups. The authors speculate the fasting blood glucose decreases seen in the OT group may be related to body weight decreases.

The authors conclude that NP06-1 has beneficial effects on cardiovascular risk factors in normal weight and overweight subjects and has the added benefit of weight loss. These effects may be attributed to berberine and PMFs. More research is needed to confirm the results.  

—Marissa Oppel, MS