| Date: 07-15-2015 | HC# 021564-524 |
Filip R, Possemiers S, Heyerick A, et al. Twelve-month consumption of a polyphenol extract from olive (Olea europaea) in a double blind, randomized trial increases serum total osteocalcin levels and improves serum lipid profiles in postmenopausal women with osteopenia. J Nutr Health Aging. January 2015;19(1):77-86.
Osteoporosis (bone loss) leads to an increased risk of fractures and affects many people, especially women, throughout the world. Olive (Olea europaea, Oleaceae) oil consumption is thought to be associated with a lower risk of osteoporosis; oleuropein, a combination of phenol compounds, has been shown to modulate bone loss in vivo. To investigate whether oleuropein and other olive compounds have beneficial cellular mechanisms in bone generation, this randomized, placebo-controlled, double-blind trial used a standardized olive leaf extract (Bonolive®; BioActor BV; Maastricht, The Netherlands) in postmenopausal osteoporosis sufferers.
This trial was conducted at the Osteoporosis Outpatient Department of the Institute of Agricultural Medicine in Lublin, Poland. From a total of 103 women, 64 were randomly assigned into a treatment or placebo group, with 32 patients in each. Enrolled patients received either 250 mg of maltodextrin (Lycatab®; Roquette; Lestrem, France) along with 1 g of calcium (placebo) or 250 mg of Bonolive (standardized to contain >40% oleuropein) along with 1 g of calcium (treatment) for 12 months daily. Both treatment and placebo contained 2.5 mg of magnesium stearate and 2.5 mg of silicium dioxide. Calcium was provided as Calperos 1000 (Pliva OTC; Zagreb, Croatia).
Patients visited the clinic for an introduction, a baseline visit, and subsequent visits at 3, 6, and 12 months of the study. Included patients were 12 months postmenopausal or post oophorectomy, and osteoporosis was defined by a bone mineral density (BMD) T-score of −1.5 to −2.5 (above −1.0 is considered healthy, and scores reflect a comparison of patients to a healthy 30-year-old). Dietary calcium was assessed using a Food Frequency Questionnaire (FFQ). Daily intake was standardized to the averages for the region, and patients were advised on how to stay within these guidelines. Patients were asked to take treatment or placebo 30 minutes prior to meals along with water. Calcium or vitamin supplements, antacids, and botanical supplements were not permitted during the study. Those who had other health problems involving bone, liver, kidney, or thyroid, or other hormone problems, were excluded. Those who had been taking medications to treat osteoporosis, such as bisphosphonates, selective estrogen receptor modulators, estrogens, or corticosteroids, were also excluded.
The difference in group changes in the biomarkers osteocalcin (OC, a hormone integral to bone remodeling) and C-terminal cross-linking telopeptide of type I collagen (CTX, integral to bone turnover) from baseline to endpoint was the primary outcome of this study. These were measured from fasting serum collected at baseline and at 3, 6, and 12 months. Secondary outcomes included changes in BMD of the lumbar spine and neck, and in bone alkaline phosphatase (BALP) and amino-terminal pro-peptide (PINP), both biomarkers of bone turnover. Fasting blood serum collected at baseline, 6, and 12 months was used to measure these biomarkers as well as serum lipid profiles and inflammation markers.
In total, 16 patients did not complete the study (11 in the placebo group and 5 in the treatment group) due to unrelated health issues, lack of compliance, or loss to follow up. Adverse side effects were considered "similar" between groups and included bronchitis, influenza, dyspepsia, elevated systolic blood pressure, and back pain. The average age of patients was 59.5 ± 4.9 years and average body mass index was 26.9 ± 4.4 kg/m2. Other parameters at baseline were not significantly different. Compliance between groups was not different as assessed by study material dispensed and returned.
The percentage change from baseline in OC concentrations was significantly higher in the treatment group as compared to the placebo group after 3, 6, and 12 months (P<0.05 for all). Although the concentration of CTX significantly increased in both groups as compared to baseline (P value not reported), no differences between groups were noted. The OC/CTX ratio, an indicator of bone turnover, significantly declined in the placebo group (P<0.05) but not in the treatment group.
BMD of the lumbar spine significantly decreased in the placebo group from baseline to endpoint of the study (P<0.05), but no changes were observed in the treatment group, and no differences were noted between groups at 12 months. No changes were seen in neck BMD. Total cholesterol and low-density lipoprotein (LDL) cholesterol decreased significantly in both groups, but the amount of decrease was significantly greater in the treatment group as compared to the placebo group (P=0.01 and P=0.02, respectively). Triglycerides increased in the placebo group (P=0.01) and slightly decreased in the treatment group. The percentage change in phosphorus from baseline was significantly greater in the treatment group (P=0.02), but increased in both groups. No changes were observed in inflammation markers or calcium.
In conclusion, there was a significant effect on OC concentrations in those taking Bonolive, suggesting a beneficial effect of this product on bone turnover. The significant increase in the OC/CTX ratio observed in the placebo group may suggest higher bone resorption, alleviated in the treatment group. Also, beneficial effects were noted in serum lipid markers. It is mentioned that applying these results to olive oil consumption is confounded by the lower concentrations of polyphenols in oil as compared with the supplement used here and that this study also controlled calcium intake. This study suggests the use of Bonolive may be beneficial to osteoporosis sufferers. BioActor provided financial support for this study; 2 of the authors (Possemiers and Heyerick) are employees of the company. —Amy C. Keller, PhD
