Scientific literature on commercially available pine bark extract (oligopin or pycnogenol) is scare. To the best of our knowledge, this is the first randomized, double-blind, placebo controlled trial of oligopin supplementation performed in women with PCOS. We hypothesis that including oligopin to our subjects would induce benefits, however, with except of change in FSH level, our intervention fail to change levels of androgens and metabolic profile. These results occurred with no unexpected safety finding.
This trial showed that an antioxidant intervention based on oligopin supplementation has no effect on serum androgen levels except for a small increase in FSH level. The changes in FSH levels observed in this trial over the 3 months are difficult to explain, even though the mean FSH increased following oligopin treatment, there was no significant changes in insulin or androgen levels. On the other hand, although the mean FSH levels were lower for women with PCOS compared to those with normal ovaries (17), this small rise in FSH concentrations is not clinically important in patients with PCOS. Whether the FSH raising effect of oligopin is partly due to catechin reminded unclear. It was reported that a significant dose responses relationship was found between catechein supplementation and FSH levels in PCOS rats (18).
Similarity, no differences could be demonstrated in any of metabolic profiles and anthropometrics parameters, blood pressure and hs-CRP levels except for increase in ALP levels in placebo group compared to oligopin. Our finding that oligopin failed to significantly influence cardiovascular disease risk factors (insulin, fasting glucose, lipid profiles and hs-CRP) is an observation that has been recorded previously in overweight and obese adults (19). The meta-analysis by Malekamadi et al. and collaborators, showing several biological effect of this extract such as decreased glycemia and lipid profile, decreased weight and blood pressure and reduced hs-CRP level, was faulted by pooling low quality and high heterogeneity studies (20). Notably, the Meta -analysis of randomized trials indicated that pycnogenol significantly raised AST levels and decreased GGT concentration by 1.53 U/I (20). In the present study we did not observe any significant changes in ALT and AST levels in oligopin group. However, there was an increase of ALP levels in both treatment groups, which to be greater in placebo group compared to oligopin. Overall, based on our results and previous study oligopin did no show toxic effects on liver function (20). The hypoglycemic effects of pine bark extract may be related to inhibition of alpha glycosidase activity in the small intestinal brush border due to procyanidins (flavonoids), independent of effect on insulin secretion (21, 22). We speculated that efficiency of oligopin on glycemia and HbA1c depends on baseline glycemia. We enrolled patients with normal glycemia (glycated hemoglobin levels less than 6% and FBS less than 126 mg/dl).
Pycnogenol (pine bark extract) has been explored as a potential natural antihypertensive agent. Although not consistent, pycnogenol supplementation has been shown to reduce systolic and diastolic blood pressure (23). The effect is mediated via nitric oxide (NO) production (23) or angiotensin converting enzyme (ACE) inhibition (24) and /or reduction of endothelin -1(25). In our study, blood pressure was reduced after oligopin treatment for 3 months, although the difference was not significant. As most of our study participants displayed well controlled blood pressure levels (97.5% SBP<140 mmHg, 85% DBS <90 mmHg) at the baseline, we postulated that oligopin supplementation could exert favorable effects on blood pressure only among hypertensive patients (20,24, 26). On the other hand, the subgroup analysis in recent meta-analysis indicated that the effect of this extract on blood pressure is more prominent in trails with longer intervention duration (>12 weeks) (23). As a result, a longer period is required to obtain results.
Supplementation with oligopin has been suggested to decrease the levels of CRP and have anti-inflammatory effect (27). However, our data failed to detect any significant change in hs-CRP levels with oligopin administration. We have not measured circulating other inflammatory factors in this study, as results we cannot conclude that oligopin is ineffective on inflammation.
There are a few possible explanations for the apparent lack of a positive finding in our study. First, the dose of oligopin may be inadequate. One study involving the use of oligopin in type 2 diabetes has shown a daily consumption in an amount of 100 mg/d to 200 mg/d is required to achieve a protective effect (28). It is uncertain whether the dose required to achieve androgen reduction is similar, or the response to oligopin may be different in different subjects, we included PCOS women. Moreover, the recent Meta –analysis suggested that a possible benefit for pine bark extract supplementation when add other treatments and no benefit when consume pine bark extracts as a solitary therapy (23).
Furthermore, the impact of oligopin on hormonal and cadiometabolic may be different between the two sexes and sex may be a modifier of the effect of pine bark extract on the cardiometabolic profile, or the link between oligopin and PCOS may be appreciated only in subpopulation of PCOS patients; insulin resistance vs. noninsulin – resistance and also between lean and obese. This can be partially explained by the fact that substantial portion of population in our trial were not insulin resistance (mean HOMA <3.8) and were relatively lean (overweight in average).
One of our study limitation was high dropout rate; which is relatively high in infertility trials (29).