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Oxidative stress and inflammation underlie many problematic and chronic issues, which may also explain why interventions that target both of these pathological processes have the potential for such broad benefits. Pycnogenol (French maritime pine bark extract) and grape seed extract (GSE) are both rich in polyphenols, proanthocyanidins specifically, and have a number of clinical trials highlighting their clinical utility, ranging from osteoarthritis to cardiovascular disease prevention.
In a systematic review and meta-analysis of clinical trials, twelve included controlled trials indicated that pycnogenol supplementation was associated with significant and meaningful reductions in both systolic blood pressure (SBP; -3.22 mmHg) and diastolic blood pressure (DBP; -1.91 mmHg), with a more pronounced effect in studies lasting more than 12 weeks. GSE has also demonstrated a hypotensive effect, with a greater reduction observed in those with initially higher pressures. For example, in a randomized and double-blinded placebo-controlled trial, subjects with prehypertension received 300 mg GSE per day in a beverage, resulting in a mean reduction of day-time SBP and DBP by 5.6% and 4.7%, respectively, compared with no change in the placebo group. Approximately double the effect was observed in participants with higher blood pressures at the beginning of the study (-13.6 mmHg SBP vs. 0.01 mmHg in the placebo group). A meta-analysis of 16 randomized and controlled trials found weighted mean differences (WMD) of −6.077 SBP and −2.803 DBP with GSE supplementation. Here too, greater effects were seen in specific populations, including in obese and younger participants, as well as in people with metabolic syndrome, who had the largest reductions (−8.487 SBP).
Pycnogenol has demonstrated other cardiometabolic benefits as well. In another systematic review of 24 randomized and controlled trials, supplementation was associated with improved glycemic control, marked by significant reductions in fasting blood glucose (WMD = -5.86) and hemoglobin A1c (WMD = -0.29%). In addition to reductions in blood pressure, supplementation was also associated with small but significant weight loss, as well as favorable effects on lipids (LDL-C WMD = -7.12 mg/dl, and HDL-C WMD = 3.27 mg/dl). Similar effects of GSE were published in a systematic review and meta-analysis of 50 trials, which documented significant reductions in fasting blood glucose, total and LDL cholesterol, triglycerides, and C-reactive protein (CRP). A systematic review of five randomized and controlled trials published in Clinical Nutrition Research also found a significant reduction in CRP with pycnogenol supplementation (pooled effect size of -1.22 mg/dL), with lower heterogeneity in studies using at least 150 mg per day.
Pycnogenol appears to partly exert its effects by increasing nitric oxide production; this may also underlie the significant improvements observed in study participants with erectile dysfunction, especially those with diabetes mellitus. Additionally, a dose of 50mg pycnogenol was shown to reduce sexual dysfunction associated with selective serotonin reuptake inhibitor use (escitalopram) by 1 month of co-treatment, one of only a few interventions to do so. It is unclear if GSE has a similar mechanism of action, as no studies examining this association have been published to date.
A number of anti-inflammatory effects of these compounds also appear to provide a benefit for musculoskeletal health. As reviewed recently in a Biotics Research Forum, a small trial found improvement in many of the symptoms of Restless Legs Syndrome with pycnogenol supplementation. Supplementation is more firmly established for osteoarthritis; in the initial double-blinded trial, just under 160 participants received either 100 mg pycnogenol or placebo over a 3-month period. Not only did WOMAC scores improve (56% vs. 9.6% placebo), but pain-relief medication decreased 58% (vs. 1% placebo), foot edema was significantly reduced, and gastrointestinal complications decreased by 63% (vs. 3% placebo). A subsequent placebo-controlled trial had similar results with 150 mg pycnogenol per day; improvements in the WOMAC score, pain reduction, and decreased analgesic use (vs. increased use in the placebo group). Data from the initial trial suggest that reductions in CRP, plasma free radicals, and fibrinogen levels may partly underlie the benefits of pycnogenol in patients with osteoarthritis. For example, in this group receiving 100 mg per day, CRP levels decreased from 3.9 to 1.1 mg/L, vs. an insignificant decrease from 3.9 to 3.6 mg/L in the control group. More recent data provided evidence that several of the constituents/metabolites of pycnogenol are distributed in the synovial fluid of patients with osteoarthritis. In addition, several catabolic and inflammatory markers in the synovial fluid of patients with severe osteoarthritis were reduced with pycnogenol supplementation, including decreases in the expression of MMP3, MMP13 and IL1B genes.
Although no clinical trials have been performed with GSE supplementation for patients with osteoarthritis, a systematic review of clinical trials related to oxidative stress and inflammation found significant decreases in malondialdehyde, oxidized low-density lipoprotein, and high-sensitivity CRP with its use. When given at a higher dose of 600 mg per day, it was also shown to significantly improve inflammation (high sensitivity CRP, 40% decrease) and glucose control (fructosamine, 3.2% decrease) as well as oxidative stress (reduced glutathione, 52% increase) in patients with obesity and type 2 diabetes who were also at high risk of cardiovascular events.
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