Review question
Can pine bark antioxidant supplements help to treat chronic diseases?
Background
The main ingredients in pine bark extract supplements are proanthocyanidins, which are antioxidants. These supplements are marketed to prevent or treat a wide range of chronic diseases. This is an update of a previously published review, where we assessed how well these supplements work for treating chronic diseases, as well as their safety.
Search date
The evidence is current to 30 September 2019.
Study characteristics
We included 27 studies (1641 participants) across 10 chronic diseases. These included: asthma (two studies; 86 participants), attention deficit hyperactivity disorder (ADHD) (one study; 61 participants), heart disease and risk factors (seven studies; 332 participants), chronic venous insufficiency (leg veins not working effectively; two studies; 60 participants), diabetes (six studies; 336 participants), erectile dysfunction (three studies; 227 participants), female sexual dysfunction (one study; 75 participants), osteoarthritis (cartilage damage in joints; three studies; 293 participants), osteopenia (beginning of bone mass loss; one study; 44 participants) and traumatic brain injury (one study; 56 participants). Two of the studies were conducted exclusively in children; the others were in adults. Studies compared pine bark supplements with placebo (i.e. a dummy supplement) or non-antioxidant interventions and participants were randomly selected for one treatment or the other. The duration of treatment ranged from four weeks to six months.
Key results
For most outcomes across the different chronic diseases we only included one study with a small number of participants. In adults with asthma, we do not know whether pine bark extract increases lung function, improves asthma symptoms or increases the number of people able to stop using albuterol inhalers (a specific type of asthma pump).
In children with ADHD, we do not know whether pine bark supplements decrease inattention and hyperactivity (assessed by parents and teachers) or whether it increases co-ordination and concentration.
In people with heart disease we do not know if pine bark supplements decrease blood pressure and LDL cholesterol (the bad type) or whether it increases HDL cholesterol (the good type).
In adults with chronic venous insufficiency we do not know whether pine bark supplements decrease pain, increase the number of people free of pain, or how well doctors think the treatment works. In people with type 2 diabetes, we do not know whether pine bark supplements improve blood sugar levels or HbA1c levels (the long-term marker for measuring blood sugar control); we also do not know if pine bark supplements decrease HbA1c in people with type 1 or type 2 diabetes.
In men with erectile dysfunction, we do not know if pine bark supplements increase erectile function. Similarly, in women with sexual dysfunction, we do not know if pine bark supplements increase sexual satisfaction or reduce pain.
In adults with osteoarthritis, it is not clear if pine bark supplements improve pain, swelling or stiffness in the knee, or whether it decreases the use of anti-inflammatory drugs. We also do not know if pine bark supplements increase bone formation in postmenopausal women with weakened bones. Lastly, in people with a traumatic brain injury, it is not clear if pine bark supplements improve memory and post-concussion symptoms .
For most comparisons, studies did not report outcomes of hospital admissions or serious adverse events.
With the available studies, we cannot clearly say how well (or not) pine bark supplements work and whether they are safe.
Quality of the evidence
The overall risk of bias was low for four studies, high for one and unclear for 22 studies. By this we mean the extent to which the methods used in a study enable it to determine the truth. The certainty of evidence was very low for all outcomes across all chronic diseases in the included studies.
Small sample sizes, limited numbers of RCTs per condition, variation in outcome measures, and poor reporting of the included RCTs mean no definitive conclusions regarding the efficacy or safety of pine bark extract supplements are possible.
Pine bark (Pinus spp.) extract is rich in bioflavonoids, predominantly proanthocyanidins, which are antioxidants. Commercially-available extract supplements are marketed for preventing or treating various chronic conditions associated with oxidative stress. This is an update of a previously published review.
To assess the efficacy and safety of pine bark extract supplements for treating chronic disorders.
We searched three databases and three trial registries; latest search: 30 September 2019.
We contacted the manufacturers of pine bark extracts to identify additional studies and hand-searched bibliographies of included studies.
Randomised controlled trials (RCTs) evaluating pine bark extract supplements in adults or children with any chronic disorder.
Two authors independently assessed trial eligibility, extracted data and assessed risk of bias. Where possible, we pooled data in meta-analyses. We used GRADE to evaluate the certainty of evidence.
Primary outcomes were participant- and investigator-reported clinical outcomes directly related to each disorder and all-cause mortality. We also assessed adverse events and biomarkers of oxidative stress.
This review included 27 RCTs (22 parallel and five cross-over designs; 1641 participants) evaluating pine bark extract supplements across 10 chronic disorders: asthma (two studies; 86 participants); attention deficit hyperactivity disorder (ADHD) (one study; 61 participants), cardiovascular disease (CVD) and risk factors (seven studies; 338 participants), chronic venous insufficiency (CVI) (two studies; 60 participants), diabetes mellitus (DM) (six studies; 339 participants), erectile dysfunction (three studies; 277 participants), female sexual dysfunction (one study; 83 participants), osteoarthritis (three studies; 293 participants), osteopenia (one study; 44 participants) and traumatic brain injury (one study; 60 participants).
Two studies exclusively recruited children; the remainder recruited adults. Trials lasted between four weeks and six months. Placebo was the control in 24 studies. Overall risk of bias was low for four, high for one and unclear for 22 studies.
In adults with asthma, we do not know whether pine bark extract increases change in forced expiratory volume in one second (FEV1) % predicted/forced vital capacity (FVC) (mean difference (MD) 7.70, 95% confidence interval (CI) 3.19 to 12.21; one study; 44 participants; very low-certainty evidence), increases change in FEV1 % predicted (MD 7.00, 95% CI 0.10 to 13.90; one study; 44 participants; very low-certainty evidence), improves asthma symptoms (risk ratio (RR) 1.85, 95% CI 1.32 to 2.58; one study; 60 participants; very low-certainty evidence) or increases the number of people able to stop using albuterol inhalers (RR 6.00, 95% CI 1.97 to 18.25; one study; 60 participants; very low-certainty evidence).
In children with ADHD, we do not know whether pine bark extract decreases inattention and hyperactivity assessed by parent- and teacher-rating scales (narrative synthesis; one study; 57 participants; very low-certainty evidence) or increases the change in visual-motoric coordination and concentration (MD 3.37, 95% CI 2.41 to 4.33; one study; 57 participants; very low-certainty evidence).
In participants with CVD, we do not know whether pine bark extract decreases diastolic blood pressure (MD -3.00 mm Hg, 95% CI -4.51 to -1.49; one study; 61 participants; very low-certainty evidence); increases HDL cholesterol (MD 0.05 mmol/L, 95% CI -0.01 to 0.11; one study; 61 participants; very low-certainty evidence) or decreases LDL cholesterol (MD -0.03 mmol/L, 95% CI -0.05 to 0.00; one study; 61 participants; very low-certainty evidence).
In participants with CVI, we do not know whether pine bark extract decreases pain scores (MD -0.59, 95% CI -1.02 to -0.16; one study; 40 participants; very low-certainty evidence), increases the disappearance of pain (RR 25.0, 95% CI 1.58 to 395.48; one study; 40 participants; very low-certainty evidence) or increases physician-judged treatment efficacy (RR 4.75, 95% CI 1.97 to 11.48; 1 study; 40 participants; very low-certainty evidence).
In type 2 DM, we do not know whether pine bark extract leads to a greater reduction in fasting blood glucose (MD 1.0 mmol/L, 95% CI 0.91 to 1.09; one study; 48 participants;very low-certainty evidence) or decreases HbA1c (MD -0.90 %, 95% CI -1.78 to -0.02; 1 study; 48 participants; very low-certainty evidence). In a mixed group of participants with type 1 and type 2 DM we do not know whether pine bark extract decreases HbA1c (MD -0.20 %, 95% CI -1.83 to 1.43; one study; 67 participants; very low-certainty evidence).
In men with erectile dysfunction, we do not know whether pine bark extract supplements increase International Index of Erectile Function-5 scores (not pooled; two studies; 147 participants; very low-certainty evidence). In women with sexual dysfunction, we do not know whether pine bark extract increases satisfaction as measured by the Female Sexual Function Index (MD 5.10, 95% CI 3.49 to 6.71; one study; 75 participants; very low-certainty evidence) or leads to a greater reduction of pain scores (MD 4.30, 95% CI 2.69 to 5.91; one study; 75 participants; very low-certainty evidence).
In adults with osteoarthritis of the knee, we do not know whether pine bark extract decreases composite Western Ontario and McMaster Universities Osteoarthritis Index scores (MD -730.00, 95% CI -1011.95 to -448.05; one study; 37 participants; very low-certainty evidence) or the use of non-steroidal anti-inflammatory medication (MD -18.30, 95% CI -25.14 to -11.46; one study; 35 participants; very low-certainty evidence). We do not know whether pine bark extract increases bone alkaline phosphatase in post-menopausal women with osteopenia (MD 1.16 ug/L, 95% CI -2.37 to 4.69; one study; 40 participants; very low-certainty evidence).
In individuals with traumatic brain injury, we do not know whether pine bark extract decreases cognitive failure scores (MD -2.24, 95% CI -11.17 to 6.69; one study; 56 participants; very low-certainty evidence) or post-concussion symptoms (MD -0.76, 95% CI -5.39 to 3.87; one study; 56 participants; very low-certainty evidence).
For most comparisons, studies did not report outcomes of hospital admissions or serious adverse events.