BACKGROUND: 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.
OBJECTIVES: To assess the efficacy and safety of pine bark extract supplements for treating chronic disorders.
SEARCH METHODS: 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.
SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating pine bark extract supplements in adults or children with any chronic disorder.
DATA COLLECTION AND ANALYSIS: 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.
MAIN RESULTS: 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.
AUTHORS' CONCLUSIONS: 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.
ANTECEDENTES: productos vegetales medicinales se utilizan por vía oral para el tratamiento de la osteoartritis. Aunque su mecanismo de acción aún no se han dilucidado en detalle, las interacciones con los mediadores inflamatorios comunes proporcionan un fundamento para usarlos para tratar quejas artrósicos.
OBJETIVOS: Actualizar una revisión Cochrane anterior para evaluar los beneficios y los daños de los productos de plantas medicinales orales en el tratamiento de la osteoartritis.
ESTRATEGIA DE BÚSQUEDA: Se realizaron búsquedas en bases de datos electrónicas (CENTRAL, MEDLINE, EMBASE, AMED, CINAHL, ISI Web of Science, de la Organización Mundial de la Salud de Ensayos Clínicos Plataforma de registros) y el 29 de agosto de 2013, sin restricciones de idioma, y las listas de referencias de los ensayos recuperados.
Ensayos controlados aleatorios de intervenciones herbarias consumidas por vía oral en comparación con los controles de placebo o activos en personas con osteoartritis fueron incluidos. Intervenciones de hierbas incluyen cualquier planta preparación pero la homeopatía o aromaterapia productos excluidos, o cualquier preparado de origen sintético.
Recopilación y análisis de datos Dos autores utilizaron métodos estándar para la selección de los ensayos y la extracción de datos y evaluaron la calidad del conjunto de pruebas utilizando el sistema GRADE para los principales resultados (dolor, la función, los cambios radiográficos conjuntas, calidad de vida, los retiros debidos a adverso eventos, los eventos adversos totales, y los eventos adversos graves).
Resultados principales: Cuarenta y nueve estudios controlados aleatorios (33 intervenciones, 5.980 participantes) fueron incluidos. Diecisiete estudios de diseño de confirmación (muestra y efecto tamaños pre-especificado) eran en su mayoría en situación de riesgo de sesgo moderado. Los 32 estudios restantes de diseño exploratorio se encuentran en mayor riesgo de sesgo. Debido a diferentes intervenciones, los meta-análisis se limita a Boswellia serrata (monoherbal) y insaponificables de aguacate-soja (ASU) (combinación de dos hierbas) los productos.
Se incluyeron cinco estudios de tres extractos diferentes de Boswellia serrata. Evidencia de alta calidad a partir de dos estudios (85 participantes) indicó que 90 días de tratamiento con 100 mg de extracto de Boswellia serrata enriquecido síntomas mejoraron en comparación con el placebo. Dolor promedio fue de 40 puntos en una escala VAS de 0 a 100 puntos (0 es ausencia de dolor) con placebo, enriquecida Boswellia serrata reduce el dolor en una media de 17 puntos (95% intervalo de confianza (IC) del 8 al 26); número necesario a tratar para lograr un resultado beneficioso adicional (NNTB) 2; IC del 95% no ha excluido una reducción clínicamente significativa de 15 puntos en el dolor. La función física fue de 33 puntos en la Western Ontario y McMaster Universidades Artrosis Index (WOMAC) 0 a 100 puntos subescala (0 no es una pérdida de la función) con placebo, enriquecido Boswellia serrata mejora de la función por 8 puntos (IC del 95%: 2 a 14); NNTB 4. Suponiendo una diferencia mínima clínicamente importante de 10 puntos, no podemos excluir un beneficio clínicamente importante en algunas personas. Calidad de evidencia moderada (un estudio, 96 participantes) indicó que los eventos adversos fueron probablemente reducen con serrata enriquecido Boswellia (18/48 frente a 30/48 eventos eventos con placebo; riesgo relativo (RR) CI 0,60, 95%: 0,39 a 0,92). Posibles beneficios de otros extractos de Boswellia serrata sobre el placebo fueron confirmados en pruebas de calidad moderada a partir de dos estudios (97 participantes) de Boswellia serrata (enriquecido) 100 mg más aceite no volátil, y la evidencia de baja calidad de los pequeños estudios individuales de un 999 mg dosis diaria de extracto de Boswellia serrata y la dosis diaria de 250 mg de enrichedBoswellia serrata. Era incierto si una dosis diaria de 99 mg de Boswellia serrata ofreció ventajas sobre valdecoxib debido a la evidencia de muy baja calidad a partir de un pequeño estudio individual. No estaba claro si había un mayor riesgo de eventos adversos o retiros con extracto de Boswellia serrata debido a una información variable de los resultados entre los estudios. Los estudios no informaron eventos adversos graves. No se midió la calidad de vida y los cambios radiográficos conjuntas.
Seis estudios examinaron el producto ASU Piasclidine®. Calidad de evidencia moderada de cuatro estudios (651 participantes) indicó que ASU 300 mg produjo una pequeña y clínicamente cuestionable mejoría de los síntomas, y, probablemente, no hay aumento de los eventos adversos en comparación con el placebo después de un tratamiento de tres a 12 meses. La media de dolor con placebo fue de 40.5 puntos en una EAV de 0 a 100 escala (0 es ausencia de dolor), ASU 300 mg redujo el dolor en una media de 8,5 puntos (IC del 95%: 1 a 16 puntos); NNTB 8. ASU 300 mg mejora de la función (diferencia de medias estandarizada (DME) -0,42; IC del 95%: -0,73 a -0,11). Función se estimó como 47 mm (escala 0 a 100 mm, donde 0 es ninguna pérdida de función) con el placebo, ASU 300 mg mejora de la función en una media de 7 mm (IC del 95%: 2 a 12 mm); NNTB 5 (3 a 19). No hubo diferencias en los eventos adversos (5 estudios, 1050 participantes) entre ASU (53%) y placebo (51%) (RR 1,04, 95% CI 0,97 a 1,12); retiros debido a eventos adversos (1 estudio, 398 participantes) entre ASU (17%) y placebo (15%) (RR 1,14; IC del 95%: 0,73 a 1,80); o eventos adversos graves (1 estudio, 398 participantes) entre ASU (40%) y placebo (33%) (RR 1,22; IC del 95%: 0,94 a 1,59). Cambios en las articulaciones radiográficas, medidas como el cambio en la anchura del espacio articular (JSW) en dos estudios (453 participantes) no difirió entre ASU 300 mg tratamiento (-0.53 mm) y placebo (-0.65 mm); diferencia de -0,12 (IC del 95%: -0,43 a 0,19) significa. Calidad de evidencia moderada de un único estudio (156 participantes) confirmó los posibles beneficios de la ASU 600 mg sobre el placebo, sin aumento de los eventos adversos. Calidad de evidencia baja (1 estudio, 357 participantes) indicó que puede haber diferencias en los síntomas o los efectos adversos entre ASU 300 mg y sulfato de condroitina. No se midió la calidad de vida.
Todas las demás intervenciones herbarias fueron investigados en estudios individuales, lo que limita las conclusiones. No se informaron efectos secundarios graves relacionados con cualquier producto vegetal.
Conclusiones de los revisores: La evidencia de la especialidad, ASU Piasclidine® en el tratamiento de síntomas de la osteoartritis parece moderada a alta para uso a corto plazo, pero los estudios a más largo plazo y en contra de un control activo aparentemente son menos convincentes. Varios otros productos de plantas medicinales, incluyendo extractos de Boswellia serrata, muestran las tendencias de los beneficios que merecen una investigación más a la luz del hecho de que el riesgo de eventos adversos parece bajo.
No hay evidencia de que Piasclidine® mejora significativamente la estructura de la articulación, y la evidencia limitada que impide estrechamiento del espacio articular. Los cambios estructurales no se han probado para con cualquier otra intervención a base de hierbas.
Se necesitan más investigaciones para determinar las dosis diarias óptimas que producen beneficios clínicos sin eventos adversos.
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.
OBJECTIVES:
To assess the efficacy and safety of pine bark extract supplements for treating chronic disorders.
SEARCH METHODS:
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.
SELECTION CRITERIA:
Randomised controlled trials (RCTs) evaluating pine bark extract supplements in adults or children with any chronic disorder.
DATA COLLECTION AND ANALYSIS:
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.
MAIN RESULTS:
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.
AUTHORS' CONCLUSIONS:
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.
