Pine bark (Pinus spp.) extract for treating chronic disorders.

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.

The Problem of Hospital Malnutrition in the African Continent.

This study aims to determine the prevalence of risk of malnutrition on admission and discharge in African hospitals, and to identify the association with selected indicators. In this multi-center prospective cohort study, adult patients from hospitals in South Africa, Kenya, and Ghana were screened on admission and discharge and contacted 3 months post-discharge. Relevant morbidity and mortality outcomes were assessed. At risk of malnutrition was indicated if NRS-2002 score ≥3. Adult patients (n = 2126; 43.11 years, IQR: 31.95-55.60; 52.2% female) were screened on admission and 61% were identified as at risk of malnutrition. The proportion of at-risk patients for the three hospitals in Kenya and Ghana (66.2%) were significantly higher than that of the three South African hospitals (53.7%) (Chi2 = 31.0; p < 0.001). Discharge risk of malnutrition was 71.2% (n = 394). Mean length of stay (LOS) was 6.46 ± 5.63 days. During hospitalization, 20.6% lost ≥5% body weight, 18.8% were referred for nutrition support, and discharge BMI (23.87 ± 7.38 kg/m2) was significantly lower than admission BMI (24.3 ± 7.3 kg/m2) (p < 0.001). Admission nutrition risk was associated with lower admission and discharge BMI (p < 0.001), longer LOS (p < 0.001), increased 3-month re-admission rates (Chi2 = 1.35; p = 0.245) and increased mortality (Chi2 = 21.68; p < 0.001). Nearly two-thirds of patients were at risk of malnutrition on admission. This was associated with longer LOS and greater hospital mortality. The nutritional status of patients deteriorated during hospitalization. Routine screening practices with appropriate nutrition support action should be implemented as a matter of urgency.

Parenteral Provision of Micronutrients to Adult Patients: An Expert Consensus Paper.

BACKGROUND: Micronutrients, an umbrella term used to collectively describe vitamins and trace elements, are essential components of nutrition. Those requiring alternative forms of nutrition support are dependent on the prescribed nutrition regimen for their micronutrient provision. The purpose of this paper is to assist clinicians to bridge the gap between the available guidelines' recommendations and their practical application in the provision of micronutrients via the parenteral route to adult patients. METHODS: Based on the available evidenced-based literature and existing guidelines, a panel of multidisciplinary healthcare professionals with significant experience in the provision of parenteral nutrition (PN) and intravenous micronutrients developed this international consensus paper. RESULTS: The paper addresses 14 clinically relevant questions regarding the importance and use of micronutrients in various clinical conditions. Practical orientation on how micronutrients should be prescribed, administered, and monitored is provided. CONCLUSION: Micronutrients are a critical component to nutrition provision and PN provided without them pose a considerable risk to nutrition status. Obstacles to their daily provision-including voluntary omission, partial provision, and supply issues-must be overcome to allow safe and responsible nutrition practice.

Community-based supplementary feeding for food insecure, vulnerable and malnourished populations - an overview of systematic reviews.

BACKGROUND: Supplementary feeding may help food insecure and vulnerable people by optimising the nutritional value and adequacy of the diet, improving quality of life and improving various health parameters of disadvantaged families. In low- and middle-income countries (LMIC), the problems supplementary feeding aims to address are entangled with poverty and deprivation, the programmes are expensive and delivery is complicated. OBJECTIVES: 1. To summarise the evidence from systematic reviews of supplementary feeding for food insecure, vulnerable and malnourished populations, including children under five years of age, school-aged children, pregnant and lactating women, people with HIV or tuberculosis (or both), and older populations.2. To describe and explore the effects of supplementary feeding given to people in these groups, and to describe the range of outcomes between reviews and range of effects in the different groups. METHODS: In January 2017, we searched the Cochrane Database of Systematic Reviews, MEDLINE, Embase and nine other databases. We included systematic reviews evaluating community-based supplementary feeding, and concerning food insecure, vulnerable and malnourished populations. Two review authors independently undertook selection of systematic reviews, data extraction and 'Risk of bias' assessment. We assessed review quality using the AMSTAR tool, and used GRADEpro 'Summary of findings' tables from each review to indicate the certainty of the evidence for the main comparisons. We summarised review findings in the text and reported the data for each outcome in additional tables. We also used forest plots to display results graphically. MAIN RESULTS: This overview included eight systematic reviews (with last search dates between May 2006 and February 2016). Seven were Cochrane Reviews evaluating interventions in pregnant women; children (aged from birth to five years) from LMIC; disadvantaged infants and young children (aged three months to five years); children with moderate acute malnutrition (MAM); disadvantaged school children; adults and children who were HIV positive or with active tuberculosis (with or without HIV). One was a non-Cochrane systematic review in older people with Alzheimer's disease. These reviews included 95 trials relevant to this overview, with the majority (74%) of participants from LMIC.The number of included participants varied between 91 and 7940 adults, and 271 and more than 12,595 children. Trials included a wide array of nutritional interventions that varied in duration, frequency and format, with micronutrients often reported as cointerventions. Follow-up ranged from six weeks to two years; three trials investigated outcomes at four to 17 years of age. All reviews were rated as high quality (AMSTAR score between eight and 11). The GRADE certainty ratings ranged from very low to moderate for individual comparisons, with the evidence often comprising only one or two small trials, thereby resulting in many underpowered analyses (too small to detect small but important differences). The main outcome categories reported across reviews were death, anthropometry (adults and children) and other markers of nutritional status, disease-related outcomes, neurocognitive development and psychosocial outcomes, and adverse events.Mortality data were limited and underpowered in meta-analysis in all populations (children with MAM, in children with HIV, and in adults with tuberculosis) with the exception of balanced energy and protein supplementation in pregnancy, which may have reduced the risk of stillbirth (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.39 to 0.94; 5 trials, 3408 women). Supplementation in pregnancy also improved infant birth weight (mean difference (MD) 40.96 g, 95% CI 4.66 to 77.26; 11 trials, 5385 participants) and reduced risk of infants born small-for-gestational age (RR 0.79, 95% CI 0.69 to 0.90; 7 trials, 4408 participants). These effects did not translate into demonstrable long-term benefits for children in terms of growth and neurocognitive development in the one to two trials reporting on longer-term outcomes. In one study (505 participants), high-protein supplementation was associated with increased risk of small-for-gestational age babies.Effects on growth in children were mixed. In children under five years of age from LMIC, one review found that supplementary feeding had a little or no effect on child growth; however, a more recent review in a similar population found that those who received food supplementation gained an average of 0.12 kg more in weight (MD 0.12 kg, 95% CI 0.05 to 0.18; 9 trials, 1057 participants) and 0.27 cm more in height (MD 0.27 cm, 95% CI 0.07 to 0.48; 9 trials, 1463 participants) than those who were not supplemented. Supplementary food was generally more effective for younger children (younger than two years of age) and for those who were poorer or less well-nourished. In children with MAM, the provision of specially formulated food improved their weight, weight-for-height z scores and other key outcomes such as recovery rate (by 29%), as well as reducing the number of participants dropping out (by 70%). In LMIC, school meals seemed to lead to small benefits for children, including improvements in weight z scores, especially in children from lower-income countries, height z scores, cognition or intelligence quotient tests, and maths and spelling performance.Supplementary feeding in adults who were HIV positive increased the daily energy and protein intake compared to nutritional counselling alone. Supplementation led to an initial improvement in weight gain or body mass index but did not seem to confer long-term benefit.In adults with tuberculosis, one small trial found a significant benefit on treatment completion and sputum conversion rate. There were also significant but modest benefits in terms of weight gain (up to 2.60 kg) during active tuberculosis.The one study included in the Alzheimer's disease review found that three months of daily oral nutritional supplements improved nutritional outcomes in the intervention group.There was little or no evidence regarding people's quality of life, adherence to treatment, attendance at clinic or the costs of supplementary feeding programmes. AUTHORS' CONCLUSIONS: Considering the current evidence base included, supplementary food effects are modest at best, with inconsistent and limited mortality evidence. The trials reflected in the reviews mostly reported on short-term outcomes and across the whole of the supplementation trial literature it appears important outcomes, such as quality of life and cost of programmes, are not systematically reported or summarised.

The association between tuberculosis and the development of insulin resistance in adults with pulmonary tuberculosis in the Western sub-district of the Cape Metropole region, South Africa: a combined cross-sectional, cohort study.

BACKGROUND: The existence of a bi-directional relationship between tuberculosis (TB) and insulin resistance (IR)/diabetes has been alluded to in literature. Although diabetes has been linked to increased tuberculosis risk, the relationship between tuberculosis as a causative factor for IR remains unclear. The study aimed to determine if an association existed between tuberculosis and IR development in adults with newly diagnosed pulmonary tuberculosis at baseline. It was additionally aimed to document changes in IR status during TB follow-up periods. METHODS: This cross-sectional study evaluated ambulatory participants at baseline for IR prevalence via anthropometry, biochemistry and diagnostic IR tests [homeostasis model assessment-IR (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI)]. A prospective cohort sub-section study was additionally performed on approximately half of the baseline study population, who were followed-up at two and five months whilst on tuberculosis treatment. Summary statistics, correlation co-efficients and appropriate analysis of variance were used to describe and analyse data. Participants were excluded if they presented with other forms of tuberculosis, were HIV-positive, obese or had any pre-disposing IR conditions such as diabetes or metabolic syndrome. RESULTS: Fifty-nine participants were included from August 2013 until December 2014 (33.95 ± 12.02 years old; 81.4% male). IR prevalence was 25.4% at baseline, determined by a calculated HOMA-IR cut-off point of 2.477. Patients with IR were younger (p = 0.04). Although the difference between IR levels in participants between baseline and follow-up was not significant, a decrease was observed over time. The majority of participants (61.0%) presented with a normal BMI at baseline. Mean baseline values of fasting glucose were within normal ranges (4.82 ± 0.80 mmol/L), whereas increased mean CRP levels (60.18 ± 50.92 mg/L) and decreased mean HDL-cholesterol levels (males: 0.94 ± 0.88 mmol/L; females: 1.14 ± 0.88 mmol/L) were found. CONCLUSIONS: The study found an association between tuberculosis and IR development in newly diagnosed pulmonary tuberculosis patients. Although not significant, IR levels decreased over time, which could be indicative of a clinical improvement. A high prevalence of IR amongst young tuberculosis patients therefore highlights the need for early identification in order to facilitate a reversal of IR and prevent possible IR-related complications.

Assessing the utilization of a child health monitoring tool

Objective: The study assessed the implementation of growth monitoring and promotion, immunisation, vitamin A supplementation, and deworming sections of the Road-to-Health Booklet. Caregivers and health care workers knowledge, attitudes and practices were investigated as well as health care workers perceptions of barriers undermining implementation.Methods: A cross-sectional descriptive study was conducted on a proportional sample of randomly selected Primary Health Care facilities across six health districts (35%; n=143) in the Western Cape Province. Health care workers involved in the implementation of the Road-to-Health Booklet, children (0-36 months) and CGs were included. Information was obtained through scrutiny of the Road-to-Health Booklet, observation of consultations and structured questionnaires.Results: A total of 2442 children, 2481 caregivers and 270 health care workers were recruited. Weight (94.7%) measurements were performed routinely. Less than half (40.2%) of caregivers reported that their child's growth was explained. Sixty-eight percent of health care workers correctly identified criteria for underweight, whereas only 55% and 39% could do so for stunting and wasting respectively. Road-to-Health Booklet sections were completed adequately for immunization (89.3%), vitamin A supplementation (94.6%) but not for deworming (48.8%). Most health care workers (94%) knew the correct regimes for vitamin A supplementation and deworming, but few caregivers knew when treatment was due for vitamin A supplementation (16.4%) and deworming (26.2%). Potential barriers identified related to inadequate training, staff shortages and limited time.Conclusion: Focussed effort and resources should be channelled towards health care workers training and monitoring regarding growth monitoring and promotion to optimize utilization of the Road-to-Health Booklet. Mobilisation of community health workers is needed to strengthen community awareness of preventative health interventions

Antioxidant intake in paediatric oncology patients.

BACKGROUND & AIMS: Antioxidant intake can affect both free radical and the nutritional status of children receiving cancer treatment. The aim of this study was to investigate whether children with cancer met their antioxidant requirements. METHODS: A prospective observational study was performed at a single hospital in England from June 2008 to February 2010. Children with a solid tumour, lymphoma or leukaemia were included. Dietary intakes including 3 modes of feeding ('diet alone', 'diet + tube' feeding or 'diet + vitamin-mineral supplementation' (VMS)) were collected with an estimated food record (EFR) 1 and 3 month post-diagnosis. Four and 24-hr food recalls were performed to validate the food records. RESULTS: Forty two children were included: 57% leukaemia or lymphoma and 43% solid tumours. Sixty seven percent underwent chemotherapy and 33% a combination of therapies. In months 1 and 3, greater numbers of children achieved ≥100% of requirements for 'diet + VMS' (p < 0.05) than for other feeding modes. However, considerable proportions of all feeding groups did not achieve 100% of the Recommended Nutrient Intake (RNI) for vitamin A, C, E, selenium and zinc. This was most marked in the 'diet alone' group. Significant proportions did not achieve the Lower Recommended Nutrient Intake (LRNI) for some antioxidants. The 'diet alone' group had the highest proportion not meeting LRNI for vitamin A (p << 0.001; 1st month) and zinc (p < 0.02; 3rd month). CONCLUSION: Inadequate antioxidant intake was observed in a significant proportion of cancer patients when feeding was not augmented in any way. More research is required to determine the clinical implications of these findings.

Randomized clinical trial: effect of Lactobacillus plantarum 299 v on symptoms of irritable bowel syndrome.

OBJECTIVES: Irritable bowel syndrome (IBS) is a common diagnosis in gastroenterology. Its etiology is unknown and therapeutic options limited. Trials suggest probiotics may be beneficial. The aim of this study was to assess the symptomatic efficacy of Lactobacillus plantarum 299 v (L. plantarum 299 v) for the relief of abdominal pain in patients with IBS fulfilling Rome II criteria. METHODS: This study was conducted in a referral hospital. Trial participants were randomized to receive either two capsules of L. plantarum 299 v at a dosage of 5 × 10(9) cfu per capsule or placebo daily for 8 wk. Severity of abdominal pain was assessed using a visual analog scale at each visit and a quality-of-life IBS (QoL-IBS) questionnaire was also completed. RESULTS: There was no significant difference in abdominal pain relief between the study and placebo groups (P = 0.800). There was also no difference in QoL- IBS scores between the groups (P = 0.687). Both groups had a significant improvement in abdominal pain scores over the study period, from an average of 251.55 to 197.90 (P < 0.0001) indicating a large placebo effect. CONCLUSION: An 8-wk treatment with L. plantarum 299 v did not provide symptomatic relief, particularly of abdominal pain and bloating, in patients fulfilling the Rome II criteria.

A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting.

BACKGROUND AND OBJECTIVES: Nausea and vomiting during pregnancy (NVP) occur commonly. Possible harmful side-effects of conventional medicine to the fetus create the need for alternative options to relieve NVP. This systematic review (SR) investigated current evidence regarding orally administered ginger for the treatment of NVP. The primary objective was to assess the effectiveness of ginger in treating NVP. The secondary objective was to assess the safety of ginger during pregnancy. METHODS: A comprehensive electronic bibliographic database search was carried out. Randomized controlled trials (RCTs) of the efficacy of orally administered ginger, as treatment for NVP in pregnant women at any stage of pregnancy, published in English, were included. Two researchers independently extracted data and assessed trial quality. RevMan5 software (Cochrane Collaboration) was used for data analysis. p < 0.05 was considered statistically significant. RESULTS: Twelve RCTs involving 1278 pregnant women were included. Ginger significantly improved the symptoms of nausea when compared to placebo (MD 1.20, 95% CI 0.56-1.84, p = 0.0002, I² = 0%). Ginger did not significantly reduce the number of vomiting episodes during NVP, when compared to placebo, although there was a trend towards improvement (MD 0.72, 95% CI -0.03-1.46, p = 0.06, I² = 71%). Subgroup analyses seemed to favor the lower daily dosage of <1500 mg ginger for nausea relief. Ginger did not pose a significant risk for spontaneous abortion compared to placebo (RR 3.14, 95% CI 0.65-15.11, p = 0.15; I² = 0%), or to vitamin B6 (RR 0.49, 95% CI 0.17-1.42, p = 0.19, I² = 40%). Similarly, ginger did not pose a significant risk for the side-effects of heartburn or drowsiness. CONCLUSIONS: This review suggests potential benefits of ginger in reducing nausea symptoms in pregnancy (bearing in mind the limited number of studies, variable outcome reporting and low quality of evidence). Ginger did not significantly affect vomiting episodes, nor pose a risk for side-effects or adverse events during pregnancy. Based on evidence from this SR, ginger could be considered a harmless and possibly effective alternative option for women suffering from NVP. International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42011001237.

Pycnogenol® (extract of French maritime pine bark) for the treatment of chronic disorders.

BACKGROUND: Oxidative stress has been implicated in the development of a number of conditions including cancer, arthritic disorders and cardiovascular disease. Pycnogenol(®), a herbal dietary supplement derived from French maritime pine bark extract, is standardised to contain 70% procyanidin which is a powerful antioxidant. Pycnogenol(®) is marketed as a supplement for preventing or treating a wide range of chronic conditions. OBJECTIVES: To assess the efficacy and safety of Pycnogenol(®) for the treatment of chronic disorders. SEARCH METHODS: We searched CENTRAL (until 18 September 2010), MEDLINE (until 18 September 2010) and EMBASE (until 13 October 2010) as well as three trial registries. We also contacted the manufacturer of Pycnogenol(®) and hand-searched bibliographies of included studies. SELECTION CRITERIA: Randomised controlled trials evaluating the effectiveness of Pycnogenol(®) in adults or children with any chronic disorder were included. We assessed clinical outcomes directly related to the disorder (stratified as participant- and investigator-reported) and all-cause mortality as primary outcomes. We also assessed adverse events and biomarkers of oxidative stress. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, extracted all data and assessed risk of bias. A third author additionally extracted information on outcomes and results. With three exceptions, results for outcomes across studies could not be pooled. MAIN RESULTS: This review includes 15 trials with a total of 791 participants that have evaluated Pycnogenol(®) for the treatment of seven different chronic disorders. These included asthma (two studies; N = 86), attention deficit hyperactivity disorder (one study; N = 61), chronic venous insufficiency (two studies; N = 60), diabetes mellitus (four studies; N = 201), erectile dysfunction (one study; N = 21), hypertension (two studies; N = 69) and osteoarthritis (three studies; N = 293). Two of the studies were conducted exclusively in children; the others involved adults.Due to small sample size, limited numbers of trials per condition, variation in outcomes evaluated and outcome measures used, as well as the risk of bias in the included studies, no definitive conclusions regarding the efficacy or safety of Pycnogenol(®) are possible. AUTHORS' CONCLUSIONS: Current evidence is insufficient to support Pycnogenol(®) use for the treatment of any chronic disorder. Well-designed, adequately powered trials are needed to establish the value of this treatment.

Pycnogenol(®) for the treatment of chronic disorders.

BACKGROUND: Oxidative stress has been implicated in the development of a number of conditions including cancer, arthritic disorders and cardiovascular disease. Pycnogenol(®), a herbal dietary supplement derived from French maritime pine bark extract, is standardised to contain 70% procyanidin which is a powerful antioxidant. Pycnogenol(®) is marketed as a supplement for preventing or treating a wide range of chronic conditions. OBJECTIVES: To assess the efficacy and safety of Pycnogenol(®) for the treatment of chronic disorders. SEARCH METHODS: We searched CENTRAL (until 18 September 2010), MEDLINE (until 18 September 2010) and EMBASE (until 13 October 2010) as well as three trial registries. We also contacted the manufacturer of Pycnogenol(®) and hand-searched bibliographies of included studies. SELECTION CRITERIA: Randomised controlled trials evaluating the effectiveness of Pycnogenol(®) in adults or children with any chronic disorder were included. We assessed clinical outcomes directly related to the disorder (stratified as participant- and investigator-reported) and all-cause mortality as primary outcomes. We also assessed adverse events and biomarkers of oxidative stress. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, extracted all data and assessed risk of bias. A third author additionally extracted information on outcomes and results. With three exceptions, results for outcomes across studies could not be pooled. MAIN RESULTS: This review includes 15 trials with a total of 791 participants that have evaluated Pycnogenol(®) for the treatment of seven different chronic disorders. These included asthma (two studies; N = 86), attention deficit hyperactivity disorder (one study; N = 61), chronic venous insufficiency (two studies; N = 60), diabetes mellitus (four studies; N = 201), erectile dysfunction (one study; N = 21), hypertension (two studies; N = 69) and osteoarthritis (three studies; N = 293). Two of the studies were conducted exclusively in children; the others involved adults.Due to small sample size, limited numbers of trials per condition, variation in outcomes evaluated and outcome measures used, as well as the risk of bias in the included studies, no definitive conclusions regarding the efficacy or safety of Pycnogenol(®) are possible. AUTHORS' CONCLUSIONS: Current evidence is insufficient to support Pycnogenol(®) use for the treatment of any chronic disorder. Well-designed, adequately powered trials are needed to establish the value of this treatment.

Micronutrient supplementation for critically ill adults: a systematic review and meta-analysis.

OBJECTIVE: This systematic review assessed the effects of micronutrient supplementation on adults recovering from critical illness. Primary outcomes included clinical endpoints (mortality, infectious complications, length of intensive care unit and of hospital stay). Secondary outcomes included descriptions of practice issues, micronutrient status, morbidity, course of the acute-phase response, and oxidative stress. METHODS: Electronic bibliographic databases, bibliographies of retrieved articles, and personal files were searched and reviewed. Randomized controlled trials (RCTs) of micronutrient supplementation in adult critically ill patients administered enterally and/or parenterally in addition to their routine care were included. Two authors independently extracted data and assessed trial quality. The random-effects model was used to estimate overall relative risk (RR)/mean difference and effect size. P<0.05 was considered statistically significant. RESULTS: Fifteen (n=1714) and 18 (n=1849) RCTs were included for the primary and secondary objectives, respectively. Fourteen trials (n=1468) showed a statistically significant decrease in overall mortality (RR 0.78, 95% confidence interval 0.67-0.90, I2=0%, P=0.0009). Six RCTs (n=1194) indicated a statistically significant decrease in 28-d mortality (RR 0.75, 95% confidence interval 0.63-0.88, I2=0%, P=0.0006). Micronutrient supplementation was not associated with a decrease in infectious complications, length of intensive care unit, or length of hospital stay. In subgroup analyses, a sensitivity analysis of combined micronutrients indicated a significant decrease in mortality (RR 0.69, 95% confidence interval 0.54-0.90, I2=2%, P=0.006). The secondary outcomes confirmed that timing, duration, and dosing appear to be key factors to ensure optimal clinical benefit. CONCLUSION: This review does suggest a potential benefit of micronutrient supplementation in critically ill adults by possibly being associated with a decrease in mortality.