Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers

<p>Abstract</p> <p>Background</p> <p>Arabinogalactan from Larch tree (<it>Larix </it>spp.) bark has previously demonstrated immunostimulatory activity. The purpose of this study was to test the hypothesis that ingestion of a proprietary arabinogalactan extract, ResistAid™, would selectively enhance the antibody response to the pneumococcal (pneumonia) vaccine in healthy adults.</p> <p>Methods</p> <p>This randomized, double-blind, placebo-controlled, parallel group pilot study included 45 healthy adults who had not previously been vaccinated against <it>Streptococcus pneumoniae</it>. The volunteers began taking the study product or placebo (daily dosage 4.5 g) at the screening visit (V1-Day 0) and continued over the entire 72 day study period. After 30 days the subjects received the 23-valent pneumococcal vaccine (V2). They were monitored the following day (V3-Day 31), as well as 21 days (V4-Day 51) and 42 days (V5-Day 72) after vaccination. Responses by the adaptive immune system (antigen specific) were measured via pneumococcal IgG antibodies (subtypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and salivary IgA levels. Responses by the innate immune system (non-specific) were measured via white blood cell counts, inflammatory cytokines and the complement system.</p> <p>Results</p> <p>Vaccination significantly increased pneumococcal IgG levels as expected. The arabinogalactan group demonstrated a statistically significant greater IgG antibody response than the placebo group in two antibodies subtypes (18C and 23F) at both Day 51 (p = 0.006 and p = 0.002) and at Day 72 (p = 0.008 and p = 0.041). These same subtypes (18C and 23F) also demonstrated change scores from baseline which were significant, in favor of the arabinogalactan group, at Day 51 (p = 0.033 and 0.001) and at Day 72 (p = 0.012 and p = 0.003). Change scores from baseline and mean values were greater in the arabinogalactan group than placebo for most time points in antibody subtypes 4, 6B, 9V, and 19F, but these differences did not reach statistical significance. There was no effect from the vaccine or arabinogalactan on salivary IgA, white blood cell count, inflammatory cytokines or complement.</p> <p>Conclusions</p> <p>The proprietary arabinogalactan extract (ResistAid™), tested in this randomized, double-blind, placebo-controlled, parallel-group pilot study, increased the antibody response of healthy volunteers to the 23-valent pneumococcal vaccine compared to placebo.</p> <p>Trial Registration</p> <p>ISRCTN98817459</p

Evaluation of Mangosteen juice blend on biomarkers of inflammation in obese subjects: a pilot, dose finding study

<p>Abstract</p> <p>Background</p> <p>The ability to reduce inflammation in overweight and obese individuals may be valuable in preventing the progression to metabolic syndrome with associated risks for heart disease and diabetes. The purpose of this study was to evaluate the effect of multiple dosages of a proprietary Mangosteen Juice blend on indicators of inflammation and antioxidant levels in obese patients with elevated C-reactive protein (CRP) levels.</p> <p>Methods</p> <p>The study was an 8 week randomized, double-blind, placebo-controlled study with a pre-study 2 week washout period. The study included four groups including placebo and three difference doses of the test product, XanGo Juice™: 3, 6 or 9 oz twice daily. The primary outcome measure of this study was high-sensitivity (HS)-CRP. Secondary outcome measures included other biochemical indicators of inflammation, anthropomorphic measures and a safety evaluation.</p> <p>Results</p> <p>One hundred twenty two (122) persons were screened for the study, 44 were randomized and 40 completed the study. HS-CRP measurements dropped after 8 weeks treatment compared to baseline in all 3 dose groups and increased in the placebo group. The changes from baseline were not significant but the comparison of change from baseline was significant for the 18 oz group when compared to placebo (p = 0.02). Other markers of inflammation (inflammatory cytokines) and a marker for lipid peroxidation (F2 isoprostane) did not show any significant differences when compared with placebo. There was a trend towards a decrease in BMI in the juice groups. There were no side effects reported in any of the groups and none of the laboratory or EKG safety assessments indicated clinically significant changes for any subject.</p> <p>Conclusion</p> <p>In this pilot, dose-finding study, a proprietary mangosteen juice blend (XanGo Juice™) reduced CRP levels (increased change from baseline) compared to placebo for those taking the highest dose of 18 oz per day. Further studies with a larger population are required to confirm and further define the benefits of this juice. The juice was administered safely.</p> <p>Trial Registration</p> <p>ISRCTN9300027</p

Effects of Açai (Euterpe oleracea Mart.) berry preparation on metabolic parameters in a healthy overweight population: A pilot study

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate the effect of açai fruit pulp on risk factors for metabolic disorders in overweight subjects. The açaí palm (<it>Euterpe oleracea </it>Mart.), which is native to South America, produces a small, black-purple fruit which is edible. The fruit has recently become popular as a functional food due to its antioxidant potential. Although several studies have been conducted in vitro and with animals, little is known about the potential health benefits in humans aside from an increase in plasma anti-oxidant capacity. Metabolic syndrome is a condition which is defined by a cluster of risk factors for cardiovascular disease and/or type-2 diabetes. Preliminary studies indicate that a reduction in reactive oxygen species can assist in the normalization of the metabolic pathways involved in this syndrome.</p> <p>Methods</p> <p>This was an open label pilot study conducted with 10 overweight adults (BMI ≥ 25 kg/m²and ≤ 30 kg/m²) who took 100 g açai pulp twice daily for 1 month. The study endpoints included levels of fasting plasma glucose, insulin, cholesterol, triglycerides, exhaled (breath) nitric oxide metabolites (eNO) and plasma levels of high sensitivity C-reactive protein (hs-CRP). The response of blood glucose, blood pressure and eNO to a standardized meal was determined at baseline and following the 30 day treatment.</p> <p>Results</p> <p>Compared to baseline, there were reductions in fasting glucose and insulin levels following the 30 day treatment (both p < 0.02). There was also a reduction in total cholesterol (p = 0.03), as well as borderline significant reductions in LDL-cholesterol and the ratio of total cholesterol to HDL-cholesterol (both p = 0.051). Compared to baseline, treatment with açai ameliorated the post-prandial increase in plasma glucose following the standardized meal, measured as the area under the curve (p = 0.047). There was no effect on blood pressure, hs-CRP or eNO.</p> <p>Conclusion</p> <p>In this uncontrolled pilot study, consumption of açai fruit pulp reduced levels of selected markers of metabolic disease risk in overweight adults, indicating that further studies are warranted.</p

Lowering the glycemic index of white bread using a white bean extract

<p>Abstract</p> <p>Background</p> <p>Phase 2^®is a dietary supplement derived from the common white kidney bean (Phaseolus vulgaris). Phase 2 has been shown to inhibit alpha-amylase, the complex carbohydrate digesting enzyme, in vitro. The inhibition of alpha-amylase may result in the lowering of the effective Glycemic Index (GI) of certain foods. The objective of this study was to determine whether the addition of Phase 2 would lower the GI of a commercially available high glycemic food (white bread).</p> <p>Methods</p> <p>An open-label 6-arm crossover study was conducted with 13 randomized subjects. Standardized GI testing was performed on white bread with and without the addition of Phase 2 in capsule and powder form, each in dosages of 1500 mg, 2000 mg, and 3000 mg. Statistical analysis was performed by one-way ANOVA of all seven treatment groups using unadjusted multiple comparisons (t tests) to the white bread control.</p> <p>Results</p> <p>For the capsule formulation, the 1500 mg dose had no effect on the GI and the 2000 mg and 3000 mg capsule doses caused insignificant reductions in GI. For the powder, the 1500 mg and 2000 mg doses caused insignificant reductions in the GI, and the 3000 mg dose had a significant effect (-20.23 or 34.11%, p = 0.023)</p> <p>Conclusion</p> <p>Phase 2 white bean extract appears to be a novel and potentially effective method for reducing the GI of existing foods without modifying their ingredient profile.</p> <p>Trial Registration</p> <p>Trial Registration: ISRCTN50347345</p

A proprietary alpha-amylase inhibitor from white bean (Phaseolus vulgaris): A review of clinical studies on weight loss and glycemic control

Obesity, and resultant health hazards which include diabetes, cardiovascular disease and metabolic syndrome, are worldwide medical problems. Control of diet and exercise are cornerstones of the management of excess weight. Foods with a low glycemic index may reduce the risk of diabetes and heart disease as well as their complications. As an alternative to a low glycemic index diet, there is a growing body of research into products that slow the absorption of carbohydrates through the inhibition of enzymes responsible for their digestion. These products include alpha-amylase and glucosidase inhibitors. The common white bean (Phaseolus vulgaris) produces an alpha-amylase inhibitor, which has been characterized and tested in numerous clinical studies. A specific and proprietary product named Phase 2® Carb Controller (Pharmachem Laboratories, Kearny, NJ) has demonstrated the ability to cause weight loss with doses of 500 to 3000 mg per day, in either a single dose or in divided doses. Clinical studies also show that Phase 2 has the ability to reduce the post-prandial spike in blood glucose levels. Experiments conducted incorporating Phase 2 into food and beverage products have found that it can be integrated into various products without losing activity or altering the appearance, texture or taste of the food. There have been no serious side effects reported following consumption of Phase 2. Gastro-intestinal side effects are rare and diminish upon extended use of the product. In summary, Phase 2 has the potential to induce weight loss and reduce spikes in blood sugar caused by carbohydrates through its alpha-amylase inhibiting activity

Development of a nurse home visitation intervention for intimate partner violence

<p>Abstract</p> <p>Background</p> <p>Despite an increase in knowledge about the epidemiology of intimate partner violence (IPV), much less is known about interventions to reduce IPV and its associated impairment. One program that holds promise in preventing IPV and improving outcomes for women exposed to violence is the Nurse-Family Partnership (NFP), an evidence-based nurse home visitation program for socially disadvantaged first-time mothers. The present study developed an intervention model and modification process to address IPV within the context of the NFP. This included determining the extent to which the NFP curriculum addressed the needs of women at risk for IPV or its recurrence, along with client, nurse and broader stakeholder perspectives on how best to help NFP clients cope with abusive relationships.</p> <p>Methods</p> <p>Following a preliminary needs assessment, an exploratory multiple case study was conducted to identify the core components of the proposed IPV intervention. This included qualitative interviews with purposeful samples of NFP clients and community stakeholders, and focus groups with nurse home visitors recruited from four NFP sites. Conventional content analysis and constant comparison guided data coding and synthesis. A process for developing complex interventions was then implemented.</p> <p>Results</p> <p>Based on data from 69 respondents, an IPV intervention was developed that focused on identifying and responding to IPV; assessing a client's level of safety risk associated with IPV; understanding the process of leaving and resolving an abusive relationship and system navigation. A need was identified for the intervention to include both universal elements of healthy relationships and those tailored to a woman's specific level of readiness to promote change within her life. A clinical pathway guides nurses through the intervention, with a set of facilitators and corresponding instructions for each component.</p> <p>Conclusions</p> <p>NFP clients, nurses and stakeholders identified the need for modifications to the existing NFP program; this led to the development of an intervention that includes universal and targeted components to assist NFP nurses in addressing IPV with their clients. Plans for feasibility testing and evaluation of the effectiveness of the IPV intervention embedded within the NFP, and compared to NFP-only, are discussed.</p

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead