Novel Hydrolyzed Chicken Sternal Cartilage Extract Improves Facial Epidermis and Connective Tissue in Healthy Adult Females: A Randomized, Double-Blind, Placebo-Controlled Trial.

CONTEXT: Dietary supplement manufacturers claim cutaneous anti-aging properties for their products; however, research supporting these claims remains sparse. OBJECTIVES: The study intended to determine if a correlation existed between the effects of a collagen dietary supplement and changes associated with skin aging. DESIGN: The study was a 12-week, double-blind, placebo-controlled trial. SETTING: The study took place at a clinical facility specializing in dermatological testing that could perform biophysical, instrumental analysis on the effects of proprietary supplement on human skin. PARTICIPANTS: Participants were 128 females, aged 39-59 (50.57 ± 5.55). INTERVENTION: Participants were randomly assigned to an intervention or a placebo. The intervention consisted of twice daily oral administration of a supplement containing 500 mg BioCell Collagen, a chicken sternal cartilage derived dietary ingredient composed of a naturally-occurring matrix of hydrolyzed collagen type-II (≥300 mg), chondroitin sulfate (≥100 mg), hyaluronic acid (≥50 mg). OUTCOME MEASURES: The primary parameters included transepidermal water loss, viscoelasticity, hydration, (indirect) collagen content, chromophore (melanin) content and hemoglobin level, and photographic analysis. An expert visually graded participants' skin to determine the intervention's efficacy, measuring facial lines and wrinkles, crow's feet lines and wrinkles, skin texture and smoothness, and skin tone. The presence of erythema and/or dryness determined tolerance. Secondary outcome measures were tolerance and incidence of adverse events, and the participant's perception of the supplement's value. RESULTS: For the 113 participants completing the study, the dietary supplementation compared to a placebo: (1) significantly reduced facial lines and wrinkles (P = .019) and crow's feet lines and wrinkles (P = .05), (2) increased skin elasticity (P = .008) and cutaneous collagen content (P < .001) by 12%, (3) improved indicators associated with a more youthful skin appearance based on visual grading and wrinkle width (P = .046), and (4) decreased skin dryness and erythema. No difference existed between the supplement and the placebo for skin-surface water content or retention. The supplement was well tolerated, with no reported adverse reactions. CONCLUSIONS: Dietary supplementation with chicken, sternal cartilage extract supports the accumulation of types-I/III collagen in skin to promote increased elasticity and reduced skin wrinkling.

Urox containing concentrated extracts of Crataeva nurvala stem bark, Equisetum arvense stem and Lindera aggregata root, in the treatment of symptoms of overactive bladder and urinary incontinence: a phase 2, randomised, double-blind placebo controlled trial.

BACKGROUND: Storage lower urinary tract symptoms (LUTS) including overactive bladder (OAB) and urinary incontinence (UI) affect millions of people worldwide, significantly impacting quality of life. Plant based medicines have been documented both empirically and in emerging scientific research to have varying benefits in reducing bladder symptoms. We assessed the efficacy of Urox®, a proprietary combination of phytomedicine extracts including, Cratevox™ (Crataeva nurvala) stem bark, Equisetem arvense stem and Lindera aggregata root, in reducing symptoms of OAB and UI. METHODS: Efficacy of the herbal combination on a variety of bladder symptoms compared to an identical placebo, were documented in a randomised, double-blind, placebo controlled trial conducted at two primary care centres. Data were collected at baseline, 2, 4 and 8 weeks, with the primary outcome being self-reported urinary frequency. Statistical analysis included mixed effects ordered logistic regression with post hoc Holm's test to account for repeated measures, and included an intention-to-treat analysis. RESULTS: One hundred and fifty participants (59% female, aged; mean ± SD; 63.5 ± 13.1 years) took part in the study. At week 8, urinary day frequency was significantly lower (OR 0.01; 95%CI 0.01 to 0.02; p < 0.001) in response to treatment (mean ± SD; 7.69 ± 2.15/day) compared to placebo (10.95 ± 2.47/day). Similarly, episodes of nocturia were significantly fewer (OR 0.03; 95%CI 0.02 to 0.05) after 8 weeks of treatment (2.16 ± 1.49/night) versus placebo (3.14 ± 1.36/night). Symptoms of urgency (OR 0.02; 95%CI 0.01 to 0.03), and total incontinence (OR 0.03; 95% CI 0.01 to 0.06) were also lower (all p < 0.01) in the treatment group. Significant improvements in quality of life were reported after treatment in comparison to placebo. No significant side effects were observed resulting in withdrawal from treatment. CONCLUSIONS: The outcome of this study demonstrated both statistical significance and clinical relevance in reducing symptoms of OAB, urinary frequency and/or urgency and incontinence. The demonstrated viability of the herbal combination to serve as an effective treatment, with minimal side-effects, warrants further longer term research and consideration by clinicians. TRIAL REGISTRATION: NCT02396160 (registered on 17 March 2015 - before any statistical analyses commenced).

Modulation of oxidative stress, inflammation, autophagy and expression of Nrf2 in hippocampus and frontal cortex of rats fed with açaí-enriched diets.

OBJECTIVE: Açaí (Euterpe spp.), an exotic palm fruit, has recently emerged as a promising source of natural antioxidants with wide pharmacological and nutritional value. In this study, two different species of açaí pulp extracts, naturally grown in two distinct regions of the Amazon, namely, Euterpe oleracea Mart. (habitat: Brazilian floodplains of the Amazon) and Euterpe precatoria Mart. (habitat: Bolivian Amazon), were studied for their effects on brain health and cognition. METHODS: Neurochemical analyses were performed in critical brain regions associated with memory and cognition of 19-month-old açaí-fed rats, in whom the cognitive benefits of açaí had been established. RESULTS: Results indicated significant reductions (P< 0.05) in prooxidant NADPH-oxidoreductase-2 (NOX2) and proinflammatory transcription factor NF-κB in açaí-fed rats. Measurement of Nrf2 expression, a transcription factor for antioxidant enzymes, and a possible link between oxidative stress, neuroinflammation and autophagy mechanisms, indicated significant overexpression (P<0.005) in the hippocampus and frontal cortex of the açaí-fed rats. Furthermore, significant activation of endogenous antioxidant enzymes GST and SOD were also observed in the açaí-fed animals when compared to control. Analysis of autophagy markers such as p62, phospho-mTOR, beclin1 and MAP1B-LC3 revealed differential expression in frontal cortex and hippocampus, mostly indicating an upregulation in the açaí-fed rats. DISCUSSION: In general, results were more profound for EP than EO in hippocampus as well as frontal cortex. Therefore, an açaí-enriched diet could possibly modulate Nrf2, which is known to modulate the intracellular redox status, thereby regulating the ubiquitin-proteosomal pathway, ultimately affecting cognitive function in the aging brain.

Toxicological and Genotoxicity Assessment of a Dihydroquercetin-Rich Dahurian Larch Tree (Larix gmelinii Rupr) Extract (Lavitol).

Safety assessment is reported of an orally ingested dihydroquercetin-rich extract (Lavitol) derived from the Dahurian larch tree, used as a food additive and as a dietary supplement ingredient. Dihydroquercetin, a potent antioxidant, is also known as taxifolin. The results of genotoxicity and toxicological tests (Comet assay, micronucleus test in human lymphocytes, chromosomal aberration test, subacute 7-day oral toxicity study, subchronic 90-day toxicology study with histopathologies, and, prenatal and postnatal developmental toxicity studies) on the extract provide further support for the safety of its consumption as a food supplement and food additive.

Restoration of stressor-induced calcium dysregulation and autophagy inhibition by polyphenol-rich açaí (Euterpe spp.) fruit pulp extracts in rodent brain cells in vitro.

OBJECTIVES: Oxidative damage to lipids, proteins, and nucleic acids in the brain often causes progressive neuronal degeneration and death that are the focal traits of chronic and acute pathologies, including those involving cognitive decline. The aim of this study was to investigate the specific effects of both Euterpe oleracea and Euterpe precatoria açaí fruit pulp on restoring stressor-induced calcium dysregulation, stunted growth of basal dendrites, and autophagy inhibition using embryonic hippocampal and HT22 hippocampal neurons. METHODS: Water-soluble whole fruit pulp extracts from two açaí species were applied to rat primary neurons and HT22 hippocampal neurons with varied time and concentrations. Recovery of neurons from dopamine-induced Ca(2+) dysregulation was measured by live cell imaging using fluorescent microscopy. The effect of açaí fruit pulp extracts on neurons following chemically-induced autophagy inhibition was measured using both immunofluorescence and immunohistochemical techniques. RESULTS: It has been postulated that at least part of the loss of cognitive function in aging may depend on a dysregulation in calcium ion (Ca(2+)) homeostasis and a loss of autophagy function in the brain, which affects numerous signaling pathways and alters protein homeostasis. In the present study, polyphenol-rich fruit pulp extracts from two species of açaí, Euterpe precatoria and Euterpe oleracea, when applied to rat hippocampal primary neuronal cells (E18), caused a significant (P < 0.05) recovery of depolarized brain cells from dopamine-induced Ca(2+) influx. Autophagy, a protein homeostasis mechanism in brain, when blocked by known inhibitors such as bafilomycin A1 or wortmannin, caused a significant reduction in the growth of primary basal dendrites in rodent primary hippocampal neurons and significant accumulation of polyubiquitinated proteins in mouse HT22 hippocampal neurons in culture. However, pretreatment with açaí extracts up to 1 mg/mL significantly increased the length of basal dendrites and attenuated the inhibitor-induced autophagy dysfunction. Açaí extracts activated the phosphorylation of mammalian target of rapamycin, increased the turnover of autophagosomes and MAP1 B LC3-II, and decreased accumulation of LC3-ubiquitin binding P62/SQSTM1. CONCLUSION: Although the polyphenol profile of Euterpe precatoria showed substantially higher concentrations of major flavonoids han Euterpe oleracea, the relative effects were essentially similar for both species. The study adds to growing evidence that supports the putative health effects of açaí fruit species on brain cells.

Safety assessment of a hydroethanolic extract of Caralluma fimbriata.

This toxicological assessment evaluated the safety of a hydroethanolic extract prepared from Caralluma fimbriata (CFE), a dietary supplement marketed worldwide as an appetite suppressant. Studies included 2 in vitro genotoxicity assays, a repeated dose oral toxicity study, and a developmental study in rats. No evidence of in vitro mutagenicity or clastogenicity surfaced in the in vitro studies at concentrations up to 5000 µg of extract/plate (Ames test) or 5000 µg of extract/mL (chromosomal aberration test). No deaths or treatment-related toxicity were seen in the 6-month chronic oral toxicity study in Sprague-Dawley rats conducted at 3 doses (100, 300, and 1000 mg/kg body weight (bw)/d). The no observed effect level for CFE in this study was considered to be 1000 mg/kg bw/d. A prenatal developmental toxicity study conducted at 3 doses (250, 500, and 1000 mg/kg bw/d) in female Sprague-Dawley rats resulted in no treatment-related external, visceral, or skeletal fetal abnormalities, and no treatment-related maternal or pregnancy alterations were seen at and up to the maximum dose tested. CFE was not associated with any toxicity or adverse events.

Effect of the novel low molecular weight hydrolyzed chicken sternal cartilage extract, BioCell Collagen, on improving osteoarthritis-related symptoms: a randomized, double-blind, placebo-controlled trial.

Osteoarthritis (OA) is a significant source of pain and disability. Current medical and surgical treatments can be costly and have serious side effects. The aim of this randomized, double-blind, placebo-controlled trial was to investigate the tolerability and efficacy of BioCell Collagen (BCC), a low molecular weight dietary supplement consisting of hydrolyzed chicken sternal cartilage extract, in the treatment of OA symptoms. Patients (n = 80) in the study had physician-verified evidence of progressive OA in their hip and/or knee joint. Joint pain had been present for 3 months or longer at enrollment, and pain levels were 4 or higher at baseline as assessed by Physician Global Assessment scores. Subjects were divided into two groups and administered either 2 g of BCC or placebo for 70 days. Other outcome measurements included visual analogue scale (VAS) for pain and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores taken on days 1, 35, and 70. The tolerability profile of the treatment group was comparable to that of the placebo. Intent-to-treat analysis showed that the treatment group, as compared to placebo, had a significant reduction of VAS pain on day 70 (p < 0.001) and of WOMAC scores on both days 35 (p = 0.017) and 70 (p < 0.001). The BCC group experienced a significant improvement in physical activities compared to the placebo group on days 35 (p = 0.007) and 70 (p < 0.001). BCC was well tolerated and found to be effective in managing OA-associated symptoms over the study period, thereby improving patient's activities of daily living. BCC can be considered a potential complement to current OA therapies.

Safety evaluation of a proprietary food-grade, dried fermentate preparation of Saccharomyces cerevisiae.

A safety evaluation was performed for EpiCor, a product produced by a proprietary fermentation process using Saccharomyces cerevisiae. Studies included the following assays: bacterial reverse mutation, mouse lymphoma cell mutagenicity, mitogenicity assay in human peripheral lymphocytes, and a cytochrome P450 ([CYP] CYP1A2 and CYP3A4) induction assessment as well as 14-day acute, 90-day subchronic, and 1-year chronic oral toxicity studies in rats. No evidence of genotoxicity or mitogenicity was seen in any of the in vitro or in vivo studies. The CYP assessment showed no interactions or inductions. No toxic clinical symptoms or histopathological lesions were observed in the acute, subchronic, or chronic oral toxicity studies in the rat. Results of the studies performed indicate that EpiCor does not possess genotoxic activity and has a low order of toxicity that is well tolerated when administered orally. The no observable adverse effect level (NOAEL) was 1500 mg/kg body weight (bw)/d for the 90-day study and 800 mg/kg bw/d for the 1 year study, for the highest doses tested.

Safety evaluation of a natural eggshell membrane-derived product.

Natural Eggshell Membrane (NEM®) is a novel dietary ingredient that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy joint and connective tissues. NEM® was evaluated for safety via in vitro and in vivo toxicological studies. This included testing for cytotoxicity, genotoxicity, acute oral toxicity, and 90-day repeated-dose oral toxicity. NEM® did not exhibit any cytotoxic effects at a dose of 100 µg in an in vitro human cell viability assay after incubation for up to 20 h. NEM® did not exhibit any genotoxic effects in an in vitro assay of four strains of histidine-dependent Salmonella typhimurium and one strain of tryptophan-dependent Escherichia coli at a dose of up to 5000 µg/plate. NEM® did not exhibit any signs of acute toxicity in rats at a single oral dose of up to 2000 mg/kg body weight, nor signs of toxicity (via urinalysis, hematology, clinical chemistry, or histopathological evaluation) in rats at a repeated oral dose of up to 2000 mg/kg body weight per day for 90 days. The results of these studies suggest that NEM® may be safe for human consumption.

Anthocyanin-rich açai (Euterpe oleracea Mart.) fruit pulp fractions attenuate inflammatory stress signaling in mouse brain BV-2 microglial cells.

Age-related diseases of the brain compromise memory, learning, and movement and are directly linked with increases in oxidative stress and inflammation. Previous research has shown that supplementation with berries can modulate signaling in primary hippocampal neurons or BV-2 mouse microglial cells. Because of their high polyphenolic content, fruit pulp fractions of açai ( Euterpe oleracea Mart.) were explored for their protective effect on BV-2 mouse microglial cells. Freeze-dried açai pulp was fractionated using solvents with different polarities and analyzed using HPLC for major anthocyanins and other phenolics. Fractions extracted using methanol (MEOH) and ethanol (ETOH) were particularly rich in anthocyanins such as cyanidin, delphinidin, malvidin, pelargonidin, and peonidin, whereas the fraction extracted using acetone (ACE) was rich in other phenolics such as catechin, ferulic acid, quercetin, resveratrol, and synergic and vanillic acids. Studies were conducted to investigate the mitigating effects of açai pulp extracts on lipopolysaccharide (LPS, 100 ng/mL) induced oxidative stress and inflammation; treatment of BV-2 cells with acai fractions resulted in significant (p < 0.05) decreases in nitrite production, accompanied by a reduction in inducible nitric oxide synthase (iNOS) expression. The inhibition pattern was emulated with the ferulic acid content among the fractions. The protection of microglial cells by açai pulp extracts, particularly that of MEOH, ETOH, and ACE fractions, was also accompanied by a significant concentration-dependent reduction in cyclooxygenase-2 (COX-2), p38 mitogen-activated protein kinase (p38-MAPK), tumor necrosis factor-α (TNFα), and nuclear factor κB (NF-κB). The current study offers valuable insights into the protective effects of açai pulp fractions on brain cells, which could have implications for improved cognitive and motor functions.

Pain reduction and improvement in range of motion after daily consumption of an açai (Euterpe oleracea Mart.) pulp-fortified polyphenolic-rich fruit and berry juice blend.

Dietary interventions involving antioxidants are of interest for reducing inflammation, improving joint motion, and altering pain perception. We evaluated the effect of oral consumption of a fruit and berry blend on pain and range of motion (ROM). This open-label clinical pilot study involved 14 study participants with limitations in ROM that was associated with pain and affected daily living. Participants included but were not limited to those with age-related osteoarthritis. Study participants consumed 120 mL MonaVie Active® fruit juice, predominantly containing açai pulp (Euterpe oleracea Mart.) and other fruit concentrates, daily for 12 weeks. Study participants were assessed at baseline and 2, 4, 8, and 12 weeks by structured nurse interviews, pain and activities of daily living (ADL) questionnaires, blood samples, and ROM assessment. Pain was scored by using a visual analogue scale. ROM was assessed by using dual digital inclinometry as recommended by American Medical Association guidelines. Consumption of the juice resulted in significant pain reduction, improved ROM measures, and improvement in ADLs. Serum antioxidant status, as monitored by the cell-based antioxidant protection in erythrocytes (CAP-e) assay, was improved within 2 weeks and continued to improve throughout the 12 weeks of study participation (P<.01). The inflammatory marker C-reactive protein was reduced at 12 weeks, but this change did not reach statistical significance. Lipid peroxidation decreased mildly at 12 weeks. The antioxidant status, as measured by the CAP-e bioassay, showed the best correlation with improvements in physical well-being (pain, ROM, and ADL). The significant association among increased antioxidant status, improved ROM, and pain reduction warrants further study.

Therapeutic applications of citicoline for stroke and cognitive dysfunction in the elderly: a review of the literature.

Citicoline (CDP-choline; cytidine 5'-diphosphocholine), a form of the essential nutrient choline, shows promise of clinical efficacy in elderly patients with cognitive deficits, inefficient memory, and early-stage Alzheimer's disease. Citicoline has also been investigated as a therapy in stroke patients, although the results of trials to date are inconclusive. Produced endogenously, citicoline serves as a choline donor in the metabolic pathways for biosynthesis of acetylcholine and neuronal membrane phospholipids, chiefly phosphatidylcholine. The principal components of citicoline, choline and cytidine, are readily absorbed in the GI tract and easily cross the blood-brain barrier. Exogenous citicoline, as the sodium salt, has been researched in animal experiments and human clinical trials that provide evidence of its cholinergic and neuroprotective actions. As a dietary supplement, citicoline appears useful for improving both the structural integrity and functionality of the neuronal membrane that may assist in membrane repair. This review, while not intended to be exhaustive, highlights the published, peer-reviewed research on citicoline with brief discussions on toxicology and safety, mechanisms of action, and pharmacokinetics.

A multicentered, open-label trial on the safety and efficacy of methylsulfonylmethane in the treatment of seasonal allergic rhinitis.

BACKGROUND: Seasonal allergic rhinitis (SAR) affects more than 23 million Americans annually, and current epidemiologic studies indicate that its prevalence within the United States is increasing. Numerous clinical observations and case studies have led researchers to hypothesize that methylsulfonylmethane (MSM) may help ameliorate the symptoms associated with SAR. OBJECTIVE: The primary goal of this study was to evaluate the efficacy of MSM in the reduction of SAR-associated symptoms. This study also examined possible adverse reactions associated with methylsulfonylmethane supplementation. Finally, this study attempted to elucidate the method of action by which MSM elicits its effect on allergy symptoms. DESIGN: Fifty-five (55) subjects were recruited for the study. All met the criteria for participation in the study. 50 subjects completed the study. Those subjects completing the study consumed 2,600 mg of MSM orally per day for 30 days. Clinical respiratory symptoms and energy levels were evaluated by a Seasonal Allergy Symptom Questionnaire (SASQ) at baseline and on days 7, 14, 21, and 30. Immune and inflammatory reactions were measured by plasma immunoglobulin E (IgE) and C-reactive protein at baseline and on day 30. An additional inflammatory biomarker, plasma histamine, was measured in a subset of subjects (n = 5). RESULTS: Day 7 upper and total respiratory symptoms were reduced significantly from baseline (p < 0.01 and p < 0.005, respectively). Lower respiratory symptoms were significantly improved from baseline by week 3 (p < 0.001). All respiratory improvements were maintained through the 30-day visit. Energy levels increased significantly by day 14 (p < 0.0001); this increase continued through day 30. No significant changes were observed in plasma IgE or histamine levels. The results of this study are promising. It would be worthwhile to conduct a larger, randomized, double-blind, placebo-controlled study to establish further if MSM would be a useful agent in the treatment of symptoms associated with SAR. CONCLUSION: The results of this study suggest that MSM supplementation of 2,600 mg/day for 30 days may be efficacious in the reduction of symptoms associated with SAR. Furthermore, few side effects are associated with the use of this compound. Recent acute and subacute chronic toxicologic data on the same source of MSM as used in this study, further validate the safety of this product.