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The potential of micronutrients to ameliorate the impact of prenatal alcohol exposure (PAE) on attentional regulation skills was explored in a randomized clinical trial conducted in Ukraine. Women who differed in prenatal alcohol use were recruited during pregnancy and assigned to one of three groups [No study-provided supplements, Multivitamin/Mineral Supplement (MVM), or MVM plus Choline]. Their offspring were seen in the preschool period and a reaction time task was administered. Participants were asked to press a response button as quickly as possible as 30 stimuli from the same category (animals) were presented consecutively and then followed by six stimuli from a novel category (vehicles). Number correct, mean latency of the response over trials, and variability in the latency were analyzed separately by sex. During the initial animal trials, boys whose mothers received MVM during pregnancy had more correct responses and reduced response latency compared to boys whose mothers had no MVM treatment. During vehicle trials, maternal choline supplementation was associated with increased response speed in males without a PAE history. Females receiving supplements did not show the same benefits from micronutrient supplementation and were more adversely impacted by prenatal alcohol exposure. Relationships between maternal levels of choline, betaine, and dimethylglycine (DMG) and task performance were also assessed. Although no effects were found for choline after adjusting for multiple comparisons, lower baseline DMG level was associated with greater accuracy and shorter latency of responses in the initial animal trials and shorter latency in the vehicle trials in female preschoolers. Level of betaine in Trimester 3 was associated with reduced variability in the latency of male responses during the animal trials. Maternal micronutrient supplementation in pregnancy appears to improve preschool reaction time performance, but the effects varied as a function of sex and PAE exposure status.

The potential of micronutrients to ameliorate the impact of prenatal alcohol exposure (PAE) was explored in a clinical trial conducted in Ukraine. Cardiac orienting responses (ORs) during a habituation/dishabituation learning paradigm were obtained from 6 to 12 month-olds to assess neurophysiological encoding and memory. Women who differed in prenatal alcohol use were recruited during pregnancy and assigned to a group (No study-provided supplements, multivitamin/mineral supplement, or multivitamin/mineral supplement plus choline supplement). Heart rate was collected for 30 s prior to stimulus onset and 12 s post-stimulus onset. Difference values (∆HR) for the first 3 trials of each condition were aggregated for analysis. Gestational blood samples were collected to assess maternal nutritional status and changes as a function of the intervention. Choline supplementation resulted in a greater ∆HR on the visual habituation trials for all infants and for the infants with no PAE on the dishabituation trials. The latency of the response was reduced in both conditions for all infants whose mothers received choline supplementation. Change in gestational choline level was positively related to ∆HR during habituation trials and levels of one choline metabolite, dimethylglycine (DMG), predicted ∆HR during habituation trials and latency of responses. A trend was found between DMG and ∆HR on the dishabituation trials and latency of the response. Supplementation did not affect ORs to auditory stimuli. Choline supplementation when administered together with routinely recommended multivitamin/mineral prenatal supplements during pregnancy may provide a beneficial impact to basic learning mechanisms involved in encoding and memory of environmental events in alcohol-exposed pregnancies as well as non- or low alcohol-exposed pregnancies. Changes in maternal nutrient status suggested that one mechanism by which choline supplementation may positively impact brain development is through prevention of fetal alcohol-related depletion of DMG, a metabolic nutrient that can protect against overproduction of glycine, during critical periods of neurogenesis.

ObjectiveTo determine the safety and efficacy of a dietary supplement with a low dose of ephedra and caffeine in overweight/obese premenopausal female subjects.DesignA 9-month, double-blind, randomized control study compared the efficacy and safety of a dietary supplement with ephedra and caffeine to a control supplement.SubjectsSixty-one healthy, premenopausal women with body mass index (BMI) from 27 to 39 kg/m2 were randomly assigned and received a dietary supplement (40 mg/day ephedra alkaloids, 100 mg/day caffeine, high potency mixture of vitamins, minerals, omega-3 fatty acids) or a control supplement for 9 months.MeasurementsEfficacychanges in body weight, body composition, lipids, insulin, leptin, adiponectin, ghrelin, and self-reports of physical activity, diet and quality of life indices.Safetyblood pressure, heart rate, electrocardiograms, urinalysis, blood histology, serum chemistry measures and self-reported symptoms.ResultsForty-one women completed the study. The treatment group lost significantly more body weight (-7.18 kg) and body fat (-5.33 kg) than the control group (-2.25 and -0.99 kg, respectively), and showed significant declines in heart rate, serum cholesterol, triglycerides, cholesterol to high-density lipoprotein ratio, glucose, fasting insulin, and leptin. Blood pressure, electrocardiograms, other clinical chemistry measures, blood histology, urinalysis, and self-reported physical activity were similar in the groups. Minor symptoms included dry mouth, insomnia, nervousness and palpitations. The treatment group reported more energy and decreased appetite compared to controls and scored higher on a quality of life domain assessing vitality.ConclusionA dietary supplement containing a low potency ephedra/caffeine mixture appeared safe and effective in causing loss of weight and body fat, and improving several metabolic parameters, including insulin sensitivity and lipid profiles when tested under physician supervision. Such supplements could be a useful tool to assist with weight loss.

Epidemiological reports have suggested that the consumption of foods rich in flavonoids is associated with a lower incidence of certain degenerative diseases, including cardiovascular disease. Flavanols and their related oligomers, the procyanidins CFP, isolated from cocoa can modulate the production and level of several signaling molecules associated with immune function and inflammation in vitro, including several cytokines and eicosanoids. To further elucidate the potential immuno-modulatory functions of flavanol-rich cocoa, the present investigation examined whether isolated CFP fractions (monomers through decamers) influence the secretion of tumor necrosis factor-alpha (TNF-alpha) from resting and phytohemagluttinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC). We used an in vitro culture system where PBMC from 14 healthy subjects were introduced to individual CFP fractions for 72 h prior to measuring the levels of TNF-alpha released. The intermediate-sized CFP fractions (tetramers through octamers) were the most active on resting cells, causing a 3-4 fold increase in TNF-alpha relative to media baseline. The monomers and dimers were the least stimulatory of the fractions tested, displaying a 42 and 31% increase, respectively, over media control, whereas the trimers, nonamers and decamers showed an intermediate stimulation of this cytokine. In the presence of PHA, the intermediate-sized CFP fractions again were the most active, enhancing TNF-alpha secretion in the range of 48-128% relative to the PHA control. The monomers and dimers were slightly inhibitory (-1.5 and -15%, respectively), while trimers, nonamers and decamers stimulated moderate increases in TNF-alpha levels (13, 19 and 15%, respectively). The above results lend support to the concept that CFP can be immunomodulatory. The stimulation of TNF-alpha secretion may contribute to the putative beneficial effects of dietary flavanoids against microbial infection and tumorigenesis.

Epidemiological reports have suggested that the consumption of foods rich in flavonoids is associated with a lower incidence of certain degenerative diseases, including cardiovascular disease. Flavanols and their related oligomers, the procyanidins CFP, isolated from cocoa can modulate the production and level of several signaling molecules associated with immune function and inflammation in vitro, including several cytokines and eicosanoids. To further elucidate the potential immuno-modulatory functions of flavanol-rich cocoa, the present investigation examined whether isolated CFP fractions (monomers through decamers) influence the secretion of tumor necrosis factor-alpha (TNF-alpha) from resting and phytohemagluttinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC). We used an in vitro culture system where PBMC from 14 healthy subjects were introduced to individual CFP fractions for 72 h prior to measuring the levels of TNF-alpha released. The intermediate-sized CFP fractions (tetramers through octamers) were the most active on resting cells, causing a 3-4 fold increase in TNF-alpha relative to media baseline. The monomers and dimers were the least stimulatory of the fractions tested, displaying a 42 and 31% increase, respectively, over media control, whereas the trimers, nonamers and decamers showed an intermediate stimulation of this cytokine. In the presence of PHA, the intermediate-sized CFP fractions again were the most active, enhancing TNF-alpha secretion in the range of 48-128% relative to the PHA control. The monomers and dimers were slightly inhibitory (-1.5 and -15%, respectively), while trimers, nonamers and decamers stimulated moderate increases in TNF-alpha levels (13, 19 and 15%, respectively). The above results lend support to the concept that CFP can be immunomodulatory. The stimulation of TNF-alpha secretion may contribute to the putative beneficial effects of dietary flavanoids against microbial infection and tumorigenesis.

Evidence for regulation of circulating leptin by insulin is conflicting. Diabetes was induced in rats with streptozotocin (STZ; 40 mg.kg(-1).day(-1) x 2 days) to examine the effect of insulin-deficient diabetes and insulin treatment on circulating leptin. After 12 wk, plasma leptin concentrations in untreated rats were all < 0.4 ng/ml versus 4.9 +/- 0.9 ng/ml in control animals (P < 0.005). In rats treated with subcutaneous insulin implants for 12 wk, which reduced hyperglycemia by approximately 50%, plasma leptin was 2.1 +/- 0.6 ng/ml, whereas leptin concentrations were 6.0 +/- 1.6 ng/ml in insulin-implanted rats receiving supplemental injections of insulin for 4 days to normalize plasma glucose (P < 0.005 vs. STZ untreated). In a second experiment, plasma leptin was monitored at biweekly intervals during 12 wk of diabetes. In rats treated with insulin implants, plasma leptin concentrations were inversely proportional to glycemia (r = -0.64; P < 0.0001) and unrelated to body weight (P = 0.40). In a third experiment, plasma leptin concentrations were examined very early after the induction of diabetes. Within 24 h after STZ injection, plasma insulin decreased from 480 +/- 30 to 130 +/- 10 pM (P < 0.0001), plasma glucose increased from 7.0 +/- 0.2 to 24.8 +/- 0.5 mM, and plasma leptin decreased from 3.2 +/- 0.2 to 1.2 +/- 0.1 ng/ml (delta = -63 +/- 3%, P < 0.0001). In a subset of diabetic rats treated with insulin for 2 days, glucose decreased to 11.7 +/- 3.9 mM and leptin increased from 0.5 +/- 0.1 to 2.9 +/- 0.6 ng/ml (P < 0.01) without an effect on epididymal fat weight. The change of leptin was correlated with the degree of glucose lowering (r = 0.75, P < 0.05). Thus insulin-deficient diabetes produces rapid and sustained decreases of leptin that are not solely dependent on weight loss, whereas insulin treatment reverses the hypoleptinemia. We hypothesize that decreased glucose transport into adipose tissue may contribute to decreased leptin production in insulin-deficient diabetes.

Objectives: Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by vascular damage, autoimmunity, and excessive collagen deposition. Despite advances in disease-specific treatment of other rheumatologic diseases, disease-targeted treatment in SSc continues to be elusive. In this review, our goal was to place the contemporary immunobiology of SSc in the perspective of clinical medicine.Methods: We performed a PubMed search for the period from 1989 to 2007, using the keyword, 'systemic sclerosis,' resulting in a total of 9099 publications, including 1252 reviews. Articles were then selected based on their discussion of recent advances in the elusive pathogenesis of SSc. A final total of 259 articles were chosen for the review.Results: The SSc hallmarks of vascular damage, immunologic activation, and collagen deposition can be traced to 4 major factors: T-cells, fibroblasts, B-cells, and cytokines/chemokines. T-cells are a major component of the infiltrate in skin and lung, exhibiting increased expression of activation markers and showing signs of antigen-driven expansion. Preliminary data indicate that induction of oral tolerance with collagen, a target of SSc T-cell responses, is associated with clinical benefits. Although this suggests that T-cells participate in the pathogenesis of SSc, their precise role and antigen specificity largely remain to be elucidated. Defective numbers and functions of certain T-cell subsets, such as natural killer and [gamma delta] T-cells, may be involved in the failure to maintain tolerance. Other data suggest that [gamma delta] T-cells may themselves be effector cells in endothelial cell cytotoxicity. There are several lines of evidence for a pathogenic role of B-cells in SSc, in particular, through the production of autoantibodies. Antibody-dependent cell-mediated cytotoxicity is a primary pathogenic event in an animal model of SSc and is likely to be involved in human SSc. Nonetheless, there is as yet no convincing evidence for the pathogenicity of SSc-specific antibodies. SSc fibroblasts exhibit a specific phenotype characterized not only by excessive collagen production but also by increased responsiveness to and production of cytokines and chemokines. This phenotype is induced by a complex network of cytokines and chemokines but appears to be maintained in the absence of exogenous stimuli via the autocrine production of some of these factors by SSc fibroblasts themselves, particularly transforming growth factor, platelet-derived growth factor, monocyte chemoattractant protein 1, and interleukin-1.Conclusions: Significant variations in laboratory data among patients suggest that the pathology reflects a heterogeneous disease. Nonetheless, the possibility of achieving clinical benefits by inducing oral tolerance highlights the importance of characterizing SSc T-cell antigens. It is hoped that the identification of some of the key players in the induction and maintenance of the SSc fibroblast phenotype may yield new disease-targeted treatment regimens for patients with SSc. © 2008 Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

BACKGROUND: Epidemiologic studies have linked flavonoid-rich foods with a reduced risk of cardiovascular mortality. Some cocoas are flavonoid-rich and contain the monomeric flavanols (-)-epicatechin and (+)-catechin and oligomeric procyanidins formed from these monomeric units. Both the monomers and the oligomers have shown potential in favorably influencing cardiovascular health in in vitro and preliminary clinical studies. Although previous investigations have shown increasing concentrations of (-)-epicatechin in human plasma after cocoa consumption, no information is available in the published literature regarding the presence of procyanidins in human plasma. OBJECTIVE: This study sought to determine whether procyanidins can be detected and quantified in human plasma after acute consumption of a flavanol-rich cocoa. DESIGN: Peripheral blood was obtained from 5 healthy adult subjects before (baseline, 0 h) and 0.5, 2, and 6 h after consumption of 0.375 g cocoa/kg body wt as a beverage. Plasma samples were analyzed for monomers and procyanidins with the use of reversed-phase HPLC with coulometric electrochemical array detection and liquid chromatography-tandem mass spectrometry. RESULTS: Procyanidin dimer, (-)-epicatechin, and (+)-catechin were detected in the plasma of human subjects as early as 0.5 h (16 +/- 5 nmol/L, 2.61 +/- 0.46 micro mol/L, and 0.13 +/- 0.03 micro mol/L, respectively) after acute cocoa consumption and reached maximal concentrations by 2 h (41 +/- 4 nmol/L, 5.92 +/- 0.60 micro mol/L, and 0.16 +/- 0.03 micro mol/L, respectively). CONCLUSION: Dimeric procyanidins can be detected in human plasma as early as 30 min after the consumption of a flavanol-rich food such as cocoa. Copyright © 2002 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Progressive myelopathy is a rare complication of chronic hepatic disease which has never been reported in the paediatric age group. We describe the 11 year course of an adolescent male with hepatic myelopathy caused by cryptogenic micronodular cirrhosis. His condition has been associated with persistent polycythaemia and extraordinary increases of whole blood manganese, with magnetic resonance imaging evidence of manganese deposition within the basal ganglia and other regions of the brain. The patient has developed neither liver failure nor parkinsonism. The pathophysiological bases of this multiorgan system disorder are described. [ABSTRACT FROM AUTHOR]

An increasing body of epidemiologic evidence supports the concept that diets rich in fruits and vegetables can promote health and attenuate, or delay, the onset of various diseases. Epidemiologic data support the idea that these health benefits are causally linked to the consumption of certain flavonoids present in fruit and vegetables. In the context of cardiovascular health, a particular group of flavonoids, namely, the flavan-3-ols (flavanols), has received attention. Flavanol-rich, plant-derived foods and beverages include wine, tea, and various fruits and berries, as well as cocoa and cocoa products. Numerous dietary intervention studies in humans and animals indicate that flavanol-rich foods and beverages might exert cardioprotective effects with respect to vascular function and platelet reactivity. This review discusses the bioactivity of flavanols in the context of cardiovascular health, with respect to their bioavailability, their antioxidant properties, and Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

OBJECTIVES: The influence of cigarette smoking on blood antioxidant status in teenage girls with a history of short-term smoking was followed over 18 mo. METHODS: Data obtained from female senior high school students (ages 14 to 18 y) in Korea were compared with data obtained from adult male smokers (ages 36 to 51 y) with a long history of smoking and living in the same geographic areas as the teenage subjects. A smoker was a person who had smoked at least three cigarettes a day for at least 1 y for teenagers (n = 35) or at least 10 cigarettes a day for at least 13 y for adults (n = 20). Serum, urine, and anthropometric data were obtained from teenagers every 6 mo over an 18-mo period. Samples were collected once from adults. Data were analyzed by Student's t test and Fisher's protected least significant difference test for comparing smokers and non-smokers and for analyzing period effects in each group. RESULTS: Serum nicotine and cotinine concentrations were higher in smokers than in non-smokers. Blood pressures were higher in teenage (at 0 and 12 mo) and adult smokers than in non-smokers. Extracellular superoxide dismutase activities and concentrations of serum vitamin C and folate were lower in smokers in the teenage (at 0, 12, or 18 mo) and adult groups. Serum ceruloplasmin activities and thiobarbituric acid-reactive substance production were not influenced by smoking. In adults, serum copper concentrations were higher in smokers than in non-smokers. This parameter for teenagers did not change consistently throughout the study. CONCLUSIONS: Similar to adults, cigarette smoking by teenagers has a negative effect on oxidant defense systems. [ABSTRACT FROM AUTHOR]

Strawberries provide a number of potential health promoting phytonutrients to include phenolics, polyphenols, fiber, micronutrients and vitamins. The objective of this review is to provide a comprehensive summary of recent human studies pertaining to the intake of strawberry and strawberry phytonutrients on human health. A literature search conducted through PubMed and Cochrane databases consolidated studies focusing on the effects of strawberry intake on human health. Articles were reviewed considering pre-determined inclusion and exclusion criteria, including experimental or observational studies that focused on health outcomes, and utilized whole strawberries or freeze-dried strawberry powder (FDSP), published between 2000-2023. Of the 60 articles included in this review, 47 were clinical trials, while 13 were observational studies. A majority of these studies reported on the influence of strawberry intake on cardiometabolic outcomes. Study designs included those examining the influence of strawberry intake during the postprandial period, short-term trials randomized with a control, or a single arm intake period controlling with a low polyphenolic diet or no strawberry intake. A smaller proportion of studies included in this review examined the influence of strawberry intake on additional outcomes of aging including bone and brain health, and cancer risk. Data support that the inclusion of strawberries into the diet can have positive impacts during the postprandial period, with daily intake improving outcomes of lipid metabolism and inflammation in those at increased cardiovascular risk.

There is a need for transformational innovation within the existing food system to achieve United Nations Sustainable Development Goal 2 of ending hunger within a sustainable agricultural system by 2030. Mycelium, the vegetative growth form of filamentous fungi, may represent a convergence of several features crucial for the development of food products that are nutritious, desirable, scalable, affordable, and environmentally sustainable. Mycelium has gained interest as technology advances demonstrate its ability to provide scalable biomass for food production delivering good flavor and quality protein, fiber, and essential micronutrients urgently needed to improve public health. We review the potential of mycelium as an environmentally sustainable food to address malnutrition and undernutrition, driven by food insecurity and caloric dense diets with less than optimal macro- and micronutrient density.

Moderate red wine intake has been associated with lower cardiovascular mortality, due in part to the intake of polyphenols and anthocyanins, whose content can vary from varietal and year of harvest. This study assessed the vascular effects in response to a single intake of 2015 and 2018 Zweigelt red wines from Hokkaido, Japan. Healthy men were randomly assigned to consume 240 mL each of a red wine, or a sparkling white grape juice as a control in a randomized three-arm cross-over design with a 7 day washout between arms. The augmentation index (AI; a measure of arterial stiffness) and AI at 75 beats/min (AI75), reactive hyperemia index, systolic and diastolic blood pressure (SBP and DBP, respectively), and platelet reactivity were assessed at baseline and two and four hours after each beverage intake. Changes from the baseline were analyzed using a linear mixed model. Significant treatment effects ( p = 0.02) were observed, with AI 13% lower after the intake of the 2015 or 2018 vintages compared to the control. Intake of the 2018 vintage reduced SBP and DBP (-4.1 mmHg and -5.6 mmHg, respectively; p = 0.02) compared to the 2015 wine and the control drink. The amount of hydroxytyrosol in the 2018 wine was almost twice the amount as in the 2015 wine, which may help explain the variable blood pressure results. Future studies exploring the vascular effects of the same red wine from different vintage years and different phenolic profiles are warranted.

Consumption of nuts and berries are considered part of a healthy eating pattern. Nuts and berries contain a complex nutrient profile consisting of essential vitamins and minerals, fiber, polyunsaturated fatty acids, and phenolics in quantities that improve physiological outcomes. The spectrum of health outcomes that may be impacted by the consumptions of nuts and berries includes cardiovascular, gut microbiome, and cognitive, among others. Recently, new insights regarding the bioactive compounds found in both nuts and berries have reinforced their role for use in precision nutrition efforts. However, challenges exist that can affect the generalizability of outcomes from clinical studies, including inconsistency in study designs, homogeneity of test populations, variability in test products and control foods, and assessing realistic portion sizes. Future research centered on precision nutrition and multi-omics technologies will yield new insights. These and other topics such as funding streams and perceived risk-of-bias were explored at an international nutrition conference focused on the role of nuts and berries in clinical nutrition. Successes, challenges, and future directions with these foods are presented here., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Lutein, zeaxanthin, and meso-zeaxanthin are three xanthophyll carotenoid pigments that selectively concentrate in the center of the retina. Humans cannot synthesize lutein and zeaxanthin, so these compounds must be obtained from the diet or supplements, with meso-zeaxanthin being converted from lutein in the macula. Xanthophylls are major components of macular pigments that protect the retina through the provision of oxidant defense and filtering of blue light. The accumulation of these three xanthophylls in the central macula can be quantified with non-invasive methods, such as macular pigment optical density (MPOD). MPOD serves as a useful tool for assessing risk for, and progression of, age-related macular degeneration, the third leading cause of blindness worldwide. Dietary surveys suggest that the dietary intakes of lutein and zeaxanthin are decreasing. In addition to low dietary intake, pregnancy and lactation may compromise the lutein and zeaxanthin status of both the mother and infant. Lutein is found in modest amounts in some orange- and yellow-colored vegetables, yellow corn products, and in egg yolks, but rich sources of zeaxanthin are not commonly consumed. Goji berries contain the highest known levels of zeaxanthin of any food, and regular intake of these bright red berries may help protect against the development of age-related macular degeneration through an increase in MPOD. The purpose of this review is to summarize the protective function of macular xanthophylls in the eye, speculate on the compounds' role in maternal and infant health, suggest the establishment of recommended dietary values for lutein and zeaxanthin, and introduce goji berries as a rich food source of zeaxanthin., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Research continues to provide compelling insights into potential health benefits associated with diets rich in plant-based natural products (PBNPs). Coupled with evidence from dietary intervention trials, dietary recommendations increasingly include higher intakes of PBNPs. In addition to health benefits, PBNPs can drive flavor and sensory perceptions in foods and beverages. Chardonnay marc (pomace) is a byproduct of winemaking obtained after fruit pressing that has not undergone fermentation. Recent research has revealed that PBNP diversity within Chardonnay marc has potential relevance to human health and desirable sensory attributes in food and beverage products. This review explores the potential of Chardonnay marc as a valuable new PBNP ingredient in the food system by combining health, sensory, and environmental sustainability benefits that serves as a model for development of future ingredients within a sustainable circular bioeconomy. This includes a discussion on the potential role of computational methods, including artificial intelligence (AI), in accelerating research and development required to discover and commercialize this new source of PBNPs.