Alcohol Consumption Moderated the Association Between Levels of High Blood Lead or Total Urinary Arsenic and Bone Loss.

Metal exposure and lifestyle are important risk factors for osteoporosis. Our study aimed to investigate the association between red blood cell lead and cadmium, total urinary arsenic, and plasma selenium levels and bone mineral density (BMD). In addition, we explored whether alcohol and coffee consumption modified the association between BMD and metals and metalloids. In total, 437 participants who underwent adult or senile physical examinations were recruited. Bone loss was defined as a calcaneus BMD T-score of <-1. Blood cadmium and lead and plasma selenium levels were measured using inductively coupled plasma mass spectrometry. Levels of urinary arsenic species were determined using high-performance liquid chromatography-hydride generator-atomic absorption spectrometry. The total urinary arsenic level was defined as the sum of the levels of urinary arsenic species. The BMD T-scores decreased significantly with increasing blood lead levels. The BMD T-scores also showed a downward trend with increasing total urinary arsenic levels. The odds ratio (OR) and 95% confidence interval (CI) for bone loss in patients with blood lead levels >57.58 versus 35.74 µg/dL were 1.98 and 1.17-3.34. In addition, the greater the lead or arsenic exposure and alcohol intake was the higher the OR for bone loss with multivariate ORs of 2.57 (95% CI 1.45-4.56) and 2.96 (95% CI 1.67-5.22), respectively. To the best of our knowledge, this study is the first to demonstrate that high total urinary arsenic or blood lead levels and frequent or occasional alcohol consumption had a significant multiplicative interaction for increasing the OR for bone loss.

Long-Chain ω-3 Levels Are Associated With Increased Alcohol Sensitivity in a Population-Based Sample of Adolescents.

BACKGROUND: The levels of the ω-3 long-chain polyunsaturated fatty acids (ω-3 LC-PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been associated with alcohol sensitivity in vertebrate and invertebrate model systems, but prior studies have not examined this association in human samples despite evidence of associations between ω-3 LC-PUFA levels and alcohol-related phenotypes. Both alcohol sensitivity and ω-3 LC-PUFA levels are impacted by genetic factors, and these influences may contribute to observed associations between phenotypes. Given the potential for using EPA and DHA supplementation in adjuvant care for alcohol misuse and other outcomes, it is important to clarify how ω-3 LC-PUFA levels relate to alcohol sensitivity. METHODS: Analyses were conducted using data from the Avon Longitudinal Study of Parents and Children. Plasma ω-3 LC-PUFA levels were measured at ages 15.5 and 17.5. Participants reported on their initial alcohol sensitivity using the early drinking Self-Rating of the Effects of Alcohol (SRE-5) scale, for which more drinks needed for effects indicates lower levels of response per drink, at ages 15.5, 16.5, and 17.5. Polygenic liability for alcohol consumption, alcohol problems, EPA levels, and DHA levels was derived using summary statistics from large, publicly available datasets. Linear regressions were used to examine the cross-sectional and longitudinal associations between ω-3 LC-PUFA levels and SRE scores. RESULTS: Age 15.5 ω-3 LC-PUFA levels were negatively associated with contemporaneous SRE scores and with age 17.5 SRE scores. One modest association (p = 0.02) between polygenic liability and SRE scores was observed, between alcohol problems-based polygenic risk scores (PRS) and age 16.5 SRE scores. Tests of moderation by genetic liability were not warranted. CONCLUSIONS: Plasma ω-3 LC-PUFA levels may be related to initial sensitivity to alcohol during adolescence. These data indicate that diet-related factors have the potential to impact humans' earliest responses to alcohol exposure.

Zinc deficiency and advanced liver fibrosis among HIV and hepatitis C co-infected anti-retroviral naïve persons with alcohol use in Russia.

BACKGROUND AND AIMS: Liver disease in people living with HIV co-infected with hepatitis C virus is a source of morbidity and mortality in Russia. HIV accelerates liver fibrosis in the setting of HCV co-infection and alcohol use. Zinc deficiency is common among people living with HIV and may be a factor that facilitates the underlying mechanisms of liver fibrosis. We investigated the association between zinc deficiency and advanced liver fibrosis in a cohort of HIV/HCV co-infected persons reporting heavy drinking in Russia. METHODS: This is a secondary data analysis of baseline data from 204 anti-retroviral treatment naïve HIV/HCV co-infected Russians with heavy drinking that were recruited into a clinical trial of zinc supplementation. The primary outcome of interest in this cross-sectional study was advanced liver fibrosis. Zinc deficiency, the main independent variable, was defined as plasma zinc <0.75 mg/L. Exploratory analyses were performed examining continuous zinc levels and fibrosis scores. Analyses were conducted using multivariable regression models adjusted for potential confounders. RESULTS: The prevalence of advanced liver fibrosis was similar for those with zinc deficiency compared to those with normal zinc levels, (27.7% vs. 23.0%, respectively). We did not detect an association between zinc deficiency and advanced liver fibrosis in the adjusted regression model (aOR: 1.28, 95% CI: 0.62-2.61, p = 0.51) nor in exploratory analyses. CONCLUSIONS: In this cohort of Russians with HIV/HCV co-infection, who are anti-retroviral treatment naïve and have heavy alcohol use, we did not detect an association between zinc deficiency or zinc levels and advanced liver fibrosis.

Effects of Phyllanthus amarus PHYLLPROTM leaves on hangover symptoms: a randomized, double-blind, placebo-controlled crossover study.

CONTEXT: Phyllanthus amarus Schumach. and Thonn. (Euphorbiaceae) is traditionally known to improve general liver health. However, its effect on hangover is unknown. OBJECTIVE: This study evaluated PHYLLPRO™, a standardized ethanol extract of P. amarus leaves for protection against oxidative stress and recovery from hangover symptoms. MATERIAL AND METHODS: Ten days daily oral supplementation of 750 mg/day followed by intoxication was evaluated in a randomized placebo-controlled (containing only excipient), crossover study in 15 subjects (21-50 years old), for oxidative stress, liver damage, alleviating hangover symptoms (Hangover Severity Score: HSS) and mood improvement (Profile-of-Mood-Scores: POMS). RESULTS: PHYLLPRO™ was able to remove blood alcohol in the active group while the placebo group still had 0.05% at 12 h post-intoxication (p < 0.0001). For HSS, the active group showed reduced hangover symptoms while there were higher levels of nausea, headache, anorexia, tremulousness, diarrhoea and dizziness in the placebo group (p < 0.05) at hour 10 post-intoxication. Increased fatigue at hour 2 and tension (p > 0.05) from baseline to hour 22 was reported in the placebo group using POMS. Significant anti-inflammatory group effect favouring the active group, by the upregulation of cytokines IL-8 (p = 0.0014) and IL-10 (p = 0.0492) and immunomodulatory effects via IL-12p70 (p = 0.0304) were observed. The incidence of adverse events was similar between groups indicating the safety of PHYLLPRO™. DISCUSSION AND CONCLUSION: Preliminary findings of PHYLLPRO™ in managing hangover, inflammation and liver functions following intoxication, is demonstrated. Future studies on PHYLLPRO™ in protecting against oxidative stress and hangover in larger populations is warranted.

Laboratory test based assessment of WHO alcohol risk drinking levels.

Low-risk thresholds for alcohol use differ across various national guidelines. To assess the novel WHO risk drinking levels in light of alcohol-sensitive common laboratory tests, we analysed biomarkers of liver status, inflammation and lipid profiles from a population-based survey of individuals classified to abstainers and different WHO risk drinking levels defined in terms of mean alcohol consumption per day. The study included 22,327 participants aged 25-74 years from the National FINRISK Study. Data on alcohol use, health status, diet, body weight and lifestyle (smoking, coffee consumption and physical activity) were recorded from structured interviews. Alcohol data from self-reports covering the past 12 months were used to categorize the participants into subgroups of abstainers and WHO risk drinking categories representing low, moderate, high and very high risk drinkers. Serum liver enzymes (GGT, ALT), C-reactive protein (CRP) and lipid profiles were measured using standard laboratory techniques. Alcohol risk category was roughly linearly related with the occurrence of elevated values for GGT, ALT and CRP. Alcohol drinking also significantly influenced the incidence of abnormalities in serum lipids. Significantly higher odds for abnormal GGT, ALT and altered lipid profiles remained in alcohol drinkers even after adjustment for age, waist circumference, physical inactivity, smoking and coffee consumption. A more systematic use of laboratory tests during treatment of individuals classified to WHO risk drinking categories may improve the assessment of alcohol-related health risks. Follow-ups of biomarker responses may also prove to be useful in health interventions aimed at reducing alcohol consumption.

Non-dietary factors associated with n-3 long-chain PUFA levels in humans - a systematic literature review.

Numerous health benefits are attributed to the n-3 long-chain PUFA (n-3 LCPUFA); EPA and DHA. A systematic literature review was conducted to investigate factors, other than diet, that are associated with the n-3 LCPUFA levels. The inclusion criteria were papers written in English, carried out in adult non-pregnant humans, n-3 LCPUFA measured in blood or tissue, data from cross-sectional studies, or baseline data from intervention studies. The search revealed 5076 unique articles of which seventy were included in the qualitative synthesis. Three main groups of factors potentially associated with n-3 LCPUFA levels were identified: (1) unmodifiable factors (sex, genetics, age), (2) modifiable factors (body size, physical activity, alcohol, smoking) and (3) bioavailability factors (chemically bound form of supplements, krill oil v. fish oil, and conversion of plant-derived α-linolenic acid (ALA) to n-3 LCPUFA). Results showed that factors positively associated with n-3 LCPUFA levels were age, female sex (women younger than 50 years), wine consumption and the TAG form. Factors negatively associated with n-3 LCPUFA levels were genetics, BMI (if erythrocyte EPA and DHA levels are <5·6 %) and smoking. The evidence for girth, physical activity and krill oil v. fish oil associated with n-3 LCPUFA levels is inconclusive. There is also evidence that higher ALA consumption leads to increased levels of EPA but not DHA. In conclusion, sex, age, BMI, alcohol consumption, smoking and the form of n-3 LCPUFA are all factors that need to be taken into account in n-3 LCPUFA research.

Effects of "Essential AD2" Supplement on Blood Acetaldehyde Levels in Individuals Who Have Aldehyde Dehydrogenase (ALDH2) Deficiency.

BACKGROUND: It is estimated that 1 billion people in the world have a point mutation in the gene encoding the aldehyde dehydrogenase 2 (ALDH2) enzyme, the primary enzyme responsible for the metabolism of acetaldehyde. The presence of this mutation is called ALDH2 deficiency. Because of limited ability to metabolize acetaldehyde, individuals with ALDH2 deficiency experience elevated levels of blood acetaldehyde after exposure to various common sources such as recreational alcohol. Because of higher levels of acetaldehyde, individuals with ALDH2 deficiency are at higher risk for numerous diseases, including liver cirrhosis, esophageal and gastric cancer, osteoporosis, and Alzheimer disease. STUDY QUESTION: The present trial was designed to study the effectiveness, safety, and tolerability of a nutritional supplement (Essential AD2). MEASURES AND OUTCOMES: The primary outcome was change in acetaldehyde levels in the blood after exposure to alcohol in individuals with ALDH2 deficiency before and after the use of study nutritional supplement. STUDY DESIGN: This was a 28-day open-label trial, comparing initial acetaldehyde levels after alcohol ingestion to levels after 28 days of a nutritional supplement (Essential AD2). The study consisted of 12 subjects genotyped to be heterozygous for the ALDH2 gene mutation. RESULTS AND CONCLUSIONS: ALDH2 deficient subjects showed a significant decrease in average blood acetaldehyde level 20 minutes after alcohol consumption (from 0.91 mg/dL to 0.71 mg/dL, P value = 0.02) after receiving 28 days of the nutritional supplement. Acetaldehyde levels taken at 10 minutes and 40 minutes also showed a decrease, although they were not statistically significant. In addition, safety tests looking at liver function tests showed a decrease in aspartate transaminase and alanine transaminase liver proteins from 27.3 to 15.2 and 20.9 to 13.2, respectively, over the 28 days. The treatment was well tolerated and no significant side effects were noted.

The Relationship Between Spirituality/Religiousness and Unhealthy Alcohol Use Among HIV-Infected Adults in Southwestern Uganda.

HIV and alcohol use are two serious and co-existing problems in sub-Saharan Africa. We examined the relationship between spirituality and/or religiousness (SR) and unhealthy alcohol use among treatment-naïve HIV-infected adults attending the HIV clinic in Mbarara, Uganda. Unhealthy alcohol was defined as having either an alcohol use disorders identification test-consumption score of ≥4 for men or ≥3 for women, or having a phosphatidylethanol level of ≥50 ng/ml based on analysis of dried bloodspot specimens. Of the 447 participants, 67.8% were female; the median age was 32 years (interquartile range [IQR] 27-40). About half reported being Protestant (49.2%), 35.1% Catholic, and 9.2% Muslim. The median SR score was high (103 [IQR 89-107]); 43.3% drank at unhealthy levels. Higher SR scores were associated with lower odds of unhealthy drinking (adjusted odds ratio [aOR]: 0.83 per standard deviation [SD] increase; 95% confidence interval [CI] 0.66-1.03). The "religious behavior" SR subscale was significantly associated with unhealthy alcohol use (aOR: 0.72 per SD increase; 95% CI 0.58-0.88). Religious institutions, which facilitate expression of religious behavior, may be helpful in promoting and maintaining lower levels of alcohol use.

Alcohol Induced Hepato Cardiotoxicity and Oxidative Damage in Rats: The Protective Effect of n-butanol Extract of Green Tea (Camellia sinensis (L.) Kuntze).

BACKGROUND: The principal aim of this study was to investigate the oxidative effects of acute alcohol consumption on the functions of the heart and the liver and the possible modification of this effect by phenolic compounds from n-butanol extract of Camellia sinensis supplementation. METHOD: Three experimental groups of rats were used: control, ethanol-exposed (40% v/v, 5 g/kg per oral every 12 hours for 3 doses, binge model), and ethanol-exposed plus n-butanol extract of Camellia sinensis (100 mg/kg once a day for three days before and simultaneously with ethanol administration). Serum transaminases, cholesterol, triglycerides, lipid peroxidation (MDA), reduced glutathione (GSH) and glutathione peroxidase (GPx) were estimated to assess organs damage. RESULTS: n-butanol extract of Camellia sinensis at a dose of 100 mg/kg body weight exhibited a significant reversal effect in all biochemical parameters measured such as extent of lipid peroxidation, GSH, lipid profile, and serum aminotransferase activities. CONCLUSION: These results suggest that n-butanol extract of Camellia sinensis protected the heart and the liver from binge ethanol induced injury through attenuating oxidative stress.

Peripheral Immune System Adaptations and Motivation for Alcohol in Non-Dependent Problem Drinkers.

BACKGROUND: Increasing evidence suggests that levels of pro-inflammatory and anti-inflammatory cytokines are dysfunctional in alcohol dependence. Moreover, some initial findings demonstrate that these adaptations in peripheral inflammation may contribute to motivation for alcohol and problem drinking via possible direct effects or the indirect effects of stress responsivity. Importantly, the role of pro-inflammatory and anti-inflammatory cytokines in the progression from healthy to problem drinking is not well understood. The aim of this study was to assess whether alcohol-related peripheral immune system changes affect stress and alcohol cue-induced craving and anxiety and behavioral alcohol motivation and intake in the laboratory among problem drinkers compared with socially drinking controls. METHODS: Twenty-six problem drinkers and 38 moderate, social drinkers participated in a laboratory challenge procedure during which they were exposed to 3 personalized 5-minute imagery conditions (stress [S], relaxing [R], and alcohol cue [C]), followed by the "alcohol taste test" (ATT) as a measure of implicit alcohol motivation and intake, presented across 3 consecutive days, 1 per day in a randomized and counterbalanced order. Measures of tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), alcohol craving, and anxiety were assessed at baseline, immediately following imagery exposure and at discreet beer cue presentation in the ATT. RESULTS: Compared with moderate drinkers, problem drinkers demonstrated tonic attenuation of IL-6 and IL-1ra. In problem drinkers, these changes also accompanied elevated levels of stress- and cue-induced alcohol craving and anxiety and were predictive of provoked alcohol craving, behavioral alcohol motivation and intake, and severity of problem drinking. CONCLUSIONS: Current findings indicate that selective immunosuppression in problem drinkers may play a key role in motivation for alcohol intake.

Thiamine deficiency, oxidative metabolic pathways and ethanol-induced neurotoxicity: how poor nutrition contributes to the alcoholic syndrome, as Marchiafava-Bignami disease.

Ethanol is an important risk factor for the occurrence of several brain disorders that depend on the amount, period and frequency of its consumption. Chronic use of ethanol often leads to the development of neurodegenerative syndromes, which cause morphological and functional impairments such as foetal alcohol syndrome in newborns exposed to ethanol during pregnancy, Wernicke-Korsakoff Syndrome and, more rarely, Marchiafava-Bignami disease (MBD). MBD is characterized by primary degeneration of the corpus callosum, without inflammation and is associated with oxidative stress and hypovitaminosis, as well as altered mental status, to mention dementia, seizures, depression and so on. This review discusses MBD and poor nutrition as a risk factor for the development of such alcoholic syndrome, with focus on diagnosis, pathogenic aspects, signs and symptoms, as well as therapeutic perspectives. On the basis of the inclusion/exclusion criteria adopted, the performed search in scientific databases (Pubmed, Scielo and Google Scholar) resulted in 100 studies that are being presented and discussed in the present work. Review, case-control and cohort studies on alcoholism-associated hypovitaminosis, oxidative stress, MBD and ethanol metabolism pathways were admitted as relevant. We highlight that MBD is a poorly described, diagnosed, insidious and progressive condition, for which evidence suggests a synergism between ethanol-induced neurotoxic effects and hypovitaminosis B. Present treatment consists of vitamin B1(thiamine) supplementation. Nonetheless, other strategies such as the inclusion of antidepressants or steroidal anti-inflammatories as add-on therapies have been employed as an attempt to improve the damage. Indeed, both the diagnosis and treatment are difficult, and death occurs within few years.

Effects of Sex, Drinking History, and Omega-3 and Omega-6 Fatty Acids Dysregulation on the Onset of Liver Injury in Very Heavy Drinking Alcohol-Dependent Patients.

BACKGROUND: Heavy alcohol consumption frequently causes liver inflammation/injury, and certain fatty acids (FAs) may be involved in this liver pathology. In this study, we evaluated the association of heavy drinking and the changes in the FA levels involved in the ω-6 (pro-inflammatory) and ω-3 (anti-inflammatory) state in alcohol-dependent (AD) patients who had no clinical manifestations of liver injury. We aimed to identify sex-based differences in patients with mild or no biochemical evidence of liver injury induced by heavy drinking. METHODS: A total of 114 heavy drinking AD female and male patients aged 21 to 65 years without clinical manifestations of liver injury, who were admitted to an alcohol dependence treatment program, were grouped by the alanine aminotransferase (ALT) levels: ≤40 IU/l, as no liver injury (GR.1), and >40 IU/l, as mild liver injury (GR.2). Patients were actively drinking until the day of admission. Comprehensive metabolic panel, comprehensive FA panel, and drinking history data were evaluated. RESULTS: Elevated ALT and aspartate aminotransferase (AST) showed close association with markers of heavy alcohol intake. In the patients with mild biochemical liver injury (GR.2), females showed significantly higher AST level than males. Significant association of AST and total drinks in past 90 days (TD90) in females, and AST and heavy drinking days in past 90 days (HDD90) in males was observed. The ω-6:ω-3 ratio showed a significant pro-inflammatory response only in females with mild liver injury (GR.2) when adjusted by drinking history marker, TD90. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were increased in males with liver injury, while females did not show any comparable rise in EPA; and DHA levels were lower. CONCLUSIONS: Measures of heavy drinking, TD90 and HDD90, predicted changes in liver injury. Changes in the ω-3 and ω-6 FA levels and the ω-6:ω-3 ratio showed a pro-inflammatory shift in patients with biochemical liver injury with a significant effect in females. Changes in FAs involved in the inflammatory state may represent one mechanism for liver inflammation/injury in response to heavy alcohol drinking.

Fibroblast growth factor 21 deficiency exacerbates chronic alcohol-induced hepatic steatosis and injury.

Fibroblast growth factor 21 (FGF21) is a hepatokine that regulates glucose and lipid metabolism in the liver. We sought to determine the role of FGF21 in hepatic steatosis in mice exposed to chronic alcohol treatment and to discern underlying mechanisms. Male FGF21 knockout (FGF21 KO) and control (WT) mice were divided into groups that were fed either the Lieber DeCarli diet containing 5% alcohol or an isocaloric (control) diet for 4 weeks. One group of WT mice exposed to alcohol received recombinant human FGF21 (rhFGF21) in the last 5 days. Liver steatosis and inflammation were assessed. Primary mouse hepatocytes and AML-12 cells were incubated with metformin or rhFGF21. Hepatic genes and the products involved in in situ lipogenesis and fatty acid ß-oxidation were analyzed. Alcohol exposure increased circulating levels and hepatic expression of FGF21. FGF21 depletion exacerbated alcohol-induced hepatic steatosis and liver injury, which was associated with increased activation of genes involved in lipogenesis mediated by SREBP1c and decreased expression of genes involved in fatty acid ß-oxidation mediated by PGC1α. rhFGF21 administration reduced alcohol-induced hepatic steatosis and inflammation in WT mice. These results reveal that alcohol-induced FGF21 expression is a hepatic adaptive response to lipid dysregulation. Targeting FGF21 signaling could be a novel treatment approach for alcoholic steatohepatitis.

Effect of Folic Acid, Betaine, Vitamin B6, and Vitamin B12 on Homocysteine and Dimethylglycine Levels in Middle-Aged Men Drinking White Wine.

UNLABELLED: Moderate regular consumption of alcoholic beverages is believed to protect against atherosclerosis but can also increase homocysteine or dimethylglycine, which are putative risk factors for atherosclerosis. We aimed (1) to investigate the effect of alcohol consumption on vitamins and several metabolites involved in one-carbon metabolism; and (2) to find the most effective way of decreasing homocysteine during moderate alcohol consumption. METHODS: Male volunteers (n = 117) were randomly divided into five groups: the wine-only group (control, 375 mL of white wine daily for one month) and four groups combining wine consumption with one of the supplemented substances (folic acid, betaine, and vitamins B12 or B6). Significant lowering of homocysteine concentration after the drinking period was found in subjects with concurrent folate and betaine supplementation. Vitamin B12 and vitamin B6 supplementation did not lead to a statistically significant change in homocysteine. According to a multiple linear regression model, the homocysteine change in the wine-only group was mainly determined by the interaction between the higher baseline homocysteine concentration and the change in dimethylglycine levels. Folate and betaine can attenuate possible adverse effects of moderate alcohol consumption. Dimethylglycine should be interpreted together with data on alcohol consumption and homocysteine concentration.

Neurometabolic Effect of Altaian Fungus Ganoderma lucidum (Reishi Mushroom) in Rats Under Moderate Alcohol Consumption.

BACKGROUND: The medications produced from natural products are widely used as prophylactics for sickness induced by alcohol consumption. One such prophylactic is produced from the Reishi mushroom, Ganoderma lucidum. Because of the antioxidant properties of these preparations, we expect neuroprotective prophylactic effects of Reishi-based medications in alcohol-treated animals. METHODS: The Reishi (R) suspension was produced as water extract from Altaian mushrooms. Sprague-Dawley male rats were separated into the following 3 experimental groups: Group A + R received R (6 days per week) starting 1 week before alcohol exposure, and during the next 3 weeks, they received both R and alcohol; group A received alcohol; and group C received water. At the end of experiment, we determined the metabolic profile using proton magnetic resonance spectroscopy ((1) H MRS) of the brain cortex and phosphorus magnetic resonance spectroscopy of the liver. Additionally, the blood cells were collected, and the serum biochemistry and liver histology were performed after euthanasia. RESULTS: Partial least squares discriminant analysis processing of the brain (1) H MRS gave 2 axes, the Y1 axis positively correlated with the level of taurine and negatively correlated with the level of lactate, and the Y2 axis positively correlated with the content of GABA and glycine and negatively correlated with the sum of the excitatory neurotransmitters, glutamate and glutamine. The Y1 values reflecting the brain energetics for the A + R group exceeded the corresponding values for groups C and A. The maximal level of Y2 reflecting the prevalence of inhibitory metabolites in the brain was observed in the rats exposed to alcohol. Moderate alcohol consumption did not cause significant pathological changes in the livers of the experimental animals. However, 20 days of alcohol consumption significantly increased the number of binuclear hepatocytes compared to the control. This effect was mitigated in the rats that received the Reishi extract. CONCLUSIONS: Regular administration of the Reishi suspension improved the energy supply to the brain cortex and decreased the prevalence of inhibitory neurotransmitters that are characteristic of alcohol consumption. The alcohol-induced increase in liver proliferation was significantly suppressed by regular administration of the G. lucidum water suspension.

Effect of GABA Extract of Black Sticky Rice with Giant Embryo on Alcohol-Related Indices After Acute Alcohol Intake in Social Drinkers.

BACKGROUND: This study was performed to evaluate the effect and safety of a high-gamma-aminobutyric acid-containing extract (GABA extract) of black sticky rice with giant embryo (BSRGE) on alcohol-related indices after acute alcohol intake in social drinkers. METHODS: Subjects were randomized to the GABA extract (G) group, GABA extract and alcohol drinking (GA) group, or placebo intake and alcohol drinking (PA) group in a double-blind design. All subjects were administered GABA extract (200 mg GABA) or placebo at 9 am on study days 2 and 3, respectively. Subjects in the GA and PA groups were administered an equivalent dose of alcohol that was diluted in a drinking beverage for a total amount of 240 ml at 11 am on day 3. Blood alcohol concentration (BAC) and the Biphasic Alcohol Effects Scale were measured just before alcohol drinking, and 6 times after alcohol drinking. RESULTS: The peak and area under the curve (AUC) of the total stimulation scale score after alcohol intake in females were significantly higher in the GA than in the PA group, whereas no significant difference was found between the 2 groups in males. The peak and AUC of the total score on the sedation scale after alcohol intake in males were significantly lower in the GA than in the PA group, whereas both were significantly higher in the GA than in the PA group of females. The AUC for BAC in males was significantly lower in the GA than in the PA group, whereas no significant difference was found in females. No adverse events were reported in any of the groups including the G group. CONCLUSIONS: Coadministration of a GABA extract to social drinkers while drinking alcohol is supposed to affect alcohol-related indices in terms of pharmacodynamics and pharmacokinetics and did not induce any adverse events.

Decrease in vitamin D status in the Greenlandic adult population from 1987-2010.

BACKGROUND: Low vitamin D status may be pronounced in Arctic populations due to limited sun exposure and decreasing intake of traditional food. OBJECTIVE: To investigate serum 25(OH)D3 as a measure of vitamin D status among adult Inuit in Greenland, predictors of low serum 25(OH)D3 concentrations and the trend from 1987 to 2005-2010. DESIGN: A total of 2877 randomly selected Inuit (≥ 18 years) from the Inuit Health in Transition study were included. A sub-sample (n = 330) donated a blood sample in 1987 which allowed assessment of time trends in vitamin D status. RESULTS: The geometric mean serum 25(OH)D3 (25[OH]D2 concentrations were negligible and not reported) in 2005-2010 was lowest among the 18-29 year old individuals (30.7 nmol/L; 95% CI: 29.7; 31.7) and increased with age. In all age-groups it decreased from 1987 to 2005-2010 (32%-58%). Low 25(OH)D3 concentrations (<50 nmol/L) were present in 77% of the 18-29 year old and decreased with age. A characteristic seasonal variation in 25(OH)D3 concentrations was observed (range 33.2-57.1 nmol/L, p<0.001), with the highest concentrations in August to October. Age (2.0% per year increase; CI: 1.7, 2.2), female gender (7.1%; CI: 2.0; 12.5), alcohol intake (0.2% per increase in drinks/week; 0.0; 0.4), and traditional diet (10.0% per 100 g/d increase; CI: 7.9; 12.1) were associated with increased serum 25(OH)D3, whereas smoking (-11.6%; CI: -16.2; -6.9), BMI (-0.6%; CI: -1.1; -0.2) and latitude (-0.7% per degree increase; CI: -1.3; -0.2) were associated with decreased concentrations. CONCLUSION: We identified a remarkable decrease in vitamin D status from 1987 to 2005-2010 and a presently low vitamin D status among Inuit in Greenland. A change away from a traditional diet may well explain the observed decline. The study argues for the need of increased dietary intake of vitamin D and supplementation might be considered.

Eicosapentaenoic acid in serum phospholipids relates to a less atherogenic lipoprotein profile in subjects with familial hypercholesterolemia.

Familial hypercholesterolemia (FH) carries an increased vascular risk due to lifelong elevation of the number of circulating low-density lipoprotein (LDL) particles, but also to alterations in triglyceride and high-density lipoprotein (HDL) metabolism. Supplementation with eicosapentaenoic (EPA) or docosahexaenoic (DHA) acids reduced LDL particle number and/or increased LDL size in different populations, but studies in FH are scarce. We investigated cross-sectionally whether intake of EPA and DHA in the usual diet is associated with a less atherogenic lipoprotein profile in subjects with FH (n=215). Lipoprotein particle number and size distributions were assessed with nuclear magnetic resonance spectroscopy. EPA and DHA proportions in serum phosphatidylcholine, a biomarker of fish intake, were determined by gas chromatography. After adjusting for cardiovascular risk factors, including fasting triglycerides, serum phosphatidylcholine EPA (but not DHA) related inversely to medium VLDL, total LDL particle number and very small LDL, resulting in a net direct association with LDL size. Additionally, EPA was directly associated with concentrations of large HDL. We conclude that increased serum phosphatidylcholine EPA derived from seafood intake with the usual diet is associated with a less atherogenic lipoprotein profile in subjects with FH. Increased fish intake and/or EPA supplements might contribute to reduce the residual risk of statin-treated FH subjects.

A standardized kudzu extract (NPI-031) reduces alcohol consumption in nontreatment-seeking male heavy drinkers.

OBJECTIVE: We previously demonstrated that short-term treatment with a standardized kudzu extract (NPI-031) reduced alcohol drinking by men and women in a natural setting. The present study was conducted in nontreatment-seeking heavy drinkers to assess the safety and efficacy of 4 weeks of kudzu extract in an outpatient setting. METHOD: This randomized between-subject, double-blind, placebo-controlled study involved 2 weeks of baseline, 4 weeks of treatment, and 2 weeks of follow-up. Seventeen men (21-33 years) who reported drinking 27.6 ± 6.5 drinks/week with a diagnosis of alcohol abuse/dependence took either kudzu extract (250 mg isoflavones, t.i.d.) or matched placebo on a daily basis. They reported alcohol consumption and desire to use alcohol using a wrist actigraphy device; twice weekly laboratory visits were scheduled to monitor medication adherence and adverse events. RESULTS: Medication adherence was excellent and there were no adverse events and changes in vital signs, blood chemistry, and renal or liver function. There was no effect on alcohol craving, but kudzu extract significantly reduced the number of drinks consumed each week by 34-57 %, reduced the number of heavy drinking days, and significantly increased the percent of days abstinent and the number of consecutive days of abstinence. CONCLUSIONS: A standardized formulation of kudzu extract produced minimal side effects, was well-tolerated, and resulted in a modest reduction in alcohol consumption in young nontreatment-seeking heavy drinkers. Additional studies using treatment-seeking alcohol-dependent persons will be necessary to determine the usefulness of this herbal preparation in reducing alcohol use in other populations.

A nutrient-wide association study on blood pressure.

BACKGROUND: A nutrient-wide approach may be useful to comprehensively test and validate associations between nutrients (derived from foods and supplements) and blood pressure (BP) in an unbiased manner. METHODS AND RESULTS: Data from 4680 participants aged 40 to 59 years in the cross-sectional International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) were stratified randomly into training and testing sets. US National Health and Nutrition Examination Survey (NHANES) four cross-sectional cohorts (1999-2000, 2001-2002, 2003-2004, 2005-2006) were used for external validation. We performed multiple linear regression analyses associating each of 82 nutrients and 3 urine electrolytes with systolic and diastolic BP in the INTERMAP training set. Significant findings were validated in the INTERMAP testing set and further in the NHANES cohorts (false discovery rate <5% in training, P<0.05 for internal and external validation). Among the validated nutrients, alcohol and urinary sodium-to-potassium ratio were directly associated with systolic BP, and dietary phosphorus, magnesium, iron, thiamin, folacin, and riboflavin were inversely associated with systolic BP. In addition, dietary folacin and riboflavin were inversely associated with diastolic BP. The absolute effect sizes in the validation data (NHANES) ranged from 0.97 mm Hg lower systolic BP (phosphorus) to 0.39 mm Hg lower systolic BP (thiamin) per 1-SD difference in nutrient variable. Inclusion of nutrient intake from supplements in addition to foods gave similar results for some nutrients, though it attenuated the associations of folacin, thiamin, and riboflavin intake with BP. CONCLUSIONS: We identified significant inverse associations between B vitamins and BP, relationships hitherto poorly investigated. Our analyses represent a systematic unbiased approach to the evaluation and validation of nutrient-BP associations.