Phenobarbital Use as Adjunct to Benzodiazepines in the Treatment of Severe Alcohol Withdrawal Syndrome

Severe AWS （alcohol withdrawal syndrome） and AWD （alcohol withdrawal associated delirium） are common indications for intensive care unit admissions. Approximately 25% of patients with severe alcohol withdrawal require prolonged critical care hospital courses, often complicated by respiratory failure, need for mechanical ventilation due to administration of sedative continuous infusions and development of nosocomial infections. Although benzodiazepines are the mainstay of therapy for alcohol withdrawal, some patients exhibit benzodiazepine-refractory alcohol withdrawal. The use of phenobarbital as adjunct to benzodiazepines has been shown in studies to be effective in enhancing therapeutic responsiveness to benzodiazepines and reducing the need for mechanical ventilation. The objective of this study is to evaluate whether severe alcohol withdrawal treatment based on combining symptom-triggered benzodiazepine therapy with adjunctive phenobarbital will result in decreased mechanical ventilation rates, decreased use of continuous sedative infusions, decreased time to withdrawal symptom resolution and decreased length of stay in the intensive care unit. Chart reviews were utilized to determine total amount of benzodiazepine and phenobarbital use, need for mechanical ventilation, requirement of continuous lorazepam, dexmedetomidine or propofol infusions, average intensive care unit length of stay and incidence of adverse effects.

Research progress on benzodiazepines to treat alcohol withdrawal syndrome

Alcohol withdrawal syndrome(AWS)refers to a series of symptoms and signs that chronic al-coholics experience when they suddenly stop drinking or reduce their drinking,usually 12 to 24 h later.These in-clude tremors,fatigue,sweating,hyperreflexia,and gas-trointestinal symptoms.This article will analyze the drug treatment of this disease and make a brief review.

Phenobarbital in the treatment of alcohol withdrawal syndrome

Alcohol withdrawal syndrome(AWS)is a serious disorder affecting alcohol-dependent patients who abruptly stop or reduce their drinking.Mild or moderate AWS usually appears within 6 to 24 h after the last drink,and symptoms may include increased blood pressure and rapid pulse,tremors,high fever,irritability,anxiety,headache,nausea,and vomiting.These symptoms may progress to a more severe AWS characterized by delirium tremens,seizures,coma,cardiac arrest,and death.This article will analyze the phenobarbital(PB)treatment of AWS and make a brief review'.

Distinctive aspects of peptic ulcer disease,Dieulafoy'slesion,and Mallory-Weiss syndrome in patients withadvanced alcoholic liver disease or cirrhosis

AIM:To systematically review the data on distinctive aspects of peptic ulcer disease(PUD),Dieulafoy’s lesion(DL),and Mallory-Weiss syndrome(MWS)in patients with advanced alcoholic liver disease(a ALD),including alcoholic hepatitis or alcoholic cirrhosis.METHODS:Computerized literature search performed via Pub Med using the following medical subject heading terms and keywords:"alcoholic liver disease","alcoholic hepatitis","alcoholic cirrhosis","cirrhosis","liver disease","upper gastrointestinal bleeding","nonvariceal upper gastrointestinal bleeding","PUD",‘‘DL’’,‘‘Mallory-Weiss tear",and"MWS’’.RESULTS:While the majority of acute gastrointestinal(GI)bleeding with a ALD is related to portal hypertension,about 30%-40%of acute GI bleeding in patients with a ALD is unrelated to portal hypertension.Such bleeding constitutes an important complication of a ALD because of its frequency,severity,and associated mortality.Patients with cirrhosis have a markedly increased risk of PUD,which further increases with the progression of cirrhosis.Patients with cirrhosis or a ALD and peptic ulcer bleeding(PUB)have worse clinical outcomes than other patients with PUB,including uncontrolled bleeding,rebleeding,and mortality.Alcohol consumption,nonsteroidal anti-inflammatory drug use,and portal hypertension may have a pathogenic role in the development of PUD in patients with a ALD.Limited data suggest that Helicobacter pylori does not play a significant role in the pathogenesis of PUD in most cirrhotic patients.The frequency of bleeding from DL appears to be increased in patients with a ALD.DL may be associated with an especially high mortality in these patients.MWS is strongly associated with heavy alcohol consumption from binge drinking or chronic alcoholism,and is associated with a ALD.Patients with a ALD have more severe MWS bleeding and are more likely to rebleed when compared to non-cirrhotics.Preendoscopic management of acute GI bleeding in patients with a ALD unrelated to portal hypertension is similar to the management of a ALD patients with GI bleeding from portal hypertension,because clinical distinction before endoscopy is difficult.Most patients require intensive care unit admission and attention to avoid over-transfusion,to correct electrolyte abnormalities and coagulopathies,and to administer antibiotic prophylaxis.Alcoholics should receive thiamine and be closely monitored for symptoms of alcohol withdrawal.Prompt endoscopy,after initial resuscitation,is essential to diagnose and appropriately treat these patients.Generally,the same endoscopic hemostatic techniques are used in patients bleeding from PUD,DL,or MWS in patients with a ALD as in the general population.CONCLUSION:Nonvariceal upper GI bleeding in patients with a ALD has clinically important differences from that in the general population without a ALD,including:more frequent and more severe bleeding from PUD,DL,or MWS.

Protective effect of alcohol consumption for fatty liver but not metabolic syndrome

AIM:To investigate the effect of alcohol on the metabolic syndrome (MS) and fatty liver in Japanese men and women.METHODS:A cross-sectional study was conducted in a medical health checkup program at a general hospital.This study involved 18 571 Japanese men and women,18-88 years of age,with a mean body mass index of 22.6 kg/m 2.A standardized questionnaire was administered.The total amount of alcohol consumed per week was calculated,and categorized into four grades.Fatty liver was examined by ultrasound modified criteria of the revised National Cholesterol Educa-tion Program Adult Treatment Panel Ⅲ and the new International Diabetes Federation.RESULTS:The prevalence of fatty liver decreased in men and women with light to moderate alcohol consumption,whereas the prevalence of MS was not so changed.The prevalence of fatty liver of any grade in men was lower than that in those with no or minimal alcohol consumption.In women with light to moderate alcohol consumption,prevalence of fatty liver was lower than that in women with no or minimal alcohol consumption.By logistic regression analysis,the odds ratio (OR) for MS in women with light alcohol consumption was decreased to < 1.0,but this change was not clear in men.The OR for fatty liver was clearly < 1.0 in men with any level of alcohol consumption and in women with light to moderate consumption.CONCLUSION:Light to moderate alcohol consumption has a favorable effect for fatty liver,but not for MS in Japanese men and women.

Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome

AIM To elucidate the mechanism of patchouli alcohol(PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome(IBS-D).METHODS We studied the effects of PA on colonic spontaneous motility using its cumulative log concentration(3 × 10^(-7) mol/L to 1 × 10^(-4)mol/L). We then determined the responses of the proximal and distal colon segments of rats to the folowing stimuli:(1) carbachol(1 × 10^(-9) mol/L to 1 × 10^(-5) mol/L);(2) neurotransmitter antagonists including N~ω-nitro-l-arginine methyl ester hydrochloride(10μmol/L) and(1 R~*, 2 S~*)-4-[2-Iodo-6-(methylamino)-9 Hpurin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt(1 μmol/L);(3) agonist α,β-methyleneadenosine 5′-triphosphate trisodium salt(100 μmol/L); and(4) single KCl doses(120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA(100 μmol/L) for 1 min. Electrical-field stimulation(40 V, 2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic, noncholinergic neurotransmitter release in IBS-D rat colon. The ATP level of Kreb's solution was also determined.RESULTS PA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle, and the half maximal effective concentration(EC_(50)) was 41.9 μmol/L. In comparison with the KCl-treated IBS-D group, the contractile response(mg contractions) in the PA + KCl-treated IBS-D group(11.87 ± 3.34) was significantly decreased in the peak tension(P < 0.01). Compared with CCh-treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat colonic smooth muscle(EC_(50) = 0.94 μmol/L) was significantly decreased by PA(EC_(50) = 37.43 μmol/L)(P < 0.05). Lack of nitrergic neurotransmitter release in stress-induced IBS-D rats showed contraction effects on colonic smooth muscle. Pretreatment with PA resulted in inhibitory effect on l-NAME-induced(10 μmol/L) contraction(P < 0.05). ATP might not be the main neurotransmitter involved in inhibitory effects of PA in the colonic relaxation of stressinduced IBS-D rats.CONCLUSION PA application may serve as a new therapeutic approach for IBS-D.

Alcohol consumption and metabolic syndrome among Shanghai adults: A randomized multistage stratified cluster sampling investigation

AIM: To examine the relations of alcohol consumption to the prevalence of metabolic syndrome in Shanghai adults. METHODS: We performed a cross-sectional analysis of data from the randomized multistage stratified cluster sampling of Shanghai adults, who were evaluated for alcohol consumption and each component of metabolic syndrome, using the adapted U.S. National Cholesterol Education Program criteria. Current alcohol consumption was defined as more than once of alcohol drinking per month. RESULTS: The study population consisted of 3953 participants (1524 men) with a mean age of 54.3 ± 12.1 years. Among them, 448 subjects (11.3%) were current alcohol drinkers, including 405 males and 43 females. After adjustment for age and sex, the prevalence of current alcohol drinking and metabolic syndrome in the general population of Shanghai was 13.0% and 15.3%, respectively. Compared with nondrinkers, the prevalence of hypertriglyceridemia and hypertension was higher while the prevalence of abdominal obesity, low serum high-density-lipoprotein cholesterol (HDL-C) and diabetes mellitus was lower in subjects who consumed alcohol twice or more per month, with a trend toward reducing the prevalence of metabolic syndrome. Among the current alcohol drinkers, systolic blood pressure, HDL-C, fastingplasma glucose, and prevalence of hypertriglyceridemia tended to increase with increased alcohol consumption. However, low-density-lipoprotein cholesterol concentration, prevalence of abdominal obesity, low serum HDL-C and metabolic syndrome showed the tendency to decrease. Moreover, these statistically significant differences were independent of gender and age.CONCLUSION: Current alcohol consumption is associated with a lower prevalence of metabolic syndrome irrespe- ctive of alcohol intake (g/d), and has a favorable influence on HDL-C, waist circumference, and possible diabetes mellitus. However, alcohol intake increases the likelihood of hypertension, hypertriglyceridemia and hyperglycemia. The clinical significance of these findings needs further investigation.

Alcohol consumption and dry eye syndrome: a Metaanalysis

AIM：To quantify the association between alcohol consumption and dry eye syndrome（DES） with Meta-analysis of published case-control and cross-sectional studies. METHODS： Three databases were screened for potentially eligible studies through Nov.30,2015,Pub Med,Web of Science,and the Cochrane Library.Odds ratios（ORs） were pooled with 95% confidence intervals（CIs） to evaluate the relationship between alcohol consumption and DES risk.Subgroup analyses were performed according to diagnostic criteria,publication year,sample size,alcohol intake and adjusted factors.RESULTS： A total of 10（9 case-control and 1 crosssectional） studies from 8 articles were included in this Meta-analysis.The pooled results showed that alcohol consumption would significantly increase the risk of DES（OR 1.15,95% CI： 1.02-1.30）,and the results were independent of smoking,hypertension,diabetes and thyroid disease history.And the results of subgroup analyses indicated an increased incidence of DES diagnosed by typical DES symptoms and positive objective tests together（OR 1.18,95% CI： 1.01-1.39）among drinkers,but not by typical DES symptoms alone（OR 1.11,95% CI： 0.94-1.32）.What＇s more,any drinkers were at higher risk of suffering from DES（OR 1.33,95%CI： 1.31-1.34）,while heavy drinkers not（OR 1.01,95% CI：0.86-1.18）.CONCLUSION： The present Meta-analysis suggests that alcohol consumption may be a significant risk factor for DES.Alcohol-induced peripheral neuropathymay falsely reduce the prevalence of DES among heavy drinkers.Future prospective studies of alcohol consumption and DES risk are needed to confirm our results.

Pentoxifylline:A first line treatment option for severe alcoholic hepatitis and hepatorenal syndrome?

Although favourable results of pentoxifylline （PTX） used in treatment of severe alcoholic hepatitis patients with a Maddrey discriminant function score ≥ 32 have been previously reported, it is not currently recommended as a first line treatment for alcoholic hepatitis owing to lack of evidence for its efficacy as compared to the standard treatment with corticosteroids. In a very recent issue of World Journal of Gastroenterology, Dr. De BK and colleagues compared for the first time the two treatment modalities head to head in a randomized controlled study, demonstrating the advantage of PTX over corticosteroids in terms of patients＇ survival and risk-benefit profile. The advantage of PTX over corticosteroids in survival of patients with severe alcoholic hepatitis was found to be related to the prevention of hepatorenal syndrome in their study. This study raises the question of the use of PI-X as a standard treatment for severe alcoholic hepatitis. Considering the fact that PTX presented a spectacular efficiency in prevention of hepatorenal syndrome in their study as well as that previous studies have shown that this effect is possibly related to a primary renoprotective action because it is irrelevant of tumor necrosis factor-c~ synthesis inhibition or improved liver function, we tempted to speculate that PXT might be an effective option for prevention and/or treatment of hepatorenal syndrome complicating other forms of advanced liver disease. This attractive theory remains to be elucidated by pressing future studies in view of the lack of effective treatment modalities for hepatorenal syndrome.

Budd-Chiari like syndrome in decompensated alcoholic steatohepatitis and liver cirrhosis

A rare case of pseudo-Budd-Chiari Syndrome in a patientwith decompensated alcoholic liver disease is reported.Although clinical and radiological findings suggestedBudd-Chiari Syndrome, the liver biopsy revealedmicronodular cirrhosis and absence of histological signsof hepatic outflow obstruction.

What about non-alcoholic fatty liver disease as a new criterion to define metabolic syndrome?

Non-alcoholic fatty liver disease (NAFLD) is currently not a component of the diagnostic criteria for metabolic syndrome (MetS); however, the development of NAFLD has some common mechanisms with the development of MetS, as they share the pathophysiologic basis of insulin resistance. It is also recognized that NAFLD is the hepatic manifestation of MetS. To define MetS, the presence of at least three of the proposed criteria is required, and sometimes it is sufficient to have only one laboratory value, modified by diet or drugs, for the classification of MetS. Ultrasonographically-detected NAFLD (US-NAFLD) is more stable, only changing during the middleto long-term. Although controversies over MetS continue, and considering that abdominal ultrasonography for diagnosing NAFLD has high specificity and guidelines to modify the natural course of NAFLD by diet composition or lifestyle have not yet been established, why should we not introduce US-NAFLD as a new criterion to define MetS?

Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome

AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis(NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.METHODS: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome(Met S) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients receivedlifestyle advice and were treated for a 12 mo period with rosuvastatin(10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid(SUA), high sensitivity C reactive protein(hs CRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values.RESULTS: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20 th, which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3rd treatment month(ANOVA P < 0.001), while alkaline phosphatase activities by the 6th treatment month(ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced(P < 0.001). Lipid values were normalised by the 3rd treatment month. No patient had Met S by the 9th treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group.CONCLUSION: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve Met S within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.

Metabolic syndrome and non-alcoholic fatty liver disease:Asian definitions and Asian studies

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), as conventionally recognized, is a metabolic disorder largely confined to residents of affluent industrialized Western countries. However, obesity and insulin resistance are not restricted to the West, as witnessed by their increasingly universal distribution. In particular, there has been an upsurge in metabolic syndrome in the Asia-Pacific region, although there are critical differences in the extent of adiposity between Eastern and Western populations. DATA SOURCES: An English-language literature search using PubMed (1999-2007) on obesity, metabolic syndrome and NAFLD, focusing on Asian definitions and Asian studies. RESULTS: NAFLD appears to be of long-standing insulin resistance and likely represents the hepatic manifestation of the metabolic syndrome. With insulin resistance as a common factor, the disease is associated with atherosclerosis and cardiovascular risk. All features of the metabolic syndrome and related events are assessed for practical management of NAFLD, although the criteria for the diagnosis of obesity and central obesity differ across racial groups. CONCLUSIONS: The increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension and ultimately metabolic syndrome, puts a very large population at risk of developing NAFLD in the coming decades. The simultaneous identification and appropriate treatment of the components of metabolic syndrome are crucial to reduce hepatic as well as cardiovascular morbidity and mortality.

What does irritable bowel syndrome share with non-alcoholic fatty liver disease?

Non-alcoholic fatty liver disease(NAFLD)and irritable bowel syndrome(IBS)are two very common diseases in the general population.To date,there are no studies that highlight a direct link between NAFLD and IBS,but some recent reports have found an interesting correlation between obesity and IBS.A systematic PubMed database search was conducted highlighting that common mechanisms are involved in many of the local and systemic manifestations of NAFLD,leading to an increased cardiovascular risk,and IBS,leading to microbial dysbiosis,impaired intestinal barrier and altered intestinal motility.It is not known when considering local and systemic inflammation/immune system activation,which one has greater importance in NAFLD and IBS pathogenesis.Also,the nervous system is implicated.In fact,inflammation participates in the development of mood disorders,such as anxiety and depression,characteristics of obesity and consequently of NAFLD and,on the other hand,in intestinal hypersensitivity and dysmotility.

Effect of testosterone on morphine withdrawal syndrome in rats

Aim： To determine whether testosterone is involved in morphine withdrawal syndrome （WS）. Methods： In order to induce dependency, rats were treated with subcutaneous injection of morphine （days 1-2, 5 mg/kg; days 3-5, 7.5 mg/kg; days 6-8, 10 mg/kg）, and after the last dose of morphine （day 8） WS was induced by intraperitoneal injection of naloxone （1 mg/kg）. Wet dog shake （WDS）, abdomen writhing （AW）, and jumps （J） were recorded as indicators of WS. Results： The severity of WDS, AW, and J in male rats was greater than that in females. Accordingly, in 4-week castrated and flutamide-treated （10 mg/kg/day for 8 days, i.p.） male rats, WDS, AW, and J were significantly decreased compared to male control rats. Testosterone replacement therapy （10 mg/kg/day for 8 days, i.m.） in 4-week castrated rats restored the severity of WDS, AW, and J behaviors to the level of non-castrated male rats, whereas testosterone potentiated the WDS behavior in non-castrated male rats. Conclusion： It can be concluded that testosterone might be effectively involved in morphine WS.

Protective effect of Ocimum sanctum Linn. leaf extract on ethanol withdrawal syndrome in Wistar rats

Objective: To evaluate the effects of Oscimum sanctum L(O. sanctum), an important medicinal herb, on alcohol withdrawal syndrome in Wistar rats. Methods: Liquid diet with 7.2%, v/v ethanol was administered to the rats for 21 d. Control group animals received sucrose as an isocaloric liquid diet. After alcohol withdrawal, rats were examined at 6 th and 24 th hour for major withdrawal signs that included anxiety and hyper locomotor activity. Ethanol withdrawal anxiety was tested using elevated plus maze, light and dark model; the hyper locomotor activity using actophotometer. O. sanctum leaf extract(100, 200 and 300 mg/kg, oral) and diazepam(2 mg/kg, i.p) were administered to the treatment group animals 30 min before alcohol withdrawal estimation. Drug treatment was also given 30 min before the second observation at 24 th hour. On the last day of the protocol, rats were sacrificed by cervical dislocation liver, kidney and brain were isolated and preserved in formalin for further histopathological examination. Results: Findings from the present study revealed that O. Sanctum leaf extract treatment at doses 100, 200 and 300 mg/kg, oral had a significant protective effect on signs and symptoms of ethanol withdrawal in alcohol-dependent rats. However, no remarkable pathological and microscopic alterations were observed in histopathological examination. Conclusions: O. sanctum seems to be an active drug for the treatment of alcohol abstinence syndrome.

Sidiming attenuates morphine withdrawal syndrome and nitric oxide (synthase) levels in morphine-dependent rats and rhesus monkeys

The present study analyzed the effects of Sidiming, a Chinese herbal compound, on withdrawal syndrome, body weight loss, and serum levels of nitric oxide and its synthase in morphine- dependent rats and rhesus monkeys. These effects were compared with clonidine, an active control drug used for clinical treatment. Results showed that 4 and 8 g/kg Sidiming, respectively, significantly suppressed morphine withdrawal syndrome and reduced body mass loss in morphine-dependent rats. In addition, 2.4 and 4.8 g/kg Sidiming, respectively, significantly attenuated withdrawal syndrome in rhesus monkeys. High-dose Sidiming （8 g/kg in rats and 4.8 g/kg in rhesus monkeys） led to significantly inhibited serum levels of nitric oxide and its synthase in morphine-dependent rats and rhesus monkeys, which were greater than clonidine. These findings suggested that Sidiming treatment attenuated withdrawal syndrome in morphine-dependent rats and rhesus monkeys by inhibiting serum nitric oxide and its synthase.

Posterior reversible encephalopathy syndrome in alcoholic hepatitis:Hepatic encephalopathy a common theme

Posterior reversible encephalopathy syndrome(PRES) is a neuro-radiologic diagnosis that has become more widely recognized and reported over the past few decades. As such, there are a number of known risk factors that contribute to the development of this syndrome, including volatile blood pressures, renal failure, cytotoxic drugs, autoimmune disorders, pre-eclampsia, and eclampsia. This report documents the first reported case of PRES in a patient with severe alcoholic hepatitis with hepatic encephalopathy and delves into a molecular pathophysiology of the syndrome.

The Effect of Bergamot-Derived Polyphenolic Fraction on LDL Small Dense Particles and Non Alcoholic Fatty Liver Disease in Patients with Metabolic Syndrome

The occurrence of Metabolic Syndrome (MS) represents an independent risk factor for developing cardiovascular disease states in patients suffering from type 2 diabetes mellitus. Moreover, both the size of LDL particles and liver dysfunction identified as non alcoholic fatty liver disease (NAFLD) represent important biomarkers for the development of cardiometabolic risk in patients with MS. Here we studied the effect of bergamot polyphenolic fraction (BPF) in patients with MS and NAFLD. 107 patients were enrolled at the San Raffaele IRCCS (Rome). All of them showed ultrasonografic evidences of NAFLD and at least three out of five previous identified criteria for the diagnosis of MS. Patients were divided into two groups: one receiving placebo and the second receiving BPF 650 mg twice a day for 120 consecutive days. In the group receiving BPF 650 mg twice a day, a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides alongside with an increase of HDL cholesterol was found. This effect was accompanied by significant reduction of both ultrasonographic and metabolic biomarkers of NAFLD. Moreover, a significant reduction of small dense LDL particles, as detected via proton NMR Spectroscopy, was found after BPF treatment. In conclusion, our data confirm the beneficial effect of bergamot-extract in patients with MS an effect highlighted by significant reduction of small dense LDL particles and by improvement of NAFLD biomarkers. This suggests a potential preventive role of bergamot derivatives in reducing cardiometabolic risk.

Vague relationship between alcohol consumption and metabolic syndrome in nonobese people

Fatty liver, including non-alcoholic fatty liver disease, is closely associated with metabolic syndrome (MS). Thus, the presence of fatty liver without MS in some conditions may be clinically important. Many studies have shown that compared with no or occasional alcohol intake, moderate alcohol consumption is associated with lower prevalence rates of hypertension and type 2 diabetes, and lower levels of circulating C-reactive protein, a valuable marker for MS and insulin resistance. Considering these findings, light to moderate alcohol consumption has theoretical benefits on fatty liver and MS. Fatty liver, including non-alcoholic fatty liver disease, may be more clinically important than MS, particularly in non-obese individuals, because fatty liver can develop before MS in several conditions, such as regular alcohol consumers. Furthermore, most of the currently used MS criteria are unable to detect "true MS" because of variations in multiple factors such as age, height, medications, and complications.