Inverse association of marijuana use with nonalcoholic fatty liver disease among adults in the United States.
ABSTRACT: BACKGROUND & AIMS:The impact of marijuana on nonalcoholic fatty liver disease (NAFLD) is largely unknown. We studied the association between marijuana and NAFLD utilizing cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 2005-2014 and NHANES III (1988-1994). METHODS:Suspected NAFLD was diagnosed if serum alanine aminotransferase (ALT) was > 30 IU/L for men and > 19 IU/L for women in the absence of other liver diseases (NHANES 2005-2014). In NHANES III cohort, NAFLD was defined based on ultrasonography. RESULTS:Of the 14,080 (NHANES 2005-2014) and 8,286 (NHANES III) participants, prevalence of suspected NAFLD and ultrasonographically-diagnosed NAFLD were inversely associated with marijuana use (p < 0.001). Compared to marijuana-naïve participants, marijuana users were less likely to have suspected NAFLD (odds ratio [OR]: 0.90, 95% confidence interval [CI]: 0.82-0.99 for past user; OR: 0.68, 95% CI: 0.58-0.80 for current user) and ultrasonographically-diagnosed NAFLD (OR: 0.75, 95% CI: 0.57-0.98 for current user) in the age, gender, ethnicity-adjusted model. On multivariate analysis, the ORs for suspected NAFLD comparing current light or heavy users to non-users were 0.76 (95% CI 0.58-0.98) and 0.70 (95% CI 0.56-0.89), respectively (P for trend = 0.001) with similar trends in ultrasonographically-diagnosed NAFLD (OR: 0.77, 95% CI: 0.59-1.00 for current user; OR: 0.71, 95% CI: 0.51-0.97 for current light user). In insulin resistance-adjusted model, marijuana use remained an independent predictor of lower risk of suspected NAFLD. CONCLUSIONS:In this nationally representative sample, active marijuana use provided a protective effect against NAFLD independent of known metabolic risk factors. The pathophysiology is unclear and warrants further investigation.
Project description:To determine the association between diabetes mellitus (DM) and marijuana use.Cross-sectional study.Data from the National Health and Nutrition Examination Survey (NHANES III, 1988-1994) conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention.The study included participants of the NHANES III, a nationally representative sample of the US population. The total analytic sample was 10?896 adults. The study included four groups (n=10?896): non-marijuana users (61.0%), past marijuana users (30.7%), light (one to four times/month) (5.0%) and heavy (more than five times/month) current marijuana users (3.3%). DM was defined based on self-report or abnormal glycaemic parameters. We analysed data related to demographics, body mass index, smoking status, alcohol use, total serum cholesterol, high-density lipoprotein, triglyceride, serum 25-hydroxy vitamin D, plasma haemoglobin A1c, fasting plasma glucose level and the serum levels of C reactive protein and four additional inflammatory markers as related to marijuana use.OR for DM associated with marijuana use adjusted for potential confounding variables (ie, odds of DM in marijuana users compared with non-marijuana users).Marijuana users had a lower age-adjusted prevalence of DM compared to non-marijuana users (OR 0.42, 95% CI 0.33 to 0.55; p<0.0001). The prevalence of elevated C reactive protein (>0.5 mg/dl) was significantly higher (p<0.0001) among non-marijuana users (18.9%) than among past (12.7%) or current light (15.8%) or heavy (9.2%) users. In a robust multivariate model controlling for socio-demographic factors, laboratory values and comorbidity, the lower odds of DM among marijuana users was significant (adjusted OR 0.36, 95% CI 0.24 to 0.55; p<0.0001).Marijuana use was independently associated with a lower prevalence of DM. Further studies are needed to show a direct effect of marijuana on DM.
Project description:The appropriate alanine aminotransferase (ALT) threshold value to use for diagnosis of chronic liver disease in children is unknown. We sought to develop gender-specific, biology-based, pediatric ALT thresholds.The Screening ALT for Elevation in Today's Youth (SAFETY) study collected observational data from acute care children's hospitals, the National Health and Nutrition Examination Survey (NHANES, 1999-2006), overweight children with and without non-alcoholic fatty liver disease (NAFLD), and children with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. The study compared the sensitivity and specificity of ALT thresholds currently used by children's hospitals vs study-derived, gender-specific, biology-based, ALT thresholds for detecting children with NAFLD, HCV, or HBV.The median upper limit of ALT at children's hospitals was 53 U/L (range, 30-90 U/L). The 95th percentile levels for ALT in healthy weight, metabolically normal, liver disease-free, NHANES pediatric participants were 25.8 U/L (boys) and 22.1 U/L (girls). The concordance statistics of these NHANES-derived thresholds for liver disease detection were 0.85 (95% confidence interval [CI]: 0.74-0.96) in boys and 0.91 (95% CI: 0.83-0.99) in girls for NAFLD, 0.80 (95% CI: 0.70-0.91) in boys and 0.79 (95% CI: 0.69-0.89) in girls for HBV, and 0.86 (95% CI: 0.77-0.95) in boys and 0.84 (95% CI: 0.75-0.93) in girls for HCV. Using current children's hospitals ALT thresholds, the median sensitivity for detection of NAFLD, HBV, and HCV ranged from 32% to 48%; median specificity was 92% (boys) and 96% (girls). Using NHANES-derived thresholds, the sensitivities were 72% (boys) and 82% (girls); specificities were 79% (boys) and 85% (girls).The upper limit of ALT used in children's hospitals varies widely and is set too high to reliably detect chronic liver disease. Biology-based thresholds provide higher sensitivity and only slightly less specificity. Clinical guidelines for use of screening ALT and exclusion criteria for clinical trials should be modified.
Project description:There is a paucity of recent data about the epidemiology and long-term outcomes of nonalcoholic fatty liver disease (NAFLD) in the female population. Our aim was to assess the prevalence, risk factors, and mortality of NAFLD in female adults of the United States. Data from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999-2014 were used. NAFLD status was determined by the U.S. Fatty Liver Index (US-FLI) in the absence of other liver diseases and excessive alcohol consumption. The prevalence rates, risk factors, and 5-year all-cause and cardiovascular mortality were determined in women with NAFLD. The most recent prevalence of NAFLD among female adults (2007-2014) in the United States was 24.4% (95% confidence interval [CI], 22.48-26.33). Prevalence was higher among women >44 years of age and those with body mass index ?30 kg/m2. In addition, the average age of the female population with NAFLD has decreased over time. The fully adjusted odds ratios in women with NAFLD compared to those without NAFLD were 1.48 (95% CI, 1.20-1.82) for cardiovascular disease (CVD), 1.89 (95% CI, 1.42-2.52) for atherosclerotic cardiovascular disease (ASCVD) score ?7.5%, and 1.76 (95% CI, 1.37-2.25) for either CVD or ASCVD ?7.5%. The 5-year mortality for female adults with NAFLD was significantly higher than for those without NAFLD (adjusted hazard ratio, 1.48; 95% CI, 1.07-2.05). Among women with NAFLD, those with ASCVD ?7.5% had significantly higher 5-year all-cause mortality and CVD mortality. Conclusion: The prevalence of NAFLD in female NHANES participants from the United States has continued over recent years. In the female population with NAFLD, ASCVD ?7.5% is an independent predictor of overall and cardiac-specific mortality.
Project description:Leukocyte telomere length is shorter in response to chronic disease processes associated with inflammation such as diabetes mellitus and coronary artery disease. Data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002 was used to explore the relationship between leukocyte telomere length and presumed NAFLD, as indicated by elevated serum alanine aminotransferase (ALT) levels, obesity, or abdominal obesity. Logistic regression models were used to evaluate the relationship between telomere length and presumed markers of NAFLD adjusting for possible confounders. There was no relationship between elevated ALT levels, abdominal obesity, or obesity and telomere length in adjusted models in NHANES (OR 1.13, 95% CI 0.48-2.65; OR 1.17, 95% CI 0.52-2.62, resp.). Mexican-American men had shorter telomere length in relation to presumed NAFLD (OR 0.07, 95% CI 0.006-0.79) and using different indicators of NAFLD (OR 0.012, 95% CI 0.0006-0.24). Mexican origin with presumed NAFLD had shorter telomere length than men in other population groups. Longitudinal studies are necessary to evaluate the role of telomere length as a potential predictor to assess pathogenesis of NALFD in Mexicans.
Project description:Marijuana has been reported to have several effects on the male reproductive system. Marijuana has previously been linked to reduced adult testosterone, however, a study in Denmark reported increased testosterone concentrations among marijuana users. This study was performed to estimate the effect of marijuana use on testosterone in U.S. males. Data on serum testosterone, marijuana use, and covariates for 1577 men from the 2011-2012 U.S. National Health and Nutrition Examination Survey (NHANES) were analyzed. Information on marijuana use was collected by a self-administered computer-assisted questionnaire. Serum testosterone was determined using isotope dilution liquid chromatography tandem mass spectrometry. The effects of marijuana use on serum testosterone concentrations were examined by frequency, duration, and recency of use. Adjusted means and 95% confidence intervals (CI) of serum testosterone across levels of marijuana use were estimated using multiple linear regression weighted by the survey weights. The majority (66.2%) of the weighted study population reported ever using marijuana with 26.6% reporting current marijuana use. There was no difference in serum testosterone between ever users (adjusted mean = 3.69 ng/mL, 95% CI: 3.46, 3.93) and never users (adjusted mean = 3.70 ng/mL, 95% CI: 3.45, 3.98) upon multivariable analysis. However, serum testosterone was inversely associated with time since last regular use of marijuana (p-value for trend = 0.02). When restricted to men aged 18-29 years, this relationship strengthened (p-value for trend <0.01), and serum testosterone was also inversely associated with time since last use (p-value for trend <0.01), indicating that recency of use, and not duration or frequency, had the strongest relationship with testosterone levels. Serum testosterone concentrations were higher in men with more recent marijuana use. Studies are needed to determine the extent to which circulating testosterone concentrations mediate the relationship of marijuana use with male reproductive outcomes.
Project description:BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) has been reported to have a negative effect on bone mineral density (BMD) in Asian populations. Whether such an association exists in Western populations is less clear. METHODS:This cross-sectional analysis of data from NHANES III, a United States national health survey conducted from 1988 to 1994, included 6089 participants aged 40-75 years, selected after excluding people with hepatitis virus serology, elevated alcohol consumption, decreased renal function, or steroid use, and pregnant females. The main outcome, BMD at the femoral neck, was measured using dual-energy X-ray absorptiometry. The primary exposure, NAFLD, was defined as moderate or severe hepatic steatosis diagnosed using abdominal ultrasonography. RESULT:After controlling for gender and menopausal status, race/ethnicity, age and body mass index, NAFLD was not significantly associated with BMD (beta coefficient: -0.006, 95%CI: -0.016, 0.003). A secondary analysis categorized participants with NAFLD according to their serum alanine aminotransferase (ALT) levels into high and normal ALT NAFLD groups, and compared these with the non-NAFLD group. NAFLD with higher levels of ALT was associated with lower levels of BMD (beta coefficient: -0.023, 95% CI: -0.044, -0.002). CONCLUSION:This study showed a relationship between NAFLD with high ALT and lower BMD in the general U.S. population.
Project description:The US prevalence of nonalcoholic fatty liver disease (NAFLD) is 30.6% and increasing. NAFLD shares some risk factors with periodontitis and dental caries. We explored the association between NAFLD and several oral conditions among US adults, using data from the cross-sectional, nationally representative National Health and Nutrition Examination Survey (NHANES), 1988 to 1994. NAFLD was assessed with ultrasonography (USON), the screening gold standard not available in the more recent NHANES, and the noninvasive Fibrosis Score (FS), Fatty Liver Index (FLI), and US Fatty Liver Index (US-FLI) as other screening alternatives. There were 5,421 eligible dentate adults aged 21 to 74 y with complete relevant data, with transferrin levels ?50%, without hepatitis B or C, who were not heavy drinkers. Multivariable models were developed to examine the independent effects of moderate-severe periodontitis, untreated dental caries, caries experience, and tooth loss (<20 teeth) on NAFLD while controlling for clinical, biological, and sociodemographic factors. Weighted estimates for odds ratios (ORs) and 95% CIs were calculated with logistic regression. Between 17% and 24% of adults had NAFLD depending on the classification criteria. In adjusted models, as compared with those with better oral health, adults with <20 teeth were more likely to have NAFLD depending on the measure (USON: OR = 1.50, 95% CI = 1.11 to 2.02; FS: OR = 4.36, 95% CI = 3.47 to 5.49; FLI: OR = 1.99, 95% CI = 1.52 to 2.59; US-FLI: OR = 2.32, 95% CI = 1.79 to 3.01). People with moderate-severe periodontitis were more likely to have NAFLD (USON: OR = 1.54, 95% CI = 1.06 to 2.24; FS: OR = 3.10, 95% CI = 2.31 to 4.17; FLI: OR = 1.61, 95% CI = 1.13 to 2.28; US-FLI: OR = 2.21, 95% CI = 1.64 to 2.98). People with any untreated caries were more likely to have NAFLD (USON: OR = 1.51, 95% CI = 1.20 to 1.90; FLI: OR = 1.80, 95% CI = 1.33 to 2.44). NAFLD was associated with tooth loss, periodontitis, and, for some NAFLD measures, untreated dental caries but not overall caries experience after controlling for several key sociodemographic and behavioral factors. Results suggest that further evaluation is needed to better understand this health-oral health interrelationship and potential opportunities for medical-dental integration.
Project description:BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation, inflammation and an imbalanced redox homeostasis. We hypothesized that systemic free thiol levels, as a proxy of systemic oxidative stress, are associated with NAFLD. METHODS:Protein-adjusted serum free thiol concentrations were determined in participants from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort study (n = 5562). Suspected NAFLD was defined by the Fatty Liver Index (FLI ? 60) and Hepatic Steatosis Index (HSI > 36). RESULTS:Protein-adjusted serum free thiols were significantly reduced in subjects with FLI ? 60 (n = 1651). In multivariable logistic regression analyses, protein-adjusted serum free thiols were associated with NAFLD (FLI ? 60) (OR per doubling of concentration: 0.78 [95% CI 0.64-0.96], P = .016) even when adjusted for potential confounding factors, including systolic blood pressure, diabetes, current smoking, use of alcohol and total cholesterol (OR 0.80 [95% CI 0.65-0.99], P = .04). This association lost its significance (OR 0.94 [95% CI 0.73-1.21], P = .65) after additional adjustment for high-sensitive C-reactive protein. Stratified analyses showed significantly differential associations of protein-adjusted serum free thiol concentrations with suspected NAFLD for gender (P < .02), hypertension (P < .001) and hypercholesterolemia (P < .003). Longitudinally, protein-adjusted serum free thiols were significantly associated with the risk of all-cause mortality in subjects with NAFLD (FLI ? 60) (HR 0.27 [95% CI 0.17-0.45], P < .001). CONCLUSION:Protein-adjusted serum free thiol levels are reduced and significantly associated with all-cause mortality in subjects with suspected NAFLD. Quantification of free thiols may be a promising, minimally invasive strategy to improve detection of NAFLD and associated risk of all-cause mortality in the general population.
Project description:In the United States, non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and associated with higher mortality according to data from earlier National Health and Nutrition Examination Survey (NHANES) 1988-1994. Our goal was to determine the NAFLD prevalence in the recent 1999-2012 NHANES, risk factors for advanced fibrosis (stage 3-4) and mortality. NAFLD was defined as having a United States Fatty Liver Index (USFLI) > 30 in the absence of heavy alcohol use and other known liver diseases. The probability of low/high risk of having advanced fibrosis was determined by the NAFLD Fibrosis Score (NFS). In total, 6000 persons were included; of which, 30.0% had NAFLD and 10.3% of these had advanced fibrosis. Five and eight-year overall mortality in NAFLD subjects with advanced fibrosis was significantly higher than subjects without NAFLD ((18% and 35% vs. 2.6% and 5.5%, respectively) but not NAFLD subjects without advanced fibrosis (1.1% and 2.8%, respectively). NAFLD with advanced fibrosis (but not those without) is an independent predictor for mortality on multivariate analysis (HR = 3.13, 95% CI 1.93-5.08, p<0.001). In conclusion, in this most recent NHANES, NAFLD prevalence remains at 30% with 10.3% of these having advanced fibrosis. NAFLD per se was not a risk factor for increased mortality, but NAFLD with advanced fibrosis was. Mexican American ethnicity was a significant risk factor for NAFLD but not for advanced fibrosis or increased mortality.
Project description:There is growing evidence that links nonalcoholic fatty liver disease (NAFLD) with impairment of renal function. As such, we aimed to demonstrate the trend of NAFLD, NAFLD with renal insufficiency (RI), disease awareness, and mortality over time. Patient data were extracted from the National Health and Nutrition Examination Survey (NHANES) 1999-2016. A total of 14,255 adult study participants without competing liver disease or heavy drinking and with complete laboratory data were included. NAFLD was defined using the U.S. Fatty Liver Index (USFLI) and RI was defined using the Chronic Kidney Disease Epidemiology Collaboration equation and urine albumin:creatinine ratio. Death data were obtained from the National Death Index (up to December 31, 2015). Prevalence of NAFLD in participants was 31.2% (95% confidence interval [CI], 30.01-32.46); of these participants, 22.05% (95% CI, 20.34-23.85) had RI. From 1999 to 2016, prevalence of both NAFLD without RI (P = 0.048) and NAFLD-RI (P = 0.006) increased significantly. Among those with NAFLD-RI, awareness of kidney disease was 8.56% (95% CI, 6.69-10.89), while awareness of liver disease among all NAFLD was 4.49% (95% CI, 3.17-6.33). Among those with NAFLD, mortality incidence per 1,000 person years was highest among those with severe RI in all-cause mortality (104.4; 95% CI, 83.65-130.39) and other residual causes of mortality (mean, 50.88; 95% CI, 37.02-69.93). Conclusion: Prevalence of NAFLD and NAFLD-RI has increased over the past 2 decades in the United States. Low kidney disease and liver disease awareness are major public health issues as those with NAFLD-RI have significantly higher mortality than those with only NAFLD.