Impact of Physical Activity on the Characteristics and Metabolic Consequences of Alcohol Consumption: A Cross-Sectional Population-Based Study.

Sedentary lifestyle and excessive alcohol drinking are major modifiable risk factors of health. In order to shed further light on the relationships between physical activity and health consequences of alcohol intake, we measured biomarkers of liver function, inflammation, lipid status and fatty liver index tests in a large population-based sample of individuals with different levels of physical activity, alcohol drinking and other lifestyle risk factors. The study included 21,050 adult participants (9940 men, 11,110 women) (mean age 48.2 ± 13.3 years) of the National FINRISK Study. Data on physical activity, alcohol drinking, smoking and body weight were recorded. The participants were classified to subgroups according to gender, levels of physical activity (sedentary, low, moderate, vigorous, extreme), alcohol drinking levels (abstainers, moderate drinkers, heavy drinkers) and patterns (regular or binge, types of beverages preferred in consumption). Serum liver enzymes (GGT, ALT), C-reactive protein (CRP) and lipid profiles were measured using standard laboratory techniques. Physical activity was linearly and inversely related with the amount of alcohol consumption, with the lowest alcohol drinking levels being observed in those with vigorous or extreme activity (p < 0.0005). Physically active individuals were less frequently binge-type drinkers, cigarette smokers or heavy coffee drinkers than those with sedentary activity (p < 0.0005 for linear trend in all comparisons). In the General Linear Model to assess the main and interaction effects of physical activity and alcohol consumption on biomarker status, as adjusted for anthropometric measures, smoking and coffee consumption, increasing levels of physical activity were found to be associated with more favorable findings on serum GGT (p < 0.0005), ALT (p < 0.0005 for men), cholesterol (p = 0.025 for men; p < 0.0005 for women), HDL-cholesterol (p < 0.0005 for men, p = 0.001 for women), LDL-cholesterol (p < 0.03 for men), triglycerides (p < 0.0005 for men, p < 0.03 for women), CRP (p < 0.0005 for men, p = 0.006 for women) and fatty liver index (p < 0.0005). The data support the view that regular moderate to vigorous physical activity may counteract adverse metabolic consequences of alcohol consumption on liver function, inflammation and lipid status. The role of physical activity should be further emphasized in interventions aimed at reducing health problems related to unfavorable risk factors of lifestyle.

Serum Calprotectin, a Marker of Neutrophil Activation, and Other Mediators of Inflammation in Response to Various Types of Extreme Physical Exertion in Healthy Volunteers.

PURPOSE: While extreme physical exertion is known to induce changes in the status of inflammation comparisons of the responses for various mediators of inflammation after acute bouts of high-intensity exercise have been limited. SUBJECTS AND METHODS: We examined the responses in serum levels of novel inflammatory proteins, calprotectin, suPAR, CD163, and pro- and anti-inflammatory cytokines in 12 physically active volunteers (10 men, 2 women, mean age 37±14 years) before and after completing various types of extreme physical exertion (marathon run, half-marathon run or 24-h cross-country skiing). For comparisons, the levels of the biomarkers were also measured at rest in 30 healthy controls (25 men, 5 women, mean age 42 ± 12 years) with low or sedentary activity. RESULTS: Extreme physical exertion induced significant increases in serum calprotectin (p < 0.0005), suPAR (p < 0.01), CD163 (p < 0.05), IL-6 (p < 0.0005), IL-8 (p < 0.01) and IL-10 (p < 0.0005) (pre- vs 3h-post-exercise). These responses were found to normalize within 48 hours. While the increases in blood leukocytes were of similar magnitude following the different types of exercise, markedly more pronounced responses occurred in serum TNF-α (p < 0.01), IL-8 (p < 0.01) and CD163 (p < 0.05) in those with more intense activity. In 3-h post-exercise samples significant correlations were observed between serum calprotectin and IL-6 (rs = 0.720, p < 0.01), IL-10 (rs = 0.615, p < 0.05), TNF-α (rs = 0.594, p < 0.05), suPAR (rs = 0.587, p < 0.05) and blood leukocytes (rs = 0.762, p < 0.01). CONCLUSION: The present results suggest distinct exercise-intensity dependent changes in mediators of inflammation (including calprotectin, suPAR and CD163) following extreme physical exertion. Our findings indicate that there is a major reversible impact of high-intensity physical exertion on the status of inflammation.

Combined effects of lifestyle risk factors on fatty liver index.

BACKGROUND: Factors of lifestyle may have a major impact on liver-related morbidity and mortality. We examined independent and joint effects of lifestyle risk factors on fatty liver index (FLI), a biomarker of hepatic steatosis, in a population-based cross-sectional national health survey. METHODS: The study included 12,368 participants (5784 men, 6584 women) aged 25-74 years. Quantitative estimates of alcohol use, smoking, adiposity and physical activity were used to establish a total score of risk factors, with higher scores indicating an unhealthier lifestyle. FLI was calculated based on an algorithm including body mass index, waist circumference, serum gamma-glutamyltransferase and triglycerides. RESULTS: The occurrence of FLI ≥ 60% indicating fatty liver increased from 2.4% in men with zero risk factors to 81.9% in those with a total risk score of 7-8 (p <  0.0005 for linear trend) and in women from 0 to 73.5% (p <  0.0005). The most striking individual impacts on the likelihood for FLI above 60% were observed for physical inactivity (p <  0.0005 for both genders) and alcohol consumption (p <  0.0005 for men). Interestingly, coffee consumption was also found to increase with increasing risk factor scores (p <  0.0005 for linear trend in both genders). CONCLUSIONS: The data indicates that unfavorable combinations of lifestyle risk factors lead to a high likelihood of hepatic steatosis. Use of FLI as a diagnostic tool may benefit the assessment of interventions aimed at maintaining a healthy lifestyle and prevention of liver-related morbidity.

Impacts of unfavourable lifestyle factors on biomarkers of liver function, inflammation and lipid status.

BACKGROUND: Adopting a healthy lifestyle is associated with prolonged life expectancy. The main modifiable lifestyle-related risk factors are hazardous alcohol drinking, smoking, excess body weight and lack of physical activity. Our aim was to estimate the impact of unfavourable lifestyle factors on abnormalities in laboratory tests reflecting liver status, inflammation and lipid metabolism in a population-based cross-sectional study. METHODS: The study included 22,273 participants (10,561 men, 11,712 women) aged 25-74 years from the National FINRISK Study. Data on alcohol use, smoking, body weight, and physical activity were recorded from structured interviews. The risk scores for the various life style factors were established on a 0-8 scale and used to stratify the population in classes to allow estimates of their joint effects. Serum liver enzymes (GGT, ALT), C-reactive protein (CRP) and lipid profiles were measured using standard laboratory techniques. RESULTS: Consistent dose-response relationships were observed between the number of unfavourable risk factors and serum levels of GGT, ALT, CRP, cholesterol, HDL, LDL and triglycerides (p < 0.0005 for linear trend in all comparisons). When compared with those with zero risk factors, the multivariable-adjusted odds ratios (ORs) for abnormalities in all biomarkers were significantly higher in those with a sum of risk score two or more. The most striking increases in ORs in the group with the highest numbers of risk factors were observed among men in serum GGT: 26.6 (12.4-57.0), ALT: 40.3 (5.3-307.8), CRP: 16.2 (7.8-33.7) and serum triglycerides: 14.4 (8.6-24.0). CONCLUSIONS: The data support the view that the presence of unfavourable life style risk factors is associated with distinct abnormalities in laboratory tests for liver function, inflammation and lipid status. Such biomarkers may prove to be of value in the assessment of interventions aimed at reducing unfavourable risk factors and in helping individuals in long-term maintenance of lifestyle modifications.

Pharmacokinetics of intra-articular vitamin D analogue calcipotriol in sheep and metabolism in human synovial and mesenchymal stromal cells.

Calcipotriol (MC903) is a side chain analogue of the biologically active 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Due to its anti-inflammatory and anti-proliferative effects on stromal cells, calcipotriol is a promising candidate for the local treatment of arthritis. In this preliminary work, we studied the pharmacokinetics and safety of calcipotriol after an IV (0.1 mg/kg given to one sheep) and intra-articular dose (0.054 mg/kg, 0.216 mg/kg and 0.560 mg/kg given to three sheep). The terminal half-life of calcipotriol was approximately 1 h after an IV dose. After intra-articular dosing, the systemic absorption was between 1 and 13% during the observed 24 h. Hypercalcemia or other clinical adverse effects did not occur in any animal during the study, and no macroscopic or microscopic alterations were seen in the synovium of the calcipotriol-injected knees compared to the vehicle knees. The in vitro metabolism of calcipotriol was analyzed with LC-MS from human synovial and mesenchymal stromal cell cultures. Both cell types were able to metabolize calcipotriol with MC1080 and MC1046 as the main metabolites. CYP24A1 transcripts were strongly induced by a 48-hour calcipotriol exposure in mesenchymal stromal cells, but not consistently in synovial stromal cells, as determined by RT-qPCR. Calcipotriol proved to be safe after a single intra-articular dose with applied concentrations, and it is metabolized by the cells of the joint. Slow dissolution of calcipotriol crystals in the joint can extend the pharmaceutical impact on the synovium, cartilage and subcortical bone.

Where should the safe limits of alcohol consumption stand in light of liver enzyme abnormalities in alcohol consumers?

OBJECTIVES: To estimate the prevalence and risk factors for abnormal liver enzymes in a large age- and gender stratified population-based sample of apparently healthy individuals with or without alcohol consumption and other health-related risk factors (adiposity, physical inactivity, smoking). METHODS: Data on alcohol use, smoking, diet and physical activity were recorded using structured questionnaires from 13,976 subjects (6513 men, 7463 women, aged 25-74 years) in the national FINRISK studies. Alcohol data was used to categorize the participants into abstainers, light drinkers, moderate drinkers and heavy drinkers. Serum gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) activities were measured using standard kinetic methods. RESULTS: Male light drinkers, moderate drinkers and heavy drinkers showed significantly higher relative risks of abnormal GGT than abstainers: 1.37 (95% confidence interval 1.11 to 1.71, p < 0.01), 2.72 (2.08 to 3.56, p < 0.0005), and 6.10 (4.55 to 7.17, p < 0.0005), respectively. Corresponding values for women were 1.22 (0.99 to 1.51, p = 0.065), 1.90 (1.44 to 2.51, p < 0.0005), and 5.91 (3.80 to 9.17, p < 0.0005). Estimated threshold doses for a significant GGT elevation was 14 standard weekly alcohol doses for men and 7 for women. Excess body weight and age over 40 years modulated the thresholds towards smaller quantities of alcohol. The risk of abnormal GGT was also significantly influenced by physical inactivity and smoking. The relative risks of abnormal ALT activities were increased in male heavy drinkers, especially in those presenting with adiposity and sedentary lifestyle. CONCLUSIONS: Alcohol use markedly increases the risk for abnormal liver enzyme activities in those presenting with age over 40 years, obesity, smoking or sedentary lifestyle. The data should be considered in public health recommendations and in the definitions of safe limits of alcohol use.

Acute Changes in Inflammatory Biomarker Levels in Recreational Runners Participating in a Marathon or Half-Marathon.

BACKGROUND: Strenuous physical activity activates the participant's immune responses; however, few studies exist, observing exercise-induced simultaneous changes in mediators of inflammation. METHODS: We examined individual responses in soluble urokinase-type plasminogen activator receptor (suPAR), a marker of immune activation, soluble endocytic receptor for haptoglobin-hemoglobin complexes (CD163), a marker of monocyte-macrophage activation, C-reactive protein (CRP), and pro- and anti-inflammatory cytokines from blood samples drawn at baseline, at 3- and 48-h post-races from recreational runners who successfully completed the marathon (199 ± 8 min, n = 4) or half-marathon (132 ± 4 min, n = 4) run. For comparisons, biomarkers reflecting muscle, heart, kidney, and liver functions were measured. RESULTS: Significant 3-h post-race increases occurred in levels of suPAR (p < 0.01), CD163 (p < 0.05), white blood cells (p < 0.001), pro-inflammatory cytokines, interleukin-6 (IL-6) (p < 0.001), IL-8 (p < 0.05), and anti-inflammatory cytokine IL-10 (p < 0.05), whereas tumor necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß) remained relatively stable. Full-marathon running lead to more pronounced increases in suPAR, CD163, IL-8, and IL-10 than half-marathon running. In addition, 3-h post-race increases of all these parameters correlated significantly with changes in serum TNF-α and cortisol. The 48-h levels of serum suPAR and both pro- and anti-inflammatory cytokines had decreased to baseline levels, whereas CRP, a marker of acute phase response, increased in those with the most prominent IL-6 and IL-10 elevations in their preceding samples. The highest suPAR, CRP, IL-6, TNF-α, IL-10, and cortisol levels were noted in the individual with the most severe post-race fatigue. CONCLUSIONS: Prolonged running increases mediators of inflammation in an exercise-dose-dependent manner which should be considered in the assessment of health status of physically active individuals after recent acute bouts of strenuous exercise.

Individual responses in biomarkers of health after marathon and half-marathon running: is age a factor in troponin changes?

Although strenuous physical activity is known to cause notable perturbations in blood chemistries, only few studies exist observing exercise-induced simultaneous changes in biomarkers of health status. We compared markers of muscle, cardiovascular, renal, hepatic and inflammatory status at baseline and at 3-h and at 48-h postrace in recreational runners who successfully completed either a marathon (mean age 27 ± 13 years, finishing time 199 ± 8 min, n = 4) or half-marathon (mean age 38 ± 13 years, finishing time 131 ± 6 min, n = 6) race. Significant postrace changes occurred in myoglobin (p < .001), creatinine kinase (p < .01), CK-MB-mass (p < .01), high sensitivity troponin I (p < .05), high sensitivity troponin T (p < .05), brain natriuretic peptide (p < .001), creatinine (p < .01), aminotransferase enzymes (p < .001 for AST and p < .01 for ALT), uric acid (p < .001) cortisol (p < .01), C-reactive protein (p < .05), leukocytes (p < .001), haematocrit (p < .05) and mean corpuscular volume (p < .01). In comparison between the two types of exercise, marathon running lead to more pronounced responses in myoglobin, CK-MB-mass, ALT, AST, lactate and phosphate. Notable elevations in troponin levels were observed only in young participants (<30 years), most strikingly in those ≤20 years of age. The data indicates that prolonged running leads to distinct biomarker alterations, which should be considered in the assessment of health status after recent acute bouts of strenuous exercise. The observations suggesting more pronounced cardiac troponin responses in young individuals warrant further studies in larger populations.

Clinical and Laboratory Responses of Cross-Country Skiing for a 24-H World Record: Case Report.

The physiological consequences of ultra-endurance cross-country skiing in cold conditions are poorly known. We report here clinical, echocardiographic and laboratory findings from a 41-y old male elite skier in a world record trial for 24-h skiing. The athlete completed a total of 406.8 km outdoors with the temperature ranging between -24°C and -5°C during the 24-h period. Post exercise, notable increases from baseline values were observed in myoglobin (50-fold), creatinine kinase (30-fold) and proBNP (6-fold), whereas troponin T or troponin I levels remained unchanged. At baseline, echocardiographic findings showed cardiac hypertrophy and after skiing, a 5% reduction of left-ventricular end-diastolic dimension. Increases in markers of kidney (creatinine) and liver function (alanine aminotransferase), serum uric acid, C-reactive protein and white blood cell counts were also noted. In addition, electrolyte disturbances including hyponatremia, hypophosphatemia and hypocalcaemia were noted during the follow-up. The data indicates that a prolonged period of high-intensity skiing leads to muscle, heart and kidney affection and activation of inflammation even in an experienced elite skier. The observed health effects underscore the need for strict medical surveillance of participants in extreme sports with long duration. Key pointsAn elite athlete was able to ski over 400 km during 24 hours with an outdoor temperature ranging between -5 °C and -24 °C.Several postrace abnormalities occurred in biomarkers of muscle, heart, kidney, liver and inflammation status.Serum troponins, specific markers of myocardial cell damage, remained stable.The report supports careful medical surveillance of participants in extreme sports with long duration.