Sarcopenic Obesity in People with Alcoholic Use Disorder: Relation with Inflammation, Vascular Risk Factors and Serum Vitamin D Levels.

In recent years, the terms sarcopenia, sarcopenic obesity, and osteosarcopenic obesity (OSO) were coined to define a situation in elderly people strongly associated with frailty and increased mortality. Possibly, a complex interplay of several hormones and cytokines are involved in its development. Ongoing research detected that OSO may occur at any age and in several conditions. The prevalence of OSO in alcoholism was poorly analyzed. The aim of this study was to analyze the prevalence of OSO in alcoholism and its relationship with proinflammatory cytokines and/or common complications of alcoholism, such as cirrhosis, cancer, or vascular disease. We included 115 patients with alcoholic use disorder. Body composition analysis was performed by double X-ray absorptiometry. Handgrip strength was recorded using a dynamometer. We assessed liver function according to Child's classification, and determined serum levels of proinflammatory cytokines (TNF-α, IL-6, IL-8), routine laboratory variables, and vitamin D. People with alcoholic use disorder showed a high prevalence of OSO, especially regarding OSO obesity (60%), OSO osteopenia (55.65%), and OSO lean mass (60.17%). OSO handgrip was closely, independently, related to the presence of vascular calcification (χ2 = 17.00; p < 0.001). OSO handgrip was related to several proinflammatory cytokines and vitamin D. Vitamin D deficiency kept a close correlation with OSO handgrip (rho = -0.54, p < 0.001). Therefore, among people with alcohol use disorder, OSO prevalence was high. OSO handgrip is related to serum proinflammatory cytokine levels supporting the possible pathogenetic role of these cytokines on OSO development. Vitamin D deficiency is related to OSO handgrip suggesting its pathogenetic involvement in sarcopenia in patients with alcohol use disorder. The close association between OSO handgrip and vascular calcification is clinically relevant and suggests that OSO handgrip may constitute a prognostic tool in these patients.

Sclerostin, vascular risk factors, and brain atrophy in excessive drinkers.

Objective: Heavy alcohol consumption causes several organic complications, including vessel wall calcification. Vascular damage may be involved in the development of brain atrophy and cognitive impairment. Recently, sclerostin (whose levels may be altered in alcoholics) has emerged as a major vascular risk factor. The objective of the present study is to analyze the prevalence of vascular calcifications in alcoholics, and the relationships of these lesions with brain atrophy, as well as the role of sclerostin on these alterations. Patients and methods: A total of 299 heavy drinkers and 32 controls were included. Patients underwent cranial computed tomography, and several indices related to brain atrophy were calculated. In addition, patients and controls underwent plain radiography and were evaluated for the presence or absence of vascular calcium deposits, cardiovascular risk factors, liver function, alcohol intake, serum sclerostin, and routine laboratory variables. Results: A total of 145 (48.47%) patients showed vascular calcium deposits, a proportion significantly higher than that observed in controls (χ2 = 16.31; p < 0.001). Vascular calcium deposits were associated with age (t = 6.57; p < 0.001), hypertension (t = 5.49; p < 0.001), daily ethanol ingestion (Z = 2.18; p = 0.029), duration of alcohol consumption (Z = 3.03; p = 0.002), obesity (χ2 = 4.65; p = 0.031), total cholesterol (Z = 2.04; p = 0.041), triglycerides (Z = 2.05; p = 0.04), and sclerostin levels (Z = 2.64; p = 0.008). Calcium deposits were significantly related to Bifrontal index (Z = 2.20; p = 0.028) and Evans index (Z = 2.25; p = 0.025). Serum sclerostin levels were related to subcortical brain atrophy, assessed by cella media index (Z = 2.43; p = 0.015) and Huckmann index (ρ = 0.204; p = 0.024). Logistic regression analyses disclosed that sclerostin was the only variable independently related to brain atrophy assessed by altered cella media index. Sclerostin was also related to the presence of vascular calcifications, although this relationship was displaced by age if this variable was also included. Conclusion: Prevalence of vascular calcification in alcoholics is very high. Vascular calcium deposits are related to brain atrophy. Serum sclerostin is strongly related to brain shrinkage and also shows a significant relationship with vascular calcifications, only displaced by advanced age.

Serum Myostatin among Excessive Drinkers.

Myostatin acts as a negative regulator of muscle growth. Its effect on fat mass is subject to debate. Among alcoholics, there is a high prevalence of muscle atrophy, and increased fat deposition has been also described in these patients. Myostatin could be involved in these alterations, but its relationships with body composition have been scarcely studied in alcoholic patients. To analyze the behavior of myostatin among alcoholics and its relationship with alcohol intake, liver function, and body composition. We investigated serum myostatin in 59 male patients and 18 controls. Patients were all heavy drinkers admitted with organic complications related to excessive ethanol ingestion. Densitometry analysis was used to assess body composition in 46 patients. Handgrip was assessed in 51 patients. Patients showed lower myostatin values than controls (Z = 3.80; p < 0.001). There was a significant relationship between myostatin and fat at the right leg (ρ = 0.32; p = 0.028), left leg (ρ = 0.32; p = 0.028), trunk (ρ = 0.31, p = 0.038), total fat proport ion (ρ = 0.33, p = 0.026), and gynecoid fat distribution (ρ = 0.40, p = 0.006) but not with lean mass (total lean ρ = 0.07; p = 0.63; trunk lean ρ = 0.03; p = 0.85; lower limbs ρ = 0.08; p = 0.58; upper limbs ρ = 0.04 p = 0.82; android ρ = 0.02; p = 0.88, or gynoid lean mass ρ = 0.20; p = 0.19). In total, 80.43% of patients showed at least one criterion of osteosarcopenic adiposity (OSA). Myostatin was related to OSA obesity. We also observed higher myostatin values among patients with body mass index > 30 kg/m2. Serum myostatin was lower among excessive drinkers, and it was related to increased fat deposition among these patients but not to lean mass, handgrip, or bone mineral density.

Sclerostin in Excessive Drinkers: Relationships with Liver Function and Body Composition.

BACKGROUND: Sclerostin was initially described as an inhibitor of the Wnt-ß catenin bone-forming pathway, but it also exerts important effects on intermediate metabolism and body composition. Osteosarcopenia and altered body fat distribution are common findings in excessive drinkers. The role of sclerostin in these patients is uncertain. We aim to analyze the behavior of sclerostin in excessive drinkers and its relationships with body composition (fat mass, lean mass, bone mass), handgrip strength, body mass index (BMI), liver function and ethanol intake. METHODS: 107 male active heavy drinkers and 26 age-matched controls were included. Serum sclerostin was determined by ELISA. Body composition analysis was performed by double X-ray absorptiometry. Handgrip strength was recorded using a dynamometer. Liver function was assessed according to Child's classification. RESULTS: Sclerostin was higher among Child's C patients, keeping a relationship with deranged liver function. Obesity, defined according to BMI, and body fat were strongly related to sclerostin, being independent of serum creatinine and of liver function. The relationship of sclerostin with total hip bone mineral density was displaced by BMI. CONCLUSION: Deranged liver function is associated with higher sclerostin levels in alcoholics. Raised sclerostin levels are related to fat deposition and increased BMI.

Brain-derived neurotrophic factor among patients with alcoholism.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is involved in neurogenesis and in the protection against oxidative damage and neuronal apoptosis. After exercise, there is an increased expression of this myokine, especially in skeletal muscle and brain. Low BDNF levels have been described in neurodegenerative diseases. Alcoholics show both muscle atrophy and brain atrophy. Thus, this study was performed in order to analyze serum BDNF levels among alcoholics and their associations with brain atrophy and muscle strength. METHODS: Serum BDNF values were determined to 82 male alcoholics and 27 age-matched controls, and compared with handgrip strength, with the presence of brain atrophy, assessed by computed tomography, and with the intensity of alcoholism and liver function derangement. RESULTS: BDNF levels and handgrip strength were significantly lower among patients. Handgrip strength was correlated with BDNF values, both in the whole population and in alcoholics, especially in patients over 59 years of age. BDNF was poorly related to liver dysfunction but showed no relationship with brain atrophy or age. CONCLUSION: Chronic alcoholics show decreased BDNF serum levels that are related to muscle function impairment rather than to age, brain atrophy, liver dysfunction, or the amount of ethanol consumed.

Alcoholism: a systemic proinflammatory condition.

Excessive ethanol consumption affects virtually any organ, both by indirect and direct mechanisms. Considerable research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of alcoholism. These cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria, which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut permeability. Reactive oxygen species (ROS) that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of ethanol. The effects of this increased cytokine secretion and ROS generation lie far beyond liver damage. In addition to the classic consequences of endotoxemia associated with liver cirrhosis that were described several decades ago, important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain, bone, muscle, heart, lung, gonads, peripheral nerve, and pancreas. These effects are even seen in alcoholics without significant liver disease. Therefore, alcoholism can be viewed as an inflammatory condition, a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent disease. In this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver.