Alcohol use disorder and muscle weakness: Original study of the effect of vitamin D supplementation in ambulatory participants with alcohol use disorder.

INTRODUCTION: Chronic alcohol-related myopathy presents with proximal muscle weakness. We studied the effect of vitamin D supplementation on muscle weakness in adults with alcohol use disorder. METHOD: Randomized controlled trial. Participants were community-dwelling adults with alcohol use disorder. Participants allocated to VIDIO, vitamin D intensive outreach, received bimonthly oral doses of 50,000‒100,000 IU cholecalciferol for 12 months. Participants allocated to CAU, care as usual, received prescriptions of once-a-day tablets containing 800 IU cholecalciferol and 500 mg calcium carbonate. Data included demographic variables, laboratory tests, alcohol use, and rating scales of help-seeking and support. Main outcomes were the participants' quadriceps maximum voluntary contractions (qMVC) and serum-25(OH)vitamin D concentrations, 25(OH)D. RESULTS: In 66 participants, sex ratio 50/16, mean age 51 year, alcohol use was median 52 [IQR 24‒95] drinks per week. Baseline qMVC values were 77% (SD 29%) of reference values. Laboratory tests were available in 44/66 participants: baseline 25(OH)D concentrations were 39.4 (SD 23.7) nmol/L. Thirty-one participants with 25(OH)D concentrations <50 nmol/L received either VIDIO or CAU and improved in qMVC, respectively with mean 51 (P<0.05) and 62 Newton (no P-value because of loss of follow-up) after one year of treatment. Vitamin D status increased with mean +56.1 and +37.4 nmol/L, respectively in VIDIO and CAU. CONCLUSION: The qMVC values improved during vitamin supplementation in adults with vitamin D deficiency and alcohol use disorder. Despite higher 25(OH)D concentrations in VIDIO, in terms of muscle health no advise could be given in favor of one vitamin strategy over the other. TRIAL REGISTRATION: Netherlands Trial Register (NTR) identifier: NTR4114.

Biomarkers of delirium as a clue to diagnosis and pathogenesis of Wernicke-Korsakoff syndrome.

BACKGROUND AND PURPOSE: Wernicke's encephalopathy (WE) and Korsakoff's syndrome are considered to be different stages of the same disorder due to thiamine deficiency, which is called Wernicke-Korsakoff syndrome (WKS). The earliest biochemical change is the decrease of α-ketoglutarate-dehydrogenase activity in astrocytes. According to autopsy-based series, mental status changes are present in 82% of WE cases. The objective of the present review is to identify possible underlying mechanisms relating the occurrence of delirium to WKS. METHODS: Studies involving delirium in WKS, however, are rare. Therefore, first, a search was done for candidate biomarkers of delirium irrespective of the clinical setting. Secondly, the results were focused on identification of these biomarkers in reports on WKS. RESULTS: In various settings, 10 biochemical and/or genetic biomarkers showed strong associations with the occurrence of delirium. For WKS three of these candidate biomarkers were identified, namely brain tissue cell counts of CD68 positive cells as a marker of microglial activation, high cerebrospinal fluid lactate levels, and MHPG, a metabolite of norepinephrine. Based on current literature, markers of microglial activation may present an interesting patho-etiological relationship between thiamine deficiency and delirium in WKS. CONCLUSIONS: In WKS cases, changes in astroglia and microglial proliferation were reported. The possible loss-of-function mechanisms following thiamine deficiency in WKS are proposed to come from microglial activation, resulting in a delirium in the initial phase of WKS.