Supplementary Thiamine Is Still Important in Alcohol Dependence

Ellen Rees; Linda R. Gowing

Disclosures

Alcohol Alcohol. 2013;48(1):88-92. 

In This Article

Abstract and Introduction

Abstract

Aims: To assess the effect of mandatory thiamine enrichment of wheat flour on blood thiamine levels in an alcohol-dependent population.

Methods: Alcohol-dependent clients (n = 100) entering an inpatient service for the management of alcohol withdrawal had thiamine blood tests and diet interviews. Approximately half (n = 46) the alcohol-dependent participants reported taking vitamin supplements prior to admission. Standard treatment included thiamine supplementation in the form of an intramuscular injection and 100 mg tablets. If consent was gained, a second thiamine blood test was taken prior to discharge (n = 77). Control participants (n = 20) with no history of treatment for alcohol abuse had thiamine blood tests and diet interviews.

Results: Control participants consumed significantly larger amounts of thiamine in their diet compared with alcohol-dependent participants (P < 0.0001). Alcohol-dependent participants who reported no use of vitamin supplements had significantly lower (P < 0.05) blood thiamine levels compared with controls, whereas controls and those who reported using vitamin supplements had no significant difference. No significant correlation was found between thiamine blood levels and reported levels of alcohol consumption.

Conclusion: Reduced blood levels of thiamine in people who are alcohol dependent, compared with those with no history of alcohol abuse, are likely to be because of the poor diet. Consumption of vitamin supplements appears to bring thiamine levels closer to those seen in control participants. Supplementation of dietary intake of thiamine in people who are alcohol dependent remains an important measure for the prevention of Wernicke–Korsakoff's syndrome in this population.

Introduction

Thiamine is required by all tissues and must be ingested in the diet. Thiamine requirements increase with total calorie intake, when the diet is rich in carbohydrate, and when basal metabolism is increased, such as in alcohol withdrawal (Sechi and Serra, 2007; Mancinelli and Ceccanti, 2009). The Australian National Health and Medical Research Council recommends daily intake of thiamine should be 1.1 mg for women and 1.2 mg for men (based on a requirement of 0.33 mg/kcal consumed). This study used these figures as the recommended daily intake (RDI), but it should be noted that other authorities recommend intake as high as 0.5 mg/kcal consumed (Sechi and Serra, 2007).

After two to three weeks of inadequate intake, thiamine deficiency can occur due to a storage limit in the body of only 25–30 mg (Mancinelli and Ceccanti, 2009). People who are alcohol dependent are prone to thiamine deficiency because of decreased dietary intake and effects of ethanol on thiamine transport, storage, absorption and utilization (Harper, 2006; Mancinelli and Ceccanti, 2009).

Two thiamine specific transport systems have been identified in human tissues that are responsible for carrier-mediated uptake and secretion (Laforenza et al., 1998; Rindi and Laforenza, 2000; Martin et al., 2003; Reidling et al., 2010). These are thiamine transporters 1 (THTR-1) and 2 (THTR-2). THTR-1 is abundantly located on skeletal and cardiac muscle with medium expression in the liver, heart and kidneys. THTR-2 is widely expressed but mainly found on the kidneys, liver and placenta (Dutta et al., 1999).

Ingested thiamine is absorbed primarily in the proximal part of the small intestine through the action of enterocytes (intestinal absorptive cells). At high concentrations, diffusion occurs, but at low concentrations absorption occurs via THTR-1 or -2 (Hoyumpa, 1980; Reidling et al., 2006; Reidling et al., 2010). This active transport mechanism is rate limited (Mancinelli and Ceccanti, 2009). Thiamine is slowly released into blood plasma from the enterocyte, where 90% is in free-form. Once it enters the blood, the free-form thiamine diffuses into erythrocytes (Rindi and Laforenza, 2000; Martin et al., 2003). The kidneys reclaim filtered thiamine to prevent loss in the urine (Reidling et al., 2006).

Once thiamine enters a cell it is converted to the active form, thiamine diphosphate (TDP) (Hoyumpa, 1980; Martin et al., 2003). TDP is a co-factor for enzymes involved primarily in carbohydrate metabolism (Herve et al., 1995; Harper, 2006; Mancinelli and Ceccanti, 2009). If thiamine levels decrease, the activity of these enzymes also decreases, interfering with cellular function (Martin et al., 2003; Harper, 2006).

Alcohol consumption has been shown to cause transcription-mediated inhibition of THRT-1 and -2 expression (Kiela, 2010; Subramanian et al., 2010; Subramanya et al., 2010), decreases in TDP (Hoyumpa, 1980), reduced liver storage (Thomson et al., 1971; Hoyumpa, 1980) and decreased intestinal absorption (Hoyumpa, 1980; Singleton and Martin, 2001; Martin et al., 2003). Brain disorders such as Wernicke–Korsakoff syndrome (WKS) can result from thiamine deficiency (Sechi and Serra, 2007). WKS is associated with memory dysfunction and characteristic lesions in the thalamus, mamillary bodies and frontal lobe of the brain (Kopelman et al., 2009).

Australia is unique in having a program of mandatory thiamine fortification of bread and wheat flour. The addition of thiamine to cereal grains was mandatory in the USA in the 1940s (Bishai and Nalubola, 2002) but currently the sale of unenriched flour is not prohibited in the USA as long as the product meets labelling requirements. The addition of thiamine to wheat flour at the level of 6.4 mg/kg was made mandatory in Australia in 1991 (Australia New Zealand Food Standards Code, 2009). This was deemed necessary after general population autopsy research showed relatively high prevalence of WKS (4.7%) in Australia (Harper, 1979; Harper, 1983). Flour enrichment appears to have made a difference, as the prevalence of WKS in autopsies subsequently decreased to 1.1% (Harper et al., 1998). However, there has been little research into the effect of the addition of thiamine to flour on thiamine levels in people abusing alcohol.

In a recent study in South Australia thiamine levels were measured in people attending a clinic for assessment of fitness to drive a motor vehicle (65% with alcohol abuse, 35% alcohol dependent). In this group blood thiamine levels were larger than expected, and significantly higher than a European reference population (Crowley and Gaughwin, 2011). Following on from this study we sought to determine blood thiamine levels in an alcohol-dependent population relative to a comparison group of people with no history of alcohol abuse, to assess changes in thiamine levels in response to thiamine treatment, and to determine factors predictive of blood thiamine levels.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....