Although it is well known that chronic alcohol abuse causes a broad range of health complications, it remains unclear how much regeneration may occur during long-term abstinence from alcohol. A new study carefully monitors major water and electrolyte regulating hormones – arginine vasopressin (AVP), atrial natriuretic peptide (ANP), aldosterone and angiotensin II – from early withdrawal up to 280 days of strict abstinence. The results, published in the May issue of Alcoholism: Clinical & Experimental Research, indicate that chronic alcohol abuse can cause severe and persistent alterations in the hormones that regulate electrolyte and water balance in the body.
"Most of the available literature on regeneration from alcoholism is restricted to the first [few] days [up to] three weeks of abstinence," said Hannelore Ehrenreich, head of Clinical Neuroscience at the Max-Planck-Institute for Experimental Medicine and corresponding author for the study. "Only rarely do papers report on persistent alterations or on patterns of regeneration associated with long-term abstinence. In fact, many disturbances are believed – but never proven – to return to normal within a few weeks."
"Both chronic alcohol consumption and alcohol withdrawal can affect cell and homeostatic functions on a variety of levels," said Claudia Spies, medical associate director of the department of anesthesiology and intensive care medicine at the University Hospital Charite Campus Mitte. "A chronic alcohol intake of at least 60g, or 1.5l beer, per day is associated with severe complications such as higher rates of infections, cardiomyopathy, cardiac arrhythmias, bleeding complications and liver insufficiency. During withdrawal, changes in electrolyte and water homeostasis occur. We know that the interaction of different homeostatic systems is complex but the specifics are poorly understood."
The consequences, however, are clear. "The hospital stay of alcoholics is prolonged compared with that of non-alcoholics," said Spies. "A major complication is alcohol withdrawal syndrome (AWS), developed by approximately half of chronic alcoholics during their hospital stay. The majority of the patients who develop AWS have hallucinations or delirium. AWS can also be deadly. In one study, the mortality rate in patients with AWS was approximately 18 percent, whereas alcohol abusers without AWS had a mortality rate of four to six percent, and non-alcohol abusers had a mortality rate of zero percent."
The study authors knew from previous research that various components of the physical and psychological stress-response systems can sustain damage despite many months of abstinence. "Vasopressin, or AVP, is a hormone that is also part of the stress regulatory system," said Ehrenreich. "In previous work, we showed that circulating levels of AVP are persistently suppressed in alcoholic patients over many weeks of abstinence. This is why we chose to further elucidate the recovery of vasopressin levels in alcoholics during long-term abstinence. Since atrial natriuretic peptide, or ANP, as well as aldosterone and angiotensin II are counter-regulatory or counterbalancing hormones to AVP, it was logical to simultaneously follow these parameters of water/electrolyte homeostasis."
Two groups of males participated in this study: alcoholics (n=35), 30 to 61years of age; and controls (n=20), 25 to 50 years of age. The two groups were matched on cigarette use. "It is well known that acute nicotine increases the secretion of AVP," explained Ehrenreich. "It has to be assumed that chronic cigarette consumption also alters AVP secretion or metabolism. Therefore, we used cigarette-matched controls in order to exclude the influence of such an interfering variable."
Following an inpatient detoxification period of two to three weeks, 21 of the 35 alcoholics were successfully monitored for the full length of the study period, 280 days. Researchers collected data from all of the participants on their AVP, ANP, aldosterone, and angiotensin II levels, as well as measures of kidney and liver function.
They found that basal AVP levels were suppressed during the entire study period. In contrast, ANP levels were elevated for the entire time. No persistent alterations were found for aldosterone or angiotensin II.
"We learned that we are dealing with profound, long-lasting alterations of key hormones of water and electrolyte balance notwithstanding at least nine months of controlled abstinence," said Ehrenreich. "These observations imply a number of causes and consequences: they may explain excessive thirst and fluid intake, what we call diabetes insipidus; may explain how alcohol-related cardiomyopathy develops; and may show that there is a subclinically impaired renal function in these patients which clearly underlines the concept of multi-organ involvement in alcoholism, that is, not only are the liver and brain affected, but basically all organs are."
Both Ehrenreich and Spies believe these results can be used to develop new therapeutic options to support abstinence in alcoholics.
"One possibility would be to substitute AVP," said Ehrenreich, "which might not only contribute to recovery of water and electrolyte homeostasis but also benefit cognitive functions such as memory. The findings of the present study imply that at least some features of craving, such as drinking behaviour and thirst, might be explained by biological alterations in the regulation of salt and water homeostasis. Therefore, approaches to substitute for vasopressin, or to normalize vasopressin regulation, might result in a reduction of craving-induced relapses."
Ehrenreich added that one of the most important findings of this study is that "chronic alcoholism is associated with long-term persistent alterations of various organs and systems even with controlled abstinence. There is no immediate recovery to be expected," she stressed. "Both for psychological as well as medical reasons, we need to consider that we are dealing with individuals severely compromised over many months of controlled abstinence. Detoxification treatments are important and necessary to overcome life-threatening withdrawal symptoms, but with respect to organic and psychological alterations in this group of patients, they only reach the tip of the iceberg."
Funding for this Addiction Science Made Easy project is provided by the Addiction Technology Transfer Center National Office, under the cooperative agreement from the Center for Substance Abuse Treatment of SAMHSA.
Articles were written based on the following published research:
Döring, W.K.H., Herzenstiel, M.N., Krampe, H., Jahn, H., Pralle, L., Sieg, S., Wegerle, S., Poser, W., Ehrenreich, H. (May 2003). Persistent alterations of vasopressin and n-terminal proatrial natriuretic peptide plasma levels in long-term abstinent alcoholics. Alcoholism: Clinical & Experimental Research, 27 (5), 849-862.
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