Reino Ylikahri

High density lipoprotein subfractions and postheparin plasma lipases in alcoholic men before and after ethanol withdrawal

Abstract Serum lipoproteins (VLDL, LDL, HDL 2 and HDL 3 ) and postheparin plasma lipase activities were measured in 10 male alcoholic subjects at the end of a long drinking period and subsequently after 8 and 15 days of complete abstinence. None of the patients showed any clinical or histological evidence of cirrhosis or other alcoholic liver disease. Reference data were obtained from healthy normolipidemic nonalcoholic men of similar age. In spite of the heavy alcohol intake the serum triglyceride and VLDL triglyceride concentrations of the alcoholics were not different from those of the reference group. On the other hand, the LDL cholesterol of the alcoholics was remarkably low and did not rise significantly during the 2 wk of abstinence. The mean HDL cholesterol concentration of the alcoholic men was 54% higher than that of the controls. This was mainly due to elevation of HDL 2 (+63%) but also the HDL 3 cholesterol was higher than that of the control subjects (+20%). The phospholipid and protein concentrations of HDL 2 and the phospholipid of HDL 3 were also significantly increased in the alcoholic men in comparison with the controls. The composition of HDL subfractions of the alcoholics was only slightly abnormal with an increase of phospholipid and decrease of protein content of HDL 3 . The concentration and composition of the HDLs returned to normal 1 wk after alcohol withdrawal. The postheparin plasma lipoprotein lipase and hepatic lipase activities of the alcoholic men were significantly higher than the respective values of the reference group. During eight off-alcohol days both enzyme activities decreased and reached the normal range. At the end of the drinking period no correlation was present between the levels of total HDL or its subfractions on the hand and any of the two lipase activities on the other. On the 8th off-alcohol day the HDL 2 phospholipid showed a highly significant positive correlation with lipoprotein lipase activity. It is concluded that the elevation of HDL during chronic use of alcohol in mainly due to increased concentration of HDL 2 and that this may be partly explained by an increase of lipoprotein lipase activity but that other mechanisms may also be involved. The low LDL concentration in alcoholic men without manifest liver disease is an interesting finding which should be studied further.

Alcohol-induced changes in serum lipoproteins and in their metabolism

The effects of alcohol intake on serum lipids and lipoproteins depend on the dose and mode of alcohol intake, individual susceptibility, genetic variables, and dietary factors. Therefore the changes of lipoprotein pattern are different among moderate and heavy drinkers. Moderate intake of alcohol increases the concentrations of apolipoproteins (apo) AI, apo AII, and high-density lipoprotein subfraction (HDL3) in plasma without any effects on other lipoproteins. If alcohol intake exceeds 60 to 80 gm per day, the synthesis of very low-density lipoprotein (VLDL) particles is stimulated. Even short-term use of alcohol stimulates lipoprotein lipase (LPL) activity in adipose tissue, and consequently the concentration of VLDL in plasma stays normal or is even subnormal. If alcohol intake continues in excessive amounts, the increased transport rate of VLDL particles as a result of high LPL activity results in the up regulation of HDL2. This is clearly evident in chronic alcoholics. Low or subnormal low-density lipoprotein (LDL) levels are another characteristic of the lipoprotein pattern in chronic alcoholics. The increase of HDL (HDL2) and reduction of LDL levels could well explain the reduced risk of coronary heart disease in chronic alcoholics, whereas the causal factors remain open among moderate drinkers.

Low plasma testosterone values in men during hangover

Abstract Plasma testosterone, estradiol, estrone and luteinizing hormone concentrations were measured by radioimmunoassay in healthy volunteers who after fasting for 10 h consumed 1.5 g ethanol/kg body wt. Of this group five suffered from severe hangover while another five had essentially no hangover. Ten to twenty hours after drinking, the testosterone concentrations were significantly decreased in all subjects, but in the 5 subjects with severe hangover the decrease was more pronounced. Estradiol values decreased during the hangover period, but were normal at the time of acute intoxication, whereas estrone values, in the few cases determined, showed a tendency to increase during acute intoxication. A compensatory increase in the plasma concentration of luteinizing hormone was found in all subjects.

Sequence of alcohol-induced initial changes in plasma lipoproteins (VLDL and HDL) and lipolytic enzymes in humans☆

The sequence of alterations in the concentration and composition of different plasma lipoproteins following alcohol intake is not known. We therefore monitored the concentrations of cholesterol, triglycerides, phospholipids, and proteins in the major lipoprotein fractions (VLDL, LDL, HDL2, and HDL3) in ten nonalcoholic healthy male volunteers who were given 5.5 g of alcohol per kilogram of body weight during 21/2 days (a weekend). In addition, lipoprotein lipase activity was measured in post-heparin plasma and in adipose tissue and hepatic lipase activity was measured in post-heparin plasma before and after the experiment. in a separate control experiment, the same subjects received meals and liquids without alcohol. Blood alcohol levels remained below 1.5 g/L. Alcohol caused a progressive increase in the fasting VLDL triglyceride and phospholipid concentrations, both of which were doubled during the experiment (P less than 0.001). In contrast, the VLDL cholesterol levels remained unchanged until the third morning, when there was a slight increase. The LDL triglyceride and phospholipid concentrations also rose without simultaneous changes in the LDL cholesterol concentration. Consistent with these changes, the HDL cholesterol concentration showed no response to alcohol during the experiment, but the HDL phospholipid level rose from 76 to 99 mg/dL (P less than 0.001). This was reflected as an increase in the HDL2 concentration from 124 to 158 mg/dL (P less than 0.01), whereas no change occurred in the HDL3 level. The increment of HDL2 concentration was due to a rise of its triglycerides, phospholipids, and apoproteins A-I and A-II but not to a rise of cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient Hypoparathyroidism during Acute Alcohol Intoxication

BACKGROUND Persons with chronic alcoholism frequently have hypocalcemia, hypomagnesemia, and osteoporosis. The short-term effects of alcohol ingestion on calcium and magnesium metabolism are poorly understood, however. METHODS We measured serum calcium, magnesium, and phosphate concentrations in 17 normal men and 7 normal women before and at intervals up to 16 hours after the ingestion of 1.2 to 1.5 g of alcohol per kilogram of body weight over a 3-hour period (doses sufficient to cause acute intoxication). Urinary excretion of calcium, magnesium, and phosphate and serum calciotropic hormone levels were measured in 16 of these subjects. As a control, the same measurements were made after the ingestion of fruit juice instead of alcohol. RESULTS The mean (+/- SE) peak blood alcohol level in the men was 37.5 +/- 1.6 mmol per liter, and in the women it was 38.0 +/- 3.2 mmol per liter. In the men the mean serum parathyroid hormone concentration decreased from 16.1 +/- 2.1 to 6.8 +/- 0.9 ng per liter at the end of the three-hour drinking period. The value at this time was 30 percent of that at the end of the three-hour session during which the men drank fruit juice (P = 0.004). The serum concentration of ionized calcium reached a nadir eight hours after the beginning of alcohol administration (decreasing from 1.18 +/- 0.01 to 1.15 +/- 0.01 mmol per liter; P less than 0.001 as compared with values during the fruit-juice study), and urinary excretion of calcium increased from 0.34 +/- 0.08 to 0.36 +/- 0.08 mmol per hour (P less than 0.01 as compared with values during the fruit-juice study). Serum parathyroid hormone levels exceeded base-line values during the last 4 hours of the 16-hour study period; this increase was accompanied by a decrease in the urinary excretion of calcium. Both serum levels of magnesium (in the first 6 hours) and urinary levels (in the first 12 hours) increased after the ingestion of alcohol. In the women, serum parathyroid hormone levels decreased from 29.2 +/- 2.8 to 17.3 +/- 2.6 ng per liter two hours after the administration of alcohol was begun (P less than 0.001) and increased above base-line values during the last four hours of the study period. The serum concentration of ionized calcium decreased from 1.20 +/- 0.01 to 1.16 +/- 0.01 mmol per liter, reaching a nadir 8 to 12 hours after alcohol administration was begun (P less than 0.001). CONCLUSIONS Short-term alcohol administration causes transitory hypoparathyroidism. This decline in the secretion of parathyroid hormone accounts at least in part for the transient hypocalcemia, hypercalciuria, and hypermagnesuria that follow alcohol ingestion.

Comparison of the effects of two different doses of alcohol on serum lipoproteins, HDL‐subfractions and apolipoproteins A‐I and A‐II: a controlled study

Abstract Our earlier studies have shown that heavy alcohol intake increases the serum concentration of HDL2. The present study aimed to test which HDL subfraction is affected by moderate alcohol intake, and to examine the time‐ and dose‐dependency of alcohol‐induced changes in serum lipoproteins. Therefore, 30 or 60 g day‐1 of alcohol were given to 10 healthy male volunteers during two 3‐week periods separated by an abstinence period of 3 weeks. Lipoproteins were fractioned by sequential flotation. On both doses the total HDL3 concentrations rose progressively, the maximum increases being 10 and 25% at the end of respective drinking periods. In contrast, the HDL2 increased slightly only on the dose of 60 g day‐1. The serum concentrations of apoprotein A‐I and A‐II increased on both doses but significantly only on the dose of 60 g day‐1; the increments being 22 and 35%, respectively. On the basis of these and our earlier findings we conclude that (i) the effects of heavy and moderate alcohol intake on serum HDL‐subfractions are different: the former preferentially increases the HDL2 whereas the latter augments the HDL3; (ii) alcohol‐induced changes in serum lipoproteins are both time‐ and dose‐dependent.

Metabolic Studies on the Pathogenesis of Hangover

Abstract. A variety of metabolic parameters were evaluated in 23 healthy male volunteers, after ethanol administration (1.5 g/kg) and correlated to the symptoms of hangover. The degree of intoxication and hangover were estimated using a simple test program according to which 11 subjects had severe and 12 mild hangover. Sequential determinations of blood ethanol, acetaldehyde, glucose, lactate, free fatty acids (FFA), triglycerides (TG) and ketone bodies were made during the 21 hours after administration. Each subject served as his own control by taking part in an identical experimental session but receiving no ethanol.

Accelerated Turnover of Very Low Density Lipoprotein Triglycerides in Chronic Alcohol Users A Possible Mechanism for the Up-Regulation of High Density Lipoprotein by Ethanol

The concentration of high density lipoproteins (HDL) is related to the catabolism of triglyceride-rich lipoproteins. In order to elucidate the mechanisms by which alcohol increases plasma HDL levels we measured the turnover kinetics of very low density lipoprotein (VLDL) triglycerides in 10 alcoholic men without liver disease and in nonalcoholic control men matched for age, weight and plasma VLDL triglyceride level. The study was repeated in the alcoholics after a 2-week abstinence period. The alcoholic men had elevated HDL cholesterol but reduced low density lipoprotein (LDL) cholesterol as compared to the controls. The fractional catabolic rate and the total turnover (production) rate of VLDL triglycerides were both significantly increased (P less than 0.05) in the alcoholic men before abstinence. After withdrawal of alcohol both the synthetic rate and the catabolic rate of VLDL triglycerides returned to normal and the HDL (HDL2 and HDL3) cholesterol fell. The per cent decrease in HDL2 cholesterol during abstinence was positively correlated to the respective fall of VLDL triglyceride fractional catabolic rate (r = +0.51). The results suggest that the absence of hypertriglyceridemia and the elevated levels of HDL in regular alcohol users may be partly based on increased metabolic clearance of VLDL particles and on subsequent accelerated transfer of the VLDL surface components to HDL.

Sex hormones and adrenocortical steroids in men acutely intoxicated with ethanol

The plasma or serum concentrations of testosterone, LH, FSH, PRL, cortisol, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, estrone and estradiol were monitored in 8 healthy male volunteers for a period of 48 hr after administration of one large dose of ethanol (1.75 g/kg BW) within the first 3 hr of the experiment. Each subject served as his own control in an identical experiment without ethanol. Blood alcohol concentration reached a maximum of 1.51 +/- 0.08 g/l (mean +/- SEM) 4 hr after the start of drinking. The maximum decrease in serum testosterone was observed at 12 hr when the serum concentrations of gonadotropins were still unchanged. The decrease in serum testosterone persisted at 24 hr despite increases in the serum levels of LH and FSH. The serum or plasma concentrations of PRL, cortisol, 17-hydroxyprogesterone, androstenedione and dehydroepiandrosterone were clearly increased 4 hr after the start of drinking. The increase in serum cortisol lasted as long as the decrease in serum testosterone. No significant changes were found in plasma concentrations of estrone and estradiol. Our results suggest that in addition to direct testicular effects of alcohol, increased adrenal secretion of cortisol may contribute to the decrease in serum testosterone in men acutely intoxicated with ethanol.

Decreased serum selenium m alcoholics — a consequence of liver dysfunction

The serum concentration of selenium was decreased by 17 and 48% in non-cirrhotic and cirrhotic alcoholics, respectively, as compared to healthy controls. In these alcoholics the serum selenium correlated positively with the serum albumin and plasma prothrombin time and inversely with the serum bilirubin, alkaline phosphatase and gamma-glutamyl transpeptidase. Abstinence from ethanol for two weeks was without effect on the serum selenium level in non-cirrhotic alcoholics and acute alcohol intake did not change the serum selenium concentration in non-alcoholic volunteers. In patients with primary biliary cirrhosis the serum concentration of selenium was similar to that in the alcoholic cirrhotics. In patients with hypoalbuminaemia of renal origin the serum selenium was normal. In conclusion our results show that the deterioration of liver function, irrespective of its aetiology, leads to the decrease in serum selenium levels. Whether a defect in removal of lipoperoxides is associated with this decrease in serum selenium concentration remains to be decided by further studies.