T. A. Miettinen

Serum lipids and fatty acids in ischemic strokes

Lipid analysis of different constituents in the blood of patients with stroke revealed that an increased level of total serum cholesterol was infrequently (that of triglycerides more frequently) associated with stroke in middle-aged men, whereas the high-density lipoprotein cholesterol content was low in all but young patients with stroke. High contents of cholestanol and low contents of n-6 polyunsaturated fatty acids predict the development of stroke in middle-aged men and are found in both middle-aged men with stroke and elderly patients with multi-infarct dementia. Young patients with unexpected stroke had normal serum sterol, triglyceride, and fatty acid contents but markedly reduced arachidonic acid levels in the platelets, a change that was normalized by treatment with aspirin. The results emphasize that the etiopathogenesis of ischemic brain damage may vary markedly from one age group to another.

Plasma lathosterol and campesterol in detection of ileal dysfunction

Plasma lathosterol levels reflect cholesterol synthesis, especially that induced by bile acid malabsorption, whereas plasma plant sterol contents change in parallel with cholesterol and fat absorption. The significance of lathosterols and plant sterols (campesterol and sitosterol) was therefore studied in detection of ileal dysfunction in 29 patients with ileal resection (7 with no malabsorption, 8 with only bile acid malabsorption, and 15 with bile acid, fat, and cholesterol malabsorption) and in 8 jejunoileal bypass patients with fat, bile acid, and cholesterol malabsorption. Ileal dysfunction-induced faecal loss of bile acids was proportionate to cholesterol synthesis, which, in turn, was proportionate to the plasma levels of lathosterols, so that the lathosterols contents were also closely correlated (r = 0.880) to faecal bile acids. The lower the cholesterol absorption, the lower was the plasma campesterol (less consistently, beta-sitosterol) level and the higher the faecal fat. Thus, elevated plasma lathosterol content is highly suggestive of bile acid malabsorption in a patient with suspected ileal dysfunction. High plasma content of lathosterols combined with a low campesterol level points to associated fat malabsorption, indicating that the lathosterol to campesterol ratio in plasma is frequently increased in patients with ileal dysfunction associated with steatorrhoea.

Serum plant sterols and lathosterol related to cholesterol absorption in coeliac disease

The concentrations of the plant sterols, campesterol and beta-sitosterol in serum, normally correlate with the efficiency of cholesterol absorption, whereas the concentration of lathosterol, a cholesterol precursor sterol, closely parallels changes in cholesterol synthesis. In this study we explored whether the plant sterol concentrations in serum in coeliac disease are determined by cholesterol absorption and whether they alone or with the serum lathosterol concentration, could be used for screening the activity of coeliac disease. In six patients the plant sterol concentrations in serum were significantly lower than in 17 control subjects, the reduction being more marked for campesterol than for beta-sitosterol: the serum lathosterol concentration was significantly higher than in the control subjects. The opposite changes in serum plant sterols and lathosterol were recorded in patients on a gluten-free diet. The plant sterol concentrations in serum (nmol/mg of cholesterol) were positively correlated with each other, and with the percentage absorption of cholesterol and with xylose absorption; they were negatively correlated with faecal fat, but not with faecal plant sterols. Thus, the low plant sterol concentrations in serum in coeliac disease were attributable to their impaired absorption, which in turn was closely associated with the absorption of cholesterol. The serum campesterol concentration clearly distinguished the untreated patients from the controls, whereas the use of serum beta-sitosterol, and the serum ratios of lathosterol/plant sterol resulted in some overlapping with the controls. It is suggested that the plant sterols in serum might be worth of determining when screening patients for coeliac disease and especially when testing their adherence to the gluten-free diet.

Chocolate, well-being and health among elderly men.

Objective:We hypothesized that chocolate preference would be related to health and psychological well-being in old men.Design, setting and participants:We have followed up a socio-economically homogenous group of men, born in 1919–1934, since the 1960s. In 2002–2003, a mailed questionnaire was used to assess the health and well-being (including questions related to positive life orientation, visual analogue scales and the Zung depression score) of survivors. In addition, candy preference was inquired. Those men who reported no candy consumption (n=108) were excluded from the analyses.Outcome measures:Psychological well-being in old age.Results:The response rate was 69% (1367 of 1991). Of the respondents, 860 and 399 preferred chocolate and other type of candy, respectively. The average age in both candy groups was 76 years. Of the respondents, 99% were home-dwelling, 96% were retired and 87% were presently married, without differences between the candy groups. Men preferring chocolate had lower body mass index and waist circumference, and they also reported more exercise and better subjective health (P=0.008) than other candy consumers. Variables related to psychological well-being were consistently better in those preferring chocolate. The differences were statistically significant in feeling of loneliness (P=0.01), feeling of happiness (P=0.01), having plans for the future (P=0.0002) and the Zung depression score (P=0.02).Conclusions:In this socioeconomically homogenous male cohort, chocolate preference in old age was associated with better health, optimism and better psychological well-being.Sponsorship:The Academy of Finland, the Päivikki and Sakari Sohlberg Foundation, the Helsinki University Central Hospital and the Finnish Foundation for Cardiovascular Research.

Cholesterol Absorption Regulates Cholesterol Metabolism and Plasma Lipoprotein Levels in Patients With Gut Exclusions

The occurrence of cholesterol malabsorption and its role in the regulation of cholesterol metabolism were studied in 30 patients with an earlier gut resection and 9 patients with a jejunoileal bypass for treatment of obesity. Fractional cholesterol absorption varied from 0.1% to 70%, and was lowest in jejunoileal bypass (8.3%) associated with severe fat and moderate bile acid malabsorptions and in 15 patients with a long small-intestinal resection (20.4%) associated with severe bile acid and moderate fat malabsorption. Seven resected patients with normal fecal fat and bile acids and 8 resected patients with malabsorption of only bile acid had normal cholesterol absorption. Low fractional cholesterol absorption was associated with a short length of the remaining proximal small intestine, high dietary intake of plant sterol, and high fecal fat and neutral sterol excretions, but not with bile acid malabsorption. In the whole study population, plasma levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol were positively correlated with fractional cholesterol absorption and the amount of total, dietary, and biliary absorbed cholesterol and were negatively correlated with fecal cholesterol elimination as neutral sterols (less so as bile acids) and cholesterol synthesis. The results emphasize that, in patients with ileal exclusion, plasma levels of low-density lipoprotein and high-density lipoprotein cholesterol are regulated more effectively by cholesterol than by bile acid malabsorption. Moreover, although the fecal loss of bile acids is the main determinant in cholesterol elimination and stimulation of cholesterol synthesis in patients with intestinal exclusions, intestinal cholesterol absorption also contributes noticeably to the regulation of cholesterol synthesis.

Serum Cholesterol Precursors, Cholestanol, and Plant Sterols in Primary Biliary Cirrhosis

We measured serum cholesterol precursors (squalene, delta 8-cholestenol, desmosterol, lathosterol, cholestanol) and plant sterols (campesterol, sitosterol, and avenasterol) from 11 patients (one man) with primary biliary cirrhosis (PBC) and 13 healthy women matched for age and weight. In PBC serum total cholesterol was increased (9.4 versus 5.9 mmol/l; p less than 0.05), whereas serum cholestanol in terms of mmol/mol of cholesterol was elevated fourfold. In similar terms, serum plant sterols, especially sitosterol and avenasterol, were modestly increased, whereas most of serum cholesterol precursors were decreased. The serum contents of cholestanol were negatively associated with those of serum cholesterol precursors and positively with those of sitosterol and avenasterol with the serum cholesterol concentration. The liver function tests were positively related to serum cholestanol contents (r value ranged from 0.588 to 0.839 for alkaline phosphatase, aspartate aminotransferase, alanine amino-transferase, and bilirubin). The findings suggest that in cholestatic liver disease reduced serum cholesterol precursor contents reflect reduced cholesterol synthesis, whereas increased serum plant sterol and cholestanol contents are determined mainly by impaired biliary elimination.

Enprostil Impairs Cholesterol and Fat Absorption

BACKGROUND Enprostil, a synthetic dehydroprostaglandin E2 structural analogue primarily developed for treatment of gastritis, has been shown also to lower serum cholesterol. METHODS We studied cholesterol metabolism in seven hypercholesterolemic subjects before, during, and after a low-dose enprostil (18 micrograms/day) treatment, measuring serum lipids, cholesterol absorption by an oral double-isotope method, fecal cholesterol elimination by the balance technique, and fecal fat. In addition, an oral fat load test with vitamin A was performed. RESULTS The drug treatment reduced serum concentrations of total and low-density lipoprotein (LDL) cholesterol by 8.2% and 7.9% (p < 0.05), respectively, and cholesterol absorption efficiency by 18% (p < 0.05), and increased fecal output of neutral sterols by 20% (p < 0.05), bile acids by 24% (NS), and cholesterol synthesis by 30% (p < 0.05). Postabsorptive concentrations of triglycerides and vitamin A in chylomicrons were reduced 3-4 h after the intake of the test meal. Fecal fat excretion was doubled during the enprostil treatment. CONCLUSIONS Enprostil reduces serum cholesterol concentrations, apparently by inhibiting cholesterol absorption so that fecal cholesterol elimination is increased in association with a mild fat malabsorption. Enhanced intestinal motility may contribute to these changes, frequently causing abdominal fullness or mild pain without diarrhea.

Plasma Fatty Acid Composition in Patients with Ileal Dysfunction

Chemical signs of essential fatty acid deficiency (EFD) were studied in 31 patients who has undergone an ileal resection on an average 7 years earlier by determining fatty acid composition in serum lipids. The subjects were divided into two groups in accordance with the presence (greater than 7 g/day) or absence (less than 7 g/day) of fat malabsorption. The two groups were matched for age, nutritional status, and essential fatty acid intake, but the patients with steatorrhea had higher levels of fecal bile acids and serum triglycerides and lower levels of serum cholesterol than those without steatorrhea. The contents of linoleic acid (LA; 18:2,n-6), the sum of n-6 polyunsaturated fatty acids, and eicosapentaenoic acid levels were lower, whereas those of the C 14-18 saturated and monoenoic fatty acids and eicosatrienoic fatty acid (ETA; 20:3,n-9), a characteristic fatty acid of EFD, were higher in the serum lipids of the patients with fat malabsorption. The LA of cholesterol esters, the ETA of phospholipids, and the ETA to arachidonic acid ratio of phospholipids were closely correlated with the amount of fecal fat, less significantly with the composition of dietary fat or the length of excluded intestine, and not at all with relative body weight or the amount of fecal bile acids. Changes in fatty acid patterns, considered characteristic of EFD, were found for almost a third of the patients with fat malabsorption; yet no clinical evidence of EFD was documented. Thus, the results demonstrate that chemical signs of EFD are common in patients with fat malabsorption after gut resections despite the good nutritional status. The findings suggest that, for preventive purposes, patients with gut resections should increase their dietary intake of polyunsaturated fatty acids in proportion to the amount of fecal fat.

In Vitro Synthesis of Triglycerides and Cholesterol in Human Gallbladder Mucosa

Triglyceride and sterol synthesis was investigated in vitro in the gallbladder mucosa from control subjects and patients with acalculous cholesterolosis. The incorporation rate of 14C-acetate was 1.6 +/- 0.2 nmol/g/h into cholesterol (sum of squalene, methyl sterols, and cholesterol) and 5.7 +/- 0.8 nmol/g/h into triglycerides. The rates were significantly correlated with each other (r = 0.667). The conversion of 3H-mevalonate into cholesterol (49 +/- 10 nmol/g/h) and triglycerides (4.7 +/- 1.2 nmol/g/h) indicated a high activity in the postmevalonate cholesterol synthesis and an active shunt pathway of mevalonate metabolism. The synthesis rates of cholesterol, triglycerides, and sterol esters were closely interrelated, were unaltered in cholesterolosis, and were not correlated with the serum, biliary, and mucosal lipid concentrations. Thus, despite marked lipid accumulation the lipid synthesis proceeds effectively in the gallbladder mucosa with cholesterolosis.

Squalene and sterol synthesis in isolated small-intestinal cells of the rat.

To compare the synthesis rate of cholesterol in different cells of the small intestine, isolated villous and crypt cells were incubated with a mixture of 14C-acetate and 3H-mevalonate in the presence of unlabeled carriers. The synthesis rate of squalene (includes the portion converted to sterols) from acetate was tenfold higher in the crypt than villous cells. The synthesis rate of squalene from mevalonate and the cyclization rate of squalene (the portion found in sterols) were about twofold higher in crypt than in villous cells. The conversion of acetate to squalene was correlated with that to fatty acids in the crypt cells only (r = 0.823), and the ratio of the two synthesis rates (squalene/fatty acids) was threefold higher in crypt than in villous cells. Despite the significant differences in the synthesis rates of squalene and sterols the concentrations of squalene and methyl sterols were similar in the two cell types. THe cholesterol content was, however, consistently higher in villous than in crypt cells, but the concentration was not correlated with the synthesis of squalene in the two cell types. The appearance of labeled squalene was clearly lower than that of labeled sterols in the lipoprotein-free incubation medium, but no differences were found between villous and crypt cells.