The effect of flaxseed supplementation in processed foods on serum fatty acids and enterolactone.

OBJECTIVE: The purpose was to study the effects of flaxseed supplementation as a part of daily diet on serum lipids, fatty acids and plasma enterolactone. DESIGN: Eighty volunteers participated in this clinical nutrition study which was carried out in a controlled, double-blind and cross-over manner. The subjects were randomized to diet sequences AB or BA. Diet A meals contained 1.3 g/100 g ground flaxseed and 5 g/100 g flaxseed oil. Also 3-4 g/100 of inulin and wheat fiber was added. AB diet with non-supplemented foods served as control. Test subjects were on both diets for 4 weeks separated by a 4-week wash-out period. Fifteen test subjects continued an open part of the study for 4 additional months. INTERVENTIONS: The dietary intake, basic blood values, serum lipids, fatty acids and enterolactone were measured at baseline, after both intervention periods and during the open study, at baseline and after 2 and 4 months. Serum thiocyanate and blood cadmium were controlled after both intervention periods. RESULTS: The percentage of flaxseed supplemented test food out of total dietary intake was 20% of energy. The test food contained significantly higher amounts of fiber, polyunsaturated fatty acids (PUFAs) and especially alpha-linolenic acid than the control food. No significant changes were observed in the basic laboratory values or in blood lipids. There was a significant increase in serum alpha-linolenic acid, eicosapentaenoic acid and docosapentaenoic acid. Serum enterolactone concentration was doubled during flaxseed supplementation. Serum thiocyanate and blood cadmium values did not exceed reference values and there was no difference between the diets. CONCLUSIONS: In this study we were able to show that, by adding ground flaxseed and flaxseed oil to one or two daily meals, it is possible to obtain significant effects on serum levels of enterolactone and alpha-linolenic acid. SPONSORSHIP: The study was sponsored by the National Technology Agency of Finland (Tekes).

The single dose pharmacokinetics and safety of deramciclane in healthy male volunteers.

The pharmacokinetics and tolerability of a new putative non-benzodiazepine type anxiolytic compound deramciclane was studied in two consecutive studies. An open dose-escalation design was used to study doses from 0.2 to 50 mg in 18 healthy male volunteers. In the second study doses from 50 to 150 mg were investigated in 14 healthy males in a double-blind, placebo-controlled, dose escalation study. Deramciclane was rapidly absorbed from the GI-tract and T(max) was 2-4 h. The elimination half-life increased from about 20 h to about 32 h with the increasing dose. Nevertheless, the AUC(0-infinity) values increased linearly within the studies over the dose ranges of 3-50 and 50-150 mg. However, the increase was more than the ratio of the dose over the total dose range of 3-150 mg. Therefore, non-linear pharmacokinetics of deramciclane at high doses cannot be excluded. N-desmethyl deramciclane, which is the active metabolite of deramciclane, was determined in plasma. C(max) was reached at about 6 h. The AUC(0-48 h) for the N-desmethyl metabolite was about one third of the AUC(0-infinity) of the parent compound and the ratio remained constant at each dose level. Deramciclane was safe, and was well tolerated at each dose level.

The effects of ursodeoxycholic acid on serum and biliary noncholesterol sterols in patients with gallstones.

Litholytic bile acid ursodeoxycholic acid (UDCA) reduces biliary cholesterol secretion and alters cholesterol metabolism by mechanisms that are not fully understood. To evaluate cholesterol metabolism during UDCA treatment, we studied serum and biliary lipids and cholesterol precursor sterols (lanosterol and other dimethyl and monomethyl sterols, lathosterols, and desmosterol), indicators of cholesterol synthesis, and plant sterols campesterol and sitosterol, indicators of cholesterol absorption, before and during administration of UDCA, 9 mg/kg/d, for 26 weeks in eight patients with radiolucent gallstones. During UDCA administration, serum lipid concentrations were unchanged, but the biliary concentration and molar percentage of cholesterol were markedly decreased. The proportions of the cholesterol precursor sterols to cholesterol were significantly interrelated between serum and bile before and especially during UDCA administration. Lanosterol and lathosterol levels, especially in bile, were significantly decreased by 43% and 34%, suggesting that UDCA may inhibit cholesterol synthesis. Levels of the other methylated precursor sterols were increased in serum and bile. The esterification percentages of all sterols were unchanged. The plant sterol-to-cholesterol ratios increased significantly in serum and bile, and there was an inverse correlation between the increment of serum plant sterols and decreased biliary molar percentage of cholesterol. In conclusion, UDCA may inhibit cholesterol synthesis possibly at the squalene synthase or 4alpha-demethylase steps, resulting in decreased biliary secretion of cholesterol. Reduced biliary sterol secretion probably increased serum plant sterol levels, indicating that under these conditions they no longer reflect the intestinal efficiency of cholesterol absorption.

Milk and egg phospholipids act as protective surfactants against luminal acid in Necturus gastric mucosa.

BACKGROUND: Our previous studies indicate that milk phospholipids have anti-ulcer properties in rats and humans, possibly by forming a hydrophobic surfactant layer at the epithelial surface. In the present study we measured intracellular pH and parameters of membrane resistances in gastric epithelium exposed to luminal acid using a microelectrode technique. METHODS: Chambered isolated Necturus maculosus antral mucosa was exposed to pH 2.3, with or without 20-25 min pre-treatment with milk or egg phospholipids. The pH in surface epithelial cells was measured with double-barrelled liquid sensor pH/PD-microelectrodes. RESULTS: Pre-treatment with phospholipids (2500-5000 micrograms P/mL) significantly (P < 0.01, n = 14) opposed intracellular acidification. Phospholipids significantly (P < 0.05, n = 14) increased the ratio of apical and basal membrane resistances, suggesting that they primarily affect the apical cell membrane. In contrast, there was no significant change in transmucosal resistance suggesting lack of effect on paracellular shunts in the 'leaky' epithelium. CONCLUSIONS: Exogenous phospholipids of dietary origin may be used to form a protective layer in the gastric mucosa against irritants.

Budesonide enema in active haemorrhagic proctitis--a controlled trial against hydrocortisone foam enema.

BACKGROUND: The aim was to compare budesonide enema, 2 mg/100 mL (Entocort) and hydrocortisone acetate foam enema, 125 mg (Colifoam) in patients with active haemorrhagic proctitis. METHODS: The trial was a controlled, randomized, investigator-blind study with two parallel groups. Endoscopy, histology and diary cards were used to assess the response to therapy. Safety was assessed by laboratory tests and adverse event recording. RESULTS: Seventy-two patients were included. Investigations were made before treatment and after 2 and 4 weeks. Both treatment groups showed statistically significant improvement in endoscopic scores but significant differences between the groups were not found. In the hydrocortisone group, plasma cortisol was significantly lowered after 4 weeks compared with budesonide. Bowel habits and quality of life variables did not differ between the treatments. The recorded adverse events were mild or moderate and may have been due to the proctitis. CONCLUSIONS: These results suggest that budesonide enema is as effective as hydrocortisone foam enema, but without the potential for side-effects associated with suppression of plasma cortisol.

Inhibition of human erythrocyte and gastroduodenal catechol-O-methyltransferase activity by nitecapone.

The effect of increasing single oral doses of the novel catechol-O-methyltransferase (COMT) inhibitor, nitecapone, on enzyme activity in red cells (RBC) and gastroduodenal COMT activity has been studied in healthy male volunteers. A dose-dependent decrease in RBC COMT activity was seen in all cases after 1 to 150 mg of the drug. The highest dose of 300 mg did not produce much more inhibition of COMT than 150 mg. The inhibition was not complete; at the highest doses the COMT activity was reduced by 50-60%. The effect and the duration of the inhibition in RBC COMT was strongly correlated with plasma nitecapone concentrations in the dose range up to 150 mg. RBC COMT activity recovered fully in 4 h after medication. Gastric mucosal COMT activity was several-fold higher than that in RBCs. It was also dose-dependently inhibited at the two doses (25 and 100 mg) studied. The inhibition of gastric and duodenal COMT was greater than that in RBCs. This also indicates that nitecapone is locally active in the gastroduodenal tract. The results confirm nitecapone as a potent COMT inhibitor in human tissues. New COMT inhibitors may provide a valuable approach to the treatment of Parkinson's disease in combination with L-dopa and dopa decarboxylase inhibitor therapy.

Low vs high dietary fiber and serum, biliary, and fecal lipids in middle-aged men.

Cholesterol metabolism was studied in 34 50-y-old men at home on high and low mixed-fiber diets. The high-fiber diet increased fiber intake (26.2 vs 11.6 g/d) and decreased slightly but significantly total energy, carbohydrate, and protein intakes and serum total, low-density-lipoprotein, and high-density-lipoprotein cholesterol values with no effect on dietary cholesterol and fat composition or body weight. Biliary molar lipid percentages were unaffected but deoxycholic acid was increased and chenodeoxycholic acid was decreased by the high-fiber diet. The high-fiber diet changed cholesterol absorption and fecal output of neutral and total sterols nonsignificantly but increased fecal bile acids by 13% (p less than 0.05) and reduced bacterial conversion of fecal sterols to secondary products. The decreased serum cholesterol concentration was probably caused by enhanced fecal output of cholesterol as bile acids resulting in enhanced cholesterol synthesis as indicated by an increased serum concentration of a cholesterol precursor, lathosterol.

Serum lipids and cholesterol metabolism during guar gum, plantago ovata and high fibre treatments.

Short-term viscous dietary fibres, plantago ovata and guar gum preparations, decreased serum cholesterol, mainly LDL cholesterol, as compared to low fibre or nonviscous high fibre periods, through enhancing cholesterol elimination as fecal bile acids. These changes were associated with significant increases in serum levels of cholesterol precursors, both in methylsterols and demethylated precursor sterols, while that of cholestanol (saturated cholesterol derivative) was decreased. In addition, cholesterol precursor contents were positively related, cholestanol negatively, to fecal cholesterol elimination both on and off viscous fibres. These findings indicate increased cholesterol synthesis, also seen by sterol balance data. As compared to low fibre diet, nonviscous high fibre diet conserved bile acids and decreased cholesterol absorption. Thus, it had no effect on cholesterol synthesis as indicated by fecal total steroids or serum levels of cholesterol precursors.

Effects of omeprazole in duodenal ulcer patients.

The efficacy of and tolerance to omeprazole, 40 mg/day, was studied in an open-label study in 18 patients with endoscopically verified duodenal ulcers. The effects of the drug on the oxyntic mucosa and pentagastrin-stimulated acid secretion during and after treatment were also studied. Fifteen patients completed the final endoscopy. The ulcers were healed in all after 4 weeks' treatment. Both basal and peak acid output were significantly reduced during omeprazole treatment, whereas 4 weeks after the cessation of treatment neither basal nor peak acid output differed from the pretreatment levels. Fasting serum gastrin levels rose by 56% during treatment but had returned to pretreatment values when tested again 4 weeks after the end of the treatment period. Histological examination of the biopsy specimens taken before and after treatment showed that omeprazole had no significant effect on the volume densities of either parietal or endocrine cells. We conclude that omeprazole is of value in the treatment of duodenal ulcer and that the effects of the drug on acid output and serum gastrin levels are fully reversible.

Morphology and dynamics of the gastric mucosa in duodenal ulcer patients and their first-degree relatives.

The prevalence of antral and body gastritis was determined in 30 duodenal ulcer patients and in 143 of their first-degree relatives, and compared by conventional mathematical and stochastic analyses with data on gastritis in a representative Finnish population sample. For conventional analysis, the controls for the duodenal ulcer patients and for the duodenal ulcer relatives, were matched for age and sex. For stochastic analysis, the duodenal ulcer patients and their 99 siblings were compared with the total control population of 434 subjects. The prevalence of gastritis affecting mainly the antral mucosa, and both antral and body mucosa to a similar extent was significantly higher in duodenal ulcer patients than in both controls and in relatives. The prevalence of antral and body gastritis in DU relatives and their controls was similar. However, the prevalence of subjects with normal antral and body mucosa was significantly lower. Stochastic analysis revealed more rapid progression of antral gastritis with age in the duodenal ulcer patients than in their siblings or controls and less rapid progression of body gastritis. The overall progression of antral and body gastritis was similar in DU siblings and their controls, but a dichotomy in the mean antral gastritis score of DU sibships was found, indicating high and low antral gastritis liability subgroups. The mean score of DU sibships having a mean age of less than 50 years behaved dynamically like DU patients, while the mean scores of sibships with a higher mean age had a low liability to develop antral gastritis. Most duodenal ulcer siblings who themselves had a duodenal ulcer, ulcer scar or duodenitis were found in the "high antral gastritis liability" subgroup.

Endoscopic and clinical findings in first-degree relative of duodenal ulcer patients and control subjects.

The first-degree relatives of duodenal ulcer patients and of control probands were evaluated clinically and by gastroduodenal endoscopy for prevalence of duodenal ulcer. The control probands were randomly selected from a control population. 199 relatives of 51 duodenal ulcer probands were interviewed, and 154 of these were endoscoped. 154 control relatives who had been endoscoped were matched with the DU relatives according to sex and age. Endoscopic evidence of present or past duodenal or pyloric ulcer was present in 20 (13.0%) of the DU relatives and in only 6 (3.9%) of the control relatives (p less than 0.01). The frequency of macroscopic duodenitis and gastric erosions was also significantly higher (p less than 0.05) in DU relatives than in controls. A history of epigastric pain was obtained in 54 (35.1%) of endoscoped DU relatives and in 24 (15.6%) of control relatives (p less than 0.01). This study has shown an increased prevalence of endoscopic evidence of duodenal ulcer in the first-degree relatives of duodenal ulcer patients. The finding that duodenitis is also more prevalent in DU relatives than in controls support the view that duodenitis is linked with duodenal ulcer.

Ulcer healing and serum pepsinogen I in cimetidine and glycopyrrolate treated duodenal ulcer patients.

Cimetidine is effective in the treatment of acute duodenal ulcers. 26 endoscopically verified duodenal ulcer patients were treated for four weeks with either cimetidine 0.8 g/day or with the anticholinergic drug glycopyrrolate 4 mg/day on a double-blind basis. Gastroscopical healing was achieved in 10/13 (77%) of cimetidine treated patients and in 4/13 (31%) of glycopyrrolate treated patients (p less than 0.05). There were no major side-effects in either group. In this study cimetidine seemed to be more effective than glycopyrrolate in the treatment of acute duodenal ulcer. The pretreatment level of serum pepsinogen I was elevated (110.1 +/- 42.8 microgram/l; mean +/- SD) in these patients (normal range 20--100 microgram/l) and increased significantly after pentagastrin stimulation to 133.2 +/- 56.4 microgram/l (p less than 0.001). The post-treatment level measured 24 hours after termination of treatment had increased significantly in the cimetidine group but not in the glycopyrrolate group. In the cimetidine group the high pretreatment level of pepsinogen I tended to predict a poor response.

Relationships between serum lipids and malabsorption of bile acids, neutral sterols, and fats in exocrine pancreatic insufficiency.

The relationship between serum lipids, fecal steroids, and fecal fat was studied in nine men with exocrine pancreatic insufficiency due to chronic pancreatitis. The mean fecal bile acid and fat outputs were significantly increased, the neutral sterol excretion was within normal limits, and total elimination and synthesis of cholesterol were slightly increased. A positive correlation between fecal fat and neutral sterols suggests that the patients actually had cholesterol malabsorption and that the normal neutral sterol excretion was apparently the result of a low biliary cholesterol secretion. In view of the fairly small increase in cholesterol elimination, the serum cholesterol level was surprisingly low, indicating that malnutrition may have limited compensatory increase in cholesterol synthesis. Serum triglycerides were negatively correlated with fecal fat. Thus, severe malabsorption apparently also limited the triglyceride production.