The time course of radioactivity in plasma and urine after oral administration of a single dose of (1-14 C) ascorbic acid has been followed in healthy male volunteers smoking more than 20 cigarettes per day. The investigation was carried out under steady state conditions with regard to ascorbic acid plasma levels at intakes of about 30 to 180 mg/day. Smokers had a higher metabolic turnover than that found for nonsmokers. It was concluded, as a consequence, that a daily intake of at least 140 mg is required for smokers to reach steady state concentrations and total body pools comparable to nonsmokers for whom a daily intake of about 100 mg was previously reported to be appropriate.

The time course of radioactivity in plasma and urine after oral administration of a single dose of (1-'4C)ascorbic acid has been followed in healthy nonsmoking male volunteers. The investigation was carried out under steady state conditions with regard to ascorbic acid intake (30 to 180 mg/day).Using pharmacokinetic principles, turnover, pool size, and rates of metabolism and excretion could be calculated. It was found that the half-life of ascorbic acid was inversely related to the dosage and that the pool could be increased to about 20 mg/kg bodyweight by increasing the dosage. It was concluded that on a daily intake of about 100 mg ascorbic acid this pool size would be reached in 95% of the population.Am.

The role of lipase in the regulation of upper gastrointestinal function is poorly understood. We studied the effect of orlistat, a new, potent, and highly specific lipase inhibitor, on gastric emptying, cholecystokinin (CCK) release, and pancreaticobiliary secretion. Three groups of studies were performed in nine healthy volunteers, using the double-indicator technique with a triple-lumen duodenal tube, polyethylene glycol 4000 as a duodenal perfusion marker, and 99mTc-diethylenetriamine pentaacetic acid as a meal marker. Gastric emptying, pancreaticobiliary output, and postprandial plasma CCK levels were measured after ingestion of the following isocaloric 500-ml liquid meals with or without 200 mg orlistat: 1) a pure fat meal (10% Intralipid), 2) a meal containing free fatty acids, or 3) an albumin-glucose meal. All experiments were performed in a randomized, placebo-controlled, crossover design. Orlistat markedly inhibited lipase activity in all three experiments. Orlistat given with the fat meal reduced CCK release and output of lipase, trypsin, and bilirubin and accelerated the rate of gastric emptying (P < 0.05). After ingestion of the free fatty acid or albumin-glucose meal, orlistat had no significant effect on any of these parameters. We conclude that lipase plays an important, nutrient-specific role in the regulation of gastric emptying and pancreaticobiliary secretion after ingestion of fatty meals in humans.

Excessive intake of dietary fat contributes to the development and maintenance of both obesity and hyperlipidemia. Inhibition of gastrointestinal lipases could decrease the amount of ingested fat that is absorbed systemically by preventing the hydrolysis of triglycerides. Ro 18-0647, a chemically synthesized derivative of the natural product lipstatin, inhibits the action of gastrointestinal lipases. Initial studies in humans have shown that Ro 18-0647 can reliably increase fecal fat excretion. Ro 18-0647 has also been shown to be well tolerated in the majority of normal volunteers and obese patients studied. Further research must be conducted to determine whether clinical endpoints of weight loss or cholesterol lowering can be produced by using this new pharmacologic principle.

Long-term oral intake of 1 and 10 mg zeaxanthin as beadlets increases plasma zeaxanthin concentrations approximately 4- and 20-fold, respectively. Evidence that all-E-3-dehydro-lutein is formed from zeaxanthin was strong.