Effects of orlistat on fat-soluble vitamins in obese adolescents.

McDuffie JR, Calis KA, Booth SL, Uwaifo GI, Yanovski JA.

Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-1862, USA. Mcduffj mail.nih.gov

STUDY OBJECTIVES: To determine whether orlistat causes fat-soluble vitamin deficiencies in African-American and Caucasian adolescents. DESIGN: Prospective, open-label pilot study. SETTING: Warren Grant Magnuson Clinical Center of the National Institutes of Health. PATIENTS: Seventeen adolescents with body mass indexes above the 95th percentile for age, race, and gender who also had at least one obesity-related comorbid condition. INTERVENTION: Subjects received orlistat 120 mg 3 times/day and a daily multivitamin supplement containing vitamin A 5000 IU, vitamin D 400 IU, vitamin E 300 IU, and vitamin K 25 microg. MEASUREMENTS AND MAIN RESULTS: During 3-6 months of orlistat treatment, acute absorption of retinol (vitamin A) was not significantly altered, but absorption of alpha-tocopherol (vitamin E) was significantly reduced compared with baseline levels (p<0.001). Serum levels of vitamins A and E did not change significantly; however, there was a nonsignificant decrease in vitamin K. Mean vitamin D levels were significantly reduced compared with baseline (p<0.02) after 1 month of orlistat, despite multivitamin supplementation. CONCLUSION: It may be prudent to monitor vitamin D concentrations in adolescents who take orlistat, even when a multivitamin is prescribed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12126214&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Intensive lifestyle intervention combined with the choice of pharmacotherapy improves weight loss and cardiac risk factors in the obese.

Frost G, Lyons F, Bovill-Taylor C, Carter L, Stuttard J, Dornhorst A.

Department of Nutrition and Dietetics, Hammersmith Hospital, Du Cane Road, London, UK. g.frost ic.ac.uk

BACKGROUND: Obesity is on the increase yet within the National Health Service (NHS) treatment approaches differ greatly and service is patchy. Our aim was to compare current practice within a general dietetic clinic with a new clinic developed specifically for patients of higher morbidity risk. METHODS: Locally referred patients to the dietitians from within or without Hammersmith Hospitals NHS Trust of higher morbidity risk were invited to attend a new Lifestyle Clinic. Treatment was of a contractual nature and included more time with the dietitian, the offer of pharmacotherapy if appropriate and an emphasis on achieving a realistic weight loss of 10% within a 6-month period. Cognitive behavioural strategies were utilized focusing on achieving changes in dietary intake and physical activity levels. RESULTS: A total of 103 patients have been enrolled of whom 34 have been discharged before completion of the clinic programme. Twenty-six patients have completed (18 started pharmocotherapy with Orlistat and eight remained on lifestyle advice only), with the remainder still attending the Lifestyle Clinic. The results for these 26 patients demonstrate clinically significant benefits with regard to exercise tolerance 390.8 +/- 37.5 m vs. 473 +/- 46.6 m (P < 0.001), waist measurement 121.5 +/- 4.4 cm vs. 110.9 +/- 3.6 cm (P < 0.001), and total cholesterol : HDL ratio 1.17 +/- 0.05 mmol L-1 vs. 1.27 +/- 0.07 mmol L-1 (P < 0.05). A weight loss comparison with historical data collected in the general dietetic clinic achieves a 7.8 +/- 0.7 kg reduction in weight (with pharmocotherapy 8.96 +/- 0.98 kg, with lifestyle only 5.23 +/- 0.657) vs. 1.7 +/- 0.4 kg (P < 0.05). CONCLUSION: Lifestyle clinics facilitate beneficial lifestyle changes which impact positively on morbidity risk factors demonstrating an improvement on current service offered within the NHS. There is an obvious resource implication of offering an intensive management package. There is need for a randomized control trial with analysis to evaluate whether there is cost benefit from this type of intervention.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12153502&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Transfer of orlistat through oil-water interfaces.

Tiss A, Lengsfeld H, Hadvary P, Cagna A, Verger R.

Laboratoire de Lipolyse Enzymatique, UPR 9025, du CNRS, Marseille, France.

The transfer of radiolabelled orlistat ([14C]orlistat), a potent gastrointestinal lipase inhibitor, through an oil-water interface from a single oil droplet to an aqueous phase was investigated, using an oil drop tensiometer. The absolute transfer fluxes were found to be very low, even in the presence of micellar concentrations of bile salts, which increased their values from 0.2 to 2.5 and 6.5 pmol cm(-2) min(-1) in the presence of 0, 4 and 15 mM NaTDC, respectively. Adding either a lipid emulsion or pure human pancreatic lipase (HPL) or human serum albumin or beta-lactoglobulin had no effect on the flux of transfer of orlistat. The presence of colipase or a mixture of colipase and HPL was found, however, to reduce the flux of orlistat transfer, probably because it partly covered the single oil drop surface, even in the presence of bile salts. Using a finely emulsified system, we investigated the partitioning of orlistat between the aqueous and oil phases, in the absence or presence of bile salts above their CMC (4 mM NaTDC, final concentration). Under these emulsified conditions, orlistat was found to be mostly associated with the oil phase, since more than 98.8% of the total radioactivity was recovered after decantation with the oil phase. The low transfer rates of orlistat, as well as its partitioning coefficient between the oil and the aqueous phases, should help us to better understand the inhibitory effects of orlistat on lipid digestion in humans.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12270672&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Glucagon-like peptide 1 and fatty acids amplify pulsatile insulin secretion from perifused rat islets.

Cunningham BA, Richard AM, Dillon JS, Daley JT, Civelek VN, Deeney JT, Yaney GC, Corkey BE, Tornheim K.

Department of Biochemistry, Boston University Medical Center, Room 815, 650 Albany Street, Boston, MA 02118, U.S.A. and The Obesity Research Center, Evans Department of Medicine, Boston University Medical Center, 650 Albany Street, Boston, MA 02118, U.S.A.

Glucose-induced insulin secretion from isolated, perifused rat islets is pulsatile with a period of about 5-10 min, similar to the insulin oscillations that are seen in healthy humans but which are impaired in Type II diabetes. We evaluated the pattern of enhancement by the potent incretin, glucagon-like peptide 1 (GLP-1). GLP-1 increased the amplitude of pulses and the magnitude of insulin secretion from the perifused islets, without affecting the average time interval between pulses. Forskolin and the phosphodiesterase inhibitor isobutylmethylxanthine had the same effect, suggesting that the effect was due to elevated cAMP levels. The possibility that cAMP might enhance the amplitude of pulses by reducing phosphofructo-2-kinase (PFK-2) activity was eliminated when the liver isoform of PFK-2 was shown to be absent from beta-cells. The possibility that cAMP enhanced pulsatile secretion, at least in part, by stimulating lipolysis was supported by the observations that added oleate had a similar effect on secretion, and that the incretin effect of GLP-1 was inhibited by the lipase inhibitor orlistat. These data show that the physiological incretin GLP-1 preserves and enhances normal pulsatile insulin secretion, which may be essential in proposed therapeutic uses of GLP-1 or its analogues.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12356335&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


[Obesity: therapeutic aspects]

[Article in French]

Scheen A.

Service de Diabetologie, Nutrition et Maladies metaboliques, Departement de Medecine, C.H.U. Sart Tilman-Liege.

Obesity is now recognized as a chronic disease. Its treatment implies a prolonged negative energy balance, by reducing caloric intake and/or increasing energy expenditure. In practice, three therapeutic approaches can be considered: 1) life-style modifications, combining well-balanced hypocaloric diet and regular physical exercise, the key-issue in obesity management; 2) in case of failure and as adjunct treatment, anti-obesity drugs, especially orlistat, an intestinal lipase inhibitor, and sibutramine, a central appetite regulator; and 3) in patients with extreme refractory obesity, surgical procedures consisting of gastric restriction (gastroplasty) or intestinal bypass. Anti-obesity treatments must be evaluated in the long run, in terms of efficacy/safety ratio, upon criteria of weight loss, reduction in associated risk factors, improvement of quality of life and, if possible, reduction of morbidity and mortality.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12371268&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)