X-Message-Number: 29163 Date: Tue, 20 Feb 2007 23:47:21 -0800 (PST) From: Subject: carnitine, choline & nicotinamide [Carnitine, choline and nicotinamide make an interesting triplet. Carnitine and nicotinamide exhibit a very powerful synergism, with the combination reversing type 1 diabetes in mice. Both also inhibit human cellular aging, with nicotinamide being the more powerful. Choline blocks megadose nicotinamide toxicity. One can't help but wonder about the results from combining all three!] Pancreas. 2006 Nov;33(4):403-11. The association of acetyl-l-carnitine and nicotinamide remits the experimental diabetes in mice by multiple low-dose streptozotocin.Cresto JC, Fabiano de Bruno LE, Cao GF, Pastorale CF, Confalonieri N, del Carmen Camberos M, Basabe JC. Centro de Investigaciones Endocrinologicas (CEDIE-CONICET), Htal. de Ninos R. Gutierrez, Buenos Aires, Argentina. OBJECTIVES: We studied the effect of acetyl-l-carnitine plus nicotinamide (AC + N) on murine diabetes mellitus induced by multiple low doses of streptozotocin. METHODS: Male C57BL/6J inbred mice were injected intraperitoneally with citrate buffer or streptozotocin (40 mg/kg) for 5 consecutive days, followed by injections of saline solution or AC + N (50 + 25 mg/kg) from days 6 to 110. Four groups were studied: normal control mice (C), treated normal control mice (TC), diabetic mice (D), and treated diabetic mice (TD). TD group was divided into 2 at day 86; treatment was suspended in one group (TDs) and continued in the other until day 110. RESULTS: Weight, plasma glucose, plasma insulin, cellular immune aggression, glucose-stimulated insulin secretion from perifused pancreatic slices, and pancreas histology were studied in each experimental group. Diabetic mice treated with AC + N showed improvements in weight, plasma glucose, and plasma insulin levels without mortality, reaching control values at day 110. Cellular immune aggression and insulin release from pancreatic slices perfusions improved without reaching control values. Histology showed that insulin-immunostained area, the index of insulin immunostained beta cells and beta-cell size, was normalized at the end of the study. CONCLUSIONS: The treatment with AC + N induced remission of autoimmune type 1 diabetes in mice produced by multiple low doses of streptozotocin. PMID: 17079947 Aging Cell. 2006 Oct;5(5):423-36. Epub 2006 Aug 25. Nicotinamide extends replicative lifespan of human cells.Kang HT, Lee HI, Hwang ES. Department of Life Science, University of Seoul, Dongdaemungu, Jeonnongdong, Seoul, Korea. We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production. PMID: 16939485 J Nutr. 1986 Dec;116(12):2409-14. Muscle creatine content in rats given repeated large doses of nicotinamide: effects of dietary methionine, choline, carnitine, and other supplements.Sun S, McKee R, Fisler JS, Swendseid ME. Rats fed a 12% casein diet without added choline were chronically injected with pharmacologic doses of nicotinamide (NAM) for 18 to 28 d in three experiments. In addition to fatty livers and lower weight gains, the creatine content of heart and skeletal muscle was lower in NAM-treated than in control saline-injected rats. Dietary supplements of methionine prevented these alterations, and choline, depending on the level of supplementation, also had some similar effects. No consistent responses could be demonstrated by supplements of carnitine, histidine or folic acid plus vitamin B-12. PMID: 2949067 Neurosci Lett. 1998 Jun 19;249(2-3):111-4. Enhancement of brain choline levels by nicotinamide: mechanism of action.Erb C, Klein J. Pharmakologisches Institut der Universitat Mainz, Germany. Following the subcutaneous (s.c.) administration of nicotinamide (10 mmol/kg), the brain and CSF levels of nicotinamide were increased to millimolar concentrations, but the concentrations of N-methylnicotinamide (NMN) in the CSF, and of NMN and NAD+ in brain tissue were not significantly altered. Concomitantly, nicotinamide caused increases of the choline levels in the venous brain blood. In hippocampal slices, nicotinamide (1-10 mM) induced choline release in a calcium- and mepacrine-sensitive manner and, in [3H]choline-labelled slices, increased the levels of [3H]lyso-phosphatidylcholine and [3H]glycerophosphocholine. We conclude that nicotinamide enhances brain choline concentrations by mobilising choline from choline-containing phospholipids, presumably via activation of phospholipase A2, while the formation of NMN does not contribute to this effect. PMID: 9682829 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=29163