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

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