Neurotransmitters
1. Dietary precursors and brain neurotransmitter formation.
Fernstrom JD.
Annu Rev Med (UNITED STATES) 1981, 32 p413-25
The rates of synthesis of serotonin, acetylcholine, and, under certain
circumstances, dopamine and norepinephrine by brain neurons depend considerably
on the availability to brain of the respective dietary precursors. This
precursor dependence seems to be related to the fact that the enzyme catalyzing
the rate-limiting step in the synthetic pathway for each transmitter is
unsaturated with substrate at normal brain concentrations. Moreover, brain
levels of the individual precursors rise following oral or parenteral
administration of the pure compound or the ingestion of certain foods.
Precursor-induced increases in brain transmitter formation seem to influence
a variety of brain functions and behaviors, which suggests that transmitter
release has been enhanced. It now appears that these precursors may become
useful as therapeutic agents for the treatment of selected disease states,
wherein the disease is related to reduced release of transmitter. Examples
of Parkinson's disease (tyrosine), myasthenia gravis (choline or phosphatidylcholine),
depression (tyrosine), and possibly abnormal appetite (tryptophan). Perhaps
the future will bring the identification of still other neurotransmitters,
whose rates of synthesis depend on precursor availability. Two potential
candidates for which some information is already available are glycine
(a spinal cord transmitter) and the prostaglandins (some of which may
function as neuromodulators or transmitters) (48, 49). Each time a new
precursor- product relationship is described, an opportunity becomes available
for determining whether the precursor might be useful in treating disease
states related to reduced transmitter release by neurons. The opportunities
are worth exploring, since the use of a natural dietary constituent, even
in purified form, is likely to produce fewer unwanted side-effects than
are seen following administration of synthetic drugs.
2. Behavioral effects of dietary neurotransmitter precursors: Basic and
clinical aspects
Young SN.
Neuroscience and Biobehavioral Reviews (USA), 1996, 20/2 (313 323)
The levels and possibly function of several neurotransmitters can be
influenced by the supply of their dietary precursors. The neurotransmitters
include serotonin, dopamine, noradrenaline, histamine, acetylcholine and
glycine, which are formed from tryptophan, tyrosine, histidine, choline
and threonine. Tryptophan has been tested more than the other precursors
in clinical trials and is currently available in some countries for the
treatment of depression. Other uses for tryptophan and the therapeutic
potential of other neurotransmitter precursors have not been tested adequately.
Given the relative lack of toxicity of dietary components, further clinical
trials with neurotransmitter precursors should be carried out.
3. Precursor control of neurotransmitter synthesis.
Wurtman RJ, Hefti F, Melamed E.
Pharmacol Rev. 1980 Dec;32(4):315-35.
Studies performed during the past decade have shown that the rates at
which
certain neurons produce and release their neurotransmitters can be affected
by
precursor availability, and thus by the changes in plasma composition
that occur
after ingestion of the precursors in purified form or as constituents
of foods.
Thus, tryptophan administration or a plasma ratio of tryptophan to other
large
neutral amino acids, thereby raising brain tryptophan levels, increasing
the
substrate saturation of tryptophan hydroxylase, and accelerating the synthesis
and release of serotonin. Tyrosine administration or a high-protein meal
similarly elevates brain tyrosine and can accelerate catecholamine synthesis
in
the CNS and sympathoadrenal cells, while the consumption of lecithin or
choline
increases brain choline levels and neuronal acetylcholine synthesis. The
physiologic and biochemical mechanisms that must exist in order for nutrient
consumption to affect neurotransmitte synthesis have been characterized
and
include: 1) the lack of significant feedback control of plasma levels
of the
precursor; 2) the lack of a real "bloodbrain barrier" for the
precursor, i.e.
the ability of the plasma level of the precursor to control its influx
into, or
efflux from, the CNS; 3) the existence of a low-affinity (and thus unsaturated)
transport system mediating the flux of the precursor between blood and
brain; 4)
low-affinity kinetics for the enzyme that initiates the conversion of
the
precursor to the transmitter; and, 5) the lack of end-product inhibition
of the
enzyme, in vivo, by its ultimate product, the neurotransmitter. The extent
to
which neurotransmitter synthesis in any particular aminergic neuron happens
to
be affected by changes in the availability of its precursor probably varies
directly with the neuron's firing frequency. This relationship allows
precursor
administration to produce selective physiologic effects by enhancing
neurotransmitter release from some but not all of the neurons potentially
capable of utilizing the precursor for this purpose. It also allows the
investigator to predict when administering the precursor might be useful
for
amplifying a physiologic process, or for treating a pathologic state.
(for
example, tyrosine administration raises blood pressure in hypotensive
rats,
lowers it in hypertensive animals, and has little effect on blood pressure
in
normotensive animals; the elevation in blood pressure probably reflects
enhanced catecholamine release from sympathoadrenal cells, while the reduction
in hypertensive animals probably results from increased catecholamine
release within the brain-stem.) Such predictions are now being tested
clinically in many institution. Available evidence suggests that lecithin
or choline administration can diminish the frequency of abnormal movements
in patients with tardive dyskinesia.
Nutrition
4. Choline and human nutrition
Zeisel SH, Blusztajn JK.
ANNU. REV. NUTR. (USA), 1994, 14:269-296
Choline is crucial for sustaining life. It modulates the basic signaling
processes within cells, is a structural element in membranes, and is vital
during critical periods in brain development. Choline metabolism is closely
interrelated with the metabolism of methionine and folate. We believe
that the normal human diet provides sufficient choline to sustain healthy
organ function. However, vulnerable populations may become choline deficient,
including the growing infant, the pregnant or lactating woman, the cirrhotic,
and the patient fed intravenously. Further studies of choline requirements
in these groups are required.
Liver
5. Choline may be an essential nutrient in malnourished patients with
cirrhosis
Chawla RK, Wolf DC, Kutner MH, Bonkovsky HL.
GASTROENTEROLOGY (USA), 1989, 97/6 (1514-1520)
Elemental diets designed for nutritional support in protein-calorie malnutrition
are often deficient in choline, a nonessential nutrient. Previously, malnourished
patients on these diets were found to be at risk of developing plasma
choline deficiency. We have now estimated the prevalence of this deficiency
by determining fasting plasma levels of choline among cirrhotic and noncirrhotic
malnourished male subjects maintained on regular hospital mixed food or
elemental parenteral and enteral formulas. Plasma choline concentrations
(microM, average plus or minus SD) were as follows: (i) mixed foods, 11.3
plus or minus 4.3 for cirrhotic (n = 22) and 9.3 plus or minus 2.4 for
noncirrhotic (n = 12) patients; (ii) parenteral formula, 5.3 plus or minus
1.6 for cirrhotic (n = 5) and 8.6 plus or minus 5.2 for noncirrhotic (n
= 16) subjects; and (iii) enteral formula, 6.1 plus or minus 1.2 for cirrhotic
(n = 5) and 11.7 plus or minus 1.9 for noncirrhotic (n = 4) subjects.
The level for healthy normal subjects eating mixed foods was 12.0 plus
or minus 2.2. The prevalence of plasma choline deficiency, i.e. plasma
levels greater than or equal to2 SD below the normal average, was as follows:
parenteral formula, all cirrhotic and 10 of 16 noncirrhotic subjects;
enteral formula, all cirrhotic and none of the noncirrhotic subjects.
The reversibility of choline deficiency was examined in a longitudinal
study of three phases involving 10 patients - 5 with alcoholic cirrhosis
(all on enteral formula); 5 noncirrhotic (1 on enteral and 4 on parenteral
formula). During phase 1 (3-day equilibration period; ad libitum regular
hospital diet), plasma choline levels were within the normal range for
all subjects. During phase 2 (2 wk, choline depletion phase, elemental
formulas), choline levels were subnormal in all cirrhotic subjects (5.1
2+ 2.0 microM) on enteral formula and all noncirrhotic patients on parenteral
formula (5.9 plus or minus 1.3 microM). During phase 3 (2 wk, choline
repletion phase, elemental formula + 6 g choline/day), the levels normalized
in all patients (cirrhotic 11.4 plus or minus 3.1 microM and noncirrhotic
11.9 plus or minus 3.2 microM). Analyses of abdominal computed tomographic
scans and plasma liver chemistries in the cirrhotic subjects during the
three phases suggested a correlation between plasma choline deficiency
and hepatic steatosis and abnormal liver enzyme levels in some patients.
Therefore, choline may be an essential nutrient in malnourished cirrhotic
patients and its deficiency may be associated with adverse hepatic effects.
6. Male rats fed methyl and folate deficient diets with or without niacin
develop hepatic carcinomas associated with decreased tissue NAD concentrations
and altered poly(ADP ribose) polymerase activity
Henning SM, Swendseid ME, Coulson WF.
Journal of Nutrition (USA), 1997, 127/1 (30 36)
Folate is an essential cofactor in the generation of endogenous methionine,
and there is evidence that folate deficiency exacerbates the effects of
a diet low in choline and methionine, including alterations in poly(ADP
ribose) polymerase (PARP) activity, an enzyme associated with DNA replication
and repair. Because PARP requires NAD as its substrate, we postulated
that a deficiency of both folate and niacin would enhance the development
of liver cancer in rats fed a diet deficient in methionine and choline.
In two experiments, rats were fed choline and folate deficient, low methionine
diets containing either 12 or 8% casein (12% MCFD, 8% MCFD) or 6% casein
and 6% gelatin with niacin (MCFD) or without niacin (MCFND) and were compared
with folate supplemented controls. Liver NAD concentrations were lower
in all methyl deficient rats after 2 17 mo. At 17 mo, NAD concentrations
in other tissues of rats fed these diets were also lower than in controls.
Compared with control values, liver PARP activity was enhanced in rats
fed the 12% MCFD diet but was lower in MCFND fed rats following a further
reduction in liver NAD concentration. These changes in PARP activity associated
with lower NAD concentrations may slow DNA repair and enhance DNA damage.
Only rats fed the MCFD and MCFND diets developed hepatocarcinomas after
12 17 mo. In Experiment 2, hepatocarcinomas were found in 100% of rats
fed the MCFD and MCFND diets. These preliminary results indicate that
folic acid deficiency enhances tumor development. Because NAD in these
animals was also low, further studies are needed to clearly define the
role of niacin in methyldeficient rats.
Memory
7. Habituation of exploratory activity in mice: effects of combinations
of piracetam and choline on memory processes.
Platel A, Jalfre M, Pawelec C, Roux S, Porsolt RD.
Pharmacol Biochem Behav (UNITED STATES) Aug 1984, 21 (2) p209-12
The effects of various piracetam + choline combinations on an experimental
model of memory were investigated. Mice were given two sessions in a simple
photo-cell activity cage and the decrease in activity at the second session
(habituation) served as an index of retention. Retention was facilitated
by post-session administration of 2000 mg/kg piracetam IP and 50 mg/kg
piracetam + 50 mg/kg choline IP. Similar injections of choline alone (10
to 200 mg/kg IP), piracetam alone (10 to 1000 mg/kg IP) or other combinations
of piracetam and choline were without ffect. These results, consistent
with those reported elsewhere, suggest that piracetam can interact with
choline to facilitate memory processes.
8. Profound effects of combining choline and piracetam on memory enhancement
and cholinergic function in aged rats.
Bartus RT, Dean RL 3rd, Sherman KA, Friedman E, Beer B.
Neurobiol Aging (UNITED STATES) Summer 1981, 2 (2) p105-11
In an attempt to gain some insight into possible approaches to reducing
age-related memory disturbances, aged Fischer 344 rats were administered
either vehicle, choline, piracetam or a combination of choline or piracetam.
Animals in each group were tested behaviorally for retention of a one
trial passive avoidance task, and biochemically to determine changes in
choline and acetylcholine levels in hippocampus, cortex and striatum.
Previous research has shown that rats of this strain suffer severe age-related
deficits on this passive avoidance task and that memory disturbances are
at least partially responsible. Those subjects given only choline (100
mg/kg) did not differ on the behavioral task from control animals administered
vehicle. Rats given piracetam (100 mg/kg) performed slightly better than
control rats (p less than 0.05), but rats given the piracetam/choline
combination (100 mg/kg of each) exhibited retention scores several times
better than those given piracetam alone. In a second study, it was shown
that twice the dose of piracetam (200 mg/kg) or choline (200 mg/kg) alone,
still did not enhance retention nearly as well as when piracetam and choline
(100 mg/kg of each) were administered together. Further, repeated administration
(1 week) of the piracetam/choline combination was superior to acute injections.
Regional determinations of choline and acetylcholine revealed interesting
differences between treatments and brain area. Although choline administration
raised choline ontent about 50% in striatum and cortex, changes in acetylcholine
levels were much more subtle (only 6-10%). No significant changes following
choline administration were observed in the hippocampus. However, piracetam
alone markedly increased choline content in hippocampus (88%) and tended
to decrease acetylcholine levels (19%). No measurable changes in striatum
or cortex were observed following piracetam administration. The combination
of choline and piracetam did not potentiate the effects seen with either
drug alone, and in certain cases the effects were much less pronounced
under the drug combination. These data are discussed as they relate to
possible effects of choline and piracetam on cholinergic transmission
and other neuronal function, and how these effects may reduce specific
memory disturbances in aged subjects. The results of these studies demonstrate
that the effects of combining choline and piracetam are quite different
than those obtained with either drug alone and support the notion that
in order to achieve substantial efficacy in aged subjects it may be necessary
to reduce multiple, interactive neurochemical dysfunctions in the brain,
or affect activity in more than one parameter of a deficient metabolic
pathway.
9. Verbal and visual memory improve after choline supplementation in long-term
total parenteral nutrition: a pilot study.
Buchman AL, Sohel M, Brown M, Jenden DJ, Ahn C, Roch M, Brawley TL.
Division of Gastroenterology and Hepatology, Northwestern University,
Chicago,
Illinois 60611, USA. a-buchman@nwu.edu
JPEN J Parenter Enteral Nutr. 2001 Jan-Feb;25(1):30-5.
BACKGROUND: Previous investigations have demonstrated that choline deficiency,
manifested in low plasma-free choline concentration and hepatic injury,
may develop in patients who require long-term total parenteral nutrition
(TPN). Preliminary studies have suggested lecithin or choline supplementation
might lead to improved visual memory in the elderly and reverse abnormal
neuropsychological development in children. We sought to determine if
choline-supplemented TPN would lead to improvement in neuropsychological
test scores in a group of adult, choline-deficient outpatients receiving
TPN.
METHODS: Eleven subjects (8 males, 3 females) who received nightly TPN
for more than 80% of their nutritional needs for at least 12 weeks before
entry in the
study were enrolled. Exclusion criteria included active drug abuse, mental
retardation, cerebral vascular accident, head trauma, hemodialysis or
peritoneal
dialysis, (prothrombin time [PT] >2x control), or acquired immune deficiency
syndrome (AIDS). Patients were randomly assigned to receive their usual
TPN
regimen (n = 6, aged 34.0 +/- 12.6 years) over a 12-hour nightly infusion
or
their usual TPN regimen plus choline chloride (2 g) (n = 5, aged 37.3
+/- 7.3
years). The following neuropsychological tests were administered at baseline
and
after 24 weeks of choline supplementation (or placebo): Weschler Adult
Intelligence Scale-Revised (WAIS-R, intellectual functioning), Weschler
Memory
Scale-Revised (WMS-R, two subtests, verbal and visual memory), Rey-Osterrieth
Complex Figure Test (visuospatial functioning and perceptual organization),
Controlled Oral Word Association Test (verbal fluency), Grooved Pegboard
(manual dexterity and motor speed), California Verbal Learning Test (CVLT,
rote verbal learning ability), and Trail Making Parts A & B (visual
scanning, psychomotor speed and set shifting). Scores were reported in
terms of standard scores including z scores and percentile ranks. Mean
absolute changes in raw scores were compared between groups using the
Wilcoxon rank sum test, where p values < .05 constituted statistical
significance. RESULTS: Significant improvements were found in the delayed
visual recall of the WMS-R (7.0 +/- 2.7 vs -.33 +/- 5.7, p = .028), and
borderline improvements in the List B subset of the CVLT (1.0 +/- 0.8
vs -2.0 +/- 2.4, p = .06) and the Trails A test (-3.8 +/- 8.1 vs 3.7 +/-
4.5 seconds, p = .067). No other statistically significant changes were
seen.
CONCLUSIONS: This pilot study indicates both verbal and visual memory
may be impaired in patients who require long-term TPN and both may be
improved with choline supplementation.
Cholinergic neurons
10. Choline and cholinergic neurons.
Blusztajn JK, Wurtman RJ.
Science. 1983 Aug 12;221(4611):614-20.
Mammalian neurons can synthesize choline by methylating phosphatidylethanolamine
and hydrolyzing the resulting phosphatidylcholine. This process is stimulated
by
catecholamines. The phosphatidylethanolamine is synthesized in part from
phosphatidylserine; hence the amino acids methionine (acting after conversion
to
S-adenosylmethionine) and serine can be the ultimate precursors of choline.
Brain choline concentrations are generally higher than plasma concentrations,
but depend on plasma concentrations because of the kinetic characteristics
of
the blood-brain-barrier transport system. When cholinergic neurons are
activated, acetylcholine release can be enhanced by treatments that increase
plasma choline (for example, consumption of certain foods).
11. Free choline and choline metabolites in rat brain and body fluids:
sensitive determination and implications for choline supply to the brain.
Klein J, Gonzalez R, Koppen A, Loffelholz K.
Department of Pharmacology, University of Mainz, Germany.
Neurochem Int. 1993 Mar;22(3):293-300.
In the central nervous system, choline is an essential precursor of
choline-containing phospholipids in neurons and glial cells and of acetylcholine
in cholinergic neurons. In order to study choline transport and metabolism
in
the brain, we developed a comprehensive methodical procedure for the analysis
of choline and its major metabolites which involves a separation step,
selective
hydrolysis and subsequent determination of free choline by HPLC and
electrochemical detection. In the present paper, we report the levels
of
choline, acetylcholine, phosphocholine, glycerophosphocholine and
choline-containing phospholipids in brain tissue, cerebrospinal fluid
and blood
plasma of the untreated rat. The levels of free choline in blood plasma
(11.4
microM), CSF (6.7 microM) and brain intracellular space (64.0 microM)
were
sufficiently similar to be compatible with an exchange of choline between
these
compartments. In contrast, the intracellular levels of glycerophosphocholine
(1.15 mM) and phosphocholine (0.59 mM) in the brain were considerably
higher
than their CSF concentrations of 2.83 and 1.70 microM, respectively. In
blood
plasma, glycerophosphocholine was present in a concentration of 4.58 microM
while phosphocholine levels were very low or absent (< 0.1 microM).
The levels
of phosphatidylcholine and lyso-phosphatidylcholine were high in blood
plasma
(1267 and 268 microM) but very low in cerebrospinal fluid (< 10 microM).
We
concluded that the transport of free choline is the only likely mechanism
which
contributes to the supply of choline to the brain under physiological
conditions.
Acetylcholine
12. Brain acetylcholine: control by dietary choline.
Cohen EL, Wurtman RJ.
Science. 1976 Feb 13;191(4227):561-2.
Acetylcholine concentrations in whole rat brain or in various brain regions
and
free choline concentrations in blood serum and brain vary with dietary
choline
consumption. The increases in brain acetylcholine after treatment with
physositigmine (an inhibitor of actylcholinesterase) or after consumption
of a
diet high in choline are additive, suggesting that choline acts by increasing
acetylcholine synthesis.
Neurochemical effects
13. Neurochemical effects of choline supplementation.
Wecker L.
Can J Physiol Pharmacol. 1986 Mar;64(3):329-33.
Whether or not the brain can use supplemental choline to enhance the
synthesis
of acetylcholine (ACh) is an important consideration for assessing the
merits of
using choline or phosphatidylcholine (lecithin) for the treatment of
neuropsychiatric disorders postulated to involve hypocholinergic activity.
While
it is well documented that administered choline is incorporated into ACh,
the
ability of supplemental choline to increase the synthesis and release
of ACh has
been questionable. Studies in my laboratory have demonstrated that acute
or
chronic choline supplementation does not, by itself, enhance the levels
of ACh
in brain under normal biochemical and physiological conditions. However,
supplemental choline prevents the depletion of ACh in brain induced by
numerous pharmacological agents that increase the firing of cholinergic
neurons. Since the levels of free choline in brains from supplemented
rats were not different from controls prior to drug challenge, evidence
suggested that the observed effects of choline were mediated by alterations
in the mobilization of choline from choline-containing compounds. Studies
investigating the release of choline from brain indicated that more choline
was released per unit time in tissues from choline-supplemented rats than
from controls. In addition, brain tissue from choline-supplemented rats
had increased concentrations of total lipid
phosphorus as compared with controls. Hence, although choline supplementation
does not alter the levels of ACh in brain under normal conditions, it
does appear to support ACh synthesis during drug-induced increases in
neuronal activity, an effect most likely mediated by alterations in the
metabolism of choline-containing phospholipids.
Decreased in older adults
14. Decreased brain choline uptake in older adults. An in vivo proton
magnetic
resonance spectroscopy study.
Cohen BM, Renshaw PF, Stoll AL, Wurtman RJ, Yurgelun-Todd D, Babb SM.
Brain Imaging Center, McLean Hospital, Belmont, MA 02178, USA.
JAMA. 1995 Sep 20;274(11):902-7.
OBJECTIVE--To test the hypothesis that uptake of circulating choline
into the
brain decreases with age, because alterations in metabolism of choline
may be a
factor contributing to age-related degenerative changes in the brain.
DESIGN--Cohort comparison in younger and older adults. PARTICIPANTS—Subjects
were chosen consecutively from lists of healthy volunteers screened by
medical and psychiatric interviews and laboratory tests. Younger adults
(n = 12) were between the ages of 20 and 40 years (mean age, 32 years),
and older adults (n = 16) were between the ages of 60 and 85 years (mean
age, 73 years).
INTERVENTIONS--After fasting overnight, subjects received choline, as
the
bitartrate, to yield free choline equal to 50 mg/kg of body weight. Blood
was
drawn for determination of plasma choline concentration by high-performance
liquid chromatography, and proton magnetic resonance spectroscopy (1H-MRS)
was performed to determine the relative concentration of cytosolic
choline-containing compounds in the brain at baseline and after ingestion
of
choline. MAIN OUTCOME MEASURES--Plasma choline and cytosolic choline-containing
compounds in the brain, estimated as the ratio of the choline resonance
to the creatine resonance on 1H-MRS scans of the basal ganglia, were compared
following blinded analyses of data from subject cohorts studied at baseline
and 3 hours after choline ingestion. RESULTS--Levels of plasma choline
and cytosolic choline-containing compounds in brain were similar at baseline
in younger and older subjects. Following ingestion of choline, plasma
choline concentration increased by similar proportions (76% and 80%) in
both younger and older subjects. Brain cytosolic choline--containing compounds
increased substantially in younger subjects (mean increase, 60%; P <
.001 vs baseline). Older subjects showed a much smaller increase in brain
choline-containing compounds (mean, 16%; P < .001 vs the increase in
younger subjects). CONCLUSION--Uptake of circulating choline into the
brain decreases with age. Given the key role of choline in neuronal structure
and function, this change may be a contributing factor in onset in late
life of neurodegenerative, particularly dementing, illnesses in which
cholinergic neurons show particular susceptibility to loss.
PREVENTION OF MEMORY LOSS FROM GESTATION
15. Metabolic imprinting of choline by its availability during gestation:
implications for memory and attentional processing across the lifespan.
Meck WH, Williams CL.
Department of Psychological and Brain Sciences, Duke University, 9 Flowers
Drive, Box 90086, 27708-0086, Durham, NC, USA
Neurosci Biobehav Rev. 2003 Jun;27(4):385-99.
A growing body of research supports the view that choline is an essential
nutrient during early development that has long-lasting effects on memory
and attentional processes throughout the lifespan. This review describes
the known effects of alterations in dietary choline availability both
in adulthood and during early development. Although modest effects of
choline on cognitive processes have been reported when choline is administered
to adult animals, we have found that the perinatal period is a critical
time for cholinergic organization of brain function. Choline supplementation
during this period increases memory capacity and
precision of the young adult and appears to prevent age-related memory
and attentional decline. Deprivation of choline during early development
leads to compromised cognitive function and increased decline with age.
We propose that this organizational effect of choline availability may
be due to relatively permanent alterations in the functioning of the cholinergic
synapse, which we have called 'metabolic imprinting'.
REDUCES URINARY CARNITINE EXCRETION
16. Choline supplementation reduces urinary carnitine excretion in humans.
Dodson WL, Sachan DS.
Department of Nutrition, University of Tennessee, Knoxville 37996-1900,
USA.
Am J Clin Nutr. 1996 Jun;63(6):904-10.
Comment in:
Am J Clin Nutr. 1997 Feb;65(2):574-5.
Two experiments were conducted to determine the effects of supplementary
choline and/or pantothenate on the carnitine and lipid status of free-living
humans. Analyses of carnitine and cholesterol fractions, triacylglycerols,
and creatinine were determined in serum and/or urine. In experiment 1,
adults receiving 13.5 mmol choline plus 1.4 mmol pantothenate/d had a
significant decline in urinary carnitine excretion and renal clearance
with nonesterfied carnitine (NEC) declining the most dramatically, 84%.
Additionally, serum NEC and total carnitine concentrations decreased significantly.
No changes were observed in any of the serum lipids examined. In experiment
2, subjects took 0.20 mmol and 0.02 mmol/kg choline or pantothenate, respectively.
Choline, but not pantothenate, supplementation significantly decreased
urinary carnitine excretion, renal clearance, and fractional clearance
of NEC. We conclude that supplementary choline maintained serum carnitine
concentrations by conserving urinary carnitine. Moreover, these observations
merit additional investigation to determine metabolic and functional consequences
of choline and carnitine interactions in humans.
17. J Nutr. 2003 Jan;133(1):84-9.
Carnitine and choline supplementation with exercise alter carnitine profiles,
biochemical markers of fat metabolism and serum leptin concentration in
healthy women.
Hongu N, Sachan DS.
Department of Nutrition and Agricultural Experiment Station, The University
of Tennessee, Knoxville, TN 37996-1900, USA.
We sought to determine the effects of supplementary choline, carnitine
and a combination of the two with or without exercise on serum and urinary
carnitine and biochemical markers of fatty acid oxidation in healthy humans.
Nineteen women were placed in three groups: 1) placebo, choline or carnitine
preloading period of 1 wk followed by 2) supplementation with choline
plus carnitine during wk 2-wk 3 and 3) all groups exercised in wk 3. Although
there were no changes in the placebo group, serum and urinary carnitine
decreased in the choline-supplemented group during wk 1. Introduction
of carnitine to the choline group restored serum and urinary carnitine.
Serum and urinary carnitine increased during wk 1 in the carnitine-supplemented
group and, although the introduction of choline to this group depressed
serum and urinary carnitine, they remained significantly greater than
control. Serum beta-hydroxybutyrate and serum as well as urinary acetylcarnitine
were elevated by the supplements. A mild exercise regimen increased the
concentration of serum beta-hydroxybutyrate, and serum and urinary acylcarnitines;
it also decreased serum leptin concentrations in all groups. The effects
of supplements were sustained until wk 2 after cessation of choline plus
carnitine supplementation and exercise. We conclude that the choline-induced
decrease in serum and urinary carnitine is buffered by carnitine preloading,
and these supplements shift tissue partitioning of carnitine that favors
fat mobilization, incomplete oxidation of fatty acids and disposal of
their carbons in urine as acylcarnitines in humans.
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