ArticlePDF AvailableLiterature Review

Choline: An Important Micronutrient for Maximal Endurance-Exercise Performance?

Abstract and Figures

Choline plays a central role in many physiological pathways, including neurotransmitter synthesis (acetylcholine), cell-membrane signaling (phospholipids), lipid transport (lipoproteins), and methyl-group metabolism (homocysteine reduction). Endurance exercise might stress several of these pathways, increasing the demand for choline as a metabolic substrate. This review examines the current literature linking endurance exercise and choline demand in the human body. Also reviewed are the mechanisms by which exercise might affect blood choline levels, and the links between methyl metabolism and the availability of free choline are highlighted. Finally, the ability of oral choline supplements to augment endurance performance is assessed. Most individuals consume adequate amounts of choline, although there is evidence that current recommendations might be insufficient for some adult men. Only strenuous and prolonged physical activity appears sufficient to significantly decrease circulating choline stores. Moreover, oral choline supplementation might only increase endurance performance in activities that reduce circulating choline levels below normal.
Content may be subject to copyright.
International Journal of Sport Nutrition and Exercise Metabolism, 2008, 18, 191-203 
© 2008 Human Kinetics, Inc.
The authors are with the Dept. of Nutrition and Exercise Sciences, Oregon State University, Corvallis,
OR 97331.
Choline: An Important Micronutrient
for Maximal Endurance-Exercise
Jason T. Penry and Melinda M. Manore
Choline plays a central role in many physiological pathways, including neurotrans-
mitter synthesis (acetylcholine), cell-membrane signaling (phospholipids), lipid
transport (lipoproteins), and methyl-group metabolism (homocysteine reduction).
Endurance exercise might stress several of these pathways, increasing the demand
for choline as a metabolic substrate. This review examines the current literature
linking endurance exercise and choline demand in the human body. Also reviewed
are the mechanisms by which exercise might affect blood choline levels, and the
links between methyl metabolism and the availability of free choline are high-
lighted. Finally, the ability of oral choline supplements to augment endurance
performance is assessed. Most individuals consume adequate amounts of choline,
although there is evidence that current recommendations might be insufficient
for some adult men. Only strenuous and prolonged physical activity appears suf-
ficient to significantly decrease circulating choline stores. Moreover, oral choline
supplementation might only increase endurance performance in activities that
reduce circulating choline levels below normal.
Keywords: betaine, lecithin, homocysteine, folate, MTHFD1, review
Choline is a micronutrient important for health in all people, from the sedentary
individual to the elite athlete. The consequences of long-term choline deficiency
have been well documented since the early 1900s, including steatosis (fatty liver)
and death (Best & Huntsman, 1932). Moreover, recent work has shown that up to
half the population might have a genetic allele related to an increased susceptibil-
ity to choline deficiency (Kohlmeier, da Costa, Fischer, & Zeisel, 2005). Thus, an
applied understanding of the role of choline in human metabolism could be very
important to a large segment of the population.
Choline is found in a variety of foods (Cho et al., 2006; see Table 1), and lim-
ited quantities of choline can be synthesized from endogenous sources (Zeisel &
Niculescu, 2005). As a result of this ubiquitous nature, it was previously thought
that rapid changes in blood choline concentrations did not occur. Current research
shows, however, that a strenuous exercise bout such as a marathon race can create
a significant, short-term decrease in “free” (non-membrane-bound) choline in the
Scholarly reviewS
192 Penry and Manore
Table 1 Choline and Betaine Content of Selected Foods and
Food or supplement Total choline (mg) Total betaine (mg)
Chicken liver (2 oz), pan fried 176 13
Large egg (2.5 oz), hard boiled 158 0.4
Pork chop (4 oz), pan broiled 112 3
Chicken breast (4 oz), roasted 75 9
Beer, pint (16 fluid oz) 47 38
Skim milk, one glass (8 fluid oz) 37 4
Medium white potato, baked 22 0.3
Firm tofu (2 oz), nigari 16 0.2
Spinach (2 oz), unprepared 13 385
Whole-wheat bread (1 oz), slice 7 98
Twinlab Choline Cocktail (choline
bitartrate), 8 oz prepared 1,500 0
Twinlab choline bitartrate, tablet 300 0
Jarrow Lecithin Mega-PC 35, 1 gel 114 0
Ultima Replenisher, 20 oz prepared 1 0
Twinlab betaine HCl, tablet 0 648
Centrum, 1 multivitamin 0 0
Note. Adapted from USDA database for the choline content of common foods (
foodcomp/Data/Choline/Choline.pdf, June 23, 2007) and product labels of included supplements.
blood (Table 2). One hypothesized mechanism for this decrease in free choline is
an increased demand for choline as a methyl-group donor during physiological
stress (Kanter & Williams, 1995). This acute drop in free choline during strenu-
ous exercise is subsequently thought to inhibit optimal muscle performance by
decreasing the amount of choline available for acetylcholine synthesis, thereby
inhibiting excitation–contraction coupling at the neuromuscular junction (Conlay,
Sabounjian, & Wurtman, 1992).
If reductions in free choline do affect other physiological variables related to
endurance performance (Conlay et al., 1992; da Costa, Badea, Fischer, & Zeisel,
2004), it is possible that supplementing this micronutrient during choline-depleting
exercise could benefit individuals engaged in such activities. No peer-reviewed stud-
ies have explored this hypothesis. Answers to this question might have implications
for any individual routinely placed under strenuous physical conditions, including
endurance athletes, participants in extreme sports, and military personnel.
This review examines the current research pertinent to the possible relationship
between choline intake and endurance performance, beginning with an outline of the
dietary sources of choline and normal intakes. Next, we explore the mechanisms by
which exercise might affect blood choline concentrations and highlight the possible
link between methyl metabolism and the availability of free choline in the blood. We
summarize research examining the link between free choline and physical exercise
in light of the increased demand for methyl groups with exercise. Finally, we assess
the ability of oral choline supplements to augment endurance performance.
Table 2 Effects of Endurance Exercise on Acute Free Blood Choline Concentrations
gender* Activity
(min) Intensity (% VO
post (nmol/mL)
Buchman et al., 1999 23 M + F marathon not given max effort 19.2† vs. 14.6 .005
Buchman et al., 2000 6 M + F marathon 156–348 max effort 9.6† vs. 7.0 .09
Burns et al., 1988 10 M cycle 120 70% (105 min) +
max effort (15 min) not given >.05
Conlay et al., 1986 17amarathon not given max effort 10.1‡ vs. 6.2 <.001
Deuster et al., 2002 13 M load carriage ~110 70% 8.5‡ vs. 6.5b>.05
Pierard et al., 2004 21 M combat course 7,200 ~35% 2.95% decrease† <.01
Spector et al., 1995 10 M cycle 72 70% 8.5† vs. 10.0b>.05
von Allwörden et al., 1993 4 M, 6 F cycle 120 35 km/hr 12.08‡ vs. 10.04 <.01
von Allwörden et al., 1993 10 M, 4 F cross-country run 30–60 max effort 14.51‡ vs. 14.95 >.05
Warber et al., 2000 14 M load carriage 240 38% 8.14‡ vs. 7.98 >.05
Note. M = male; F = female.
aGender of participants not disclosed in published paper. bEstimated from published figure.
194 Penry and Manore
Dietary Sources of Choline
The recommended adequate intake for choline is 550 mg/day in adult men and 425
mg/day in adult women (>19 years of age; Institute of Medicine [IOM], 1998).
Pregnant and lactating women require additional choline, up to 450 and 550 mg/
day, respectively (IOM), because large amounts of this nutrient are lost across the
placenta and in breast milk (Zeisel, Mar, Zhou, & da Costa, 1995). There is cur-
rently inadequate information to set a recommended dietary allowance (RDA) for
choline (IOM), although it appears that some men might require more than is cur-
rently recommended. In a study by Fischer et al. (2007), 6 of 26 male participants
developed symptoms of choline deficiency, including increased liver lipid content
and possible muscle-cell membrane damage, when fed a diet containing the current
adequate intake of 550 mg/day. Thus, it appears that additional research is needed
to better understand the dietary requirements of free-living individuals.
In the typical free-living diet, more than half the dietary choline demand is met
by consuming red meat, poultry, milk, eggs, and fish (Cho et al., 2006). Coffee, beer,
potatoes, and orange juice also contain significant amounts of choline (Cho et al.;
see Table 1). Fischer et al. (2005) allowed 32 individuals (16 men and 16 women
19–67 years of age) to consume food ad libitum from a metabolic kitchen and found
that most met meet the daily recommended adequate intake for choline, with men
consuming an average of 631 mg/day and women consuming 443 mg/day. The same
researchers then used a 3-day food record to indirectly monitor choline intake in the
same population and found values as low as 313 mg/day in both men and women.
These low intakes of choline were attributed to the underreporting of total energy
intake, which is common with food-recall records (Fischer et al., 2005).
Most dietary choline is consumed in the form of phosphatidylcholine, a primary
constituent of cell membranes (Cho et al., 2006). Choline can then be synthesized
de novo from phosphatidylcholine in the liver by phosphatidylethanolamine N-
methyltransferase (PEMT; Zeisel, 2006). PEMT activity is enhanced in individuals
when estrogen is present (Fischer et al., 2007), allowing for additional synthesis of
choline from physiological stores. Choline availability is paramount to a healthy
fetus, and it is possible that this mechanism acts to buffer a developing fetus against
dietary variability in choline consumption (Zeisel, 2006).
Betaine, a metabolic derivative of choline, is also consumed in the diet. Because
betaine plays a large role in regulating the osmotic balance in plants, it is found in
large concentrations in plant foods (Craig, 2004; see Table 1). Most betaine in the
diet comes from green leafy vegetables such as spinach (25% of the total choline
consumed) and grain-derived foods including pasta (12%), white bread (9%), and
cold cereal (8%; Cho et al., 2006). Although betaine cannot be converted directly
into choline, it can be used as a methyl donor in the same metabolic pathways and,
thus, reduces the amount of choline required by the body (Zeisel & Niculescu,
2005). As a result of this interrelated nature, researchers have begun to consider
the two nutrients together when determining the total amount of choline intake
per day (Cho et al.).
Information concerning the dietary intakes of choline and betaine is limited,
in part because of the previous lack of a valid database containing the choline and
betaine content of common foods (Cho et al., 2006). With the recent advent of such
Choline and Endurance Performance     195
a database, however, it appears that choline and betaine intakes can be adequately
measured by a semiquantitative food-frequency questionnaire (Cho et al.). In addi-
tion, a food-frequency questionnaire can accurately detect variance in consumed
choline and betaine in a free-living population (Cho et al.), a key factor in better
understanding choline and betaine intakes in humans.
Individuals can complement their dietary intake of choline via a large range
of supplements. Currently, most sport supplements contain choline in the form of
choline bitartrate, a choline salt that has been shown to affect free blood choline
concentrations within 45 min of ingestion (Spector et al., 1995). Another common
supplemental form of choline is lecithin, a compound that is ~35% phospatidylcho-
line when purchased at health-food stores (Zeisel, 1994). Lecithin appears to have
a larger (+265% vs. +86%) and more long-lasting (12 hr vs. 4 hr) impact on free
blood choline concentrations than do choline salts (Wurtman, Hirsch, & Growden,
1977). Lecithin, however, has not been used in studies in which individuals receive
supplementation during physical activity, which might be because of the small
percentage of choline found in lecithin.
In recent years, a number of choline-derived compounds such as cytidine
5-diphosphocholine (CDP-choline) and alphaglyceryl-phosphorylcholine (alpha-
GPC) have been used to successfully treat cognitive impairment in dementia dis-
orders when phosphatidylcholine supplementation has been ineffective (Parnetti,
Mignini, Tomassoni, Traini, & Amenta, 2007). Both CDP-choline and alpha-GPC
are intermediary metabolites in the metabolic synthesis of phosphatidylcholine from
choline (Deuster & Cooper, 2005), but it is currently unknown why CDP-choline
and alpha-GPC are effective in treating such disorders but phosphatidylcholine is
not (Parnetti et al.). It is possible that there is a similar form-specific effect when
supplementing athletes, but no study to date has examined the effect of supplement-
ing these metabolites in an athletic population. Additional research is necessary to
determine which form of supplemental choline might have the greatest performance
effect for strenuous physical activity.
Choline Physiology
The role of choline in the body is complex; it plays both a functional and a struc-
tural role in cells. Free choline can be found inside cells or circulating in the blood;
choline in this form plays an important role in providing a substrate for cellular pro-
cesses including acetylcholine synthesis and methyl-group metabolism (Deuster &
Cooper, 2005). Normal concentrations of free choline are 10–15 nmol/ml, although
this value can be significantly higher after choline supplementation (Burns, Cos-
till, & Fink, 1988). Alternatively, bound choline refers to choline in its structural
role, incorporated into cell membranes (as phosphatidylcholine), lipoproteins,
cell-signaling proteins, or other biological molecules (Deuster & Cooper). Blood
baseline values for phospholipid-bound choline range from 2,000 to 2,500 nmol/ml
(Buchman, Awal, Jenden, Roch, & Kang, 2000; Buchman, Jenden, & Roch, 1999).
It is possible to exchange free and bound choline, because phosphatidylcholine is
synthesized from free choline in the liver (Zeisel & Niculescu, 2005) and phospha-
tidylcholine is hydrolyzed to form choline in cholinergic neurons (Zhao, Frohman,
& Blusztajn, 2001).
196 Penry and Manore
Choline Utilization During Exercise
Choline metabolism during exercise might be altered through a number of hypoth-
esized mechanisms that are discussed as follows.
Acetylcholine Synthesis
Free choline concentrations are of particular interest to exercise physiologists,
because reduced concentrations of free choline have been associated with weak-
ened impulse transmission and impaired performance in skeletal muscle (Conlay et
al., 1992). Because choline is an important building block of the neurotransmitter
acetylcholine, it is not surprising that reductions in free choline result in an acute
decline in acetylcholine synthesis (Bierkamper & Goldberg, 1980; Maire & Wurt-
man, 1985). This reduction in acetylcholine production can have a marked influence
on muscle performance, because it inhibits the ability of the α-motor neuron to
communicate with the motor end plate in muscle excitation–contraction coupling
(Conlay et al., 1992). Reduced acetylcholine availability might also impair neuron
function in the brain, but the degree to which free choline concentrations influence
cognitive performance in adults is not clear (Deuster, Singh, Coll, Hyde, & Becker,
2002; Pierard et al., 2004).
Cell-Membrane Integrity
Choline can also be incorporated as a phospholipid (phosphatidylcholine) in cell
membranes. Prolonged choline deficiencies cause the body to mobilize the phospha-
tidylcholine located in its own cell membranes, compromising membrane integrity
and allowing intramembranous materials to leak into the surrounding fluid (da
Costa et al., 2004). In fact, the increased amount of serum creatine phosphokinase
that leaks from porous muscle-cell membranes has been suggested as a diagnostic
tool for choline deficiency (da Costa et al.). Stripping muscle-cell membranes of
phospholipids also reduces the mechanical stress these cells can withstand (da Costa
et al.), resulting in muscle damage that might be associated with muscle fatigue
similar to that induced by reduced acetylcholine availability.
Methyl-Group Metabolism
Methionine, an essential amino acid, is used as a methyl-group donor in many
metabolic reactions. After donating its methyl group, methionine is metabolized to
homocysteine (Figure 1). Homocysteine is an extremely bioreactive molecule and
has been identified as a major contributor to endothelial damage and cardiovascular
disease (Refsum & Ueland, 1998). To “recycle” homocysteine into methionine, a
methyl-group donor must be used.
There are two pathways for the conversion of homocysteine to methionine
(Olthof, Brink, Katan, & Verhoef, 2005). The first uses methyl tetrahydrofolate
(methyl-THF) as the methyl donor and is catalyzed by the enzyme methionine syn-
thase (MS). The alternative homocysteine–methionine pathway uses betaine as the
methyl donor and is catalyzed by the enzyme betaine-homocysteine S-methyltrans-
ferase (BHMT). Betaine is synthesized from choline in a nonreversible oxidation
Choline and Endurance Performance     197
reaction (Olthof et al.). As stated previously, betaine can also be consumed in foods
(Cho et al., 2006), and dietary betaine appears to be more efficient than dietary
choline in its ability to convert homocysteine to methionine (Olthof et al.).
Both the MS and BHMT pathways operate simultaneously, but certain con-
ditions can cause the body to favor one pathway over the other. Folate plays an
important role in the performance of the MS pathway, and cells with low folate
availability will show reduced MS activity (Fiskerstrand, Ueland, & Refsum, 1997).
It is not surprising that activity of the BHMT pathway must also be increased
under reduced folate concentrations to maintain stable homocysteine concentra-
tions (Jacob, Jenden, Allman-Farinelli, & Swendseid, 1999), thus placing a greater
demand on physiological betaine stores (Trimble, Molloy, Scott, & Weir, 1993).
Recent research has shown that up to half the population might carry an allele for
a less effective methyl-THF dehydrogenase (MTHFD1 1958A; Kohlmeier et al.,
2005), indicating that some individuals might require higher amounts of dietary
folate to minimize BHMT activity and spare available choline (Kohlmeier et al.,
2005). Unfortunately, there is no inexpensive and quick method to determine
whether an individual carries the MTHFD1 1958A allele.
Another factor that might influence the degree to which the body uses the
BHMT pathway is the quantity of methyl metabolism that must be carried out in
the liver. Blood homocysteine concentrations are attenuated after a methionine load
when supplemented with betaine or phosphatidylcholine but not when supplemented
with folate (Olthof et al., 2005). Thus, the body might use the BHMT pathway more
when homocysteine production is high (and the demand for methyl metabolism is
Figure 1A brief overview of methionine-homocysteine methyl metabolism. Note the two
pathways used to recycle homocysteine to methionine: the choline-dependent BHMT pathway
on the left and the folate-dependent MS pathway on the right. Adapted from Olthof et al.
198 Penry and Manore
high), such as during strenuous endurance exercise (Herrmann et al., 2003; Konig et
al., 2003). No research to date has examined this possible link between an increase
in blood homocysteine and any change in free choline concentrations.
Fluid Redistribution
Transient shifts in fluid between the bloodstream and interstitial space might inter-
fere with the ability to detect changes in free choline in the bloodstream during
exercise (Kanter & Williams, 1995). Researchers must take this factor into account
when designing experiments. Otherwise, choline utilization during exercise might
appear greater than it actually is because of the redistribution of free choline stores
dissolved in the interstitial fluid.
Changes in Free Choline Concentrations
With Exercise
Generally, research has shown that free choline concentrations decrease during
intense endurance exercise (Table 2). The impact of exercise on free choline con-
centrations was first described by Conlay et al. (1986), who observed a significant
decrease in free choline concentrations (40% decrease, p < .001) from prerace to
postrace in marathon runners. Later, von Allwörden, Horn, Kahl, and Feldheim
(1993) observed significant decreases in free choline concentrations in triathletes
cycling for 2 hr at 35 km/hr, and Buchman et al. (1999) measured significant
decreases in a second cohort of marathon runners. Pierard et al. (2004) also noted
significant reductions in free choline in military cadets after they completed a 5-
day combat-training course.
Not all types of exercise, however, have been shown to elicit a significant
decrease in free choline concentrations. Burns, Costill, and Fink (1988) found that
trained male cyclists who pedaled at 70% of their VO2max for 105 min and then
completed a 15-min time trial showed no change in free choline concentrations.
A similar result was observed by Spector et al. (1995) in trained cyclists who
exercised at 150% VO2max for 2 min and 70% VO2max for 70 min. Moreover, von
Allwörden et al. (1993) found no significant decrease in free choline concentra-
tions in adolescent cross-country runners after a local competition. Finally, neither
a 4-hr treadmill load carriage test at 38% VO2max (Warber et al., 2000) nor a 1.5-hr
treadmill load carriage test at 70% VO2max (Deuster et al., 2002) decreased free
choline concentrations in male soldiers.
These equivocal findings might result from differences in experimental design.
Research protocols showing a significant postexercise decline in free choline con-
centrations are especially arduous in nature. Warber et al. (2000) suggest that free
choline depletion does not depend on mode of exercise but, rather, on duration and
intensity of the work bout. Moreover, results published by Spector et al. (1995)
showed a mild negative relationship between time spent cycling and plasma choline
concentrations (r = –.60). Longer work bouts at lower intensities or shorter work
bouts at higher intensities do not appear to be sufficient to deplete free choline
concentrations below baseline concentrations. To significantly reduce the amount
of free choline found in the blood, it appears that an individual must be exposed
Choline and Endurance Performance     199
to a relatively long work bout (>2 hr) at a relatively high work intensity (>70%
VO2max). If this is true, the situations when free choline is significantly reduced below
baseline concentrations might be limited to those participating in ultraendurance
events (Warber et al.).
Impact of Reductions in Free Choline
on Endurance Performance
Although research consistently shows a decrease in free choline concentrations
with strenuous endurance activity, little research has examined the effect of such
changes on endurance performance. The conclusions from current research have
been limited because of small sample sizes or confounding study variables.
Two hypothesized mechanisms through which decreases in free choline
concentrations could influence endurance performance are reduced work capacity
and impaired cognitive function. Buchman et al. (1999) showed a weak correla-
tion (r = .47, p = .036) between actual and predicted time to finish in marathoners
who best maintained their free choline concentrations. In other words, individuals
whose free choline concentrations did not drop were better able to maintain their
goal pace throughout the marathon. Concurrently, Pierard et al. (2004) found that
performance on several cognitive tests was compromised after a 5-day combat-
training course that significantly depleted free choline stores. The participants’
bodies were affected by the 5-day ordeal in many other respects, however, not the
least of which were severe negative energy balance (5,000–8,000 kcal/day expended
vs. 3,500 kcal/day consumed) and sleep deprivation (4 hr/night). Thus, additional
research is needed to ascertain the relationship, if indeed there is one, between
reduced free choline concentrations and endurance performance.
Impact of Choline Supplementation
on Endurance Performance
Studies examining the effect of choline supplementation on endurance performance
fall into two general groups. The first consists of studies in which supplementation
elevates free choline concentrations above those that are normally found in the
blood. The second group of studies uses a choline supplement to offset a drop in
free choline concentrations that would normally occur with strenuous exercise.
Supplementation Above Normal Physiological
Most exercise studies have examined the effect of increasing free choline con-
centrations above an individual’s normal physiological concentrations before
an exercise bout (Buchman et al., 2000; Burns et al., 1988; Deuster et al., 2002;
Warber et al., 2000). These studies found no significant performance effect of this
type of supplementation, nor did they find significant change in any cognitive or
physical variable measured, including memory tasks, time to fatigue, and %VO2max
during an activity.
200 Penry and Manore
In one noteworthy study, Spector et al. (1995) examined the effect of choline
supplementation on cycling time to exhaustion in 10 trained cyclists. A double-
blind crossover design was employed, with the participants’ diets screened to
ensure relative homogeneity of choline intake. Forty-five minutes before each test,
participants consumed 200 ml of a beverage containing 6% glucose, 70 mg sodium,
25 mg potassium, and a mixture of B vitamins (specific quantities unnamed) or a
similar beverage containing 2.43 g of choline bitartrate. The participants then began
cycling at 70% of their VO2max. Twenty-five minutes into the test, the participants
received 200 ml of the same beverage they had consumed before the test began.
No significant difference was observed between trials in cycle time to exhaus-
tion or any physiological variable. It should be noted, however, that although the
supplement significantly increased free choline concentrations above baseline
values, free choline concentrations of both the control and treatment trials were not
significantly different from baseline at the conclusion of the cycling test. Because
research has shown that particularly strenuous exercise can significantly decrease
free choline concentrations, additional research is needed to determine the effect
of choline supplementation under the conditions of an acute exercise-induced free
choline deficiency.
Supplementation to Maintain Normal Physiological
Only one study (published as an abstract; Sandage, Sabounjian, White, & Wurtman,
1992) has examined the effect of choline supplementation on endurance perfor-
mance in individuals who demonstrated a significant exercise-induced decrease in
free choline from baseline concentrations. In that crossover study, Sandage et al.
reported that ingestion of a 2.8 g choline citrate supplement 1 hr before and at the
10-mile mark of a 20-mile run maintained plasma choline concentrations, whereas
plasma choline concentrations fell in individuals receiving a placebo. Participants
who ingested the choline supplement also had faster finish times for the 20-mile
run than those who consumed a placebo (p < .05, actual times not reported). It is
unknown why this study was never published as a full paper, although it is important
as the only choline-supplementation study in which the authors were able to elicit
a significant drop in plasma choline concentrations in the control group.
Although Sandage et al.’s (1992) study is thought provoking, it is also quite
interesting that no subsequent studies have examined the effect of choline supple-
mentation under these specific circumstances. It is likely that this is because of
a combination of factors, notably the arduous nature of the exercise protocol
needed to cause a decline in free choline and the difficulty of finding a suitable
performance measure. Moreover, it is also possible that trained individuals have
some resistance to acute choline depletion (Conlay et al., 1992), although this has
not been studied.
Choline and Endurance Performance     201
Summary and Recommendations
Current research underscores the importance of choline in proper functioning of
the human body. It appears that maintaining free blood choline concentrations is
necessary for optimal cognitive and muscular performance; however, the effect
of oral choline supplementation on endurance performance is equivocal. It seems
certain that raising free blood choline concentrations above those normally found
in the circulation has no beneficial effect on cognitive or physical-endurance
In physical endeavors of a particularly long and strenuous nature, free choline
might drop below baseline concentrations. To date, only one abbreviated study has
examined the effect of choline supplementation in these types of physical events. It
is possible that choline supplementation in situations when free choline concentra-
tions are acutely decreased improve performance by preventing a decline in free
choline concentrations. Future research on this topic must select an exercise modal-
ity that will minimize the ancillary effects of strenuous exercise while retaining the
ability to stimulate the types of metabolism that cause a significant decrease in an
unsupplemented test population.
The link between blood homocysteine concentrations and free choline concen-
trations also deserves attention. Blood homocysteine concentrations are increased
after a bout of exercise, provided that the activity is both continuous and strenuous
in nature (Joubert & Manore, 2006). Free choline concentrations have been shown
to decrease under similar physiological conditions. Moreover, the central role that
choline plays in converting homocysteine to methionine under exercise conditions
supports a link between these findings. Choline supplementation during such exer-
cise bouts might reduce the accumulation of blood homocysteine concentrations via
increased BHMT activity, and adequate folate status might offset the depletion of
choline during exercise by encouraging MS activity and lessening the demand on
the BHMT pathway. Accordingly, it would seem that choline stores would be used
more slowly and performance improved by limiting the amount of homocysteine
produced during endurance exercise or by directly reducing the amount of choline
used by the body for purposes other than acetylcholine synthesis. This latter point
might be particularly important in athletes carrying the MTHFD1 1958A allele,
who might need to consume extra folate in their diets to spare physiological choline
stores. Additional research is needed to clarify the relationship among acute changes
in blood homocysteine, free choline, genetics, and endurance performance.
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... Choline is a nitrogen-containing compound and an essential micronutrient for the human body. Choline plays a role in human metabolism and participates in cell membrane functions, methyl transport and neurotransmission [34,35]. Choline is mainly absorbed from the diet but can also be obtained via de novo synthesis [34]. ...
... Choline and TMA are small molecules that play an extremely important role in human life [35]. Choline is utilized as an energy source by microorganisms in the human gastrointestinal tract and other anaerobic environments. ...
... In the human body, redundant TMA is oxidized into TMAO via liver FMOs, eventually increases plasma TMAO concentrations and causes a variety of diseases [4]. As an essential micronutrient, choline participates in cell membrane signals related to phospholipids, lipid transport by lipoproteins, methyl metabolism through the reduction in homocysteine, and neurotransmitter synthesis via acetylcholine [34,35]. However, choline treatment significantly reduces the metabolism of certain amino acids, peptidoglycans and nucleotides, and gene repair function, which may be due to excessive plasma TMAO concentrations. ...
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Atherosclerosis is the main cause of myocardial infarction and stroke, and the morbidity and mortality rates of cardiovascular disease are among the highest of any disease worldwide. Excessive plasma trimethylamine-N-oxide (TMAO), an intestinal metabolite, promotes the development of atherosclerosis. Therefore, effective measures for reducing plasma TMAO production can contribute to preventing atherosclerosis. Probiotics are living microorganisms that are beneficial to the human body, and some of them can attenuate plasma TMAO production. To explore the effects of probiotic supplementation on plasma TMAO in choline-fed mice, we intragastrically administered eight strains of Bifidobacterium breve and eight strains of Bifidobacterium longum to mice for 6 weeks. B. breve Bb4 and B. longum BL1 and BL7 significantly reduced plasma TMAO and plasma and cecal trimethylamine concentrations. However, hepatic flavin monooxygenase (FMO) activity, flavin-containing monooxygenase 3 (FMO3), farnesoid X receptor (FXR) protein expression and TMAO fractional excretion were not significantly affected by Bifidobacterium supplementation. The treatment of Bifidobacterium strains modulated the abundances of several genera such as Ruminococcaceae UCG-009, Ruminococcaceae UCG-010, which belong to the Firmicutes that has been reported with cut gene clusters, which may be related to the reduction in intestinal TMA and plasma TMAO. Additionally, a reduction in Ruminococcaceae indicates a reduction in circulating glucose and lipids, which may be another pathway by which Bifidobacterium strains reduce the risk of atherosclerosis. The effect of Bifidobacterium strains on Bacteroides also suggests a relationship between the abundance of this genus and TMA concentrations in the gut. Therefore, the mechanism underlying these changes might be gut microbiota regulation. These Bifidobacterium strains may have therapeutic potential for alleviating TMAO-related diseases.
... Vulnerable membranes and reduced acetylcholine production during intense physical exercise might promote muscle damage and decrease muscle stimulation resulting in muscle exhaustion [17]. In addition to being essential for neurotransmitter synthesis, choline is involved in cell-membrane signaling, transport of fat and methyl group metabolism, which are all important functions for optimal sports performance [24]. However, plasma choline concentrations are known to be challenged during strenuous physical exercise. ...
... (a) Enhanced choline availability A depletion of circulating choline has previously been described in endurance athletes with stronger observed decreases after strenuous and prolonged physical training or competition events [24]. It is therefore interesting to note, that one hour of intense PT can also lead to a 7.3% reduction in plasma choline concentrations when looked at all pre-supplementation participants pooled together. ...
... This suggests that without optimal oral choline intake, the body cannot fully recover and will further deplete choline stores [22]. It was suggested that for activities that reduce circulating choline levels below normal, oral choline supplementation might increase endurance performance [24], since choline is needed to produce acetylcholine for optimal muscle performance [25,64]. Assessing performance was not part of this pilot study and it is unclear if a 7.3% drop in circulating choline concentrations can have an effect on power performance but could be of interest in a follow-up study. ...
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There is evidence that both omega-3 polyunsaturated fatty acids (n-3 PUFAs) and choline can influence sports performance, but information establishing their combined effects when given in the form of krill oil during power training protocols is missing. The purpose of this study was therefore to characterize n-3 PUFA and choline profiles after a one-hour period of high-intensity physical workout after 12 weeks of supplementation. Thirty-five healthy power training athletes received either 2.5 g/day of Neptune krill oilTM (550 mg EPA/DHA and 150 mg choline) or olive oil (placebo) in a randomized double-blind design. After 12 weeks, only the krill oil group showed a significant HS-Omega-3 Index increase from 4.82 to 6.77% and a reduction in the ARA/EPA ratio (from 50.72 to 13.61%) (p < 0.001). The krill oil group showed significantly higher recovery of choline concentrations relative to the placebo group from the end of the first to the beginning of the second exercise test (p = 0.04) and an 8% decrease in total antioxidant capacity post-exercise versus 21% in the placebo group (p = 0.35). In conclusion, krill oil can be used as a nutritional strategy for increasing the HS-Omega-3 Index, recover choline concentrations and address oxidative stress after intense power trainings.
... Table 2 Comparison of clinical pathological features between human NASH and animal NASH models induced by diets and chemical inductors. - [53,54,56,57] NAFLD, non-alcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; HCC, hepatocellular carcinoma; STAM, NASH-HCC; HFD, high-fat diet, CDHFD, choline-deficient high-fat diet, WD, western diet CCl4, carbon tetrachloride; DEN, diethylnitrosamine; STZ, streptozotocin; PI3K, phosphatidylinositol-3 kinase; AKT, protein kinase B; mTOR, mammalian target of rapamycin; ALT, alanine transaminase; AFP, alpha-fetoprotein; TGF-β, transforming growth factor-beta; HFD/DEN, high-fat diet/diethylnitrosamine; NF-κB, nuclear factor kappa B; PCNA, proliferating cell nuclear antigen; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-α; IL-6, interleukin-6; HSCs, hepatic stellate cells. ...
... In addition, to mimic the sequential events of human NASH, this model induces HCC development through the intraperitoneal administration of a single injection of 25 mg/kg DEN (Fig. 3) [52]. Choline or trimethyl-β-hydroxyethylammonium is a quaternary ammonium compound classified as an essential nutrient for humans since it is a key component in the functioning of distinct neurochemical processes [53,54]. Additionally, choline is a vital component of the cell membrane, participates in the metabolism of the methyl group and is required for hepatic secretion of very-low-density lipoproteins (VLDL) [53,54]. ...
... Choline or trimethyl-β-hydroxyethylammonium is a quaternary ammonium compound classified as an essential nutrient for humans since it is a key component in the functioning of distinct neurochemical processes [53,54]. Additionally, choline is a vital component of the cell membrane, participates in the metabolism of the methyl group and is required for hepatic secretion of very-low-density lipoproteins (VLDL) [53,54]. ...
Hepatocellular carcinoma (HCC), the most common primary liver cancer, arises after a long period of exposure to etiological factors. Nonalcoholic steatohepatitis (NASH) is ranked as the main risk factor for developing HCC; hence, experimental models of NASH leading to HCC have become key tools both to investigate the molecular mechanisms underlying the pathophysiology and to evaluate new putative drugs for treating chronic liver diseases in humans. Animal models of NASH induced by a high-fat diet (HFD) plus chemical inducers, such as the NASH-HCC (STAM), high-fat diet/diethylnitrosamine (HFD/DEN), choline-deficient high-fat diet/DEN (CDHFD/DEN), and Western diet/carbon tetrachloride (WD/CCl4) models, are promising because they exacerbate liver damage and significantly shorten the experimental time. In this review, we critically summarize and discuss the ability of these models to recapitulate the liver alterations that precede and lead to HCC progression, as well as the impact of the diet in promoting liver injury progression. We also emphasize the strengths and weaknesses of the models’ ability to closely mimic the stages of liver injury development that occur in humans. Based on the molecular mechanisms induced by the currently available NASH models leading to HCC, we argue that although several NASH models have importantly contributed to describing the disease chronology, the progress in emulating the progression from NASH to HCC has been partial. Thus, the development of novel NASH/HCC models remains an unmet need.
... Anti-inflammatory and antioxidant, improving membrane fluidity Calder, 2016;Burchakov et al., 2017;Godhamgaonkar et al., 2020;Sundaram et al., 2020 Folate (Vitamin B9) Antioxidant activity and plays a role in mTOR signaling Williams et al., 2011;Rosario et al., 2017 Vitamin E Antioxidant activity and modulating protein-membrane interaction Howard et al., 2011;Zingg, 2015 Choline Generates phosphatidylcholine and prevents intramembranous material leakage Penry and Manore, 2008;Godoy-Parejo et al., 2020; Zinc Binding site of copper and iron, membrane rheology, cell signaling, enzyme activities, lipid composition maintenance Verstraeten et al., 2004;Wilson et al., 2017 apoptosis could be activated, which, if it progresses, may lead to necroptosis, resulting in abnormal placentation and vascular remodeling and therefore preeclampsia (Raguema et al., 2020;Zhang et al., 2020). Folic acid is crucial to healthy pregnancy as it contributes to angiogenesis and vasculogenesis via a nitric oxide-dependent mechanism, DNA methylation, antioxidant protection, and endothelial-dependent vascular relaxation. ...
... Deficiency of choline may cause intramembranous material to leak into extracellular fluid as the cell integrity is compromised. It is also involved in synthesis of lipoprotein, acetylcholine, and homocysteine (Penry and Manore, 2008;Godoy-Parejo et al., 2020). Moreover, an in vivo study showed that reduction of folate is associated with the increased breakdown of phosphatidylcholine and glycerophosphocholine (GPC), due to a high demand for the methyl group (Chew et al., 2011). ...
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Preeclampsia is one of the most common obstetrical complications worldwide. The pathomechanism of this disease begins with abnormal placentation in early pregnancy, which is associated with inappropriate decidualization, vasculogenesis, angiogenesis, and spiral artery remodeling, leading to endothelial dysfunction. In these processes, appropriate cellular deaths have been proposed to play a pivotal role, including apoptosis and autophagy. The proper functioning of these physiological cell deaths for placentation depends on the wellbeing of the trophoblasts, affected by the structural and functional integrity of each cellular component including the cell membrane, mitochondria, endoplasmic reticulum, genetics, and epigenetics. This cellular wellness, which includes optimal cellular integrity and function, is heavily influenced by nutritional adequacy. In contrast, nutritional deficiencies may result in the alteration of plasma membrane, mitochondrial dysfunction, endoplasmic reticulum stress, and changes in gene expression, DNA methylation, and miRNA expression, as well as weakened defense against environmental contaminants, hence inducing a series of inappropriate cellular deaths such as abnormal apoptosis and necrosis, and autophagy dysfunction and resulting in abnormal trophoblast invasion. Despite their inherent connection, the currently available studies examined the functions of each organelle, the cellular death mechanisms and the nutrition involved, both physiologically in the placenta and in preeclampsia, separately. Therefore, this review aims to comprehensively discuss the relationship between each organelle in maintaining the physiological cell death mechanisms and the nutrition involved, and the interconnection between the disruptions in the cellular organelles and inappropriate cell death mechanisms, resulting in poor trophoblast invasion and differentiation, as seen in preeclampsia.
... ; doi: medRxiv preprint neurotransmitters, cell membrane signaling, methyl metabolism, lipid transport, and metabolism. [18][19][20] Many studies demonstrated that whole egg consumption results in increased blood protein and lipoprotein levels. 21-23 Recent evidence from a middle-income country suggests the early introduction of 1 medium size egg per day for 6 months markedly enhanced growth in young children. ...
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Background Protein-energy malnutrition is still problematic worldwide. It directly impacts growth and development, especially in children. We investigated the long–term effects of egg supplementation on the growth, biochemical indices, and microbiota of primary school children. Methods A randomized controlled cluster study was carried out in six rural schools in Thailand. Participants were randomly assigned into three groups: 1) whole egg (WE) – consuming 10 additional eggs/week [n = 238], 2) protein substitute (PS) – consuming yolk–free egg substitute equivalent to 10 eggs/week [n = 200], and 3) control group (n= 197]). Demographic and biochemical indices, and microbiota composition were measured at weeks 0, 14, and 35. Findings 635 students (8 to 14 years old) were recruited (51·5% female). At baseline, 17% of the participants were underweight, 18% were stunted, and 13% were wasted. At week 35, compared to the control group, body weight and height increased significantly in WE (3·6 ± 23·5 kg, P<0·001 and 5·1 ± 23·2 cm, P<0·001). No significant differences in weight or height were observed between PS and Control. Prealbumin levels were higher (1·5 ± 8·4 mg/dL, P<0·001) in WE, but not in PS, compared to control. Significant decreases in total cholesterol, triglycerides, and LDL cholesterol were observed in the WE, but not in the PS groups. HDL cholesterol tended to increase in WE (0·7 ± 25·2 mg/dL, ns). Neither the alpha nor beta diversity of the bacterial diversity was significantly different among all groups. After WE supplementation, the overall relative abundance of Bifidobacterium increased by 1·28-fold as compared to baseline and the differential abundance analysis also indicated that Lachnospira increased significantly and Varibaculum decreased. Interpretation Long-term whole egg supplementation is an effective, feasible and low-cost intervention to reduce protein-energy malnutrition, particularly in low-middle-income countries. Whole egg supplementation improves growth and nutritional biomarkers, and positively impacts gut microbiota without adverse effects on blood cholesterol levels. Funding Agricultural Research Development Agency (ARDA) of Thailand (PRP6105022310, PRP6505030460).
... Oral choline supplementation might only increase endurance performance in activities that reduce circulating choline levels below normal [27]. Thus, many studies examined the effect of choline ingredient supplementation on fatigue [28][29][30]. ...
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Various choline-based multi-ingredient supplementations (CMS) have been suggested in the current market, but the research is limited. The purpose of this study was to investigate the acute effect of a CMS on physical performance. Fourteen male college football players (20.4 ± 1.0 years) participated in a randomized double-blind crossover experiment separated by 7 days. Subjects were given a CMS or a placebo 60 min before physical performance testing measures, including maximum vertical jumps, maximum voluntary isometric contractions (MVIC), maximal voluntary concentric contractions (MVCC), and fatiguing contractions. Four MVICs and seven sets of two MVCCs at various loads (1 N·m to 60% MVIC torque) were performed with the knee extensor muscles while seated on a dynamometer before and after the fatiguing tasks. During the fatiguing tasks, 120 MVCCs (4 sets × 30 reps) were performed with a load equivalent to 20% MVIC. Twitch interpolation technique was used to assess muscle contractile properties and voluntary activation. No significant differences were seen at baseline between sessions for all testing measures including vertical jump height, strength, power, muscle contractile properties and voluntary activation. Rate of torque development and impulse was higher in supplemental session compared to control session throughout the fatiguing contractions (p = 0.018, p < 0.001, respectively). Acute CMS can improve explosive strength by delaying the onset of fatigue.
The prognosis in neonatal hypoxic ischemic encephalopathy (HIE) depends on early differential diagnosis for justified administration of emergency therapeutic hypothermia. The moment of therapy initiation directly affects the long-term neurological outcome: the earlier the commencement, the better the prognosis. This review analyzes recent advances in systems biology that facilitate early differential diagnosis of HIE as a pivotal complement to clinical indicators. We discuss the possibilities of clinical translation for proteomic, metabolomic and extracellular vesicle patterns characteristic of HIE and correlations with severity and prognosis. Identification and use of selective biomarkers of brain damage in neonates during the first hours of life is hindered by systemic effects of hypoxia. Chromatography– mass spectrometry blood tests allow analyzing hundreds and thousands of metabolites in a small biological sample to identify characteristic signatures of brain damage. Clinical use of advanced analytical techniques will facilitate the accurate and timely diagnosis of HIE for enhanced management.
Aims: To identify biomarkers of cardiomyopathy in patients with type 2 diabetes mellitus (T2DM) using cardiovascular magnetic resonance (CMR) and to identify associations between functional status, metabolomic profile and myocardial fibrosis. Methods: In this prospective case control study, patients (n = 49) with T2DM without significant coronary artery disease, and matched controls (n = 18) underwent CMR, cardiopulmonary exercise testing, and plasma metabolomic analyses. Results: Patients with T2DM (n = 49, median [interquartile range] age 61 [56-63] years, 61% male, diabetes duration 11 [7-20] years), historical HbA1c 7.6% (60 mmol/mol) (6.9-8.6) and matched controls (n = 18) were examined. Study patients had increased myocardial extracellular volume (ECV) (26.9 [23.8-30.0] vs 23.4 [22.4-25.5) %, p < 0.001). Increased ECV was associated with male sex (p = 0.04), time with T2DM (p = 0.02), reduced peak VO2 (R2 = 0.48, p = 0.01), increased circulating choline (p = 0.002) and cysteamine (p = 0.002) both of which were also associated with reduced peak VO2 (p < 0.025 and 0.014 respectively). Conclusions: Patients with well-controlled T2DM without significant coronary disease exhibit focal and diffuse myocardial fibrosis and diffuse myocardial fibrosis is associated with reduced exercise tolerance and metabolites. Plasma metabolites may provide mechanistic insights into diffuse myocardial fibrosis, and cardiopulmonary fitness.
A range of synthetic approaches for metal oxide-gold nanocomposites from conventional method such as chemical vapor deposition (CVD), pulse laser ablation to more simple and facile synthetic approaches using mild condition have been discussed. These nanocomposites have found diverse potential biological applications including cell imaging, photothermal therapy, chemotherapy, radiotherapy, determining oxidative stress in tumor cells, glucose oxidation, enzyme mimic activity, nitrogen fixation and diagnosis purpose such as detecting cancer biomarkers such as prostate protein antigen (PSA), alpha fetoprotein (AFP), melanoma adhesion molecule antigen (CD146), DNA sensing. The biosensing applications along with quantitative estimation of bioanalytes such as choline (CHO), NADH, epinephrine (EP), 17β-estradiol (E2), uric acid (UA), ascorbic acid (AA), glucose and dopamine, α-synuclein, amyloid beta (Aβ) peptide, glutathione (GSH), calcium dipicolinate have been explored with these nanocomposites as platforms. Abnormal levels of hydrazine (principal component of various pharmaceutical derivative), Cr(VI), tertracyclin (broad spectrum antibiotic), 6-mercaptopurine (anticancer drug), Bisphenol A (BPA), chlorpyrifos and carbamate pesticides have been estimated with these metal oxide-gold nanocomposites. Various detection strategies for quantitative analysis based on electrochemical, fluorometric and colorimetric methods have been briefly summarized.
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Betaine is distributed widely in animals, plants, and microorganisms, and rich dietary sources include seafood, especially marine invertebrates (≈1%); wheat germ or bran (≈1%); and spinach (≈0.7%). The principal physiologic role of betaine is as an osmolyte and methyl donor (transmethylation). As an osmolyte, betaine protects cells, proteins, and enzymes from environmental stress (eg, low water, high salinity, or extreme temperature). As a methyl donor, betaine participates in the methionine cycle—primarily in the human liver and kidneys. Inadequate dietary intake of methyl groups leads to hypomethylation in many important pathways, including 1) disturbed hepatic protein (methionine) metabolism as determined by elevated plasma homocysteine concentrations and decreased S-adenosylmethionine concentrations, and 2) inadequate hepatic fat metabolism, which leads to steatosis (fatty accumulation) and subsequent plasma dyslipidemia. This alteration in liver metabolism may contribute to various diseases, including coronary, cerebral, hepatic, and vascular diseases. Betaine has been shown to protect internal organs, improve vascular risk factors, and enhance performance. Databases of betaine content in food are being developed for correlation with population health studies. The growing body of evidence shows that betaine is an important nutrient for the prevention of chronic disease.
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Choline is an important nutrient that is actively transported from mother to fetus across the placenta and from mother to infant across the mammary gland. Thus, pregnancy and lactation are times when dietary requirements for choline may be increased. Pregnant rats eating AIN-76A diet (with and without choline) for 6 d (d 12-18 gestation) were compared with nonmated female and male rats eating the same diets. Similarly, lactating rats were compared with nonmated female rats, both groups eating these same diets for 25 d (gestation d 12-postpartum d 15). We measured choline and choline metabolites in livers on the last day of feeding. Nonmated female rats, eating the control diet, had higher hepatic choline metabolites concentrations than did male rats (choline, 98%; betaine, 96%; and phosphorylcholine, 55% higher), pregnant rats (phosphorylcholine, 47%; and betaine, 42% higher) or lactating rats (phosphorylcholine, 49%; phosphatidylcholine, 37%; and betaine, 273% higher). We found that nonmated females eating a choline deficient diet had only a modest diminution (33%) of the labile choline metabolite PCho in liver, compared with similar rats eating a control diet. When compared with similar rats fed a choline-adequate diet, pregnant rats fed a choline-deficient diet had significantly great diminution of hepatic phosphorylcholine (83% lower) than did nonmated females. Liver phosphorylcholine was only 12% lower than in controls in nonmated females fed the deficient diet for the same 25-d period. Lactating rats were the most sensitive to choline deficiency, with liver phosphorylcholine 88% lower than in similar rats fed control diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Choline, a quaternary amine and natural component of most plants and meats, is found in cell membranes, particularly nervous tissue, with brain tissue having the highest concentration. ¹⁻³ Choline, which was named after the Greek word for anger “chole” was first characterized in bile as a nitrogen-containing substance by the German chemist, AFL Strecker in 1862. ⁴ Despite its identification, it was not until the 1930s that choline became recognized as an important dietary constituent. ⁵ The term “lipotropic” was used in association with choline based on the finding that it prevented the accumulation of lipids in the liver. ⁶ In 1977 Wurtman et al. ⁷ reported that choline administration was associated with an increase in the neurotransmitter acetylcholine (ACh) and this finding stimulated much interest in choline. However, it was not until 1998 that choline was classified as an essential nutrient by the National Academy of Sciences. This resulted in the establishment of an adequate intake level (AI) for humans by the Food and Nutrition Board of the Institute of Medicine. ⁸.
Previous investigations have shown that plasma free choline decreases during long distance running. This study was undertaken to determine if body choline status changes during a marathon run and whether performance is thereby adversely affected. Twenty-three accomplished marathon runners 25 to 49 years of age were studied before and after the 1997 Houston-Methodist Marathon. Fasting blood and five-hour urine samples were obtained in the morning, 14 days prior to the race, immediately after the race and approximately 48 hours after completion of the race. Runners were asked to predict their finish times two weeks prior to the race. Performance was indicated by the ratio of predicted to actual time. Both plasma free and phospholipid-bound choline concentrations as well as urinary free choline concentration decreased immediately following the race (19.2+/-4.5 to 14.6+/-4.2 nmol/mL, p=0.005, and 2565.2+/-516.4 to 2403.4+/-643.0 nmol/mL, p=0.068, respectively) and, except for the phospholipid-bound choline, rebounded towards baseline after 48 hours (15.6+/-3.2 and 2299.9+/-426.7 nmol/mL), although plasma concentrations remained significantly below baseline. Plasma free and phospholipid-bound choline concentrations were significantly correlated (r=0.46, p=0.0001), although urinary free choline concentration was not correlated with either. There was no correlation between plasma free, phospholipid-bound or urinary free choline concentration and actual finish time or the ratio of predicted to actual finish time. However, the percent decrease in urinary free choline concentration was significantly correlated with the ratio of predicted to actual time (r=0.47, p=0.036). No relationship was seen between this ratio and the percent decrease in either plasma free or phospholipid-bound choline concentrations immediately after the race. Our finding of both decreased free and phospholipid-bound choline suggests the decrease in choline status is related to accelerated choline metabolism or enhanced choline uptake by tissues rather than decreased hepatic choline release. The role of choline supplementation during endurance running requires further investigation.
Consumption of choline by rats sequentially increases serum-choline, brain-choline, and brain-acetylcholine concentrations. In man consumption of choline increases in levels in the serum and cerebrospinal fluid; its administration is an effective way of treating tardive dyskinesia. We found that oral lecithin is considerably more effective in raising human serum-choline levels than an equivalent quantity of choline chloride. 30 minutes after ingestion of choline chloride (2-3 g free base), serum-choline levels rose by 86% and returned to normal values within 4 hours; 1 hour after lecithin ingestion, these levels rose by 265% and remained significantly raised for 12 hours. Lecithin may therefore be the method of choice for accelerating acetylcholine synthesis by increasing the availability of choline, its precursor in the blood.
Certain neurotransmitters (i.e., acetylcholine, catecholamines, and serotonin) are formed from dietary constituents (i.e., choline, tyrosine and tryptophan). Changing the consumption of these precursors alters release of their respective neurotransmitter products. The neurotransmitter acetylcholine is released from the neuromuscular junction and from brain. It is formed from choline, a common constituent in fish, liver, and eggs. Choline is also incorporated into cell membranes; membranes may likewise serve as an alternative choline source for acetylcholine synthesis. In trained athletes, running a 26 km marathon reduced plasma choline by approximately 40%, from 14.1 to 8.4 uM. Changes of similar magnitude have been shown to reduce acetylcholine release from the neuromuscular junction in vivo. Thus, the reductions in plasma choline associated with strenuous exercise may reduce acetylcholine release, and could thereby affect endurance or performance.
The presence of 5 or 20 microM choline in the eserinized medium superfusing striatal slices enhanced the spontaneous release of acetylcholine (ACh) at both concentrations and, at 20 microM, the release of transmitter evoked by electrical field stimulation. Neither the electrical stimulation nor the addition of choline altered choline acetyltransferase activity. These results show that ACh release is dependent on the availability of extracellular choline. The rate of choline efflux was 7 times higher than the rate of ACh release, was not affected by stimulation, and was increased by 40% when hemicholinium-3 (HC-3), an inhibition of choline uptake, was present. The muscarinic antagonist atropine (1 microM) increased the evoked release of ACh into both the choline-free medium and that containing 20 microM choline. An adenosine receptor antagonist, 1,3-diethyl-8-phenyl xanthine (10 microM), failed to affect ACh release or the enhancement of release produced by atropine. In medium containing HC-3, stimulation of the slices elicited ACh release for the first 20 min of the 30 min stimulation period (15 Hz); thereafter, although stimulation was continued, the rate of release decreased to that associated with spontaneous release. Tissue ACh contents were not modified by the addition of choline or atropine to the medium, but were depressed by HC-3. Neither atropine nor HC-3 altered tissue choline content. The total amount of ACh + choline released during an experiment was 5-15 times higher than the decrease in tissue levels of these two compounds during the same period of time.(ABSTRACT TRUNCATED AT 250 WORDS)
Three nutritional products that have very different mechanisms of action are antioxidant vitamins, carnitine, and choline. Antioxidant vitamins do not appear to have a direct effect on physical performance in well-fed people but have been touted for their ability to detoxify potentially damaging free radicals produced during exercise. Carnitine purportedly enhances lipid oxidation, increases VO2max, and decreases plasma lactate accumulation during exercise. However, studies of carnitine do not generally support its use for ergogenic purposes. Choline supplements have been advocated as a means of preventing the decline in acetylcholine production purported to occur during exercise; this decline may reduce the transmission of contraction-generating impulses across the skeletal muscle, an effect that could impair one's ability to perform muscular work. However, there are no definitive studies in humans that justify choline supplementation. Much of the scientific data regarding the aforementioned nutrients are equivocal and contradictory. Their potential efficacy for improving physical performance remains largely theoretical.