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,
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
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 (www.nal.usda.gov/fnic/
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
(min) Intensity (% VO
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.
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.
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).
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.
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 1 — A 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.
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
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
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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