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Effect of folic acid supplementation on homocysteine concentration and association with training in handball players


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Strenuous physical activity can alter the status of folic acid, a vitamin directly associated with homocysteine (Hcy); alterations in this nutrient are a risk factor for cardiovascular disease. Handball players are a population at risk for nutrient deficiency because of poor dietary habits. The aims of this study were to evaluate nutritional status for macronutrients and folic acid in members of a high-performance handball team, and determine the effect of a nutritional intervention with folic acid supplementation and education. A total of 14 high-performance handball players were monitored by recording training time, training intensity (according to three levels of residual heart rate (RHR): <60%, 60%–80% and >80%), and subjective perceived exertion (RPE) during a 4-month training period. Nutritional, laboratory and physical activity variables were recorded at baseline (Week 0), after 2 months of dietary supplementation with 200 μg folic acid (50% of the recommended daily allowance) (Week 8) and after 2 months without supplementation (Week 16). We compared training load and analyzed changes in plasma concentrations of Hcy before and after the intervention. Bivariate analysis showed a significant negative correlation (P < 0.01) between Hcy and folic acid concentrations (r = −0.84) at Week 8, reflecting a significant change in Hcy concentration (P < 0.05) as a result of hyperhomocysteinemia following the accumulation of high training loads. At Week 16 we observed a significant negative correlation (P < 0.01) between Hcy concentration and training time with an RHR <60%, indicating that aerobic exercise avoided abrupt changes in Hcy and may thus reduce the risk of cardiovascular accidents in high-performance athletes. Integral monitoring and education are needed for practitioners of handball sports to record their folic acid status, a factor that directly affects Hcy metabolism. Folic acid supplementation may protect athletes against alterations that can lead to cardiovascular events related to exertion during competition.
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R E S E A R C H A R T I C L E Open Access
Effect of folic acid supplementation on
homocysteine concentration and association with
training in handball players
Jorge Molina-López
, José M Molina
, Luís J Chirosa
, Daniela I Florea
, Laura Sáez
and Elena Planells
Background: Strenuous physical activity can alter the status of folic acid, a vitamin directly associated with
homocysteine (Hcy); alterations in this nutrient are a risk factor for cardiovascular disease. Handball players are a
population at risk for nutrient deficiency because of poor dietary habits.
Objective: The aims of this study were to evaluate nutritional status for macronutrients and folic acid in members
of a high-performance handball team, and determine the effect of a nutritional intervention with folic acid
supplementation and education.
Design: A total of 14 high-performance handball players were monitored by recording training time, training
intensity (according to three levels of residual heart rate (RHR): <60%, 60%80% and >80%), and subjective
perceived exertion (RPE) during a 4-month training period. Nutritional, laboratory and physical activity variables
were recorded at baseline (Week 0), after 2 months of dietary supplementation with 200 μg folic acid (50% of the
recommended daily allowance) (Week 8) and after 2 months without supplementation (Week 16). We compared
training load and analyzed changes in plasma concentrations of Hcy before and after the intervention.
Results: Bivariate analysis showed a significant negative correlation (P< 0.01) between Hcy and folic acid
concentrations (r=0.84) at Week 8, reflecting a significant change in Hcy concentration (P< 0.05) as a result of
hyperhomocysteinemia following the accumulation of high training loads. At Week 16 we observed a significant
negative correlation (P< 0.01) between Hcy concentration and training time with an RHR <60%, indicating that
aerobic exercise avoided abrupt changes in Hcy and may thus reduce the risk of cardiovascular accidents in high-
performance athletes.
Conclusion: Integral monitoring and education are needed for practitioners of handball sports to record their folic
acid status, a factor that directly affects Hcy metabolism. Folic acid supplementation may protect athletes against
alterations that can lead to cardiovascular events related to exertion during competition.
Keywords: Nutritional status, Sport, Folic acid, Supplementation, Homocysteine
Folic acid is a vitamin needed by a number of enzymes
essential for DNA synthesis and amino acid metabolism
[1]. This nutrient is an important co-factor in the me-
thionine pathway, the most important source of methyl
groups in the human organism [2]. Low folic acid intake
is known to contribute to increased levels of homocyst-
eine (Hcy) as a result of its interrelation with methionine
metabolism [2-6]. Inadequate intake of folic acid has
been described in athletes who practice different sports
[1], and athletes are often deficient in their intake of
total calories, carbohydrate, protein, and micronutrients
[7]. Some authors consider supplementation with folic
acid as an efficient way to reduce elevated Hcy levels
[8,9], and it has been suggested that in certain cases,
folic acid supplementation should be used for preventive
purposes [10]. Earlier findings have suggested that doses
* Correspondence:
Equal contributors
Department of Physiology, Institute of Nutrition and Food Technology,
University of Granada, Granada 18071, Spain
Full list of author information is available at the end of the article
© 2013 Molina-López et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the
Creative Commons Attribution License (, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
Molina-López et al. Journal of the International Society of Sports Nutrition 2013, 10:10
of 0.2 to 0.4 mg/d can achieve maximal reductions in
Hcy in healthy young populations, whereas doses up to
0.8 mg/d are needed to reduce Hcy in individuals with
coronary heart disease [11].
Regular physical activity (PA) can alter the requirements
for some micronutrients [1]. This makes it important
to choose foods carefully, taking into account the
quality and quantity of macronutrient intakes, since
requirements can vary depending on the type of exer-
cise performed [12].
Elevated plasma levels of Hcy are considered a risk
factor for cardiovascular disease (CVD) [13]. Regular
physical activity is now well established as a key compo-
nent in the maintenance of good health and disease pre-
vention, and has been specifically recognized to reduce
the risk of appearance of CVD by reducing chronic in-
flammation, which plays a key role in the atherogenic
process, blood pressure, body composition, insulin sensi-
tivity and psychological behavior [14,15].
In contrast, acute intense exercise has been shown to
increase plasma Hcy concentrations [14]. Several factors
have been reported to be associated with increases in
Hcy, such as endothelial cell injury, which stimulates
vascular smooth muscle cell growth, increases platelet
adhesiveness, enhances LDL cholesterol oxidation and
deposition in the arterial wall, and directly activates the
coagulation cascade [16]. Some research has concluded
that Hcy levels may be influenced by the duration, inten-
sity and type of exercise [6,14,17,18], whereas other
studies have identified lifestyle factors such as smoking,
eating habits and alcohol consumption [6,19,20], as well
as age, elevated blood pressure, renal failure [17,21] and
genetic factors [22], as factors that contribute to
increased plasma concentrations of Hcy. In addition, nu-
tritional factors such as reduced folic acid intake have
been implicated [3,13].
Several authors [4,13,22,23] have established a direct
relationship between regular physical exercise (PA) and
a reduction in CVD risk, although the data regarding
the effect of PA on plasma Hcy concentrations remain
controversial because of methodological differences
among different studies. Murakami et al. [13] noted that
these discrepancies may reflect differences in the
methods used to evaluate PA, the lack quantitative infor-
mation on training intensity or training time, and in
some cases the lack of adjustment for folate intake status
[4]. However, Venta et al. [14] suggested three possible
mechanisms that may explain the increase in Hcy with
increasing exercise intensity: increased free radical pro-
duction [15], increases in methylated forms such as cre-
atine and acetylcholine, and increases in the amino acid
pool as a result of protein catabolism. The need for re-
search in athletes who take part in different sports has
been suggested to be important in order to account for
the high prevalence of hyperchromocysteinemia [15]. To
date, however, there have been no studies that evaluated
plasma Hcy levels while taking into account nutrient
intakes, training intensity and training time, and rate of
perceived exertion (RPE). Moreover, the relationship be-
tween PA and Hcy has not been studied in team sports
such as handball, in which intermittent activity
alternates with periods of intense aerobic activity [24].
In the present study our aims were to evaluate macronu-
trient and folic acid nutritional status in high-performance
athletes (handball players), and to determine the effect
on these parameters of training and a nutritional inter-
vention based on dietary supplementation with folic acid.
We analyzed the data in the light of training load and
plasma Hcy concentrations.
The study was done during the February to June 2010
sports season and all participants were members of the
handball team (n = 14) sponsored by the Club Deportivo
Puente Genil de Balonmano (Granada, Spain), in the
Honor B Division of the Spanish professional handball
league. The sample comprised 14 men (mean age 22.9 ±
2.7 years) who trained for a mean of 4 days per week in
addition to competing in matches on weekends.
Participation in the study was voluntary. None of the
participants had evidence of CVD, diabetes or hyperten-
sion. All participants provided their informed consent in
writing, and were given detailed information at the be-
ginning and end of the study regarding the aims and
procedures involved. The study was approved by the Re-
search Ethics Committee of the University of Granada.
Anthropometric and biochemical measures
Body weight, body mass index and body fat percentage in
all participants were determined with a Tanita TBF-300WA
Body Composition Analyzer. Height was measured on a
scale to within the nearest 0.01 cm.
Blood samples for laboratory analyses were obtained
after a 12-h fast after the last training session in each
time period. Venous blood was drawn, centrifuged to
separate plasma and red blood cells, and stored at
80C. Folic acid concentration was measured with an
electrochemical luminescence immunoassay (ECLIA, Elecsys
2010 and Modular Analytics E 170, Roche Diagnostics,
Mannheim, Germany) with a reference value of 3 pg/l
[25]. Plasma concentrations of Hcy were measured with
a fluorescence polarization immunoassay (IM
, Abbott
Laboratories, Abbott Park, IL, USA) [25]. Laboratory
values were determined for transferrin, prealbumin,
high-density lipoprotein, low-density lipoprotein and
total cholesterol to verify adequate nutritional status in
Molina-López et al. Journal of the International Society of Sports Nutrition 2013, 10:10 Page 2 of 8
all participants and rule out the possibility of nutri-
tional alterations that might have affected the findings.
Assessment of macronutrient and folic acid intake
To evaluate dietary intakes we used a food consumption
questionnaire [26] consistent with a 72-h recall system
during 3 consecutive days (2 working days and 1 non-
working day). During the educational intervention the
participants were instructed to abstain from consuming
caffeine or alcohol. Three time points were used during
a 4-month period: baseline (Week 0), followed by 2
months of dietary supplementation (Week 8), followed
by 2 months without supplementation (Week 16). Food
intakes were recorded with the help of a manual
containing photographs of standard amounts of different
foods and prepared dishes. To record portion sizes and
the amounts of different foods as accurately as possible,
the participants were asked to identify the foods
consumed and describe the size of the portions. Food
intakes were analyzed with Nutriber
software [27] to
convert them into data for absolute nutrient intakes and
percentage values of adequate intakes according to indi-
vidual needs.
Macronutrient intakes (carbohydrates, protein, and fat
and folic acid) were compared to reference intakes [28].
Percentage macronutrient intakes referred to total en-
ergy intake were compared with recommended dietary
allowances (RDA) [29].
Nutritional supplementation and education intervention
Dietary supplementation consisted of folic acid at 200
μg/d, starting on day 1 in Week 0 and ending on the
final day of this 2-month period in Week 8. For the
following 2 months no dietary supplementation was
used; this period lasted from Week 8 to Week 16, when
the study period ended.
The educational intervention was designed ad hoc for
this type of study population by a team of nutrition
specialists. The intervention consisted of three phases.
First, the nutrition team explained aspects related with
nutrition in general, with emphasis on the different types
of nutrients and their importance for maintaining good
health in basically healthy persons. This was followed by
education focusing more specifically on nutrition and
PA. In this second phase the emphasis was on specific
nutritional requirements in persons who perform con-
tinuous PA, since nutrition in this population is often
not well balanced, and supplements are often used to in-
crease performance [1]. In the third phase, team members
responded to the questions participants raised at any
time throughout the study period to provide additional
information and clarification.
Training profile
To record training parameters we used three variables
that define training load: training time, intensity and
RPE. All participants trained for a mean of 4 days per
week in addition to participating in competition matches
on weekends.
Training time was recorded during a 4-month period
covering the professional handball competition season,
divided into four 1-month mesocycles. In each training
session we recorded the number of minutes spent on
each type of exercise until the desired training time was
reached. The first 2 months (mesocycles 1 and 2)
comprised the period of training when supplementation
was used (STp), and the following 2 months (mesocycles
3 and 4) comprised the period of training without diet-
ary intervention (NSTp). Total training time in each
mesocycle was calculated as the sum for all training
sessions and competition match times.
Training intensity was recorded with Polar S610
and Polar Team pulse meters (Polar Electro Ibérica,
Barcelona, Spain) once per training week, for a total of
22 final recorded training sessions (11 for each training
period). To calculate maximum heart rate (HR
used the course navette test of maximum aerobic power.
We also recorded baseline heart rate during 7 days to
obtain an accurate mean value. Heart rate reserve or re-
sidual heart rate (RHR) was calculated as HR
basal heart rate to establish the level of intensity and
the time each athlete spent in each level [30]. We used
three ranges of intensity: <60%, between 60% and 80%,
and >80% RHR.
The RPE was used to determine whether the amount
of exertion each participant perceived was consistent
with actual intensity of exertion once per training week,
for a total of 22 final recorded training sessions (11 for
each training period). The participants indicated one of
the three levels of perceived exertion at the end of each
training session. We calculated RPE as the mean ±
standard deviation (SD) (n= 14) to evaluate perceived
load in each mesocycle or month of training.
Training sessions were monitored and standardized by
using the same exercises in the same order and with the
same duration across sessions. The results were
compared as the mean ± SD (n= 14) for each of the
three study periods.
Data analysis
The data are reported with descriptive statistics. For nu-
merical variables we used the arithmetic mean, SD and
standard error of the mean. The results for categorical
variables are reported as percentage frequencies. To de-
termine whether the data fitted a parametric model, the
Kolmogorov-Smirnov test was used to verify normal dis-
tribution. To check the homoscedasticity of the
Molina-López et al. Journal of the International Society of Sports Nutrition 2013, 10:10 Page 3 of 8
variables, the Levene test was used. Between-group
comparisons were made with the chi-squared test and
single-factor analysis of variance. Linear regression ana-
lysis was used to identify correlations by calculating
Pearsons bivariate correlation coefficient. All statistical
analyses were done with SPSS v. 16.0 for Windows.
The general characteristics of the participants are shown
in Table 1, and these characteristics did not change sig-
nificantly during any of the three study periods.
Assessment of macronutrient and folic acid intake
Energy, macronutrient and folic acid intakes are
summarized in Table 2, and are referred to RDAs for
athletes [28,29]. The main finding was a significantly
higher (P< 0.01) folic acid intake in Week 8 compared
to Week 0 and Week 16, as a result of supplementation.
When folic acid intake was adjusted for energy intake in
Week 8 regardless of supplementation, the difference be-
came nonsignificant.
Macronutrient intakes were significantly higher (P< 0.05)
in Week 0 compared to Week 8 and Week 16 for
carbohydrates. Fat intake was significantly higher in
Week 0 and Week 8, and protein intake was significantly
higher in Week 0 and Week 16.
Table 3 shows the percentages of participants whose
macronutrient and folic acid intakes were within each
tercile of the RDA, or were above the RDA, in each of
the three study periods. The results show that folic acid
intake was above 100% the RDA in Week 8. In Week 0
and Week 16, intake was below 2/3 of the RDA in 42.9%
of the participants [29]. Mean carbohydrate intake was
below the RDA [28] at all time points, whereas fat and
protein intakes were above 100% of the RDA [28].
Training profile
The results in Figure 1 show the training loads recorded
during the study period. Training load is reported here
as training time, RPE and distribution among three
levels of intensity during the intervention (STp) and
post-intervention periods (NSTp). There were no
statistically significant differences in training time be-
tween STp and NSTp.
Overall RPE during STp was significantly lower (P<0.05)
than during NSTp. With regard to the durations of diffe-
rent RHR levels (training intensity), a significant diffe-
rence (P< 0.05) was found for the 60%80% range,
which accounted for 30.35% of the total training time
during STp, and for 35.87% of the training time du-
ring the NSTp. There were no significant differences for
training intensity levels in the <60% range or the >80%
Bivariate analysis to calculate Pearsons correlation
coefficient detected statistically significant correlations
(P< 0.01) between overall RPE and training intensity levels
of 60%80% RHR (r= 0.64) and >80% RHR (r=0.76).
Biochemical assays
The results of biochemical analyses are shown in Table 4.
There were no significant changes in plasma folic acid at
any time point, and all values were within the normal
range for the healthy population. However, plasma
concentrations of Hcy increased significantly (P< 0.05)
to above the normal range of values during the Week 8
and Week 16 periods compared to baseline values in
Week 0. Regarding the relationship between plasma
concentrations of Hcy and folic acid and training inten-
sity, we found that both plasma concentrations showed a
significant negative correlation (r=0.75) (P< 0.01) with
the level of intensity of <60% RHR. Bivariate analysis
disclosed a significant negative correlation (P< 0.01) be-
tween Hcy and folic acid concentrations (r=0.84) in
Week 8.
The other nutritional parameters studied here (albu-
min and prealbumin) showed no statistically significant
changes at any time point. Among the lipid parameters
we measured, HDL, LDL and total cholesterol were sig-
nificantly higher (P< 0.05) in Week 0 compared to Week
16, and HDL and LDL were significantly higher in Week
8 compared to Week 16.
The results of the present study suggest that after the
dietary and educational intervention, there were no sig-
nificant changes in plasma concentrations of folic acid.
However, we did note changes in plasma Hcy levels, des-
pite the significant inverse correlation between the two
values. Folic acid supplementation may have reduced
cardiovascular risk during the NSTp in the handball
players we studied.
In the present study, increased food intake as a result
of nutritional education may have contributed to weight
maintenance throughout the experimental period, which
Table 1 Characteristics of the participants at three time
Measurement Mean SD
Age (years) 22.9 2.7
Height (m) 1.87 0.06
Week 0 Week 8 Week 16
Mean SD Mean SD Mean SD
Weight (kg) 86.72 5.36 86.47 5.59 86.38 4.81
Body mass index (kg/m
) 24.72 1.12 24.61 1.30 24.62 1.14
Body fat (%) 11.58 2.53 11.60 2.45 11.57 2.34
SD, standard deviation.
Molina-López et al. Journal of the International Society of Sports Nutrition 2013, 10:10 Page 4 of 8
would avoid possible alterations in body weight as a re-
sult of poor dietary habits [1]. Regular PA is known to
alter the requirements for certain micronutrients [1].
Folic acid intake in the athletes studied here (Table 2)
was below the RDA except during Week 8, and was simi-
lar to the values reported by Rousseau et al. [12]. In this
connection, a meta-analysis by Woolf and Manore [1]
concluded that most studies which had analyzed folic
acid intake based on a 3-day (72-h) recall period obtained
values similar to those found in the present study. Sup-
plementation with folic acid was implemented after an
initial evaluation which showed the intake of this nutri-
ent to be inadequate. The amount used in the dietary
supplement was consistent with the theoretical basis
described by McNully et al. [11], who suggested that
doses of 0.2 to 0.4 mg folic acid per day may achieve
maximal reductions in Hcy in healthy young people,
whereas doses up to 0.8 mg folic acid per day would be
needed to reduce Hcy in individuals with coronary artery
disease. However, in the present study plasma Hcy con-
centration did not change despite the significant increase
in folic acid intake.
Regular PA is known to reduce the risk of CVD [6,12].
Handball, like other team sports such as soccer and field
hockey, is considered an intermittent intensity sport on
the basis of the aerobic energy pathways involved [31].
When we analyzed training load, we found a significant
negative correlation between exercise training time at an
intensity range of <60% RHR and plasma Hcy level
(Figure 2). Rousseau et al. [12] reported that athletes
who performed aerobic exercise had lower levels of Hcy.
This finding is consistent with our results; moreover, our
direct method for quantifying training load provided
data that can be considered accurate and reliable. How-
ever, a potential limitation that should be taken into ac-
count is that the present study was done under actual
Table 2 Energy, macronutrient and folic acid intakes at three time points
N = 14 RDA Week 0 Week 8 Week 16
Mean SD Mean SD Mean SD
Energy (kcal/kg/day) 44* 34.45 3.56 38.91
4.15 38.54
Macronutrients (g/day)
Protein 104 147* 133.43 14.32 146.64 35.64 147.04
Carbohydrate 519 865* 360.91 27.64 421.50
49.24 416.80
Fat 78 95* 118.57 22.52 132.22
17.75 129.57 21.79
Macronutrients (g/kg/day)
Protein 1.2 - 1.7* 1.54 0.22 1.70 0.44 1.70
Carbohydrate 6 10* 4.17 0.41 4.88
0.60 4.82
Fat 0.9 1.1* 1.37 0.28 1.53
0.19 1.49 0.21
Macronutrients (% energy intake)
Protein 12 15%* 17.97 1.83 17.47 3.73 17.65 2.54
Carbohydrate 45 65%* 48.66 4.10 50.21 2.54 50.20 3.62
Fat 20 35%* 35.71 4.88 35.51 3.81 34.92 4.01
Vitamins (μg/day)
Folic acid 400* 301.97 89.05 516.11
54.49 290.35
RDA, recommended daily allowance. SD, standard deviation.
* Values used for comparison were from previous publications [28,29].
Statistically significant differences (P< 0.05) between Week 0 vs. Week 8 and Week 16.
Statistically significant differences (P< 0.05) between Week 8 vs. Week 16.
Table 3 Recommended daily allowance covered for
energy, macronutrients and folic acid at three time
Nutrient 2/3 RDA > 2/3 RDA RDA > RDA
Macronutrients (%)
Protein Week 0 - - 100
Week 8 - - 100
Week 16 - - 100
Carbohydrate Week 0 35.7 64.3 -
Week 8 - 92.9 7.1
Week 16 - 100 -
Fat Week 0 - - 100
Week 8 - - 100
Week 16 - - 100
Vitamins (%)
Folic acid Week 0 42.9 42.9 14.3
Week 8 - - 100
Week 16 42.9 50.0 7.1
RDA, recommended daily allowance.
Molina-López et al. Journal of the International Society of Sports Nutrition 2013, 10:10 Page 5 of 8
training conditions, although it seems that a better study
design would have been to (prospectively) control the
volume and intensity of PA to keep them equal among
Other authors reported different values for Hcy levels
after exercise; the variations among different studies
may reflect the use of indirect methods to quantify PA,
the lack of nutritional studies and differences between
studies in mean age of the participants [4,31,32].
It is worth noting that folic acid levels in plasma
were near the lower limit of normality. Other authors
found that a 5-mmol/l increase in plasma Hcy levels
(>10 mmol/l) was associated with a 60% increase in the
risk of coronary artery disease in men [8,33]. McCully
[10] noted that if the concentration of Hcy is between 8
and 12 mmol/l, improvements in the quality of the diet
are needed to provide adequate vitamin intakes able to
maintain Hcy at concentrations that can reduce the risk
of coronary disease in adults. As described in the Results
section, there was a significant negative correlation be-
tween plasma Hcy levels and plasma folic acid levels in
Week 8. However, Hcy concentration increased despite
dietary folic acid supplementation. This finding suggests
that in contrast to the expected increase in plasma folic
acid concentrations and decrease in Hcy, the opposite ef-
fect was likely attributable to training. In most
participants in the present study, plasma levels of folic
acid were near the lower limit of the reference values
(4.219.l ng/ml), and after the intervention there was no
significant change at the end of the supplementation
period or at the end of the post-supplementation period.
König et al. [5] showed that the increase in Hcy was
dependent on the initial plasma level of folic acid as well
as on training time. These authors attributed the increase
in Hcy to increased methionine catabolism, which
induced a greater influx of molecules with methyl groups
as a result of high-intensity PA [4]. A study by Borrione
et al. [15] analyzed team sports similar to handball but
did not use dietary supplementation. They found Hcy
levels that were much higher than those we found, and
folic acid levels similar to those in the athletes we
Our experimental approach was designed to evaluate
training load, nutritional and biochemical indicators in
an integrated manner to obtain accurate data in profes-
sional athletes during the sports season. Our method
emphasized accurate data capture for both training load
and dietary intakes. Variations in either of these factors
Figure 1 Comparison of training variables throughout the experimental trial.
Statistically significant difference (P < 0.05) STp vs NSTp.
Table 4 Biochemical values of clinical and nutritional parameters at three time points
N=14 Study period
Biochemical parameters Reference value Week 0 Week 8 Week 16
Mean SD Mean SD Mean SD
Transferrin (mg/dl) 200 360 261.21 27.82 261.71 33.00 265.50 28.67
Prealbumin (mg/dl) 20 40 26.76 3.53 27.19 3.12 26.76 2.77
HDL (mg/dl) 40 60 58.29 13.58 57.29 12.28 61.00
LDL (mg/dl) 70 150 74.00 22.89 71.35 20.84 83.07
Total cholesterol (mg/dl) 110 200 147.86 26.74 149.71 27.68 154.57
Folic acid (ng/ml) 4.2 19.9 8.14 1.17 7.73 2.57 7.62 2.36
Homocysteine (μmol/l) 5 12 11.64 2.65 13.92
2.39 13.14
HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol.
Statistically significant differences (P< 0.05) Week 0 vs. Week 8 and Week 16.
Statistically significant differences (P< 0.05) Week 8 vs. Week 16.
Molina-López et al. Journal of the International Society of Sports Nutrition 2013, 10:10 Page 6 of 8
can affect plasma levels of Hcy and folic acid, so it was
important to avoid alterations that might compromise
the data this study was designed to seek.
Our study appears to be the first to use careful controls
for participantstraining load and nutritional and bio-
chemical status before, during and after the professional
sports season. Our results suggest that high-performance
athletes such as handball players may require preventive
dietary supplementation with folic acid to curtail the
effects of a sharp increase in blood Hcy concentrations.
This increase may be associated with a sudden increase in
the risk of CVD as a result of the high training load
accumulated in successive training sessions during the
professional competition season.
Hcy: Homocysteine; PA: Physical activity; RDA: Recommended daily
allowance; RHR: Residual heart rate; RPE: Rate of perceived exertion;
SD: Standard deviation.
Competing interests
The authors declare no conflicts of interest.
All the authors contributed to and approved the final manuscript.
This work was supported by the Spanish Ministry of Education (grant
number AP2009- 3701) and by FIS Project PI07/1228 form the Carlos III
Health Institute. The authors thank K. Shashok for translating the manuscript
into English and for advice on technical editing.
Author details
Department of Physiology, Institute of Nutrition and Food Technology,
University of Granada, Granada 18071, Spain.
Department of Physical
Education and Sports, Faculty of Sports Sciences, University of Granada,
Granada 18071, Spain.
Received: 11 January 2012 Accepted: 31 December 2012
Published: 21 February 2013
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Molina-López et al. Journal of the International Society of Sports Nutrition 2013, 10:10 Page 8 of 8
... It has often been reported that inadequate intake may compromise athletic performance [1], so the work of the sports nutritionist plays a key role in the athlete's nutritional status by developing appropriate and individualized intervention strategies. In handball [29,33,34], Molina et al. observed an insufficient intake of energy and macronutrients in elite handball players. These players underwent a nutrition education program to improve the quantity and quality of nutrient intake, observing improvement after the intervention, yet they failed to present a correct balance between the energy consumed and the energy intake recorded by a retrospective 72-h questionnaire. ...
... According to different authors, in relation to body mass, male handball players reported ingesting an average of 4.1-4.8 g/kg/d CHO [33], while female players consumed about 3.7-4.0 g/ kg/d CHO, again falling below the recommendations proposed by the ASCM or ISSN for CHO intake (6-10 g/kg/d) [1,2]. ...
... There have been limited studies examining whether exercise increases the need for B complex vitamins in handball players. Be that as it may, a recent study analyzed the role of B vitamins at the cardiovascular level [33]. It was concluded that folic acid supplementation could protect athletes from alterations that may lead to cardiovascular events related to exercise during training and competition. ...
Full-text available
Handball players face a variety of nutritional challenges during the competitive season. Although there has been an increase in nutrition research and exercise over the last decade, nutrition remains a largely unknown area in sports such as handball. There is little information on the nutritional habits of handball players at any level of the game. This updated document performs a rigorous, systematic, and evidence-based analysis of nutrition and specific literature with current scientific data related to energy needs, nutrient requirements, and hydration during training as well as competition on athletes in team sports, particularly among handball players. Energy and macronutrient needs, especially carbohydrates and proteins, must be met during periods of high physical activity to maintain body weight, replenish glycogen stores, and provide adequate protein to build and repair tissue. Fat intake should be sufficient to supply essential fatty acids and fat-soluble vitamins and to contribute energy for weight maintenance. Micronutrients play an important role in energy production, hemoglobin synthesis, and the maintenance of bone health, adequate immune function, and protecting the body against oxidative damage. Due to the absence of specific micronutrient recommendations in team sports like handball, the consumption of unbalanced diets with low micronutrient density may be insufficient to cover the players’ increased needs. Athletes should be well hydrated before exercise and drink enough liquids during and after exercise to balance fluid loss. Sports drinks containing carbohydrates and electrolytes can be consumed before, during, and after exercise to help maintain blood glucose concentration, provide fuel for muscles, and decrease the risk of dehydration and hyponatremia.
... Therefore, blood levels of Vit D influence athletic performance, and its supplementation appears to be an effective strategy to alleviate muscle damage and inflammation after exercise [2][3][4][5]. It is also claimed that iron, vitamin B12 and folic acid may have an ergogenic effect, and current research suggests that exercise may increase the requirements for these substances [6]. Therefore, athletes at risk of nutrient deficiency may show a decreased ability to perform exercise at high intensities [7,8]. ...
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Vitamins, hormones, free radicals, and antioxidant substances significantly influence athletic performance. The aim of this study was to evaluate whether these biological mediators changed during the season and if this was associated with the rate of improvement in performance after training, assessed by means of a standardized test. Professional male soccer players took part in the study. Two evaluations were performed: the first in the pre-season period and the second at the mid-point of the official season, after about 6 months of intensive training and weekly matches. Blood levels of vitamins D, B12, and folic acid, testosterone and cortisol, free radicals, and antioxidant substances were measured. Two hours after breakfast, a Yo-Yo test was performed. The relationships between the biological mediators and the rate of improvement after training (i.e., the increase in meters run in the Yo-Yo test between the pre-season and mid-season periods) were evaluated by means of a linear mixed models analysis. Results: Eighty-two paired tests were performed. The athletes showed better performance after training, with an increase in the meters run of about 20%. No significant relationships between the vitamin and hormone values and the gain in the performance test were observed. Plasmatic levels of free radicals increased significantly, as did the blood antioxidant potential. An indirect relationship between oxidative stress and the improvement in performance was observed (free radicals β ± SE: = −0.33 ± 0.10; p-value = 0.001), with lower levels of oxidative stress being associated with higher levels of performance in the Yo-Yo test. Monitoring the measures of oxidative stress could be a useful additional tool for coaches in training and/or recovery programs tailored to each player.
... The results are expressed as mean value (95% confidence interval/CI). P values between the followed groups are presented in Table 3. increase due to minor or major deficiency of these vitamins [26,27]. ...
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Purpose: Glioblastoma multiforme and anaplastic astrocytoma represent one of the most frequently occurring primary brain tumors with dismal survival rates. The aim of our study was to investigate whether values of homocysteine, folates and vitamin B12 can be prognostic markers in relapse diagnosis, treatment and monitoring of adult patients with malignant brain tumors. Methods: Twenty-seven patients from the Neurosurgical Clinic, Clinical Center of Serbia with diagnosed malignant brain tumors (anaplastic astrocytoma GR III and glioblastoma multiforme GR IV), were included in the study. The patients were divided in two groups according to the progression of disease, 15 with and 12 without progression. Results: Mean values of homocysteine were significantly higher in the group with progression compared to the group without malignant tumor progression, at the baseline point and after six months. Mean values of folate were similar across groups in all measurements, except in the 3rd month after surgery. Results regarding vitamin B12 were similar to folate, without any significance in group comparisons in the examined time points, as well as in vitamin B12 values change. Conclusions: Our results pointed out that total homocysteine in blood circulation appears to be a tumor marker for monitoring primary malignant brain tumor patients before and after surgery. The association of hyperhomocysteinemia with folate deficiency, also provides strong support for viewing hyperhomocysteinemia as a predictive marker for carcinogenesis. It is hoped that future research will continue to explore the clinical relevance of homocysteine as a tumor marker and a risk factor for astrocytoma and glioblastoma.
... decreased tHcy after training) was observed in subjects with hyperhomocysteinaemia at baseline. Molina-López et al. (2013) and Guzel et al. (2012) also found increased tHcy levels after exercise training programs. Konig et al. (2003) concluded that although acute exercise significantly increased tHcy, chronic endurance exercise was not associated with higher plasma tHcy concentrations. ...
Full-text available
This study aimed to assess the effect of rehydration during and after acute aerobic submaximal exercise on total homocysteine (tHcy) concentrations and related parameters in physically active adult males. Twenty trained males (29.4 ± 7.9 years old) completed four exercise tests: two without rehydration during exercise (NH1 and NH2), one with rehydration during exercise using water (H1) and one with rehydration during exercise using an isotonic sports drink (H2). After finishing the exercise tests, subjects followed a rehydration protocol for 2 h. Serum tHcy, vitamin B12, folate, creatine and creatinine were analysed before, after and at 2, 6 and 24 h after exercise. Data were analysed with and without correcting for haemoconcentration to assess the changes in tHcy related. The methylenetetrahydrofolate reductase (MTHFR) 677TT genotype was also analysed. THcy (uncorrected by haemoconcentration) increased significantly after exercise (P < 0.05) in the NH1 and NH2 tests [mean increase ± SD: 1.55 ± 0.33 (15.18%) and 1.76 ± 0.25 (17.69%) µmol/L, respectively], while no significant differences were found in the H1 and H2 tests [mean increase: 0.65 (6.29%) and 0.90 (8.69%) μmol/L, respectively]. The increase was partly due to haemoconcentration and partly due to the metabolism underlying acute exercise. THcy concentrations recovered to baseline after 24 h in all tests. In conclusion, adequate rehydration during acute aerobic exercise using either water or a sports drink maintains tHcy concentrations at baseline and for up to 2 h after exercise in physically active male adults and prevents further increases when compared to no rehydration.
... Randeva (24) and Dankner (25) reported that regular exercise can decrease plasma tHcy concentration. Guzel (26) and Molina (27) on the other hand provided data supporting the opposite, that regular training could increase plasma tHcy levels. Other studies found no difference in plasma tHcy concentrations after training (28). ...
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Objective: This study aimed to investigate the prevalence of hyperhomocysteinemia (Hhcy) and its major determinants in Chinese urban population with new-onset hypertension. Methods: A total of 574 adults (404 men and 170 women) with newly diagnosed primary hypertension were recruited from seven communities in Nanjing, China. Data on lifestyle factors, such as physical activities, current smoking and drinking status, dietary habits, and familial factors were collected in interviews, and laboratory examinations were performed by well-trained personnel. Potential factors related to the prevalence of Hhcy in this population were analyzed using a logistic regression model. Results: Of the 574 participants, 421 (73.3%) were diagnosed with Hhcy whereas the remainder were only hypertensive. The study highlighted a number of factors that were significantly correlated (p
The aim of this study was to analyse dietary intake (macronutrients and micronutrients) in young female and male handball athletes. A transversal study was performed with young handball players from sub 16 and 18 Portuguese Handball Federation, who volunteered to participate in this study. Anthropometric (weight and height measure), nutritional intake (using food frequency questionnaire) and position in the game were evaluated. The final sample comprised 64 athletes (48.4% female and 51.6% male). The mean age was 16± 1 years, average body mass index was higher in females (24.1± 3.5kg/m2) than males (23.8± 3.0 kg/m2). Mean energy intake per day was significantly lower in females than males 2167.4± 1185.0 and 2952.9± 1315.8 kcal/day (p= 0.015, 95CI), respectively. According to the recommendations from food, most of the young handball athletes reported a generally higher dietary intake (protein intake was near to the upper recommendation limit; the carbohydrate intake was below and the fat intake higher) and a lower for some micronutrients. A process to identify the athletes that need nutritional support should be considered by handball coaches to optimise their performance and safeguard their health.
Basketball players face a variety of nutritional challenges during the precompetitive and competitive season. In recent years, top-level team sports have become more competitive, with an increasingly condensed game schedule. These changes have made the game faster, affecting the physical and physiological characteristics of the players, and have generated a range of physiological challenges and nutritional needs in basketball. The American Dietetic Association (ADA), the American College of Sports Medicine (ACSM), and the International Society of Sports Nutrition (ISSN) support the need to cover the energy and macronutrient requirements of players, especially carbohydrates and proteins, in order to maintain body weight, replenish glycogen stores, and build and repair tissues. Micronutrients play an important role in energy production, hemoglobin synthesis, the maintenance of bone health, adequate immune function, and in decreasing oxidative and DNA damage. The consumption of unbalanced diets with low micronutrient densities therefore may not suffice to cover increased player needs. Additionally, hydration strategies should be considered, especially before, during, and after exercise, in order to maintain exercise performance. This chapter offers an evidence-based analysis of nutritional aspects in basketball with current scientific data related to energy demands, nutrient requirements, and hydration strategies among basketball players.
Elevated plasma homocysteine concentration is a risk factor for cardiovascular disease, which seems to be the main cause of increased mortality in patients with type 2 diabetes. Previous studies have demonstrated the effect of exercise on homocysteine levels and the magnitude of these benefits seems to depend on the type, mode and frequency of training. The present study aimed to compare the effects of aerobic and resistance training on plasma homocysteine in individuals with type 2 diabetes. The study included 15 individuals undergoing aerobic training, 14 subjects undergoing resistance training, and 18 individuals in the control group. Homocysteine, total cholesterol and fractions, glucose, and anthropometric measurements were conducted. The training program lasted 16 weeks. Aerobic training was performed twice a week and lasted 75 min, and resistance training was performed twice a week and lasted 75 min. Homocysteine levels were not significantly different between before and after training. High-density lipoprotein levels increased in both training groups and decreased in the control group. Glucose levels decreased after aerobic and resistance training. Body fat mass (percentage and total) decreased in both training group, but with more expression in the aerobic group. We conclude that 16-week aerobic and resistance training programs did not significantly affect plasma homocysteine levels in patients with type 2 diabetes. Nevertheless, these training programs yielded positive results in HDL control, plasma glucose, and body composition.
Objective: The relationship between total plasma homocysteine (tHcy) and exercise remains controversial. This study aimed to investigate the association between regular aerobic exercise and hyperhomocysteine (hHcy) in patients with hypertension. Methods: A total of 497 hypertensive patients from 7 communities of Nanjing were enrolled in this cross-sectional study. All participants were asked to complete standard questionnaires by themselves. Physical and laboratory examination were performed within 1 week after enrollment. The association between regular aerobic exercise and hHcy in hypertensive patients was estimated by a multiple logistic regression analysis. Results: Of the 497 patients, 210 had a regular aerobic exercise habit and 274 of them were detected with hHcy. Multivariate analysis revealed that exercisers have the less risk of hHcy (adjusted odds ratio [OR] 0.42, 95% confidence interval [CI] 0.26-0.66) as compared to non-exercisers controlling for the established and potential confounders. Intensity, frequency and total energy expenditure of aerobic exercise were found to be independently associated with lower hHcy risk in hypertensive patients. Gender subgroup analyses showed that this inverse relationship between regular aerobic exercise and hHcy exists in both male and female groups (adjusted OR 0.41 95%CI 0.21-0.80, and adjusted OR 0.40 95%CI 0.20-0.80, respectively). Conclusions: Regular aerobic exercise has a negative association with hHcy in this cross-sectional study. That suggests a hypothesis that doing aerobic exercise might decrease the risk of hHcy in hypertensive patients.
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This study investigated athletic performance and homocysteine (Hcy) levels in relation to the methylenetetrahydrofolate reductase (MTHFR) C677T mutation and explored the relationship between this mutation and other cardiac risk factors in soccer players and sedentary individuals. The study groups consisted of randomly selected soccer players (n=48) from the Turkish Super and Major League and sedentary male students (n=48) aged 18-27. Anthropometric variables, aerobic and anaerobic thresholds were measured, furthermore, biochemical assays were performed. The level of HDL cholesterol, LDL cholesterol, triglyceride, Hcy, folate, vitamin B12, hemogram and MTHFR C677T was investigated. The results showed that there was a statistical difference between the two groups in terms of body mass, body fat, the BMI, the aerobic threshold heart rate (ATHR), aerobic threshold velocity (ATVL) and anaerobic threshold velocity (ANTVL). The soccer players were found to have lower levels of triglyceride, total cholesterol and LDL cholesterol, and higher levels of folate than the sedentary participants. The analysis of the alleles of the MTHFR C677T polymorphism showed that the participants that carried TT genotypes had a lower level of vitamin B12 and folate, and a higher level of Hcy than the participants carrying CC and CT genotypes. In conclusion, the baseline homocysteine and cardiovascular fitness levels of healthy young males with the TT genotypes of the MTHFR C677T genotype were found to strongly correlate with their levels of Hcy.
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Implementation of a nutrition programme for team sports involves application of scientific research together with the social skills necessary to work with a sports medicine and coaching staff. Both field and court team sports are characterized by intermittent activity requiring a heavy reliance on dietary carbohydrate sources to maintain and replenish glycogen. Energy and substrate demands are high during pre-season training and matches, and moderate during training in the competitive season. Dietary planning must include enough carbohydrate on a moderate energy budget, while also meeting protein needs. Strength and power team sports require muscle-building programmes that must be accompanied by adequate nutrition, and simple anthropometric measurements can help the nutrition practitioner monitor and assess body composition periodically. Use of a body mass scale and a urine specific gravity refractometer can help identify athletes prone to dehydration. Sports beverages and caffeine are the most common supplements, while opinion on the practical effectiveness of creatine is divided. Late-maturing adolescent athletes become concerned about gaining size and muscle, and assessment of maturity status can be carried out with anthropometric procedures. An overriding consideration is that an individual approach is needed to meet each athlete's nutritional needs.
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The aim of the present study was to evaluate the levels of homocysteine and 8-iso PGF(2a) in football and hockey players before and soon after a match, on the predisposition for development of atherosclerosis. We measured 8-iso-PGF(2a) and homocysteine in 21 football athletes aged 21.8 ± 3.7 years old and 18 hockey athletes 22.2 ± 3.3 years old, respectively. All the athletes presented significant increases in serum homocysteine levels following the match (p = 0.001 for football and p = 0.001 for hockey players) Also a statistically significant increase of 8-iso-PGF(2a) levels was found in hockey and football athletes following the match (p < 0.001 and p = 0.071). Our findings suggest that strenuous exercise such as a football or a hockey match causes a marked increase in serum homocysteine and 8-iso-PGF(2a). Due to the fact that homocysteine and 8-iso-PGF(2a) are contributing to atheromatosis, it may be useful to follow a restoration exercise program that involves mild exercise and to pay special attention to folate, vitamin B6, and vitamin B12 balance during the first 24 h after the match.
Objective. —To determine the risk of elevated total homocysteine (tHcy) levels for arteriosclerotic vascular disease, estimate the reduction of tHcy by folic acid, and calculate the potential reduction of coronary artery disease (CAD) mortality by increasing folic acid intake.Data Sources. —MEDLINE search for meta-analysis of 27 studies relating homocysteine to arteriosclerotic vascular disease and 11 studies of folic acid effects on tHcy levels.Study Selection and Data Extraction. —Studies dealing with CAD, cerebrovascular disease, and peripheral arterial vascular disease were selected. Three prospective and six population-based case-control studies were considered of high quality. Five cross-sectional and 13 other case-control studies were also included. Causality of tHcy's role in the pathogenesis of vascular disease was inferred because of consistency across studies by different investigators using different methods in different populations.Data Synthesis. —Elevations in tHcy were considered an independent graded risk factor for arteriosclerotic vascular diseases. The odds ratio (OR) for CAD of a 5-μmol/L tHcy increment is 1.6(95% confidence interval [Cl], 1.4 to 1.7) for men and 1.8 (95% Cl, 1.3 to 1.9) for women. A total of 10% of the population's CAD risk appears attributable to tHcy. The OR for cerebrovascular disease (5-μmol/L tHcy increment) is 1.5 (95% Cl, 1.3 to 1.9). Peripheral arterial disease also showed a strong association. Increased folic acid intake (approximately 200 μg/d) reduces tHcy levels by approximately 4 μmol/L. Assuming that lower tHcy levels decrease CAD mortality, we calculated the effect of (1) increased dietary folate, (2) supplementation by tablets, and (3) grain fortification. Under different assumptions, 13 500 to 50 000 CAD deaths annually could be avoided; fortification of food had the largest impact.Conclusions. —A 5-μmol/L tHcy increment elevates CAD risk by as much as cholesterol increases of 0.5 mmol/L (20 mg/dL). Higher folic acid intake by reducing tHcy levels promises to prevent arteriosclerotic vascular disease. Clinical trials are urgently needed. Concerns about masking cobalamin deficiency by folic acid could be lessened by adding 1 mg of cobalamin to folic acid supplements.(JAMA. 1995;274:1049-1057)
Hyperhomocysteinemia is an independent risk factor for the development of cardiovascular disease. Exposure of endothelial cells to elevated levels of homocysteine (HCY) results in decreased availability of nitric oxide (NO) and impaired vascular function, both of which are early events in atherogenesis. Exercise training improves vascular function by increasing endothelial NO production secondary to an increase in the enzyme responsible for its synthesis, endothelial nitric oxide synthase (eNOS). We hypothesized that exercise training would increase endothelial NO production, which would attenuate the endothelial dysfunction associated with HCY exposure. Rats were randomly assigned to either sedentary (SED) or exercise (EX) groups. The exercise regimen consisted of treadmill running at 20-25 m/min, 15% grade, 30 min/day, 5 day/week for 6 weeks. Aortic rings obtained from SED and EX trained rats were incubated with 2 mM HCY for 120 min, then exposed to norepinephrine (NE 100 nM) to induce vasoconstriction. Once a stable contraction plateau was achieved, rings were exposed to increasing concentrations of the receptor-mediated endothelium-dependent vasodilator acetylcholine (ACh; 0.1, 1, 10, 100 nM). This procedure was repeated with the non-receptor-mediated endothelium-dependent vasodilator A-23187 (0.1, 1, 10, 100 nM), and the endothelium-independent vasodilator, NaNO(2) (0.1, 1, 10, 100 muM). In addition, eNOS protein content and eNOS enzyme activity were determined. Aortic rings obtained from exercise trained rats demonstrated significantly (P<0.05) greater relaxation to both ACh and A-23187 in comparison to aortic rings obtained from SED rats following exposure to HCY. Additionally, exercise training increased aortic eNOS protein content and activity. Our data demonstrate that exercise training improves endothelium-dependent vasorelaxation following HCY exposure and this may be due, at least in part, to elevated levels of eNOS protein and an increase in eNOS activity. These results suggest the possible role exercise may play in attenuating the endothelial dysfunction associated with hyperhomocysteinemia.
Homocysteine (tHcy) is an intermediate sulfur-containing amino acid which acts as a methyl group donor for methionine metabolism. Increased serum concentrations (=hyperhomocysteinemia, >10 μmol/l) have been associated with an increased cardiovascular risk. Homocystinuria, an infrequent genetic disease usually due to lack of cystathione beta-synthase, has been found with severely elevated serum homocysteine values (>150 μmol/l). Functional gene polymorphisms of key enzymes (e.g., N5,N10-methylene-tetrahydrofolate reductase) and dietary B-vitamin deficiencies in the elderly are, however, frequent in the ‘Western’ population. Hyperhomocysteinemia has been associated with other vascular effects such as atherothrombosis and endothelial dysfunction due to its auto-oxidative potential, thereby increasing the production of reactive oxygen species. Other effects may involve neurodegenerative diseases such as Alzheimer or dementia praecox of the elderly. Therapeutic interventions lowering tHcy may therefore offer novel tools for the prevention and treatment of atherosclerosis. B-vitamin supplementation (folic acid=vitamin B9, vitamin B6 and vitamin B12) is an efficient and safe tHcy-lowering therapy, decreases tHcy by 30%–50% and has been shown to lower cardiovascular morbidity and mortality. Furthermore, folic acid supplementation has been shown to reduce or even almost eliminate neurotubular birth defects (spina bifida) and to markedly decrease the rate of megaloblastic anemia. Thus, fortification of flour with folic acid in the USA was advocated several years ago in order to prevent these entities.
Elevated levels of total homocysteine (tHcy) are associated with an increased risk of many common diseases. Supplementation with folic acid has been shown to significantly reduce tHcy levels. We used the classical twin model to partition the variability in changes in plasma tHcy levels through folic acid supplementation into genetic, environmental, and confounding epidemiological factors. We carried out an intervention study of folic acid using 101 healthy, female, identical and non-identical twins aged 50-80 years. Each twin was administered folic acid (0.8 mg/day) for 6 weeks. Total plasma folate, cobalamin and tHcy were measured at both baseline and after dosing. We calculated the heritability and tested for associations between the MTHFR C677T functional variant and response to folic acid supplementation. Supplementation with folic acid led to a significant reduction in tHcy levels. The mean tHcy changed from 12.14 to 10.42 μmol/l after supplementation (p < 10(-5)). Moreover, the change in tHcy levels was highly heritable (64%), not associated with the C677T functional variant at MTHFR and not confounded by age, BMI or diet. Our results highlight the need to identify genetic factors associated with biomarkers of response to folate supplementation.
Elevated fasting plasma homocysteine (Hcy) level is a vascular disease risk factor. Plasma Hcy is affected by 5,10-methylenetetrahydofolate reductase (MTHFR) genotype and dietary folate intake. This cross-sectional study in 434 Japanese adults examined the associations among objectively measured physical activity (PA), plasma Hcy adjusting for dietary folate intake, and MTHFR C677T genotype. Daily PA was measured by triaxial accelerometry and all subjects completed a questionnaire about their dietary habits. Plasma Hcy and MTHFR C677T genotype were determined. Plasma Hcy in subjects with the TT genotype was significantly higher than in those with CC or CT genotype (p < 0.001). Plasma Hcy was significantly different between ≥ 200 (7.6 ± 0.2 nmol/mL) and <200 µg/day (8.3 ± 0.3 nmol/mL) folate intake groups (p = 0.003). There were no differences in plasma Hcy adjusting for age, sex, and folate intake between groups according to PA category in all subjects. However, there were significant interactions between time spent in light PA (p = 0.003), vigorous PA (p = 0.001), or inactivity (p = 0.004), and MTHFR genotype. In only the TT genotype, shorter time spent in light PA was associated with higher plasma Hcy than a longer time spent in light PA (11.5 ± 3.3 nmol/mL vs. 8.5 ± 3.3 nmol/mL, p < 0.001), and longer time spent in vigorous PA and inactivity were associated with higher plasma Hcy (11.8 ± 3.3 nmol/mL vs. 8.4 ± 3.2 nmol/mL, 11.6 ± 3.3 nmol/mL vs. 8.4 ± 3.3 nmol/mL, respectively, p < 0.001). In conclusion, light and vigorous PA were associated with plasma Hcy only in the TT genotype, but there were no such associations in all genotypes.
The breast cancer resistance protein (BCRP/ABCG2) is a member of the G-subfamiliy of the ATP-binding cassette (ABC)-transporter superfamily. This half-transporter is assumed to function as an important mechanism limiting cellular accumulation of various compounds. In context of its tissue distribution with localization in the sinusoidal membrane of hepatocytes, and in the apical membrane of enterocytes ABCG2 is assumed to function as an important mechanism facilitating hepatobiliary excretion and limiting oral bioavailability, respectively. Indeed functional assessment performing mouse studies with genetic deletion or chemical inhibition of the transporter, or performing pharmacogenetic studies in humans support this assumption. Furthermore the efflux function of ABCG2 has been linked to sanctuary blood tissue barriers as described for placenta and the central nervous system. However, in lactating mammary glands ABCG2 increases the transfer of substrates into milk thereby increasing the exposure to potential noxes of a breastfed newborn. With regard to its broad substrate spectrum including various anticancer drugs and environmental carcinogens the function of ABCG2 has been associated with multidrug resistance and tumor development/progression. In terms of cancer biology current research is focusing on the expression and function of ABCG2 in immature stem cells. Recent findings support the notion that the physiological function of ABCG2 is involved in the elimination of uric acid resulting in higher risk for developing gout in male patients harboring genetic variants. Taken together ABCG2 is implicated in various pathophysiological and pharmacological processes.
There is no consensus on the best diet for exercise, as many variables influence it. We propose an approach that is based on the total energy expenditure of exercise and the specific macro- and micronutrients used. di Prampero quantified the impact of intensity and duration on the energy cost of exercise. This can be used to determine the total energy needs and the balance of fats and carbohydrates (CHO). There are metabolic differences between sedentary and trained persons, thus the total energy intake to prevent overfeeding of sedentary persons and underfeeding athletes is important. During submaximal sustained exercise, fat oxidation (FO) plays an important role. This role is diminished and CHO's role increases as exercise intensity increases. At super-maximal exercise intensities, anaerobic glycolysis dominates. In the case of protein and micronutrients, specific recommendations are required. We propose that for submaximal exercise, the balance of CHO and fat favors fat for longer exercise and CHO for shorter exercise, while always maintaining the minimal requirements of each (CHO: 40% and fat: 30%). A case for higher protein (above 15%) as well as creatine supplementation for resistance exercise has been proposed. One may also consider increasing bicarbonate intake for exercise that relies on anaerobic glycolysis, whereas there appears to be little support for antioxidant supplementation. Insuring minimal levels of substrate will prevent exercise intolerance, while increasing some components may increase exercise tolerance.