Vitamin C and Exercise PDF

ORIGINAL RESEARCH
Vitamin C and Exercise / 125
International Journal of Sport Nutrition and Exercise Metabolism, 2003, 13, 125-151
2003 Human Kinetics Publishers, Inc.
Vitamin C: Effects of Exercise

and Requirements With Training
Jonathan M. Peake
Ascorbic acid or vitamin C is involved in a number of biochemical pathways
that are important to exercise metabolism and the health of exercising individuals. This review reports the results of studies investigating the requirement for
vitamin C with exercise on the basis of dietary vitamin C intakes, the response to
supplementation and alterations in plasma, serum, and leukocyte ascorbic acid
concentration following both acute exercise and regular training. The possible
physiological significance of changes in ascorbic acid with exercise is also
addressed. Exercise generally causes a transient increase in circulating ascorbic
acid in the hours following exercise, but a decline below pre-exercise levels
occurs in the days after prolonged exercise. These changes could be associated
with increased exercise-induced oxidative stress. On the basis of alterations in
the concentration of ascorbic acid within the blood, it remains unclear if regular
exercise increases the metabolism of vitamin C. However, the similar dietary
intakes and responses to supplementation between athletes and nonathletes
suggest that regular exercise does not increase the requirement for vitamin C in
athletes. Two novel hypotheses are put forward to explain recent findings of
attenuated levels of cortisol postexercise following supplementation with high
doses of vitamin C.
Key Words: ascorbic acid, antioxidant, cortisol, adrenal gland, exercise, oxidative stress, gluconeogenesis
Introduction
Ascorbic acid, or vitamin C, is a six-carbon compound similar in structure to glucose. It exists in two active forms: the reduced form known as ascorbic acid and the
oxidized form, dehydroascorbic acid. The molecular structure contains two ionizable enolic hydrogen atoms that give the compound its acidic character (Figure 1;
54). Ascorbic acid is considered to be an outstanding antioxidant. Chemically,
ascorbic acid exhibits redox characteristics as a reducing agent. Physiologically,
ascorbic acid provides electrons for enzymes, for chemical compounds that are
oxidants, or other electron acceptors (91). The intermediate free radical formed in
J.M. Peake is with the School of Human Movement Studies at the University of
Queensland, St Lucia QLD 4072 Australia.
125
126 / Peake
Figure 1 Redox properties of ascorbic acid (modified with permission from 36).
the oxidation of ascorbic acid to dehydroascorbic acid is relatively non-reactive,

particularly with oxygen (14). Furthermore, dehydroascorbic acid is reduced by
cells back to ascorbate, which can then be reutilized (107).
Ascorbic acid is distributed in varying concentrations throughout the body
and is involved in a variety of metabolic reactions relating to exercise, such as the
synthesis and activation of neuropeptides, collagen, carnitine, and protection against
the harmful effects of reactive oxidant species (79). In light of this involvement, it is
conceivable that exercise may enhance the utilization, metabolism, and excretion of
ascorbic acid, thereby increasing the dietary requirement for the vitamin. The first
evidence of a possible link between vitamin C and exercise came rather unexpectedly from the observation of scurvy symptoms exhibited by explorers on early polar
expeditions (78). The diets consumed by these explorers were likely to be seriously
lacking in fresh foods containing vitamin C. However, it is also plausible that such a
stressful existence could have exacerbated the effects of a vitamin Cdeficient diet
in such a way that the turnover and requirement for ascorbic acid may have increased. While vitamin C does not appear to improve athletic performance (39),
athletes may have increased dietary vitamin C requirements, and supplementation
may have important effects on athletes that are more subtle than improvements in
aerobic capacity or performance measures (30).
The purpose of this review is to: (a) discuss the role of ascorbic acid in exercise
metabolism, (b) summarize the results of studies examining dietary intakes of vitamin C and the responses to supplementation, and (c) address exercise-induced
alterations in the distribution of ascorbic acid within the body, with reference to the
mechanisms and physiological significance of such changes.
The Distribution, Transport, Function,

and Metabolism of Ascorbic Acid
The distribution of ascorbic acid within the human body is outlined in Table 1.
Exercise studies have been limited to examining changes in ascorbic acid concentrations within plasma/serum and leukocytes. Saturated plasma ascorbic acid concentrations are in the range of 70 to 80 mol/L, whereas saturated lymphocyte,
monocyte, and neutrophil ascorbic acid concentrations occur at 3.4, 3.2, and 1.3
mol/L, respectively (64). Leukocytes store ascorbate against very high concentration gradients (43), probably for protection against intracellular reactive oxidants
(91). Ascorbic acid and its oxidized form, dehydroascorbic acid, are transported
independently. Whereas dehydroascorbic acid is transported into cells by GLUT 1
Table 1 Distribution of Ascorbic Acid Within the Organs and Fluids

of the Human Body (49)
Organ/fluid
Pituitary gland
Adrenal gland
Eye lens
Liver
Pancreas
Spleen
Kidney
Cardiac muscle
Brain
Lungs
Skeletal muscle
Plasma
Ascorbic acid concentration

(mg/100 g)
4050
3040
2531
1016
1015
1015
515
515
315
7
34
0.41
and GLUT 3, the transport protein for ascorbic acid is yet to be identified. Substrate
availability is likely to be critical in determining which molecule (i.e., ascorbic acid
or dehydroascorbic acid) is transported at any particular time. Under non-oxidizing
conditions, ascorbate is present in greater amounts and is therefore more likely to be
transported. In contrast, when oxidants are present, ascorbate is oxidized, resulting
in the transient formation of dehydroascorbic acid (91). Now available to surrounding cells, dehydroascorbic acid is preferentially transported for intracellular reduction (91) either by enzymatic reduction (80) or glutathione (109). This recycling of
ascorbic acid is likely to be important under conditions of oxidative stress (91).
The redox properties of ascorbic acid (Figure 1) make it an effective reducing
agent in several important enzymatic reactions within the body, all of which require
that enzyme-bound metal ions are maintained in their reduced state (79). In the
adrenal gland ascorbic acid is stored in high concentrations where it is utilized by the
enzyme dopamine -monooxygenase within chromaffin granules to synthesize
noradrenaline (Figure 2A; 24). In the pituitary gland and the brain, ascorbic acid is
involved with the enzyme peptidyl-glycine -amidating monooxygenase (72) for
the activation of a variety of neuropeptides and hormone releasing-factors (Figure
2D; 79). The vitamin is required by the prolyl- and lysyl-hydroxylase enzymes for
the hydroxylation of proline and lysine residues, respectively, in the production of
collagen (Figure 2B; 12), and also by the enzymes 6-N-trimethyllysine hydroxylase
and -butyrobetaine hydroxylase in carnitine synthesis (Figure 2C; 74). This latter
role could possibly account for the ascorbic acid content of both cardiac and skeletal
muscle (74). In the liver, ascorbic acid is possibly involved in glucose (11), cholesterol, and lipid metabolism (54). A variety of immune functions are enhanced by
ascorbic acid (2), which could explain the concentration of the vitamin in the spleen.
128 / Peake
Figure 2 Role of ascorbic acid in the synthesis of (A) norepinephrine, (B) collagen, (C)
carnitine, and (D) the -amidation of neuropeptides (modified with permission from
79).
It is currently unclear exactly how ascorbic acid influences pancreatic or renal

function. It has been suggested that high doses of vitamin C might influence insulin
secretion and blood glucose concentrations (8, 10), possibly through competition
between dehydroascorbic acid and glucose for GLUT 1 and GLUT 3 transporters
(92). However, this possible regulatory influence seems unlikely to account for the
levels of ascorbic acid found within these tissues. It is the antioxidant activity of
ascorbic acid which is important in many tissues such as the lungs (68), the eye (23),
the cardiovascular system (67), and plasma (37). This antioxidant activity is discussed in more detail in a later section.
In light of these exercise-related metabolic requirements for ascorbic acid, it
is plausible that periods of regular intense exercise, musculoskeletal growth, and
repair may promote the need for vitamin C in the diets of athletes. However, owing
to obvious limitations inherent to the biopsy of internal tissue in humans, any direct
assessment of the actual utilization of ascorbic acid in these reactions as a result of
either acute or chronic exercise is difficult. Given that ascorbic acid is an antioxidant
in plasma (37), changes in the plasma content of ascorbate may provide indirect
evidence of its utilization in neutralizing reactive oxidant species; nevertheless, no
studies of exercise-induced oxidative stress have reported changes in the circulating
levels of ascorbic acid derivatives, such as dehydroascorbic acid, which would offer
some indication of the metabolism of ascorbic acid itself. Two studies compared the
urinary output of ascorbic acid between sedentary individuals and athletes and
found no difference (32, 89). Hence, although there is in vitro evidence that ascorbic
acid is likely utilized in several exercise-related metabolic pathways, measurements
of ascorbic acid concentrations in blood and urine do not reflect its consumption
within these reactions.
An alternative approach to determining the physiological requirement for
ascorbic acid has been to compare the dietary intake of vitamin C between athletes
and nonathletes, in addition to assessing the response of athletes to vitamin C

supplementation. If athletes exhibit low plasma/serum ascorbic acid concentrations
pre-supplementation, then it may be anticipated that these values would increase
upon the addition of extra vitamin C within the diet.
Vitamin C Status
The vitamin C status of individuals has been assessed using several different methods. Dietary intakes of ascorbic acid have been used for the general assessment and
prediction of vitamin C status. The correlation between plasma/serum ascorbic acid
concentration and dietary ascorbic acid intake is only modest (r = 0.320.55; 89).
One group failed to find any relationship (44). The normal ranges for plasma and
leukocyte ascorbic acid concentrations are listed in Table 2. There has been some
debate as to which component of whole blood provides the most reliable index of
vitamin C status and whether whole blood does in fact reflect the true tissue stores of
the vitamin (18, 29, 42, 53, 65). In two studies, the responses to supplementation
with vitamin C were similar between plasma and leukocytes (9, 55). Furthermore,
plasma and leukocyte ascorbic acid concentrations are correlated with each other
(15). In view of the inherent difficulties associated with measuring the ascorbic acid
content of internal organs in humans, a combination of measurement of dietary
intakes, plasma/serum, and leukocyte ascorbic acid concentrations appears to be the
best available indication of vitamin C status.
Vitamin C Intakes of Exercising

and Non-exercising Individuals
The recommended daily allowance for vitamin C varies among countries. In Great
Britain and Canada, it is 30 mg, in New Zealand and Australia it is 40 mg, in the
United States it is 60 mg, whereas in Germany it is 75 mg (108). Vitamin C consumption is related to total energy intake (17). Some investigators have assessed the
dietary vitamin C intake of athletes on the basis of the recommended daily allowance (25, 75, 96, 106). With the exception of a small number of athletes in two
studies (25, 96), the majority of data on vitamin C intakes in athletes have indicated
that most athletes are receiving adequate amounts of vitamin C in their diets. Mean
Table 2 Normal Range for Whole-Body Ascorbic Acid Content, Plasma,

and Leucocyte Concentrations (54)
Body pool
(mg)
Plasma
mol/L
(mg/dL)
Mixed leucocytes
g/108 cells
(nmol/108 cells)
Mononuclear
leucocytes g/108 cells
(nmol/108 cells)
5001500
(1022 mg/kg)
2384
(0.41.5)
114301
(2053)
142250
(2544)
130 / Peake
intakes in athletes are reported to range from 90 to 140 mg per day. Intakes were
even higher in those athletes taking vitamin C supplements, which in one study was
found to be the most commonly used supplement among a large number of athletes
(34). Others have compared the intakes of exercising individuals with those of
sedentary controls and have generally observed higher intakes within the athletic
population (33, 34, 44, 81, 89).
Several studies have examined vitamin C intakes in athletes from a variety of
sports (25, 44, 89, 96). The results from a 24-h dietary recall suggested wide variation among sports, with some indication of seasonal variation, but no consistent
trends emerged (96). Low intakes have been observed in male gymnasts and wrestlers (96), and also in female athletes (25). In contrast to these findings, the results
from another study indicated very little difference in 1- or 7-day vitamin C intakes
among athletes from different sports, including wrestlers (96). Lower intakes in
some athletes may reflect dietary interventions directed at weight control in these
athletes, as it has been demonstrated that vitamin C intakes are related to total energy
intakes (34). Therefore, the amount of vitamin C in the diets of most athletes appears
to be sufficient, based on the recommended daily allowance. Another approach to
measuring vitamin C status has been to examine the response of plasma or serum
ascorbic acid concentrations to supplementation with varying doses of vitamin C.
Supplementation Studies
Athletes have been given vitamin C supplements ranging from 85 to 1500 mg
vitamin C, for periods of 1 day up to 8 months (5, 44, 58, 69, 76, 81, 83, 98, 106). The
effects of supplementation on both resting and exercise-induced changes in ascorbic acid concentration have been investigated (Table 3). There was little or no effect
of supplementation on plasma or serum ascorbic acid concentrations in several
studies (48, 58, 95, 98), whereas others have demonstrated increases in the concentration of ascorbic acid in blood following supplementation (5, 44, 69, 90, 106).
However, there are several issues to consider when interpreting these results.
The dose of vitamin C in the supplement, the regular dietary intakes of vitamin
C, and the concentration of ascorbic acid within plasma/serum and leukocytes prior
to supplementation would all appear to be important determinants of the response to
supplementation. Plasma ascorbic acid concentrations in one study plateaued at
vitamin C intakes of 250 mg and above per day, whereas the ascorbic acid content of
neutrophil, monocytes, and lymphocytes plateaued at lower intakes of 200 mg per
day (64). In another study, the optimal intake for absorption capacity was reported to
be 3 mg vitamin C per kilogram of body weight per day (89). The athletes in many of
the studies in Table 3 were receiving 200 mg of vitamin C per day in total.
Therefore, plasma/serum levels were likely close to saturation. Himmelstein et al.
(48) have reported that the athletes in their study had higher total dietary intakes of
vitamin C than sedentary individuals and consequently showed a smaller response
to supplementation. Similarly, Thompson et al. (101) observed a modest but significant increase in plasma ascorbic acid concentration but no change in the ascorbic
acid of lymphocytes following 2 weeks of supplementation with 400 mg vitamin C
per day. The mean (SD) dietary intake of vitamin C prior to supplementation was
147 (70) mg per day, and this level of intake was offered in explanation for the lack
of change in lymphocyte ascorbic acid content with supplementation.
1 month
2 weeks
Basketballers (n = 16) 250-mg placebo
500-mg placebo
200-mg placebo
1000-mg placebo
1000-mg placebo
1000-mg placebo
1000-mg placebo
Runners (n = 10)
Runners (n = 16)
Runners (n = 41)
Runners (n = 30)
Inactive (n = 29)
Inactive (n = 35)
227 ( 226) mg
312 ( 360) mg
378 ( 518) mg
442 ( 457) mg
ND
ND
ND
ND
201 ( 205) mg
320 ( 257) mg
ND
ND
ND
Plasma
Plasma
Plasma
Plasma
Serum
Plasma
Serum
Serum
Plasma
Serum
Whole blood
Blood
compartment
51 ( 19)
62 ( 22)
83 ( 10)
78 ( 13)
50.0 ( 53.0)
42.6 ( 33.3)
40.0 ( 21.4 )
34.0 ( 16.0)
49.1 ( 22.3)
52.9 ( 23.1)
76.3 ( 34.8)
53.3 ( 12.4)
ND
ND
67.0 ( 22.8)
73.3 ( 28.9)
ND
ND
Presupplement
52 ( 14)
72 ( 16)
80 ( 10)
80 ( 10)
69.8 ( 80.0)*
43.1 ( 29.4)
66.0 ( 29.5 )*
35.0 ( 16.0 )
47.0 ( 45.0)
15.4 ( 10.9)*
112.5 ( 36.3)*
56.2 ( 18.1)
55.7 ( 22.6)a
101.0 ( 16.1)
101.0 ( 22.2)
76.0 ( 17.0)a
57.3 ( 17.0)
Postsupplement
(48)
(90)
(84)
(95)
(69)
(98)
(44)
(106)
Ref.
Note. ND = no data available. *Significantly different compared to placebo (p < .01); significant increase (p < .05); significant increase (p = .005).
Placebo group used as comparison for effect of supplementation; bathletes from a variety of sports.
2 months
2 months
2 months
2 months
4.5 weeks
3 weeks
400-mg placebo
Inactive (n = 8)
Athletes (n = 86)
78 months
94.9 ( 17.5) mg
ND
550-mg placebo
1 month
108.7 ( 56.6) mg
Athletes (n = 86)b
200 mg
Athletes (n = 55)b
3 months
Dietary intake
87.8 ( 50.6) mg
85-mg placebo
Runners (n = 30)
Supplementation period
Inactive (n = 20)
Supplement
Ascorbic acid concentration (mol L1)
Mean (SD) Changes in Ascorbic Acid Concentration Following Dietary Supplementation Including Vitamin C
Subjects
Table 3
132 / Peake
Pre-supplementation levels of plasma/serum ascorbic also seem to affect the

response to supplementation. In one study (106), the athletes were seemingly randomly assigned to either a supplement or placebo group with no attempt to match the
groups for pre-supplementation whole blood ascorbic acid concentrations. Considering also that these pre-supplementation values were not reported, the true efficacy
of supplementation in this study is difficult to evaluate. Among the studies listed in
Table 3, serum ascorbic acid concentration increased by 4050% in those individuals with serum levels in the middle of the normal range (44, 69, 90). A much more
dramatic increase was reported among individuals with plasma ascorbic acid concentrations below the normal range; administration of an acute 500-mg dose of
vitamin C increased plasma ascorbic acid significantly from 26.3 (18.2) to 117
(28.3) mol/L (5). This latter result may indicate that athletes with low circulating
levels of ascorbic acid are more likely to exhibit a greater response to supplementation. Alternatively, it has been suggested that there may be an initial transient
increase in plasma ascorbic acid followed by a decrease during prolonged supplementation (98). However, data from Levine et al. (64) indicate that with a 60-mg
dose of vitamin C, plasma levels of ascorbic acid were saturated after 3 weeks and
remained stable thereafter. Hence, although no data are available on the saturation
of cellular stores of ascorbic acid, based on the plasma response, a minimum period
of 3 weeks of vitamin C supplementation may be necessary for the saturation of
cellular stores of ascorbic acid.
In several of the studies listed in Table 3, the participants were given a combination of vitamins and minerals, which may have influenced the absorption of
ascorbic acid and, consequently, the response to supplementation (98). The assessment of the effectiveness of supplementation is also likely to be influenced by the
type of vitamin C supplement and the timing of supplementation and blood sampling. In the study by Levine et al. (64), intravenous injection of vitamin C predictably caused a very rapid increase in plasma ascorbic acid concentration when compared to oral ingestion of the same dose. Furthermore, the appearance of ascorbic
acid in plasma occurred at a two-fold faster rate following the oral ingestion of 1250
mg compared to 250 mg vitamin C. Plasma ascorbic acid concentrations also returned to baseline twice as rapidly following the higher dose. Following the 200-mg
dose, plasma ascorbic acid remained elevated up to 10 hours after ingestion (64). In
contrast, Alessio et al. (1) found no difference in the effects of supplementation with
1000 mg for either 1 day or 2 weeks on postexercise changes in thiobarbituric acid
reactive substances or oxygen radical absorbance capacity. These factors should be
borne in mind when evaluating the alterations in blood measures following supplementation.
Several groups have attempted to address the issue of ascorbic acid requirements of athletes and have reported conflicting findings. One group observed that
athletes had intakes of vitamin C that were, on average, around 40% higher than the
controls (34). Together with the finding that plasma ascorbic acid concentrations
were in fact similar between the athletes and controls, this difference in intakes
would suggest that either athletes do have increased requirements for ascorbic acid,
and/or they retain more. In contrast, in the study by Guilland et al. (44), although
athletes demonstrated a marked increase in serum ascorbic acid concentration after
supplementation, this increase was of similar magnitude to that of sedentary controls.
The dietary intakes were also similar between the two groups. The fact that the
athletes did not exhibit a greater response to supplementation is suggestive that
regular exercise does not actually increase the requirement for ascorbic acid. Nevertheless, it is reasonable to contend that through its utilization in metabolic pathways
such as carnitine, noradrenaline, and collagen synthesis and antioxidant reactions,
athletes may require more vitamin C than sedentary individuals. At similar dietary
intakes, athletes may use a greater proportion of the vitamin C consumed in their diet
than nonathletes. Nonathletes may not need all of the vitamin C they consume and
may excrete the excess. In such a way, athletes would actually have increased
requirements. However, two studies of the ascorbic acid content in urine revealed no
difference between athletes and sedentary controls (32, 89).
In conclusion, the majority of existing data from dietary and supplementation
studies do not support the concept that athletes have increased requirements for
vitamin C for the following reasons. First, the dietary intake of athletes and sedentary controls is similar, as is the response to supplementation with vitamin C. Second, there does not appear to be a strong association between dietary intakes of
vitamin C and the concentration of ascorbic acid within the blood. Last, the
excretion of ascorbic acid in urinewhich may be taken as an assessment of
the utilization of vitamin C within the bodydoes not differ between athletes
and nonathletes.
Changes in Plasma, Serum, and Lymphocyte Ascorbic Acid

Concentrations Following Acute Exercise
Transient alterations in the concentration of ascorbic acid in plasma and lymphocytes have been reported in plasma and lymphocytes following acute exercise.
These changes are summarized in Table 4. Some studies have observed a rise of
variable magnitude in circulating ascorbic acid levels following exercise (28, 41,
42, 69, 84, 90), some have found no change (40, 66, 76, 82, 83, 101, 104), while
others have reported a reduction (16). Meydani et al. (70) observed that after 45 min
of downhill running, when the increase in plasma ascorbic acid was corrected for
changes in plasma volume, no significant change was seen. Several studies have
also demonstrated significant increases in lymphocyte ascorbic acid concentration
(41, 42, 100, 101).
It is worthy of note that in several of the studies listed in Table 4, plasma
ascorbic acid concentrations in the days following exercise were actually below
baseline (42, 66, 76, 83, 90). In the study by Gleeson et al. (42) post-race haemodilution
accounted for the reduced plasma ascorbic acid concentration at days 2 and 3;
however, it could not account for the significant decrement seen after 24 hours. This
decrement could possibly reflect alterations in the antioxidant demands of tissues in
the days following exercise. In the study by Liu et al. (66), commensurate with
reduced plasma ascorbic acid concentrations 4 days postexercise, there was also a
significant diminution of trapping antioxidant capacity of plasma and a significant
increase in the susceptibility of low-density lipoprotein (LDL) to oxidation. Muscle
damage resulting from strenuous exercise such as a marathon is likely to cause local
inflammatory reactions (97), and phagocytes involved with tissue damage are a
source of reactive oxidants (47). Although ascorbic acid is a water-soluble antioxidant
60 min box stepping
35 min uphill (+5%) walking

at 60% VO2max
Untrained (n = 24)
Untrained (n = 8)
90 min at 65% VO2max
Ironman triathlon
Marathon
Half-marathon
Half-marathon
Cyclists (n = 11)
Triathletes (n = 39)
Runners (n = 8)
Runners (n = 9)
Runners (n = 7)
35 min downhill (20%)

running at 60% VO2max
Activity
Plasma
Plasma
Lymphocytes
Plasma
Lymphocytes
Plasma
Plasma
Plasma
Serum
Blood
compartment
( 12.4)p
( 20.9)c
( 46.4)e
( 2.27)
( 21.2)p
( 20.6)c
( 56.6)e *
( 2.27)
38.4 ( 15.3)
52.7 ( 12.3)
15.6 ( 1.80)a
54.7 ( 26.6)
17.4 ( 3.96)a
51.5 ( 26.2)*
67.0 ( 15.9)
19.9 ( 2.70)a
79.0 ( 34.7)*
21.3 ( 7.35)a
95.4 ( 23.3)
94.8 ( 35.8)
96.0 ( 26.7)
98.9 ( 35.8)
48.1 ( 29.5)
10.8 ( 2.27)*
59.6
140.4
110.4
19.3
Post-exercise
41.1 ( 25.2)
18.2 ( 2.95)
53.3
112.5
99.9
21.0
Pre-exercise
Ascorbic Acid Concentration (mol L1)
Mean (SD) Changes in Ascorbic Acid Concentration Immediately Post-exercise
Subjects
Table 4
(42)
(28)
(continued)
(41)
(104)
(16)
(69)
Ref.
Corrected
for HC
134 / Peake
Plasma
Marathon
Ultramarathon
90 min running at 75% VO2max
Ultramarathon
Ultramarathon
Ultramarathon
Runners (n = 11)
Runners (n = 29)
Runners (n = 20)
Runners (n = 29)
Runners (n = 16)
Runners (n = 28)
103 ( 33.2)
134 ( 19.9)p
150 ( 14.8)c
161 ( 6.81)c
42.0 ( 21.4)p
95 ( 39.1)c,e
125 ( 22.0)p
145 ( 35.0)c
146 ( 30.0)c
116 ( 15.9)c
107 ( 11.9)p
183 ( 14.2)c
73.8 ( 8.5)p
82.9 ( 10.8)p
128 ( 10.2)c
153 ( 10.2)c
35.0 ( 16.0)p
66 ( 29.5)c,e
82 ( 40.0)p
130 ( 35.0)c
150 ( 40.0)c
118 ( 15.9)c
85.8 ( 11.9)p
69.8 ( 8.50)c
39.7 ( 6.8)p
56.8 ( 52.0)p
105.6 ( 117) c,e
41.9 ( 25.2)p
72.8 ( 55.2)c,e
86.0 ( 33.2)
Post-exercise
Pre-exercise
Ascorbic Acid Concentration (mol L1)
ND
(77)
(83)
(82)
(84)
(76)
(66)
(90)
Ref.
Corrected
for HC
Note. ND = no available data, HC = haemoconcentration. *Significant (p < .05); significant (p < .01); significant (p < .001); significant (p < .05)
versus placebo. aConcentration expressed as mol g1 of protein; cvitamin Csupplemented group; evitamin Esupplemented group; pplacebo group.
Plasma
Serum
Serum
Plasma
Serum
Serum
Marathon
Runners (n = 16)
Blood
compartment
Activity
(continued)
Subjects
Table 4
136 / Peake
and is therefore not directly involved in the protection of LDL against oxidation, it
does neutralize free radicals that can lead to oxidation of LDL (36) through mechanisms explained below. Hence, the decline in plasma ascorbic acid content observed
in the days following the marathon (66) may be attributed to the consumption of
ascorbic acid in oxidative reactions contributing to LDL oxidation. Alternatively, it
could also reflect the involvement of ascorbic acid in maintaining -tocopherol in a
reduced state (57)the plasma concentration of which was unchanged 4 days after
the marathon (66). Further research is warranted to confirm these concepts.
The reasons for differences with regard to exercise-induced changes between
these studies are not immediately clear, but some suggestions may be offered.
Differences in assay techniques to measure plasma ascorbic acid concentrations
may have contributed to the variability of findings between studies. Alternatively,
the validity of measuring ascorbic acid in the plasma or serum compared to leukocyte concentrations has been questioned (70, 88).
Differences in the extent of oxidative stress caused by exercise could also
have been a factor. Many of the studies in Table 4 involved prolonged endurance
exercise, which is likely to cause an increase in oxidative stress (28, 40, 66, 90), and
it has been suggested that oxidative stress is a stimulus for the release of ascorbic
acid from the adrenal gland (82). During exercise, it has been proposed that a prooxidant-antioxidant equilibrium is in operation, and that the intensity of exercise is
the critical factor in determining alterations in this equilibrium (110). It is possible
that differences in the degree of oxidative stress induced by exercise among the
studies might have caused some variation in the amount of ascorbic acid released. If
this concept is in fact true, then it follows logically that pre-exercise plasma/serum
ascorbic acid concentrations would also influence the extent of exercise-induced
oxidative stress and consequently, the magnitude of ascorbic acid release during
exercise in response to any oxidative challenge. Among the studies in Table 4, there
is partial support for this idea. When pre-exercise plasma/serum ascorbic acid concentrations were in the middle of the range (i.e., 4060 mol/L), there was an
increase in plasma/serum ascorbic acid (28, 41, 42, 69, 77, 90). In contrast,
when pre-exercise plasma/serum ascorbic acid concentrations were at the high end
of the range (i.e., 80 mol/L), less ascorbic acid was released (40, 66, 69). This was
particularly apparent in those studies involving supplementation (76, 82, 83).
There is also tentative evidence for an exercise mode effect on the magnitude
of changes in plasma ascorbic acid concentration. Among cyclists and triathletes the
increase was modest (40, 104), whereas among runners plasma ascorbic acid levels
appear to be elevated to a greater extent (41, 42, 66, 76, 82, 83, 90). Considering that
there are no existing data with respect to the possible effect(s) of exercise mode on
the degree of oxidative stress, the differences above cannot be reconciled on the
basis of differences in exercise-induced oxidative stress. Differences in tissue damage resulting from each form of exercise also seem an unlikely influence, in light of
the recent findings that supplementation with vitamin C did not influence inflammatory reactions to exercise-induced muscle damage (77, 84). Therefore, it remains to
be determined what exercise factors (i.e., intensity, duration, mode) affect changes
in plasma ascorbic acid during exercise. Future exercise studies could investigate
possible differences between different forms of exercise with respect to alterations
in antioxidant capacity and oxidative stress.
Chronic Effects of Exercise on Resting Plasma, Serum, and

Leukocyte Ascorbic Acid Concentrations
Despite evidence from comparisons of exercising and non-exercising individuals
indicating similar dietary intakes of vitamin C and similar responses to supplementation, the limited existing data on the effect of training or chronic exercise on
circulating ascorbic acid concentrations are unclear. A marginal deficiency in plasma
or serum ascorbic acid concentration has been reported in only a small number of
athletes (34, 90, 98), although the deficiency criteria varied among these studies.
Contrasting results have been obtained from cross-sectional comparisons of plasma
ascorbic acid concentrations between athletes and sedentary controls. In their study
of a variety of athletes, Fogelholm et al. (34) reported similar levels. The percentage
of both controls and athletes classified as ascorbic acid deficient (<22.7 mol/L)
was similar (01%). There was also no effect of weight or energy expenditure.
Brites et al. (13) found higher plasma ascorbic acid levels in soccer players compared to sedentary controls. Eight weeks of endurance training did not alter the
serum ascorbic acid concentration of athletes (32), yet the levels of ascorbic acid
were still higher than those of sedentary controls. In contrast, 3 months of training in
marathon runners caused a decline in all circulating antioxidants, except serum
ascorbic acid, which increased from a mean (SEM) serum concentration of 107
(5) to 180 (22) mol/L with training (7).
The concentration of ascorbic acid within plasma may be a less reliable index
of vitamin C status than that within leukocytes. The relationship between regular
physical training and circulating ascorbic acid concentrations was investigated in 6
sedentary subjects and 12 runners (88). The runners were divided into two groups of
6 based on training status. Whereas the plasma concentrations were not related to
training status, the lymphocyte concentrations in the highly trained runners were
significantly higher compared to the controls. In cyclists, measurements of leukocyte ascorbic acid concentration were made in the 3rd year of a 4-yr training cycle
and immediately prior to the Olympics (31). A significant reduction in the ascorbic
acid content of both lymphocytes and neutrophils was observed over the course of
the study. Compared to the pre-Olympic values, after the Olympics the mean (SD)
ascorbic acid concentration within lymphocytes had declined from 326 (86) to 24
(2) nmol per 108 cells, whereas neutrophil ascorbic acid concentration fell from 94
(22) to 69 (17) nmol per 108 cells. The decline in the ascorbic acid content of both
these cell types could be due to the consumption of ascorbic acid in neutralizing
reactive oxidants (3), particularly if the athletes in this study suffered any infections
(52).
For several reasons, few definitive conclusions can be drawn regarding the
effects of regular exercise on vitamin C status in athletes, as indicated by the levels
of ascorbic acid in serum, plasma, and leukocytes. First, the magnitude and direction
of changes in circulating ascorbic acid concentrations among the studies reported
above are variable. Second, in the studies reported above, it was not indicated if any
attempt was made to control the effect of exercise in the days prior to blood sampling
on circulating ascorbic acid concentrations, which fluctuate in the period following
exercise (42, 66, 76, 83, 90). Last, it is unclear whether comparisons can reasonably
be made for changes in ascorbic acid within different blood compartments.
138 / Peake
Ascorbic Acid and Cortisol

In spite of available data from several studies, the precise relationship between
changes in ascorbic acid and cortisol with exercise is yet to be elucidated. It was
originally suggested that ascorbic acid and cortisol are released simultaneously as
part of the general stress response to exercise (42). More recently, it has been
reported that when rats (a species capable of synthesizing ascorbic acid endogenously) performed one bout of intense exercise, there was a significant increase in
plasma ascorbic acid concentration 2 hrs postexercise that also corresponded to a
significant decline in the ascorbic acid content of the adrenal glands. These authors
suggested that the responses were indicative of a stress response (102). Unfortunately, no data were available on changes in cortisol. Others have proffered that
ascorbic acid and cortisol release during exercise are linked through oxidative stress
and inflammatory reactions (82). The evidence for and against these concepts is
discussed below.
The biosynthesis of cortisol in the adrenal gland begins with the conversion of
cholesterol to pregnenolone (see Figure 2). This is the rate-limiting step and is the
major site of action for ACTH. This step involves two hydroxylation reactions,
followed by the side-chain cleavage of cholesterol. The process requires molecular
oxygen and a pair of electrons and is regulated by a single enzyme, CYP11A1. The
electrons are donated by NADPH first to adrenodoxin reductase, a flavoprotein,
then to adrenodoxin, an iron-sulphur protein, and lastly to CYP11A1. Pregnenolone
is then transported out of the mitochondria before further synthesis of steroids
occurs. Both adrenodoxin reductase and adrenodoxin are also involved in the action
of CYP11B1 (11--hydroxylase) (4).
It was originally suggested that ascorbic acid must first be released from the
adrenal gland in order to permit the synthesis of cortisol, as ascorbic acid was
believed to impede electron transport required for the side-chain cleavage of cholesterol (61). In theory, this concept could explain several experimental observations.
First, it may be responsible for the apparent depletion of ascorbic acid within the
adrenal gland following ACTH treatment or conditions of stress (27, 51). Second, in
young chickens it has been shown that vitamin C administered in doses of 1000 mg
per kg of body weight ameliorated the immunosuppressive effects of exogenous
cortisol and high environmental temperatures, in addition to reducing the mortality
rates associated with such stress (99). Last, this concept may also account for the
observation of Gleeson et al. (42) that following exercise, increases in plasma
ascorbic acid correlated with a rise in plasma cortisol concentration (r = 0.89, p <
.01). They interpreted this finding as possible evidence that ascorbic acid and cortisol release from the adrenal gland could be coupled as part of the stress response to
exercise (42).
There is evidence against this coupling, however. Kipp and Rivers (60) demonstrated that the injection of ACTH in guinea pigs caused an increase in plasma
cortisol concentrations, in addition to a significant reduction in the ascorbate content within the adrenal gland. Moreover, ACTH significantly enhanced the uptake
of radio-labeled ascorbic acid into the adrenal gland. Nevertheless, despite the
release of cortisol, there was no change in the concentration of ascorbic acid within
plasma or any other tissues (60). Although Kipp and Rivers did not measure dehydroascorbic acid, the oxidation of ascorbic acid to dehydroascorbic acid during the
synthesis of cortisol (62) could account for its apparent depletion within the adrenal
gland upon ACTH stimulation. Freeman (35) has reported that 1 hour after the
injection of ACTH, relative to chickens not supplemented with vitamin C, there was
a greater increase in plasma corticosteroid concentrations in those chickens receiving additional vitamin C in their diet.
In another study by the same group, the vitamin C content of diets fed to
guinea pigs was manipulated, injections of ACTH were administered to the animals,
and the resultant alterations in adrenal ascorbic acid and plasma cortisol concentrations were measured (63). Although dietary vitamin C strongly influenced the concentration of ascorbic acid in the adrenal glands, it was without effect on basal or
ACTH-stimulated changes in plasma cortisol. Furthermore, among the animals
treated with ACTH, only a weak association was found between adrenal ascorbic
acid and plasma cortisol concentrations. Last, similarly to earlier findings (60),
ACTH treatment did not influence plasma ascorbic acid concentrations. Taken
together these data indicate that the absolute concentration of ascorbic acid within
the adrenal gland is not critical for the synthesis of cortisol (63). While ascorbic acid
is required for the synthesis of cortisol, ascorbic acid does not appear to be released
simultaneously with cortisol as a stress response.
In 1962, Jenkins (56) demonstrated a role for ascorbic acid in the synthesis of
cortisol, specifically in the terminal step of the conversion of 11-deoxycortisol to
cortisol (Figure 3). This finding was supported more recently by Moser (71) who
Figure 3 Biosynthesis of cortisol in the adrenal gland (4).
140 / Peake
cultured porcine adrenal cells for one week with and without 50 mol/L ascorbic
acid and stimulated the cells on days 2, 3, and 4 with ACTH. While the release of
cortisol on day 2 was not dependent on ascorbic acid, on days 3 and 4, the amount of
cortisol produced was significantly higher in those cells cultured with ascorbic acid.
In contrast, there was a marked decline in cortisol release after repetitive stimulation
in the cells cultured without ascorbic acid. Hence, ascorbic seems to be a critical
factor in the synthesis of cortisol. It has since been shown that ascorbic acid exerts its
influence in this process by acting as an antioxidant in this process, which stands to
reason considering the high concentration of ascorbic acid within the adrenal gland
(49). The transfer of electrons between NADPH, adrenodoxin reductase, adrenodoxin
and CYP11A1, produces superoxide radicals (46), which may impair the activity of
CYP11B1 (11--hydroxylase). Hornsby et al. (50) demonstrated that when primary
bovine adrenocortical cells were cultured in a serum-free medium, the addition of
cortisol as a pseudosubstrate caused a decline in 11--hydroxylase activity. However, in the presence of 50 mol/L cortisol, the addition of 5 mmol/L ascorbic acid
almost completely prevented this loss of 11--hydroxylase activity. This effect was
synergistic with low oxygen in the culture medium. Hence, rather than stimulating
steroidogenesis per se, ascorbic acid appears to act by protecting cytochromes, such
as CYP11B1.
Several other groups have subsequently investigated the possible relationship
between the release of ascorbic acid and cortisol during exercise by supplementing
athletes with 5001500 mg vitamin C in the week before, and on the day of, an
ultramarathon (76, 82, 83). In each of these studies, vitamin C caused a significant
increase in pre-race plasma/serum ascorbic acid concentrations and significantly
attenuated the post-exercise serum cortisol responses, relative to the placebo group.
In contrast to the work of Gleeson et al. (42), modest negative correlations have been
reported between changes in plasma/serum ascorbic acid and cortisol postexercise
(76, 77, 83). These findings are supported by other studies not involving athletes.
Supplementation with 1000 mg vitamin C for 16 weeks caused a significant reduction in resting serum cortisol concentrations in aged women with coronary heart
disease, but not in healthy age-matched controls (22). Patients who were given 1000
mg vitamin C while under anesthetic demonstrated a transient suppression of blood
ACTH and cortisol concentrations (73).
In accounting for these findings, it has been suggested that ascorbic acid is
utilized during exercise to counter oxidative stress, while cortisol is released to
counter inflammatory reactions resulting from exercise-induced muscle damage
(82). Oxidative stress has been implicated in chronic inflammation. The findings of
De la Fuente et al. (22) outlined above, are supportive of a link between oxidative
stress and inflammation. Under some conditions and in certain cell lines, a shift in
the glutathione redox state can activate NFB (26). It is unknown whether there is a
signal transduction pathway directly linking alterations in the glutathione redox
state with the release of cortisol, or if increases in ascorbic acid and cortisol with
exercise are incidental. Certainly, it is tempting to support the concept that oxidative
stress is a stimulus for the release of cortisol during exercise, particularly on the
basis that elevated plasma ascorbic acid concentrationswhich presumably signaled adequate antioxidant defense capacityattenuated the cortisol response (76,
82, 83). Nevertheless, it must be questioned whether there is in fact a link between
oxidative stress reactions and the inflammatory response to exercise-induced muscle
damage (77, 84).
Figure 4 Proposed relationship between exercise-induced oxidative stress and inflammatory responses to muscle damage.
Despite the attenuation of cortisol release following vitamin C supplementation, this effect may actually have promoted the inflammatory response (see Figure
4), as indicated by significantly higher levels of acute phase reactants such as Creactive protein and creatine kinase (83), and significantly reduced concentrations
of anti-inflammatory cytokines such as interleukin-1 receptor antagonist and
interleukin-10 (76, 82). Another group demonstrated that supplementation with a
smaller dose of vitamin C (400 mg) for 2 weeks prior to exercise did not alter the
cortisol response, yet the postexercise plasma concentration of the anti-inflammatory cytokine interleukin-6 was significantly reduced (101). Therefore, it seems
unlikely that exercise-induced oxidative stress causes the release of cortisol from
the adrenal gland, at least not in order to counter inflammation. However, the effects
of vitamin C could depend on the supplementation dosage.
Two novel, yet largely speculative hypotheses are presented below to account
for the observation of attenuated postexercise cortisol levels following vitamin C
supplementation (76, 82, 83). High doses of vitamin C may inhibit the synthesis of
cortisol, possibly through pro-oxidant effects. Under certain conditions in vitro,
ascorbic acid may work as a pro-oxidant rather than as an antioxidant by reducing
transition metal ions (reaction 1), which in turn drives the Fenton reaction (reactions
2 and 3), potentially resulting in oxidative stress (45).
AH + Fe3+ A + Fe2+ + H+ (reaction 1)
(1)
H2O2 + Fe2+ HO + Fe3+ + OH (reaction 2)
(2)
LOOH + Fe2+ LO + Fe3+ + OH (reaction 3)
(3)
There is also strong evidence against a pro-oxidant effect of ascorbic acid,

however (6). A series of in vitro trials were performed in which iron was added to
plasma in amounts exceeding the latent iron-binding capacity. While this caused
appreciable oxidation of ascorbic acid and an increase in bleomycin detectable iron,
which is potentially catalytic for free radical reactions, ascorbic acid maintained its
antioxidant activity, and there was no detectable alteration in the concentration of
F2-isoprostane and protein carbonyls as markers of oxidative stress (6).
In spite of this evidence, data from a more recent study do lend support to the
concept that ascorbic acid can act as a pro-oxidant under some conditions (21).
Individuals were given either a placebo, or 12.5 mg vitamin C and 10 mg of the
142 / Peake
antioxidant N-acetylcysteine per kg body weight for 7 days prior to a brief, intense
session of eccentric resistance exercise. The plasma concentration of serum bleomycin
detectable iron was elevated in both groups in the days after exercise but was
significantly higher in the supplement group. Supplementation also significantly
increased plasma total antioxidant status. Importantly, there was evidence of oxidative stress. In the supplemented group, the plasma concentrations of 8isoprostaglandin F2 tended to be higher (p = .07), whereas lipid hydroperoxide
levels were significantly higher (p < .001). Although no correlations were reported,
it is tempting to speculate that the combination of increases in serum-free iron,
plasma antioxidant capacity, and lipid peroxidation markers were indicative of prooxidant effects of ascorbic acid during exercise. Unfortunately, plasma ascorbic
acid concentrations were not measured, as this may have provided further insight
into the mechanisms in operation. The interaction between Fe3+ and ascorbic acid
may depend on the ratio of ascorbic acid to dehydroascorbic acid (87). It is also
unknown if there was any effect of the N-acetylcysteine on plasma ascorbic acid
concentration (21).
Of interest to the current discussion is whether interactions between ascorbic
acid and iron could also influence the synthesis of cortisol in the adrenal gland
during exercise. There is evidence suggesting that oxidative conditions impair the
activity of the enzyme responsible for cortisol synthesis, 11--hydroxylase (50).
The production of superoxide anions by polymorphonuclear cells during exercise
(47) could possibly induce the release of catalytic iron from ferritin (86) and/or
myoglobin (85). The combined effects of elevated concentrations of serum-free
iron and ascorbic acid in the circulation during exercise could promote the formation of reactive oxidants (93), leading in turn to impaired activity of 11--hydroxylase and less synthesis of cortisol, which could possibly explain the recent findings
of Peters et al. (82, 83). In evidence against this novel hypothesis, Nieman et al. (77)
recently reported that vitamin C supplementation had no effect on plasma F2isoprostane and lipid hydroperoxide concentrations following an ultramarathon
race, yet postexercise serum cortisol correlated negatively with plasma ascorbic
acid (r = 0.50, p = .0006).
The second hypothesis offered presently is related to a possible role for ascorbic acid in glucose metabolism during exercise. Although ascorbic acid within the
adrenal gland may not influence ACTH activity and cortisol synthesis directly (63),
high concentrations of ascorbic acid in other tissues such as the liver could possibly
have a regulatory effect on the release of cortisol. The evidence for this concept
comes from a study by Kodama et al. (62) who investigated the effect of infusing a
glucose-electrolyte solution containing 200 mmol/L ascorbic acid over 1.5 h into a
male volunteer. The concentration of ascorbic acid in plasma rose above 1000
mol/L within 0.5 h, and began to decrease thereafter, reaching baseline 3 h later.
Interestingly, the decline in plasma ascorbic acid corresponded to a rapid and dramatic increase in plasma cortisol and ACTH concentrations. Kodama et al. proposed that the liver acts as a vitamin C/cortisol absorber for two reasons: First, the
liver contains high concentrations of ascorbic acid (49) and, second, both cortisol
(59) and possibly even ascorbic acid are involved in the regulation of carbohydrate
metabolism within the liver (11).
Using human erythrocytes as a model of peripheral tissues, Braun et al. (11)
demonstrated that the oxidized form of ascorbic acid, dehydroascorbic acid, is
converted to glucose-6-phosphate through the pentose phosphate pathway and/or
gluconeogenesis. They proposed that through glycolysis, glucose-6-phosphate is

metabolized to form lactate, which is then transported to the liver to be converted
back to glucose-6-phosphate and eventually, glucose (11). Interestingly, it has also
been demonstrated that glucose can inhibit the cellular uptake of dehydroascorbic
acid (105), and that high concentrations of plasma ascorbic acid inhibit the glucoseinduced secretion of insulin from the pancreas (8). These factors could influence the
role of ascorbic acid in gluconeogenesis described above. Recently, cortisol was
also shown to enhance gluconeogenesis in humans. A high dose cortisol infusion
was administered to fasted individuals, and this caused a significant 10% increase in
gluconeogenesis as a proportion of hepatic glucose production (59). Therefore, it
may be hypothesized that high plasma concentrations of ascorbic acid following
supplementation with large doses of vitamin C could possibly compete with cortisol
by maintaining blood glucose concentrations via the stimulation of gluconeogenesis during prolonged exercise. There is support for this concept in the study by
Peters et al. (82) because although supplementation with 1500 mg vitamin C attenuated the cortisol response to exercise relative to those athletes taking 500 mg vitamin
C or a placebo, the postexercise alterations in plasma glucose concentrations were
similar between the three groups. These are novel concepts that warrant further
investigation.
In summary, ascorbic acid is necessary for the synthesis of cortisol within the
adrenal gland. Increases in the plasma concentration of ascorbic acid during exercise likely occur to counter exercise-induced oxidative stress, but do not appear to
cause the release of cortisol, either as a general stress response or to counter inflammatory reactions. It is possible, yet unproven, that the synthesis of cortisol during
exercise may be influenced by interactions between ascorbic acid and free iron and/
or that ascorbic acid may have a role in glucose metabolism during prolonged
exercise.
Ascorbic Acid and Exercise-Induced Oxidative Stress

If ascorbic acid is released during exercise in response to oxidative stress (82), then
what exactly is the stimulus for its release? A comprehensive review of free radicals
in their regulation of physiological functions was published recently (26). The
concentration of reactive oxygen species depends on the balance between their rate
of production and their rate of clearance by various antioxidant compounds and
enzymes. Cells or tissues are in a stable state if the rates of oxidant formation and
antioxidant scavenging capacity are constant and in balance. The intracellular thiol/
dilsulfide redox state is the key determinant of this redox homeostasis. An alteration
of this redox state, which may occur either by an increase in the concentration of
reactive oxidant species or a decline in the activity of one or more antioxidant
systems, induces redox-sensitive signal cascades that lead to enhanced expression
of antioxidant enzymes, elevated concentrations of nonenzymatic antioxidants or
an increase in the cysteine transport system. This latter response may in turn facilitate an increase in intracellular glutathione in certain cell types (26). Within the
context of exercise, the thiol/disulphide ratio may represent the concept of the prooxidant-antioxidant equilibrium, as discussed by Zembron-Lacny and Szyszka (110).
If the production of reactive oxidants during exercise disturbs the intracellular
redox state, what role does ascorbic acid play in restoring the balance? Ascorbic acid
represents the first line of antioxidant defense in human plasma, and also effectively
144 / Peake
Figure 5 Antioxidant activity of ascorbic acid in neutralizing aqueous radicals and

regenerating alpha-tocopherol. See text for further explanation. AscH, ascorbate; Asc,
ascorbyl radical; DHA, dehydroascorbic acid; GSSG, oxidized glutathione; GSH, reduced glutatione; LOO, lipid peroxyl radical; LOOH, non-radical product, TocH,
alphatocopherol; Toc, alphatocopherol radical.
protects low-density lipoprotein against oxidative stress reactions (37, 38). During
exercise, ascorbic acid likely exerts its antioxidant activity both directly and also in
concert with alpha-tocopherol and glutathione (Figure 5). The hydrogen atoms
produced in the oxidation of ascorbic acid first to ascorbyl radical and then to
dehydroascorbate (see Figure 1), react with a lipid peroxyl radical (LOO) to form
the non-radical product, LOOH. Trapping of LOO prevents this radical from attacking polyunsaturated fatty acid side chains (LH) and other lipoproteins in plasma,
and thereby halts the chain reaction of lipid peroxidation (reaction 4) (36).
LOO + L'H LOOH + L' (reaction 4)
(4)
Dehydroascorbic acid is reduced back to ascorbic acid by glutathione (109) and

enzymatic reduction (80). Ascorbic acid may assist alpha-tocopherol in trapping
aqueous radicals. Alpha-tocopherol also traps peroxyl radicals before they propagate radical chain reactions leading to lipid peroxidation (36). By donating a hydrogen atom, ascorbic acid may reduce the alpha-tocopherol radical produced in this
trapping reaction back to alpha-tocopherol (57) (Figure 5).
In view of this role for ascorbic acid, it has been suggested that oxidative stress
induced by regular exercise could increase vitamin C requirements (13, 31, 95).
However, the evidence for this postulate is conflicting. Some studies have noted
changes in biomarkers of oxidative stress without any change in circulating levels of
ascorbic acid (28, 40, 90), some have demonstrated increases in ascorbic acid without a change in indices of oxidative stress (7, 77, 95, 104), and others have reported
commensurate increases in both ascorbic acid and oxidative stress indicators (58,
101). While an increase in indices of oxidative stress following exercise may not
necessarily correspond to an elevation of ascorbic acid levels per se, there is some
evidence supporting more generalized antioxidant responses to oxidative stress
during exercise. Following a half-marathon, plasma malondialdehyde increased
after exercise, in conjunction with a dramatic increase in the total antioxidant capacity of blood (19, 20). The majority of data have indicated that the vitamin C supplementation does not completely prevent, but attenuates, exercise-induced oxidative
stress as indicated by increases in the levels of serum diene conjugation (103),
thiobarbituric acidreactive substances (90), malondialdehyde and exhaled pentane

(5, 58, 101), the oxidation of low-density lipoproteins (5, 94), and electron spin
resonance (5). Another group (1) demonstrated that supplementation with 1000 mg
vitamin C attenuated the increase in thiobarbituric acidreactive substances following submaximal exercise, but there was no effect on oxygen radical absorbance
capacity.
The results from two other groups contrast with the findings above. Relative
to a placebo group, supplementation with 1000 mg vitamin C pre-exercise was
without effect on plasma malondialdehyde concentrations after 90 min of highintensity shuttle running (100). This suggests that supplementation was ineffective
because endogenous antioxidant defenses were adequate prior to supplementation.
However, in apparent contradiction to this suggestion, they also contended that
antioxidant defenses had been overwhelmed as indicated by increased levels of
malondialdehyde after exercise. One month of supplementation with 1000 mg vitamin C was also without effect on serum ascorbic acid concentrations, yet it reduced
resting levels of plasma lipoperoxide. The placebo group displayed a decline in
serum ascorbic acid concentration but no change in plasma lipoperoxide (95). It was
not stated whether the effects of recent exercise had been controlled for at the time of
sampling, as this factor could have influenced the results.
The disparity among these studies could be due to the fact that ascorbic acid is
a water-soluble antioxidant, and indices of oxidative stress are based on lipid
peroxidation. Ascorbic acid is effective in preventing the initiation of lipid
peroxidation. Aside from the chain-propagating reaction (reaction 4), lipid peroxyl
radicals may also be converted to a cyclic peroxide, which then degrades to other
breakdown products, such as malondialdehyde (36). Ascorbic acid is not effective
in preventing the formation of these products, and this could explain some of the
discrepancies between changes in plasma/serum ascorbic acid concentration and
markers of oxidative stress in the studies above.
Conclusions
Ascorbic acid is known to be involved in a number of metabolic pathways that are
important to exercise. Nevertheless, reports of alterations in the concentration of
ascorbic acid within plasma/serum or urine following vitamin C supplementation
and exercise do not support the concept that athletes have a greater requirement for
vitamin C in their diets. During acute exercise, it is commonly contended that the
major role of ascorbic acid is in counteracting oxidative stress. However, whether
ascorbic acid is oxidized to dehydroascorbic acid in these reactions during exercise
has not been investigated to date. Future exercise studies should investigate measuring the concentration of ascorbic acid derivatives, such as dehydroascorbic acid
following exercise. It is conceivable that ascorbic acid is efficiently recycled by
exercise, thereby obviating the need for supplementation beyond regular dietary
intakes. Two novel hypotheses have been put forward in this review. First, in addition to causing lipid peroxidation, the products of prooxidant reactions that potentially follow supplementation with high doses of vitamin C may have more wideranging effects on other aspects of physiological function. Second, although it has
been questioned whether cortisol is a factor in stimulating gluconeogenesis, there is
recent evidence that lends tentative support to the idea that both cortisol and ascorbic
acid have a regulatory influence on gluconeogenesis. These concepts await further
146 / Peake
investigation before they can be applied to the control of physiological systems

during exercise.
References
1. Alessio, H.M., A.H. Goldfarb, and G. Cao. Exercise-induced oxidative stress before and
after vitamin C supplementation. Int. J. Sport. Nutr. 7:1-9, 1997.
2. Anderson, R. The immunostimulatory, anti-inflammatory and anti-allergic properties of
ascorbate. Adv. Nutr. Res. 6:19-45, 1984.
3. Anderson, R., M. Smit, G. Joone, and A. van Staden. Vitamin C and cellular immune
functions. Ann. N.Y. Acad. Sci. 587:33-48, 1989.
4. Aron, D., J. Findling, and J. Tyrrell. Glucocorticoids and adrenal androgens. In: Basic
and Clinical Endocrinology, F. Greenspan and D. Gardner (Eds.). New York: Lange
Medical Books/McGraw-Hill, 2001, pp. 338-339.
5. Ashton, T., I.S. Young, J.R. Peters, E. Jones, S.K. Jackson, B. Davies, and C.C. Rowlands.
Electron spin resonance spectroscopy, exercise, and oxidative stress: an ascorbic acid
intervention study. J. Appl. Physiol. 87:2032-2036, 1999.
6. Berger, T.M., M.C. Polidori, A. Dabbagh, P.J. Evans, B. Halliwell, J.D. Morrow, L.J.
Roberts, 2nd, and B. Frei. Antioxidant activity of vitamin C in iron-overloaded human
plasma. J. Biol. Chem. 272:15656-15660, 1997.
7. Bergholm, R., S. Makimattila, M. Valkonen, M.L. Liu, S. Lahdenpera, M.R. Taskinen,
A. Sovijarvi, P. Malmberg, and H. Yki-Jarvinen. Intense physical training decreases
circulating antioxidants and endothelium-dependent vasodilatation in vivo. Atherosclerosis. 145:341-349, 1999.
8. Bergsten, P., A.S. Moura, I. Atwater, and M. Levine. Ascorbic acid and insulin secretion
in pancreatic islets. J. Biol. Chem. 269:1041-1045, 1994.
9. Blanchard, J., K. Conrad, R. Watson, P. Garry, and J. Crawley. Comparison of plasma,
mononuclear and polymorphonuclear leucocyte vitamin C levels in young and elderly
women during depletion and supplementation. Eur. J. Clin. Nutr. 43:97-106, 1989.
10. Branch, D. High-dose vitamin C supplementation increases plasma glucose. Diabetes
Care. 22:1218-1219, 1999.
11. Braun, L., F. Puskas, M. Csala, G. Meszaros, J. Mandl, and G. Banhegyi. Ascorbate as a
substrate for glycolysis or gluconeogenesis: evidence for an interorgan ascorbate cycle.
Free Radic. Biol. Med. 23:804-808, 1997.
12. Bremer, J. Carnitinemetabolism and functions. Physiol. Rev. 63:1420-1480, 1983.
13. Brites, F., P. Evelson, M. Christiansen, M. Nicol, M. Basilico, R. Wikinski, and S.
Llesuy. Soccer players under regular training show oxidative stress but an improved
plasma antioxidant status. Clin. Sci. 96:381-385, 1996.
14. Buettner, G.R. The pecking order of free radicals and antioxidants: lipid peroxidation,
alpha-tocopherol, and ascorbate. Arch. Biochem. Biophys. 300:535-543, 1993.
15. Burr, M., P. Elwood, D. Hole, R. Hurley, and R. Hughes. Plasma and leucocyte ascorbic
acid levels in the elderly. Am. J. Clin. Nutr. 27:144-151, 1974.
16. Camus, G., A. Felekidis, J. Pincemail, G. Deby-Dupont, C. Deby, A. Juchmes-Ferir, R.
Lejeune, and M. Lamy. Blood levels of reduced/oxidised glutathione and plasma concentration of ascorbic acid during eccentric and concentric exercises at similar energy
cost. Arch. Int. Physiol. Biochim. Biophys. 102:67-70, 1994.
17. Carbajal, A., C. Nunez, and O. Moreiras. Energy intake as a determinant factor of
vitamin status in healthy young women. Int. J. Vitam. Nutr. Res. 66:227-231, 1996.
18. Castelli, A., G. Martorana, E. Meucci, and G. Bonetti. Vitamin C in normal human
mononuclear and polymorphonuclear leucocytes. Acta. Vitaminol. Enzymol. 4:189-196,
1982.
19. Child, R., D. Wilkinson, and J. Fallowfield. Effects of a training taper on tissue damage
indices, serum antioxidant capacity and half-marathon running performance. Int. J.
Sports Med. 21:325-331, 2000.
20. Child, R., D. Wilkinson, J. Fallowfield, and A. Donnelly. Elevated serum antioxidant
capacity and plasma malondialdehyde concentration in response to a simulated halfmarathon run. Med. Sci. Sports Exerc. 30:1603-1107, 1998.
21. Childs, A., C. Jacobs, T. Kaminski, B. Halliwell, and C. Leeuwenburgh. Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an
acute muscle injury induced by eccentric exercise. Free Rad. Biol. Med. 31:745-753,
2001.
22. De la Fuente, M., M. Ferrandez, M. Burgos, A. Soler, A. Prieto, and J. Miquel. Immune
function in aged women is improved by ingestion of vitamins C and E. Can. J. Physiol.
Pharmacol. 76:373-380, 1998.
23. Delamere, N. Ascorbic acid and the eye. In: Ascorbic Acid: Biochemistry and Biomedical Cell Biology, J. Harris (Ed.). New York: Plenum, 1996, pp. 313-329.
24. Dhariwal, K., P. Washko, W. Hartzell, and M. Levine. Ascorbic acid within chromaffin
granules. In situ kinetics of norepinephrine biosynthesis. J. Biol. Chem. 264:1540415409, 1989.
25. Di Chen, J., J. Wang, K. Li, Y. Zhao, S. Wang, Y. Jiao, and X. Hou. Nutritional problems
and measures in elite and amateur athletes. Am. J. Clin. Nutr. 49:1084-1089, 1989.
26. Droge, W. Free radicals in the physiological control of cell function. Physiol. Rev. 82:4795, 2002.
27. Dugal, L., and M. Therein. Ascorbic acid and acclimatization to cold environment. Can.
J. Res. 25:111-136, 1947.
28. Duthie, G., J. Robertson, R. Maughan, and P. Morrice. Blood antioxidant status and
erythrocyte lipid peroxidation following distance running. Arch. Biochem. Biophys.
282:78-83, 1990.
29. Evans, R., L. Currie, and A. Campbell. The distribution of ascorbic acid between various
cellular components of blood, in normal individuals, and its relation to the plasma
concentration. Br. J. Nutr. 47:473-482, 1982.
30. Evans, W. Vitamin E, vitamin C, and exercise. Am. J. Clin. Nutr. 72:647S-652S, 2000.
31. Ferrandez, M., M. Maynar, and M. De la Fuente. Effects of a long-term training program
of increasing intensity on the immune function of indoor Olympic cyclists. Int. J. Sports
Med. 17:592-596, 1996.
32. Fishbaine, B., and G. Butterfield. Ascorbic acid status of running and sedentary men. Int.
J. Vit. Nutr. Res. 54:273, 1975. (Abstract)
33. Fogelholm, G. Micronutrient status in females during a 24-week fitness-type exercise
program. Ann. Nutr. Metab. 36:209-218, 1992.
34. Fogelholm, G., J.-J. Himberg, K. Alopaues, C.-G. Gref, J. Laakso, J. Lehto, and H.
Mussalo-Rauhamaa. Dietary and biochemical indices of nutritional status in male athletes and controls. J. Am. Coll. Nutr. 11:181-191, 1992.
35. Freeman, B. Ascorbic acid and adrenal cortical activity in the immature domestic fowl.
Comp. Biochem. Physiol. A. 67:183-186, 1980.
36. Frei, B. Reactive oxygen species and antioxidant vitamins: mechanisms of action. Am. J.
Med. 97:3A-13S, 1994.
148 / Peake
37. Frei, B., L. England, and B. Ames. Ascorbate is an outstanding antioxidant in human
plasma. Proc. Natl. Acad. Sci. U.S.A. 86:6377-6381, 1989.
38. Frei, B., R. Stocker, and B. Ames. Antioxidant defenses and lipid peroxidation in human
blood plasma. Proc. Natl. Acad. Sci. U.S.A. 85:9748-9752, 1988.
39. Gerster, H. The role of vitamin C in athletic performance. J. Am. Coll. Nutr. 8:636-643,
1989.
40. Ginsburg, G., A. Agil, M. OToole, E. Rimm, P. Douglas, and N. Rifai. Effects of a single
bout of ultraendurance exercise on lipid levels and susceptibility of lipids to peroxidation
in triathletes. J. Am. Med. Assoc. 276:221-225, 1996.
41. Gleeson, M., and R. Maughan. Acute effect of exercise on ascorbate content of plasma
and lymphocytes. Proc. Nutr. Soc. 46:89A, 1986. (Abstract)
42. Gleeson, M., J. Robertson, and R. Maughan. Influence of exercise on ascorbic acid status
in man. Clin. Sci. 73:501-505, 1987.
43. Goldenberg, H., H. Landertshamer, and H. Laggner. Functions of vitamin C as a mediator of transmembrane electron transport in blood cells and related cell culture models.
Antiox. Redox Signal. 2:189-196, 2000.
44. Guilland, J.-C., T. Peneranda, C. Gallet, V. Boggio, F. Fuchs, and J. Klepping. Vitamin
status of young athletes including the effects of supplementation. Med. Sci. Sports Exerc.
21:441-449, 1989.
45. Halliwell, B. Vitamin C: antioxidant or pro-oxidant in vivo? Free Radic Res. 25:439454, 1996.
46. Hanukoglu, I., R. Rapoport, L. Weiner, and D. Sklan. Electron leakage from the mitochondrial NADPH-adrenodoxin reductase- adrenodoxin-P450scc (cholesterol side chain
cleavage) system. Arch. Biochem. Biophys. 305:489-498, 1993.
47. Hessel, E., A. Haberland, M. Muller, D. Lerche, and I. Schimke. Oxygen radical generation of neutrophils: a reason for oxidative stress during marathon running? Clin. Chim.
Acta. 298:145-156, 2000.
48. Himmelstein, S., R. Robergs, K. Koehler, S. Lewis, and C. Qualls. Vitamin C supplementation and upper respiratory tract infections in marathon runners. J. Exerc. Physiol.
Online. 1:1998.
49. Hornig, D. Distribution of ascorbic acid, metabolites and analogues in man and animals.
Ann. NY Acad. Sci. 258:103-118, 1975.
50. Hornsby, P.J., S.E. Harris, and K.A. Aldern. The role of ascorbic acid in the function of
the adrenal cortex: studies in adrenocortical cells in culture. Endocrinology. 117:12641271, 1985.
51. Hughes, R., and P. Nicholas. Effects of caging on the ascorbic acid content of the adrenal
glands of the guinea-pig and gerbil. Life Sci. 10:53-55, 1971.
52. Hume, R., and E. Weyers. Changes in leucocyte ascorbic acid during the common cold.
Scott. Med. J. 18:3-7, 1973.
53. Jacob, R. Assessment of human vitamin C status. J. Nutr. 120:1480-1485, 1990.
54. Jacob, R. Vitamin C. In: Modern Nutrition in Health and Disease, M. Shils, J. Olson and
M. Shike (Eds.). Hagerstown, MD: Williams & Wilkins, 1994, pp. 432-448.
55. Jacob, R., J. Skala, and S. Omaye. Biochemical indices of human vitamin C status. Am. J.
Clin. Nutr. 46:818-826, 1987.
56. Jenkins, J. The effect of ascorbic acid on adrenal steroid synthesis in vitro. Endocrinology. 70:267-271, 1962.
57. Kagan, V.E., E.A. Serbinova, T. Forte, G. Scita, and L. Packer. Recycling of vitamin E in
human low density lipoproteins. J. Lipid Res. 33:385-397, 1992.
58. Kanter, M., L. Nolte, and J. Holloszky. Effects of an antioxidant vitamin mixture on lipid
peroxidation at rest and post-exercise. J. Appl. Physiol. 74:965-969, 1993.
59. Khani, S., and J.A. Tayek. Cortisol increases gluconeogenesis in humans: its role in the
metabolic syndrome. Clin Sci. 101:739-747, 2001.
60. Kipp, D., and J. Rivers. Uptake and release of ascorbic acid in the guinea pig after
injection of ACTH. J. Nutr. 117:1570-1575, 1987.
61. Kitabchi, A.E. Ascorbic acid in steroidogenesis. Nature. 215:1385-1386, 1967.
62. Kodama, M., T. Kodama, M. Murakami, and M. Kodama. Vitamin C infusion treatment
enhances cortisol production of the adrenal via the pituitary ACTH route. In Vivo.
8:1079-1086, 1994.
63. Laney, P., J. Levy, and D. Kipp. Plasma cortisol and adrenal ascorbic acid levels after
ACTH treatment with a high intake of ascorbic acid in the guinea pig. Ann. Nutr. Metab.
34:85-92, 1990.
64. Levine, M., C. Conry-Cantilena, D. Wang, R. Welch, P. Washko, K. Dhariwal, J. Park,
A. Lazarev, J. Graumlich, J. King, and L. Cantilena. Vitamin C pharmacokinetics in
healthy volunteers: evidence for a recommended dietary allowance. Proc. Natl. Acad.
Sci. U.S.A. 93:3704-3709, 1996.
65. Levine, M., and W. Hartzell. Ascorbic acid: the concept of optimum requirements. Ann.
NY Acad. Sci. 498:424-444, 1987.
66. Liu, M.-L., R. Bergholm, S. Kimattila, S. Lahdenpera, M. Valkonen, H. Hilden, H. YkiJarvinen, and M.-R. Taskinen. A marathon run increases the susceptibility of LDL to
oxidation in vitro and modifies plasma antioxidants. Am. J. Physiol. 276:E1083-E1091, 1999.
67. Lynch, S., J. Gaziano, and B. Frei. Ascorbic acid and atherosclerotic cardiovascular
disease. In: Ascorbic Acid: Biochemistry and Biomedical Cell Biology, J. Harris (Ed.).
New York: Plenum, 1996, pp. 331-367.
68. Maritz, G. Ascorbic acid. Protection of lung tissue against damage. In: Ascorbic Acid:
Biochemistry and Biomedical Cell Biology, J. Harris (Ed.). New York: Plenum, 1996,
pp. 265-291.
69. Maxwell, S., P. Jakeman, C. Leugen, and G. Thorpe. Changes in plasma antioxidant
status during eccentric exercise and the effect of vitamin supplementation. Free Rad.
Res. Comm. 19:191-202, 1993.
70. Meydani, M., W.J. Evans, G. Handelman, L. Biddle, R.A. Fielding, S.N. Meydani, J.
Burrill, M.A. Fiatarone, J.B. Blumberg, and J.G. Cannon. Protective effect of vitamin E
on exercise-induced oxidative damage in young and older adults. Am. J. Physiol. 264:R992R998, 1993.
71. Moser, U. Physiology and metabolism of ascorbic acid. In: Ascorbic Acid in Domestic
Animals: Proceedings of the Second Symposium, C. Wenk, R. Fenster, and L. Volker
(Eds.). Basel: F Hoffman-La Roche, 1992, pp. 3-16.
72. Murthy, A.S., H.T. Keutmann, and B.A. Eipper. Further characterization of
peptidylglycine alpha-amidating monooxygenase from bovine neurointermediate pituitary. Mol. Endocrinol. 1:290-299, 1987.
73. Nathan, N., J. Vandroux, and P. Feiss. Role of vitamin C on adrenocortical effects of
etomidate. Ann. Fr. Anesth. Reanim. 10:329-332, 1991.
74. Nelson, P.J., R.E. Pruitt, L.L. Henderson, R. Jenness, and L.M. Henderson. Effect of
ascorbic acid deficiency on the in vivo synthesis of carnitine. Biochim. Biophys. Acta.
672:123-127, 1981.
75. Nieman, D., J. Butler, L. Pollett, S. Dietrich, and R. Lutz. Nutrient intake of marathon
runners. J. Am. Diet. Assoc. 89:1273-1278, 1989.
150 / Peake
76. Nieman, D., E.M. Peters, D. Henson, E. Nevines, and M. Thompson. Influence of vitamin C supplementation on cytokine changes following an ultramarathon. J. Interferon
Cytokine Res. 20:1029-1035, 2000.
77. Nieman, D.C., D.A. Henson, S. McAnulty, L. McAnulty, N. Swick, A. Utter, D. Vinci,
S.J. Opiela, and J.D. Morrow. Influence of vitamin C supplementation on oxidative and
immune changes after an ultramarathon. J. Appl. Physiol. 92:1970-1977, 2002.
78. Norris, J. The scurvy disposition: heavy exertion as an exacerbating influence on
scurvy in modern times. Bull. Hist. Med. 57:325-338, 1983.
79. Padh, H. Cellular functions of ascorbic acid. Biochem. Cell Biol. 68:1166-1173, 1990.
80. Park, J.B., and M. Levine. Purification, cloning and expression of dehydroascorbic acidreducing activity from human neutrophils: identification as glutaredoxin. Biochem. J.
315:931-918, 1996.
81. Peters, E., J. Goetzsche, B. Grobbelaar, and T. Noakes. Vitamin C supplementation
reduces the incidence of post-race symptoms of upper respiratory tract infection in
ultradistance runners. Am. J. Clin. Nutr. 57:170-174, 1993.
82. Peters, E.M., R. Anderson, D.C. Nieman, H. Fickl, and V. Jogessar. Vitamin C supplementation attenuates the increases in circulating cortisol, adrenaline and anti-inflammatory polypeptides following ultramarathon running. Int. J. Sports Med. 22:537-543,
2001a.
83. Peters, E.M., R. Anderson, and A.J. Theron. Attenuation of increase in circulating cortisol and enhancement of the acute phase protein response in vitamin C-supplemented
ultramarathoners. Int. J. Sports Med. 22:120-126, 2001b.
84. Petersen, E.W., K. Ostrowski, T. Ibfelt, M. Richelle, E. Offord, J. Halkjaer-Kristensen,
and B.K. Pedersen. Effect of vitamin supplementation on cytokine response and on
muscle damage after strenuous exercise. Am. J. Physiol. 280:C1570-C1575, 2001.
85. Prasad, M.R., R.M. Engelman, R.M. Jones, and D.K. Das. Effects of oxyradicals on
oxymyoglobin. Deoxygenation, haem removal and iron release. Biochem J. 263:731736, 1989.
86. Reif, D.W. Ferritin as a source of iron for oxidative damage. Free Radic. Biol. Med.
12:417-427, 1992.
87. Retsky, K.L., M.W. Freeman, and B. Frei. Ascorbic acid oxidation product(s) protect
human low density lipoprotein against atherogenic modification. Anti- rather than
prooxidant activity of vitamin C in the presence of transition metal ions. J. Biol. Chem.
268:1304-1309, 1993.
88. Roberston, J., R. Maughan, G. Duthie, and P. Morrice. Increased blood antioxidant
systems of runners in response to training load. Clin. Sci. 80:611-618, 1991.
89. Rokitzki, L., S. Hinkel, C. Klemp, D. Cufi, and J. Keul. Dietary, serum and urine ascorbic
acid status in male athletes. Int. J. Sports Med. 15:435-440, 1994a.
90. Rokitzki, L., E. Logemann, A. Sagredos, M. Murphy, W. Wetzel-Roth, and J. Keul.
Lipid peroxidation and antioxidative vitamins under extreme endurance stress. Acta
Physiol. Scand. 151:149-158, 1994b.
91. Rumsey, S., and M. Levine. Absorption, transport, and disposition of ascorbic acid in
humans. Nutr. Biochem. 9:116-130, 1998.
92. Rumsey, S.C., O. Kwon, G.W. Xu, C.F. Burant, I. Simpson, and M. Levine. Glucose
transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. J. Biol. Chem.
272:18982-18989, 1997.
93. Samuni, A., J. Aronovitch, D. Godinger, M. Chevion, and G. Czapski. On the cytotoxicity of vitamin C and metal ions. A site-specific Fenton mechanism. Eur. J. Biochem.
137:119-124, 1983.
94. Sanchez-Quesada, J.L., O. Jorba, A. Payes, C. Otal, R. Serra-Grima, F. GonzalezSastre, and J. Ordonez-Llanos. Ascorbic acid inhibits the increase in low-density lipoprotein (LDL) susceptibility to oxidation and the proportion of electronegative LDL
induced by intense aerobic exercise. Coron. Artery Dis. 9:249-255, 1998.
95. Schroder, H., E. Navarro, A. Tramullas, J. Mora, and D. Galiano. Nutrition antioxidant
status and oxidative stress in professional basketball players: effects of a three compound antioxidative supplement. Int. J. Sports Med. 21:146-150, 2000.
96. Short, S., and W. Short. Four-year study of university athletes dietary intake. J. Am.
Diet. Assoc. 82:632-645, 1983.
97. Starkie, R.L., J. Rolland, D.J. Angus, M.J. Anderson, and M.A. Febbraio. Circulating
monocytes are not the source of elevations in plasma IL-6 and TNF-alpha levels after
prolonged running. Am. J. Physiol. 280:C769-C774, 2001.
98. Telford, R., E. Catchpole, V. Deakin, A. McLeay, and A. Plank. The effect of 7 to 8
months of vitamin/mineral supplementation on the vitamin and mineral status of athletes. Int. J. Sport Nutr. 2:123-134, 1992.
99. Thaxton, J., and S. Pardue. Ascorbic acid and physiological stress. In: Ascorbic Acid in
Domestic Animals, I. Wegger, F. Tagwerker, and J. Moustgaard (Eds.). Copenhagen:
The Royal Danish Agricultural Society, 1984, pp. 25-31.
100. Thompson, D., C. Williams, M. Kingsley, C.W. Nicholas, H.K. Lakomy, F. McArdle,
and M.J. Jackson. Muscle soreness and damage parameters after prolonged intermittent shuttle-running following acute vitamin C supplementation. Int. J. Sports Med.
22:68-75, 2001.
101. Thompson, D., C. Williams, S.J. McGregor, C.W. Nicholas, F. McArdle, M.J. Jackson,
and J.R. Powell. Prolonged vitamin C supplementation and recovery from demanding
exercise. Int. J. Sport. Nutr. Exerc. Met. 11:466-481, 2001.
102. Umegaki, K., P. Daohua, A. Sugisawa, M. Kumara, and M. Higuchi. Influence of one
bout of vigorous exercise on ascorbic acid in plasma and oxidative damage to DNA in
blood cells and muscle in untrained rats. J. Nutr. Biochem. 11:401-407, 2000.
103. Vasankari, T., U. Kujala, S. Sarna, and M. Ahotupa. Effects of ascorbic acid and
carbohydrate ingestion on exercise induced oxidative stress. J. Sports Med. Phys.
Fitness. 38:281-285, 1998.
104. Viguie, C., B. Frei, M. Shigenega, B. Ames, L. Packer, and G. Brooks. Antioxidant
status and indexes of oxidative stress during consecutive days of exercise. J. Appl.
Physiol. 75:566-572, 1993.
105. Washko, P., and M. Levine. Inhibition of ascorbic acid transport in human neutrophils
by glucose. J. Biol. Chem. 267:23568-23574, 1992.
106. Weight, L., T. Noakes, D. Labadarios, J. Graves, P. Jacobs, and P. Berman. Vitamin and
mineral status of trained athletes including the effects of supplementation. Am. J. Clin.
Nutr. 47:186-191, 1988.
107. Welch, R., Y. Wang, A.J. Crossman, J. Park, K. Kirk, and M. Levine. Accumulation of
vitamin C (ascorbate) and its metabolite dehydroascorbic acid occurs by separate
mechanisms. J. Biol. Chem. 270:12584-12592, 1995.
108. Whitney, E., and S. Rolfes. Understanding Nutrition. St Paul, MN: West Publishing,
1993.
109. Winkler, B., S. Orselli, and T. Rex. The redox couple between glutathione and ascorbic
acid: a chemical and physiological perspective. Free Rad. Biol. Med. 17:333-349,
1994.
110. Zembron-Lacny, A., and K. Szyszka. Exercise modification of the prooxidantantioxidant equilibrium. Med Sportiva. 4: 247-255, 2000.

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ORIGINAL RESEARCH

Vitamin C and Exercise / 125

Vitamin C: Effects of Exercise

the oxidation of ascorbic acid to dehydroascorbic acid is relatively non-reactive,

The Distribution, Transport, Function,

Vitamin C and Exercise / 127

Table 1 Distribution of Ascorbic Acid Within the Organs and Fluids

Ascorbic acid concentration

It is currently unclear exactly how ascorbic acid influences pancreatic or renal

Vitamin C and Exercise / 129

and nonathletes, in addition to assessing the response of athletes to vitamin C

Vitamin C Intakes of Exercising

Table 2 Normal Range for Whole-Body Ascorbic Acid Content, Plasma,

Basketballers (n = 16) 250-mg placebo

Ascorbic acid concentration (mol L1)

Vitamin C and Exercise / 131

Pre-supplementation levels of plasma/serum ascorbic also seem to affect the

Vitamin C and Exercise / 133

Changes in Plasma, Serum, and Lymphocyte Ascorbic Acid

60 min box stepping

35 min uphill (+5%) walking

90 min at 65% VO2max

35 min downhill (20%)

Ascorbic Acid Concentration (mol L1)

Mean (SD) Changes in Ascorbic Acid Concentration Immediately Post-exercise

90 min running at 75% VO2max

Ascorbic Acid Concentration (mol L1)

Vitamin C and Exercise / 135

Vitamin C and Exercise / 137

Chronic Effects of Exercise on Resting Plasma, Serum, and

Ascorbic Acid and Cortisol

Vitamin C and Exercise / 139

Figure 3 Biosynthesis of cortisol in the adrenal gland (4).

Vitamin C and Exercise / 141

H2O2 + Fe2+ HO + Fe3+ + OH (reaction 2)

LOOH + Fe2+ LO + Fe3+ + OH (reaction 3)

There is also strong evidence against a pro-oxidant effect of ascorbic acid,

Vitamin C and Exercise / 143

gluconeogenesis. They proposed that through glycolysis, glucose-6-phosphate is

Ascorbic Acid and Exercise-Induced Oxidative Stress

Figure 5 Antioxidant activity of ascorbic acid in neutralizing aqueous radicals and

Dehydroascorbic acid is reduced back to ascorbic acid by glutathione (109) and

Vitamin C and Exercise / 145

thiobarbituric acidreactive substances (90), malondialdehyde and exhaled pentane

investigation before they can be applied to the control of physiological systems

Vitamin C and Exercise / 147

Vitamin C and Exercise / 149

Vitamin C and Exercise / 151

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