VitaminsMetabolic Functions

Chapter 20
Vitamins: Metabolic Functions
MIKAEL FOGELHOLM
Introduction
Vitamins in sports
Vitamin supplements, including especially
vitamin C, but also the B-complex vitamins and
vitamin E, are frequently used by athletes (Sobal
& Marquart 1994). The common motivation for
vitamin supplementation is to improve sports
performance and enhance recovery (Williams
1986). Reversing the view, many athletes and
coaches fear that a normal diet will eventually
lead to marginal vitamin supply and to a deterioration in sports performance.
As regards vitamins and optimal physical performance, there are two questions with substantial practical importance. First, if vitamin supply
is marginal, would an athlete’s functional capacity be less than optimal? Second, if vitamins
are given in excess of daily needs, would
this improve functional capacity? This chapter
reviews the basic metabolic functions of different
vitamins (Table 20.1) and aims at giving answers
to the two above-mentioned questions. The
vitamin requirements of physically active people
are reviewed in Chapter 21, and antioxidant
functions in Chapter 22.
What are vitamins?
Vitamins are organic compounds required in
very small amounts (from a few micrograms to a
few milligrams on a daily basis) to prevent development of clinical deficiency and deterioration in
266
health, growth and reproduction (McCormick
1986). A distinct feature of vitamins is that the
human body is not able to synthesize them. Classification of vitamins is based on their relative
solubility (McCormick 1986): fat-soluble vitamins (A, D, E and K) are more soluble in organic
solvents, and water-soluble vitamins (B-complex
and C) in water.
Ubiquinone and ‘vitamin B15’ are examples
of compounds announced as ‘vitamins’ and as
ergogenic substances for athletes. Ubiquinone,
an electron carrier in the mitochondrial respiratory chain, is indeed needed for normal body
function and health, and it is found in a Western
mixed diet (Greenberg & Frishman 1988).
Nevertheless, because the body can synthesize
ubiquinone, the name ‘vitamin Q’ is misleading
and should not be used.
‘Vitamin B15’, in contrast to ubiquinone, cannot
be synthesized by the human body. However,
it is not a vitamin, because there are no specific
diseases or signs associated with depletion. In
fact, ‘vitamin B15’ in products with ergogenic
claims does not even have a well-defined
chemical identity (Williams 1986). There is no
evidence that supplementation with ubiquinone or ‘vitamin B15’ would increase athletic
performance (Williams 1986; Laaksonen et al.
1995).
Vitamin supply and functional capacity
Adequate nutritional status means a sufficiency
of the host nutriture to permit cells, tissues,
vitamins: metabolic functions
267
Table 20.1 Summary of the most important effects of vitamins on body functions related to athletic performance.
Cofactors
for energy
metabolism
Water-soluble
vitamins
Thiamin
Riboflavin
Vitamin B6
Folic acid
Vitamin B12
Niacin
Pantothenic
acid
Biotin
Vitamin C
X
X
X
X
X
Nervous
function
Haemoglobin
synthesis
X
X
X
X
X
X
(X)
X
X
X
Immune
function
Antioxidant
function
Bone
metabolism
X
X
Fat-soluble
vitamins
Vitamin A
Vitamin D
Vitamin E
organs, anatomical systems or the host him/
herself to perform optimally the intentioned,
nutrient-dependent function (Solomons & Allen
1983). Vitamins — like all micronutrients — are
needed directly or indirectly (because of activity
on structural integrity) for innumerable functions. Metabolic functions may be viewed from
an isolated, molecular viewpoint (i.e. a single
biochemical reaction in a single metabolic pathway), or from a perspective of the entire human
body.
The metabolic functions of vitamins required
in sports are mainly those needed for production
of energy and for neuromuscular functions
(skills). Physical performance involve several
metabolic pathways, all including several biochemical reactions. The relation between vitamin
supply and functional capacity is S-shaped or
‘bell-shaped’, depending on whether the examination is extended to megadoses (Fig. 20.1)
(Brubacher 1989). The core in the above relation is that the output (functional capacity) is
not improved after the ‘minimal requirement
for maximal output’ is reached (Brubacher 1989).
(X)
X
X
X
X
X
X
X
In contrast, overvitaminosis may in some
cases reduce the output below the maximal
level.
Different body functions (single biochemical reactions, metabolic pathways, function of
anatomical systems, and function of the host
him/herself) reach their maximal output at
different levels of supply. In other words,
the supply needed for optimal function of an
anatomical system (e.g. the muscle) may be quite
different from the supply needed to maximize
the activity of a single enzyme (Solomons &
Allen 1983).
Short-term inadequacy of vitamin intake is
characterized by lowering of vitamin concentrations in different tissues and lowering of certain
enzyme activities (Fig. 20.2) (Piertzik 1986).
However, functional disturbances (such as
decreased physical performance capacity)
appear later (Solomons & Allen 1983; Fogelholm
1995). In the opposite case, very large vitamin
intakes increase the body pool and activity of
some enzymes, but do not necessarily improve
functional capacity (Fogelholm 1995).
268
nutrition and exercise
Minimal requirement
of maximal output
Functional output
Max.
Min.
Marginal
Adequate
Excess
Fig. 20.1 The association between vitamin
supply and functional output.
Vitamin supply
Toxic supply
Functional
changes
Excess supply
Increase in tissue
levels, enzyme
activity, etc.
Adequate
supply
Normal
function
Marginal supply
Lowering of tissue
levels, metabolites
and enzyme activity
Subclinical
depletion
Functional
changes
Clinical
depletion
Severe
functional
changes
Water-soluble vitamins and
functional capacity
Thiamin
chemistry and
biochemical functions
Thiamin or vitamin B1, the former being the
Fig. 20.2 Dietary micronutrient intake and
stages of nutritional status. Adapted from
Solomons and Allen (1983), Piertzik (1986)
and Brubacher (1989).
accepted chemical name, consists of a pyrimidine ring joined to a thiazole ring (Halsted 1993).
The principal, if not sole, cofactor form of
thiamin (vitamin B1) is thiaminpyrophosphate
(TPP) (McCormick 1986). TPP is needed as a
cofactor in muscle metabolism and in the central
nervous system. Body stores are small, about
30 mg, almost half of which is stored in the
muscles (Johnson Gubler 1984).
vitamins: metabolic functions
Two important enzyme complexes of glycolysis and the citric acid cycle require TPP as a cofactor, namely, pyruvate dehydrogenase (formation
of acetyl-coenzyme A from pyruvate) and aketoglutarate dehydrogenase (formation of
succinyl-coenzyme A from a-ketoglutarate)
(Johnson Gubler 1984). If the decarboxylation of
pyruvate is inadequate to match the increased
speed of glycolysis, pyruvate will accumulate in
the tissue (Sauberlich 1967). The accumulation of
pyruvate will eventually lead to increased lactic
acid production (Johnson Gubler 1984), which
is lowered after thiamin supplementation
(Sauberlich 1967). By interfering with the citric
acid cycle, improper function of a-ketoglutarate
dehydrogenase would affect aerobic energy production, and through feedback reactions, also the
overall rate of glycolysis.
Although the muscle tissue contains more
than 40% of the total body thiamin, the vitamin
concentration is much higher in the liver, kidney
and brain (Johnson Gubler 1984). Also, the
nerves contain a constant and significant amount
of TPP (Johnson Gubler 1984), and thiamin is
indeed very important for the function of the
brain and the nervous system (McCormick 1986;
Halsted 1993).
In addition to the two above-mentioned
enzyme complexes, thiamin is also needed in the
pentose phosphate pathway (PPP) as a cofactor
for transketolase (Johnson Gubler 1984). PPP is
important for production of pentoses for RNA
and DNA synthesis, and nicotinamide adenine
dinucleotide phosphate (NADPH) for biosynthesis of fatty acids. The role of PPP in energy
production is minor (Johnson Gubler 1984).
However, the interesting feature about transketolase is that the activity of erythrocyte transketolase, with and without in vitro added TPP,
is widely used as an indicator of thiamin status
(Bayomi & Rosalki 1976). Several papers have
been published on erythrocyte transketolase
activity in athletes (for a review, see Fogelholm
1995).
supply and metabolic functions
In subclinical thiamin deficiency, the exercise-
269
induced blood lactate concentrations are elevated, especially after a pre-exercise glucose
load (Sauberlich 1967). The deterioration of
physical capacity in marginal deficiency is
less evident. Wood et al. (1980) did not find
decreased working capacity, neurophysiological changes or adverse psychological reactions
in male students, despite a 5-week thiamindepleted diet. However, the erythrocyte transketolase activity decreased, showing that the
activity of this enzyme is affected faster than
the activity of the enzymes of glycolysis and
the citric acid cycle.
A combined depletion of thiamin, riboflavin,
vitamin B6 and ascorbic acid has been found to
affect both erythrocyte transketolase activity and
aerobic working capacity (van der Beek et al.
1988). However, because of the multiple depletion, the independent role of thiamin could not
be demonstrated. The uncertainty of the independent role of thiamin was a concern also in
studies showing improved shooting accuracy
(Bonke & Nickel 1989) or neuromuscular
irritability (van Dam 1978) after combined
thiamin, riboflavin, vitamin B6 or vitamin B12
supplementation.
A 1–3-month vitamin B-complex supplementation (> 7.5 mg · day–1) usually improves the
activity of erythrocyte transketolase (van Dam
1978; Guilland et al. 1989; Fogelholm et al. 1993b).
Nevertheless, despite improved erythrocyte
transketolase activity or increased blood thiamin
concentration, several studies have shown that
vitamin supplementation did not improve functional capacity in athletes (Telford et al. 1992a,
1992b), young adults (Singh et al. 1992a, 1992b;
Fogelholm et al. 1993b) or in elderly subjects
(Suboticanec et al. 1989).
safety of elevat ed thiamin intake
Adverse reactions of chronic, elevated oral
administration of thiamin are virtually unknown
(Marks 1989). Hypersensitivity reactions may
sometimes occur after very high oral loads (5–
10 g), or following much lower doses (5–10 mg)
by parenteral administration (Marks 1989). For
chronic oral use, the safe dose is at least 50–100
270
nutrition and exercise
times the recommended daily intake; that is,
above 100 mg daily.
Riboflavin
chemistry and
biochemical functions
Riboflavin (correct chemical name) or vitamin B2
is composed of an isoalloxazine ring linked to a
ribityl side chain (Halsted 1993). Modification of
the side chain yields flavin mononucleotide
(FMN). When linked to adenine monophosphate, FMN forms flavin adenine dinucleotide
(FAD). FMN and FAD function as coenzymes in
numerous oxidation-reduction reactions in glycolysis and the respiratory chain (Cooperman &
Lopez 1984). Enzymes requiring FAD are, e.g.
pyruvate dehydrogenase complex (glycolysis),
a-ketoglutarate dehydrogenase complex and
succinate dehydrogenase (citric acid cycle). FAD
is also needed in fatty acid oxidation, whereas
FMN is necessary for the synthesis of fatty acids
from acetate (Cooperman & Lopez 1984).
Riboflavin has also indirect effects on
body functions by affecting iron utilization
(Fairweather-Tait et al. 1992). The mechanism is
still unknown in humans, but some results indicate that correction of riboflavin deficiency also
raises low blood haemoglobin concentrations
(Cooperman & Lopez 1984; Fairweather-Tait
et al. 1992). Severe riboflavin deficiency can also
affect the status of other B-complex vitamins,
mainly by decreased conversion of vitamin B6 to
its active coenzyme and of tryptophan to niacin
(Cooperman & Lopez 1984).
Like thiamin, the activity of an enzyme isolated from the erythrocytes is widely used as an
indicator of riboflavin status (Bayomi & Rosalki
1976; Cooperman & Lopez 1984). The enzyme,
glutathione reductase, catalyses the reduction of
oxidized glutathione with simultaneous oxidation of NADPH. The enzyme activity in vitro is
related to activity after saturation by FAD. The
better the vitamin status, the smaller the increase
in activity after added FAD (Bayomi & Rosalki
1976).
supply and metabolic functions
Changes in riboflavin supply have been postulated to affect both muscle metabolism and
neuromuscular function. Data on the effects of
marginal riboflavin supply are, however, scarce.
In three studies (Belko et al. 1984, 1985; Trebler
Winters et al. 1992), a 4–5-week period with marginal riboflavin intake resulted in lowering of the
erythrocyte glutathione reductase activity, but no
relation with aerobic capacity was found. Similarly, Soares et al. (1993) did not find changes in
muscular efficiency during moderate-intensity
exercise after a 7-week period of riboflavinrestricted diet.
In contrast to the above studies, van der Beek
et al. (1988) reported impaired maximal oxygen
uptake and increased blood lactate appearance
after a 10-week period with marginal thiamin,
riboflavin and vitamin B6 intake. The independent role of riboflavin was, however, uncertain.
Decreased urinary riboflavin excretion might
be one mechanism in preventing changes in
riboflavin-dependent body functions during
marginal depletion (Belko et al. 1984, 1985; Soares
et al. 1993). More severe riboflavin deficiency is
obviously likely to affect both maximal and submaximal aerobic work capacity, as well as neuromuscular function (Cooperman & Lopez 1984).
A 1–3-month vitamin B-complex supplementation improves the activity of erythrocyte
glutathione reductase (van Dam 1978; Weight
et al. 1988b; Guilland et al. 1989; Fogelholm et al.
1993b) in athletes or trained students, even
without indications of impaired vitamin status
(Weight et al. 1988b). Two studies have suggested
that supplementation and improvement in
riboflavin status (judged by changes in erythrocyte glutathione reductase activity) were
related to improved neuromuscular function
(Haralambie 1976; Bamji et al. 1982).
Riboflavin supplementation, in combination
with one or more water-soluble vitamins, has
been shown to affect both erythrocyte enzyme
activity and maximal oxygen uptake (Buzina
et al. 1982; Suboticanec-Buzina et al. 1984) or
work efficiency (Powers et al. 1985) in children
vitamins: metabolic functions
with known nutritional deficiencies. In contrast,
several other studies did not find an association between increased erythrocyte glutathione
reductase activity and maximal oxygen uptake
(Suboticanec-Buzina et al. 1984; Weight et al.
1988a, 1988b; Suboticanec et al. 1990; Singh et al.
1992a, 1992b), exercise-induced lactate appearance in the blood (Weight et al. 1988a, 1988b;
Fogelholm et al. 1993b), work efficiency (Powers
et al. 1987) or grip strength (Suboticanec et al.
1989).
safety of elevated
riboflavin intake
As with thiamin, there is no evidence of any
harmful effects even with oral doses exceeding
100 times the recommended daily intake (Marks
1989). Riboflavin in large doses may cause a
yellow discoloration of the urine which might
obviously cause concern in people not aware of
the origin of the colour (Alhadeff et al. 1984).
Vitamin B6
chemistry and
biochemical functions
Vitamin B6 is a common name for pyridoxine,
pyridoxamine and pyridoxal (McCormick 1986).
Pyridoxine hydrochloride is the synthetic pharmaceutical form of vitamin B6 (Halsted 1993). All
three chemical forms of vitamin B6 are metabolically active after phosphorylation. The most
common cofactor in human body is pyridoxal
phosphate (PLP) (Driskell 1984). It is a prosthetic
group of transaminases, transferases, decarboxylases and cleavage enzymes needed in many
reactions involving for instance protein breakdown (Manore 1994). PLP is also an essential
structural component of glycogen phosphorylase, the first enzyme in glycogen breakdown
pathway (Allgood & Cidlowski 1991). In fact,
muscle-bound PLP represents 80% of the approximately 4-g body pool of vitamin B6 (Coburn et al.
1988).
In addition to energy metabolism, vitamin B6
271
is needed for synthesis and metabolism of many
neurotransmitters (e.g. serotonin), and in the
development and maintenance of a competent
immune system (Allgood & Cidlowski 1991).
PLP-dependent enzymes are involved in synthesis of catecholamines (Driskell 1984), and
perhaps in regulation of steroid hormone action
(Allgood & Cidlowski 1991). Vitamin B6 is also
needed for the synthesis of aminolevulic acid, an
intermediate compound in the formation of the
porphyrin ring in haemoglobin (Manore 1994).
From a physiological viewpoint, vitamin B6
depletion could decrease glycogen breakdown
and impair capacity for glycolysis and anaerobic
energy production. Because glycogen phosphorylase is not a rate-limiting enzyme in
glycogenolysis, small changes in its activity
would, however, not affect glycogen metabolism. Severe depletion would also affect
haemoglobin synthesis, and impair oxygen
transport in the blood. The contribution of amino
acids in total energy expenditure is not likely to
exceed 10%, even in a glycogen depleted state.
Therefore, it is unclear how an impairment in
amino acid breakdown would affect physical
performance.
The activity of two enzymes involved in erythrocytic protein metabolism, namely aspartate
aminotransferase (ASAT) and alanine aminotransferase (ALAT), are used as indicators of
vitamin B6 status (Bayomi & Rosalki 1976;
Driskell 1984). The principle of the assay, with
and without in vitro saturation, is similar to that
explained earlier for thiamin (transketolase) and
riboflavin (glutathione reductase) (Bayomi &
Rosalki 1976).
supply and metabolic functions
In male wrestlers and judo-athletes, a decrease in
the erythrocyte ASAT activity indicated deterioration in vitamin B6 supply during a 3-week
weight-loss regimen (Fogelholm et al. 1993a).
Maximal anaerobic capacity, speed or strength
were, however, not affected. Coburn et al. (1991)
showed that the muscle tissue is, in fact, quite
resistant to a 6-week vitamin B6 depletion.
272
nutrition and exercise
Marginal vitamin B6 supply has been related to
impaired aerobic functions only in combination
with a simultaneous thiamin and riboflavin
depletion (van der Beek et al. 1988).
In an interesting study, indices of vitamin B6
status were examined during a 3-month submarine patrol (Reynolds et al. 1988). The results
indicated deterioration in status and marginal
vitamin B6 supply at the end of the patrol. Psychological tests indicated pronounced depression after submergence and at the midpatrol
point. However, the depression measures were
neither correlated with indicators of vitamin B6
status nor affected by vitamin supplementation.
Chronic supplementation of vitamin B6
increases the erythrocyte ASAT activity (van
Dam 1978; Guilland et al. 1989; Fogelholm et al.
1993b) and plasma PLP-concentration (Weight
et al. 1988a; Coburn et al. 1991) even in healthy
subjects. However, an increase in the above indicators of vitamin B6 status is not necessarily associated with a marked increase in intramuscular
vitamin B6 content (Coburn et al. 1991).
It appears that vitamin B6, either as an infusion
(Moretti et al. 1982) or given orally as a 20 mg ·
day–1 supplement (Dunton et al. 1993), has a
stimulating effect on exercise-induced growth
hormone production. The hypothetical mechanism behind this effect is that PLP acts as the
coenzyme for dopa decarboxylase, and high
concentrations might promote the conversion of
L-dopa to dopamine (Manore 1994). The physiological significance of the above effect is not
known (Manore 1994). Moreover, the effects of
chronic vitamin B6 administration on the 24-h
growth hormone concentration of plasma have
not been studied.
Supplementation of vitamin B6, alone
(Suboticanec et al. 1990) or in combination with
other B-complex vitamins (van Dam 1978; Bonke
& Nickel 1989), has improved maximal oxygen
uptake in undernourished children (Suboticanec
et al. 1990), and shooting performance (Bonke &
Nickel 1989) and muscle irritability (van Dam
1978) in male athletes. In contrast, a number of
other studies did not find any association
between improved indicators of vitamin B6
status and maximal oxygen uptake (SuboticanecBuzina et al. 1984; Weight et al. 1988a, 1988b),
exercise-induced lactate appearance in blood
(Manore & Leklem 1988; Weight et al. 1988a,
1988b; Fogelholm et al. 1993b), grip strength
(Suboticanec et al. 1989) or other tests of physical
performance (Telford et al. 1992a, 1992b).
safety of elevated
vitamin b 6 intake
In contrast to thiamin and riboflavin, megadoses
of vitamin B6 may have important toxic effects.
The most common disorder is sensory neuropathy, sometimes combined with epidermal vesicular dermatosis (Bässler 1989). The safe dose
for chronic oral administration of vitamin B6
appears to be around 300–500 mg daily (Bässler
1989). However, it is recommended that
long-term supplementation should not exceed
200 mg · day–1 — that is, 100 times the recommended dietary allowance (Marks 1989).
Folic acid and vitamin B12
chemistry and
biochemical functions
Folate and folic acid are generic terms for compounds related to pteroic acid. The body pool is
5–10 mg (Herbert 1987), and liver folate is a major
part of the total. Folate coenzymes are needed
in transportation of single carbon units in, for
instance, thymidylate, methionine and purine
synthesis (Fairbanks & Klee 1986).
Deficiency of folate results in impaired cell
division and alterations in protein synthesis.
The effects are most significant in rapidly
growing tissues (Herbert 1987). A typical
deficiency symptom is megaloblastic anaemia
(lowered blood haemoglobin concentration,
with increased mean corpuscular volume;
Halsted 1993). Decreased oxygen transport
capacity would affect submaximal and eventually also maximal aerobic performance. If iron
deficiency exists simultaneously with folate deficiency, red cell morphology does not necessarily
vitamins: metabolic functions
deviate from reference values (Fairbanks & Klee
1986). Folate is also needed in the nervous
system, and depletion during pregnancy might
cause lethal neural tube defects (Reynolds 1994).
Vitamin B12 and cobalamin refer to a larger
group of physiologically active cobalamins
(Fairbanks & Klee 1986). Cyanocobalamin is the
principal commercial and therapeutic product
(Halsted 1993). Cobalamin is a cofactor for two
reactions: the synthesis of methionine and the
conversion of methylmalonic acid to succinic
acid (Halsted 1993). Through these reactions,
cobalamin is needed in normal red blood cell
synthesis and neuronal metabolism (Fairbanks &
Klee 1986).
Cobalamin deficiency leads to megaloblastic
anaemia and to neurological disorders. As in
anaemia caused by folate deficiency, erythrocyte
volume is usually increased, in contrast to frank
iron-deficiency anaemia (Fairbanks & Klee 1986).
Compared with the daily requirements, the 2–
3 mg body pool of cobalamin is very large. Even
with no dietary cobalamin, the body pool would
suffice for about 3–5 years (Fairbanks & Klee
1986).
supply and metabolic functions
There are only a few studies linking folic acid or
vitamin B12 supply to sports-related functional
capacity. Folate supplementation and increased
serum folate concentration did not affect
maximal oxygen uptake (Matter et al. 1987),
anaerobic threshold (Matter et al. 1987), grip
strength (Suboticanec et al. 1989) or other
measures of physical performance (Telford et al.
1992a, 1992b). Together with thiamin and
vitamin B6 supplementation, elevated intake of
vitamin B12 was, however, associated with
improved shooting performance (Bonke &
Nickel 1989).
safety of elevated folic acid and
v i ta m i n b 12 intake
The effects of high doses of folic acid have not
been studied very much, but some results indi-
273
cate a possible interference with zinc metabolism
(Marks 1989; Reynolds 1994). The current estimate of the safety dose is between 50 and 100
times the daily recommended intake (Marks
1989). The safety margin for vitamin B12 appears
to be much larger, because even doses as high as
30 mg · day–1 (that is, 10 000 times the recommended intake) have been used without noticeable toxic effects (Marks 1989).
Other vitamins of the B-group
niac in
Niacin is used as a name for nicotinic acid as well
as for its derivatives nicotinamide and nicotinic
acid amide (McCormick 1986). About 67% of
niacin required by an adult can be converted
from the amino acid tryptophan; 60 mg of tryptophan is needed for the formation of 1 mg niacin.
Nicotinamide, as a part of nicotinamide
adenine dinucleotide (NAD) and NADPH,
participates in hundreds of oxidation-reduction
reactions (McCormick 1986; Halsted 1993). NAD
is needed as an electron acceptor in glycolysis
(enzyme: glyceraldehyde-3-phosphate dehydrogenase) and the citric acid cycle (pyruvate
dehydrogenase, isocitrate dehydrogenase, aketoglutarate dehydrogenase and malate dehydrogenase), and the reduced form of NADPH as
an electron donor in fatty acid synthesis.
Because of its important role in mitochondrial
metabolism, niacin deficiency has the potential
to affect both muscular and nervous function.
Unfortunately, there are no direct studies on the
effects of niacin deficiency on physical performance. In contrast, high-dose supplementation
(e.g. intravenous administration) of niacin blocks
the release of free fatty acids from the adipose tissue, and impairs long-term submaximal
endurance (Pernow & Saltin 1971).
Acute oral intake of at least 100 mg of nicotinic
acid per day (i.e. at least five times the recommended daily allowance) causes vasodilatation
and flushing, which is a rather harmless effect
(Marks 1989). Very large, chronic supplementation of niacin has been reported to cause hepato-
274
nutrition and exercise
toxicity, cholestatic jaundice, an increased serum
concentration of uric acid, cardiac dysrhythmias
and various dermatologic problems (Alhadeff
et al. 1984). The safe chronic dose appears to be
at least 50 times the recommended allowance,
i.e. 1 g · day–1 (Marks 1989).
biotin
The main function of biotin is as cofactor in
enzymes catalysing transport of carboxyl
units (McCormick 1986). In the cytosol, a
biotin-dependent enzyme, acetyl-coenzyme A
carboxylase, catalyses the formation of malonylcoenzyme A from acetyl-coenzyme A. Malonylcoenzyme A is used for fatty acid synthesis. In
the mitochondria, biotin is an integral part of
pyruvate carboxylase. This enzyme catalyses the
conversion of pyruvate to oxaloacetate, which is
an intermediate in gluconeogenesis and the citric
acid cycle.
Through the function of pyruvate carboxylase,
biotin has a critical role in maintaining the level
of citric acid cycle intermediates. Although it is
likely that aerobic performance would be
impaired by biotin deficiency, the physical performance of biotin deficient patients has never
been investigated. Moreover, excluding individuals with an excessive intake of raw egg-white
(which contains avidin, a biotin-binding
glycoprotein), dietary biotin deficiency is almost
impossible in practice (McCormick 1986).
There are no reported toxic effects of biotin
intake up to 10 mg · day–1 (> 100 times the recommended allowance) (Marks 1989; Halsted 1993).
symptoms have been induced with a semisynthetic diet practically free of pantothenate.
Symptoms include general fatigue and increased
heart rate during exertion (McCormick 1986).
Relations between pantothenic acid status and
physical performance capacity have not been
investigated.
Pantothenic acid has not been reported to
cause any toxic affects even at doses up to 10 g
daily, i.e. 1000 times the recommended intake
level (Alhadeff et al. 1984; Marks 1989).
Vitamin C
chemistry and
biochemical functions
Vitamin C or ascorbic acid is a strong reducing
agent, which is reversibly oxidized to dehydroascorbic acid in numerous biochemical
reactions (Padh 1991). By its reducing capacity,
ascorbic acid stimulates enzymes involved in, for
instance, biosynthesis of collagen, carnitine,
pyrimidine and noradrenaline (McCormick
1986; Padh 1991).
In addition to the above biosynthetic pathways, ascorbic acid has a very important role as
an extracellular antioxidant against many types
of free radical compounds (see Chapter 22). In
the gastrointestinal tract, ascorbic acid enhances
iron absorption by keeping iron in a reduced
ferrous state (Gershoff 1993). In contrast, high
doses of ascorbic acid may suppress copper
absorption by reducing copper to a less
absorbable monovalent state (Finley &
Cerklewski 1983).
pantothenic acid
Pantothenic acid functions as a cofactor in
coenzyme A, which, as acetyl-coenzyme A, is in a
central position for both energy production
and fatty acid synthesis (McCormick 1986).
Pantothenic acid is also needed in the 4¢phosphopantetheine moiety of acyl carrier
protein of fatty acid synthetase.
Pantothenic acid deficiency due to dietary
reasons has never been reported. Deficiency
supply and metabolic functions
Ascorbic acid is needed in carnitine synthesis,
and therefore indirectly for transfer of long-chain
fatty acids across the inner mitochondrial
membrane. A substantial decrease in muscle carnitine would theoretically decrease submaximal
endurance capacity by increasing the dependence on glycogen instead of fatty acids
(Wagenmakers 1991). In one study (van der Beek
vitamins: metabolic functions
et al. 1990), a vitamin C restricted diet was followed by reduced whole blood ascorbic acid concentration. The marginal vitamin C supply did
not produce any significant effects on maximal
aerobic capacity or lactate threshold in healthy
volunteers. Carnitine, or any other metabolites
related to vitamin C status, was not measured.
Vitamin C supplementation has been associated with increased maximal aerobic capacity
(Buzina et al. 1982; Suboticanec-Buzina et al. 1984)
and work efficiency (Powers et al. 1985) in malnourished children. However, the above positive
effects were seen simultaneously with supplementation of one or more vitamins of the Bcomplex group. Hence, the independent role of
ascorbic acid was not shown. The majority of
other studies have not shown any measurable
effects of vitamin C supplementation on maximal oxygen uptake, lactate threshold or exerciseinduced heart-rate in well-nourished subjects
(Gerster 1989).
Due to its function as an antioxidant in phagocytic leucocytes, supplementary vitamin C may
slightly decrease the duration of common cold
episodes (Hemilä 1992). The study of Peters et al.
(1993) provided evidence that 600 mg vitamin C
daily reduced the incidence (33% vs. 68%) and
duration (4.2 vs. 5.6 days) of upper-respiratorytract infection in runners after a 90-km ultramarathon race. It is not known, however,
whether the potential effect of vitamin C supplementation on the common cold in athletes has
any significant long-term effects on performance.
In a large epidemiological survey in the US,
dietary vitamin C intake was weakly but
positively associated with pulmonary function
(forced expiratory volume in 1 s) in healthy subjects, but a stronger relationship was found in
asthmatic patients (Schwartz & Weiss 1994). The
authors postulated that the antioxidant effects of
vitamin C have a protective role on pulmonary
function. Finally, earlier results suggest that
vitamin C supplementation (≥ 250 mg daily)
might reduce heat strain in unacclimatized individuals (Kotze et al. 1977) which could theoretically enhance physical performance in certain
circumstances.
275
safety of elevat ed
vitamin c intake
There are reports suggesting that very high (> 1 g
daily), chronic doses of vitamin C might lead to
formation of oxalate stones, increased uric acid
excretion, diarrhoea, vitamin B12 destruction and
iron overload, and induce a dependency state
(Alhadeff et al. 1984). However, excluding diarrhoea, the risk for the above toxic effects is likely
to be very low in healthy individuals, even with
intake of several grams daily (Marks 1989; Rivers
1989).
Fat-soluble vitamins
Vitamin E
chemistry and
biochemical functions
Vitamin E consists of a trimethylhydroquinone
head and a diterpenoid side chain (Jenkins 1993).
The most active biological form of vitamin E is atocopherol. It is stored in many tissues, with the
largest amount in the liver. Vitamin E is transported mainly in very low density lipoproteins.
Vitamin E is one of the most important antioxidants in cellular membranes (see Chapter 22),
and it stabilizes the structural integrity of membranes by breaking the chain reaction of lipid
peroxidation (Jenkins 1993). Vitamin E is also
essential for normal function of the immune
system (Meydani 1995).
supply and metabolic functions
It has been hypothesized that free radical
damage to mitochondrial membranes in vitamin
E depletion would impair the reactions of oxidative phosphorylation, and hence physical work
capacity. Vitamin E deficiency is, however, very
rare, and the relationship between decreased
vitamin E supply and physical capacity has not
been investigated (Jenkins 1993).
Supplementation of vitamin E has wellestablished and rather consistent effects on some
276
nutrition and exercise
metabolic functions even in well-nourished
humans: after chronic vitamin E supplementation (typical dose, > 100 mg · day–1), indices of
exercise-induced lipid peroxidation, mainly
serum malondialdehyde concentration and
breath pentane exhalation, are reduced (Jenkins
1993; Rokitzki et al. 1994; Kanter & Williams 1995;
Tiidus & Houston 1995). There are some interpretation problems, however, mainly because of the
lack of specificity and/or reliability of most indicators of lipid peroxidation (Kanter & Williams
1995).
In one study (Simon-Schnass & Pabst 1988),
vitamin E supplementation helped to maintain
aerobic working capacity at very high altitude
(> 5000 m). Other studies have not conclusively
proven that vitamin E intake exceeding daily recommendations would have any beneficial effects
on athletic performance (Rokitzki et al. 1994;
Kanter & Williams 1995; Tiidus & Houston 1995).
safety of elevated
vitamin e intake
Vitamin E, in contrast to two other fat-soluble
vitamins (A and D), is apparently not toxic for
healthy individuals (Machlin 1989). The safety
factor for long-term administration is at least 100
times the recommended daily intake — that is, at
least 1 g daily in oral use (Marks 1989). Overdoses of vitamin E are contraindicated only in
individuals receiving vitamin K antagonists
(Machlin 1989).
Other fat-soluble vitamins
v i ta m i n a
The two natural forms of vitamin A are retinol
and 3-dehydroretinol, of which retinol is the
more abundant in the human body (Bates 1995).
All higher animals can convert plant-derived
carotenes and cryptoxanthin to retinol. The most
common and effective provitamin in the human
diet is b-carotene. Retinol is transported in
chylomicrons from the gut, and later bound to a
protein (retinol-binding protein, RBP). Several
hundred milligrams of retinol are stored in the
liver (McCormick 1986).
The best known function of retinol is as an
essential component in vision. In vitamin A deficiency, worsening of night vision is an early clinical sign (McLaren et al. 1993). Both retinol and
b-carotene are capable of scavenging singlet
oxygens and hence act as antioxidants (Bates
1995). Vitamin A is also important for immunity.
The literature provides no evident data on
relations between vitamin A status and physical
performance.
Chronic toxicity of retinol will cause joint or
bone pain, hair loss, anorexia and liver damage.
The safety level for chronic use is estimated to be
10 times the recommended daily intake — that is,
10 mg retinol daily (Marks 1989). Because of an
increased risk for spontaneous abortions and
birth defects (Underwood 1989), the safe level
during pregnancy might be only four to five
times the daily recommendation (Marks 1989). bcarotene, in contrast to retinol, is not toxic. This
provitamin is stored under the skin and it is converted to retinol only when needed.
vi tamin d
In the diet, vitamin D occurs mainly as cholecalciferol (D3), which can also be synthesized in skin
after ultraviolet irradiation (Fraser 1995). In the
liver, D3 is hydroxylated to 25-hydroxycholecalciferol (25-OH-D3), and further in the kidneys
to 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3,
active form) or to 24,25-dihydroxycholecalciferol
(24,25-(OH)2-D3, inactive form). Vitamin D is
stored in several parts in the body, e.g. in the liver
and under the skin.
Vitamin D stimulates calcium absorption in
the small intestine and increases calcium reabsorption by the distal renal tubules. Deficiency
results in bone demineralization (rickets and
osteomalacia), and this may eventually increase
the risk for stress fractures (Fraser 1995).
Vitamin D is potentially toxic, especially
for young children, causing hypercalcaemia,
hypercalciuria, soft-tissue calcification, anorexia
and constipation, and eventually irreversible
vitamins: metabolic functions
renal and cardiovascular damage (Davies 1989).
Intakes of 10 times the recommendation should
not be exceeded (Marks 1989). High calcium
intakes may enhance the toxicity of vitamin D.
v i ta m i n k
Vitamin K is the general name of compounds containing a 2-methyl-1,4-napthoquinone moiety. Vitamin K is needed for
formation of prothrombin in the blood, and
defective blood coagulation is the only major
sign of deficiency (McCormick 1986). No evident
associations between vitamin K and exercise
metabolism are to be found. Further, very little is
known about the safety of orally administered
vitamin K (Marks 1989).
Conclusion
Vitamins are extremely important for the functional capacity of the human body (see Table
20.1). Many B vitamins participate as enzyme
cofactors in pathways of energy metabolism and
in neuromuscular functions. Folic acid and vitamins B12 and B6 are needed for haemoglobin synthesis, and consequently for optimal oxygen
transport from the lungs to the working tissues.
Some vitamins (e.g. vitamins A, B6 and C) are
required for normal immune function. Finally,
vitamins A, C and E have important antioxidant
properties.
Studies have clearly shown that the output of
many vitamin-dependent functions both in vivo
(e.g. breath pentane exhalation) and in vitro (e.g.
erythrocyte enzymes) may increase after supplementation above normal dietary intake. Similarly, the output of many functions is decreased
at marginal vitamin supply. However, the output
of the entire human body (e.g. athletic performance) was only rarely related to marginal
vitamin supply or to supplementation.
The dietary intake of vitamins is not high
enough to ensure maximal output of many isolated functions. However, it appears that the
vitamin intake, at least in developed countries, is
above the minimal requirement for maximal
277
output of the human body. Consequently, the
evidence that vitamin supplementation would
increase athletic performance is not very encouraging. On the other hand, the risk for toxic intake
also seems to be marginal.
The above conclusions are made with some
reservations. First, the results on marginal
supply and physical function were mostly
extrapolated from nonathletic subjects. Moreover, there were hardly any data on athletes from
developing countries. Finally, many studies had
a very low statistical power, that is, there were
too few subjects to detect anything else than substantial effects.
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