Overconsumption of fluids by athletes
BMJ 2003; 327 doi: https://doi.org/10.1136/bmj.327.7407.113 (Published 17 July 2003) Cite this as: BMJ 2003;327:113
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Does adinistering oxygen to a collapsed marathon runner increase the
likelihood of him/her having an adverse outcome?
We were not able to induce a gut intramucosal acidosis in dogs by
causing hypoxaemia (1). This is because tissues have a remarkable capacity
for extracting oxygen from blood and using it as the final elecron
acceptor in the respiratory chain. Cytokines deplete intracellular levels
in enterocytes of NAD(+)/NADH by generating the release of free radicals
which activate the nuclear enzyme poly(ADP-ribose) polymerase (PARP)(2).
This is accompanied by a reduction in oxygen consumption completely
abrogated by the adminstration of liposomal NAD+.
In unpublished animal studies we have observed that the intramucosal
pH may on occasions remain abnormally low upon reperfuson of ischaemic gut
despite the expected rise in intramucosal pO2 to a supranormal level. The
implication is that reperfusion of ischaemic gut in a collapsed marathon
runner might do the same to oxygen consumption, and hence uptake and
utilisation. Hence the systemic impairment of oxygen uptake and
utilisation in patients with the systemic inflammatory response syndrome
(SIRS).
If cytokines and free radicals decrease oxygen uptake and utilisation
they might do so to protect tissues from the harmful effects of free
radicals,, the generation of free radicals being a function of oxygen
consumption. ATP resynthesis in these anaerobic circumstances may be more
than enough to maintain tissue viability for glycolytic turnover maybe
increases 4 or even 8-fold, oxygen transport (delivery) increases as much
as 3-fold and there may in addition be a Q10 effect. The resynthesis of
ATP by gycolytic means alone will, however, only be maintained at
effective levels if there are adequately oxygenated organs (liver, heart,
brain) to metabolise the lactate and replenish the NADH needed to convert
pyruvate into lactate. Without theem ATP resynthesis by glycolytic means
would cease abruptly as it does in circulatory arrest.
Intensivists focus much of their attention upon maintaining and even
increasing to supranormal levels oxygen transport in patients with SIRS
and overt sepsis. This may not only be unnecesary because of the capacity
to extract oxygen from blood and use it effctively but also harmful.
Indeed a therapeutically induced increase in free radical generation, and
accompaying translocation of toxins and release of cytokines from ischamic
gut mucosa, might account for the unpredictability and frequent failure
of conventional haemodynamic management in the citically ill(3).
The premise upon which much of modern intensive care for patients
with SIRS may be based upon the false premise that inceasing oxygen
transpot and uptake is beneficial.
The concerns expressed about the inappropriateness of the routine
administration of supplemental oxygen to patients with an MI apply to
collapsed marathon runners (4). They may be extended to include other
measures for improving arterial oxygenation, such as PEEP.
The manner in which collapsed marathon runners are routinely managed
on the track, in an ambulance and in hospital may be doing more harm than
good. Hypoxaemia may be cytoprotective.
1. Grum CM, Fiddian-Green RG, Pittenger GL, Grant BJ, Rothman ED,
Dantzker DR. Adequacy of tissue oxygenation in intact dog intestine.
J Appl Physiol. 1984 Apr;56(4):1065-9.
2. Khan AU, Delude RL, Han YY, Sappington PL, Han X, Carcillo JA, Fink
MP.Liposomal NAD(+) prevents diminished O(2) consumption by
immunostimulated Caco-2 cells.
Am J Physiol Lung Cell Mol Physiol. 2002 May;282(5):L1082-91.
3. Fiddian-Green RG. Haemodynamic and/or tonometric monitoring in cardiac
surgery.
Br J Anaesth. 2000 Jan;84(1):128.
4. Giving oxygen for an MI: a seriously false medical meme
Richard G Fiddian-Green
http://bmj.com/cgi/eletters/325/7375/1287#27554, 3 Dec 2002
Competing interests:
None declared
Competing interests: No competing interests
One of the features of gut mucosal ischaemia, which appears to a
common occurrence in marathon runners, is diarrhoea. This may be due to an
inhibition of the absorptive flux of water, which is dependent upon the
carrier-mediated absorption of solute (principally sodium), or due to the
active stimulation of a secretory flux as in cholera. Of these two
possibilities the former is the more likely for the ischaemia is greatest
and often confined to the superficial layers of the mucosa, where
absorption occurs, rather than the crypts where secretion evidently
occurs. In runners who develop ischaemic mucosa net absorption and weight
gain is, therefore, unlikely to occur unless the fluids the drink are
accompanied by glucose as in those fluids used to induce a net absorptiive
flux in patients with cholera.
Those who develop gut mucosa ischaemia are more likely to have
hepatic ischaemia and even ischaemia in other organs. In which case their
intracellular pH may be abnormally low, their K(atp) channel activated,
and their sodium pump impaired. If a net flux of sodium and other solute
occurs into the cells as a result of these changes the sodium
concentration in ECF may fall and the ICF volume may rise as the ECF
volume falls independently of the volume of fluid drunk.
Shires's "third spacing", to which I referred in my earlier
communication, is evidently an intracellular rather than an extracellular
event, as I had erroneously suggested. In which case any weight gain and
oedema that might occur will not induce or compound the severity of
ischaemia by increasing the intercapillary distance, as I had suggested,
but by increasing the distance between blood and mitochondria.
Knowing whether marathon runners have developed gut mucosal ischaemia
or not would seem essential in determining the causes of hyponatraemia and
more importantly in deciding the most appropriate therapy for collapsed
runners. Any organ dysfunction or failure that occurs is likely to be
confined to those who have developed gut mucosal ischaemia.
Excessive oral fluid intake would seem, therefore, more likey to
cause pathological problems in those who do not develop gut mucosal
ischaemia (?the occasional marathon runner) than in those that do (?the
serious marathon runners). As in surgery fluid intake during a marathon
would seem to be desirable for it can prevent the development of gut
mucosa ischaemia and its adverse consequences. It is much more difficult
to reverse gut mucosal ischaemia and prevent its adverse consequences.
There is, therefore, the danger that overzealous intravenous therapy in a
collapsed runner may do more harm than good.
Competing interests:
None declared
Competing interests: No competing interests
Dr Shephard's understanding of basic electrolyte and fluid balance
during exercise appears to be in error. Almost all the body's sodium is
distributed essentially in the extracellular fluid (ECF) volume which has
a volume of approximately 17 litres and not in the total body water of
approximately 40 litres. Thus it takes a relatively small increase in the
volume of ECF to drop the serum sodium concentration as we have repeatedly
stressed (1). For example without any sodium loss at all, an increase in
the ECF volume from 17 to 19.5 litres will drop the serum sodium
concentration to 125mmol per litre, sufficient to cause significant mental
impairment and perhaps coma in some athletes. This theoretical
calculation fits exactly the findings in our clinical studies (2) as noted
by Dr Shephard.
I am not certain why Dr Shephard believes that I have stated that a
female marathon runners needs to gain 12-15kg to become significantly
hyponatraemic; this is clearly not in line with either our clinical
findings (2)or our theoretical calculations (1). That a self-reported
fluid intake of 15 litres has been described in one female marathon runner
in the United States is correct (3) but Dr Shephard incorrectly credits me
with that finding. This lady's post-race serum sodium concentration was
however 118mmol per litre (3). This suggests that her ECF volume
increased by about 3.7 litres. Given that the ECF volume is about 42% of
the total body water, this would represent a body weight increase during
the race of approximately 8.8 kg, not the 12-15kg that his calculations
require. Presumably if this athlete did indeed ingest 15 litres she also
lost a substantial amount (3-5 litres) of fluid in urine and sweat during
the marathon. Such a loss is not inconceivable during 5 hours of exercise.
We have indeed measured increases in body weight of up to 6kg (2) in
South African ultramarathon runners; that these increases are not greater
is because, unlike the situation in the United States, South African
runners have never been encouraged to "drink as much as tolerable" during
exercise. If they had, the probability is that hundreds if not thousands
of runners in our very popular 90km Comrades ultramarathon, which annually
attracts 10 000 or more runners, would have succumbed to this condition.
Instead we have had relatively few such cases (2).
Perhaps Dr Shephard's more subtle point is that the injudicious use
of intravenous fluids might very rapidly turn a moderate case of exercise-
related hyponatraemia into a potentially fatal condition. Indeed I have
often wondered how fatalities occur in this condition since the assumption
would seem to be that a self-inflicted condition should begin to reverse
itself immediately the athlete falls unconscious and is unable to continue
the causative mechanism - overdrinking.
That there have been no fatalities from this condition in South
Africa may indeed result from our absolute rule that collapsed athletes
may not receive intravenous fluids unless their is an evidence-based
reason for such treatment.
1. Noakes TD. Hyponatremia in distance runners: Fluid and sodium
balance during exercise. Curr Sports Med Rep 2002; 4: 197-207.
2. Irving RA, Noakes TD, Buck R, van Zyl Smit R, Raine E, Godlonton J, et
al. Evaluation of renal function and fluid homeostasis during recovery
from exercise induced hyponatremia. J Appl Physiol 1991; 70: 342-348.
3. Hew TD, Chorley JN, Cianca JC, Divine JG. The incidence, risk factors
and clinical manifestations of hyponatremia in marathon runners. Clin J
Sports Med 2003; 13: 41-47.
Competing interests:
Receives research funding from Bromor Foods, manufacturer of sports drinks in South Africa
Competing interests: No competing interests
In the article “Overconsumption of fluids by athletes” BMJ Volume
327, 19 July 2003(1), Dr. Noakes argues correctly that excessive intake of
water or drinks low in sodium chloride before, during, and after exercises
in heat can be dangerous leading to water intoxication, seizures, and
death (1). He also implies that “ … the most dehydrated won those 32 (? 42
km) km races, as is usually the case.” Fortunately, he recommends in the
end that thirst is the best guide for anyone as to how much to drink
during and after exertion. As a general rule of physiology and medicine
replacement of the volume lost is important, but solutes (especially
sodium chloride) must be replaced as well.
Exercise by unacclimatized individuals under conditions of high
ambient temperature increase sweat volume as well as its content of sodium
chloride(2). Current sports drinks have low sodium concentration relative
to sweat losses at maximum sweat gland function. Thus, it may be safer to
increase the salt content of sports drinks to protect athletes performing
under high heat rather than discouraging adequate replacement of losses.
An added benefit would be that less serious athletes performing under
lower ambient heat would not over consume beverages with a higher
electrolyte content. Normally hydrated individuals would find the brackish
taste of more salty drinks less palatable. Such an idea obviously works
against the thrust of the beverage industry that seek to cajole us all to
drink as much as possible of any fluid they produce.
1. Noakes, TD. Overconsumption of fluids by athletes. BMJ. 2003 Jul
19;327(7407):113-4.
2. Gordon, RS Jr and Cage, GW. Mechanism of water and electrolyte
secretion by the eccrine sweat gland. Lancet. 1966 Jun 4;1(7449):1246-
1250.
Competing interests:
None declared
Competing interests: No competing interests
What Manninen writes about glucose and insulin (1) is true of GLUT-1
glucose transporters but not of GLUT-4 transporters, both being present in
muscle fibres as exercise physiologists should know (2). The GLUT-1
transporters are insulin-independent and the GLUT-4 insulin-dependent.
With high blood glucose or insulin concentrations, as occurs after eating
or during exercise, muscle cells receive glucose via the insulin-dependent
GLUT-4 transporter.
Upon leafing through this recent textbook of exercise physiology it
was apparent that the dogma preached about nutrition not only for athletes
but also for weight reduction in obesity and type 2 diabetes is based upon
the premises that "complete combustion of food takes place at the expense
of oxygen" and that "the heat generated in these exergonic reactions can
readily be determined from measurements of oxygen consumption". Hence the
use of the Haldane transformation to calculate exercise oxygen consumption
(VO2).
The main conclusion from Krough and Linhard's seminal study in 1920
is that energy expenditure is inversely related to the respiratory
quotient [CO2 production/VO2]. A major problem with this conclusion is
that CO2 production in exercise would seem to be due to the buffering of
the protons accumulating from unreversed ATP hydrolysis rather than from
the declining levels being generated by oxidative phosphorylation (3,4).
The implication is that assessments of energy needs and expenditures in
stress by direct or indirect calorimetry [which are dependent upon the
measurement of CO2 generation] are seriously flawed.
The more relevant observation in Krough' and Lindhard's study is that
a high fat diet, administered two weeeks before testing, released less
energy than the high carbohydrate diet. In which case exergy generation
per unit of oxygen consumption was less in those subjects who had been on
the high fat diet than in those who had been on the high carbohydrate
diet. Does this not mean that energy generation was more dependent upon
glycolysis than upon oxidative phosphorylation in those who had been on
the high fat diet than in those who had been on the high carbohydrate
diet? Put in another way might the respiratory quotients, 1 for
carbohydrates, 0.7 for fats and 0.8 for proteins, be more a reflection of
the relative dependences of the three nutrients upon glycolysis and
oxidative phosphorylation than of their relative capacities for generating
metabolic energy?
There does not appear to be any meaningful data comparing the
capacity to generate energy from glycolysis alone in exercise from
endogenous sources of carbohydrates, fats and proteins other than tissue
lactate generation and blood lactate levels. Since these are dependent
upon the ability of the liver and other organs to dispose of the lactate,
the NAD(+)/NADH and adenine nucleotide pool size and the tissue pH they
are difficult if not impossible to interpret in this context.
The relative nutrient values of carbohycrates, fats and proteins,
expressed in kcal/g, are derived from complete oxidation in a bomb
calorimeter. What of their capacity to generate energy from nutrient
consumption by glycolysis independently of that generated by oxidative
phosphorylation? The respiratory quotient changes with increasing
exercise. This is at least partly a reflection of a shift from dependence
upon ATP resynthesis by oxidative phosphorylation to ATP resynthesis by
glycolysis alone. The relative contributions change with increasing
degrees of exercise.
How very little we seem to know about the relative nutritional values
of carbohydrates, fats and proteins and their relevance to the energy
released by ATP hydrolysis and manner in which it is replenished when the
demand for energy changes in health or disease.
1. Glucose and insulin
Anssi H. Manninen (15 August 2003)
2. Exercise physiology, 5th edition. Lippincott Williams and Wilkens,
Philadelphia, 2001.
3. Fiddian-Green RG. Gastric intramucosal pH, tissue oxygenation and acid-
base balance.
Br J Anaesth. 1995 May;74(5):591-606.
4. Fiddian-Green RG. Monitoring of tissue pH: the critical measurement.
Chest. 1999 Dec;116(6):1839-41.
Competing interests:
None declared
Competing interests: No competing interests
"Unlike glucose fructose does not require insulin to enter muscle or
liver cells".
Glucose does NOT require insulin to enter muscle cells.
Competing interests:
None declared
Competing interests: No competing interests
In his interesting editorial, Dr. Noakes quite rightly
renews his earlier criticism (1) that much early research on
hypohydration in marathon runners lacks an evidence base.
Shortly thereafter, he puts forward the view that
hyponatremia arises because female marathin runners have
consumed in excess of 15 litres of fluid in 5-6 hours of
competition. He suggests in his other writings that
hyponatremia is most likely to develop in cool weather, when
sweat loss would be at most 3 litres. Assuming that a
female marathoner runner was indeed able to absorb the
postulated 15 litres of fluid over an event (which in itself
seems most unlikely), and given an initial body mass of 55
kg, her final body mass would rise to at least 67 kg. Is
there any documentation that females gain 12-15 kg over a
marathon race?
Assuming also that there was a uniform distribution of the
12 litres of excess fluid throughout an initial body fluid
volume of 40 litres, serum sodium would necessarily drop
from 140 to less than 108 mMol/L., whereas in the eight
cases of hyponatremia reported by Irving et al. (2). the
average serum sodium dropped no lower than 123 mMol/L
(equivalent to a 5.5 litre excess of fluid), despite a total
race distance of 88 km. Again, is there any evidence-base
for the idea that self-administration of water can be
sufficient to reduce the average serum sodium to less than
108 mMOL/L over a 42 km marathon?
References
1. Noakes TD. Lore of Running (4th Ed). Champaign, IL.:
Human Kinetics, 2003.
2. Irving RA, Noakes TD, Buck R et al. Evaluation of renal
function and fluid homeostasis during recovery from exercise
induced hyponatremia. J Appl
Competing interests:
None declared
Competing interests: No competing interests
Whilst the benefits of carbohydrate loading in marathon runners,
which is intended to increase glycogen stores, are equivocal fructose
loading might enhance performance significantly by increasing the capacity
for ATP resynthesis by anaerobic means and potentially limit the risks of
over-hydration addressed in this paper. The capacity of the liver for
metabolising lactate and other metabolites may, however, be the ultimate
determinant of performance in marathion runners.
Unlike glucose fructose does not require insulin to enter muscle or
liver cells. Neither does fructose stimulate the release of insulin, as
glucose does, certainly in aerobic conditions. Fructose also enhances
the rate of lipolysis in adipose tissues and the availability of free
fatty acids for the synthesis of acetyl coenzyme A and of glycerol for
entry into the Embden-Meyhoff pathway in anaerobic tissues (1,2). Insulin,
which is released by glucose, does the reverse in adequately perfused and
oxygenated tissues.
Fructose competes unsuccessfully with glucose for hexokinase, the
enzyme catalysing the formation of fructose-6-phosphate from both glucose
and from fructose. The relative rates of reactions in aerobic conditions
are 20/1. Fructose may, however, also enter the Embden-Meyhoff pathway by
being catalysed by fructokinase an enzyme that does not catalyse glucose
reactions but is not present in muscle. In by-passing the
phosphofructokinase step fructose bypasses the fructokinase pathway and
escapes the negative feedback controls hypoxia, a fall in pH and a fall in
[ATP]/[AMP] exerts upon the rate and direction of metabolism within the
glyocolytic pathway (3). Indeed this pathway evades all of the negative
feed back controls exerted upon glucose metabolism as the severity of
anaerobiosis increases.
To circumvent the inhibitory controls in anaerobiosis glucose may be
converted to fructose by activating the polyol pathway. The first enzyme
in the polyol pathway, aldose reductase, reduces glucose to sorbitol,
which is then converted to fructose by sorbitol dehydrogenase [if as is
likely it also exists in man]. Thus fructose may be the preferred
substrate by muscle in marathon runners the glucose being used for
reductive biosynthesis, if necessary, and more importantly to provide
substrate for the brain.
An intravenous infusion of fructose has a half-life of 18 minutes,
half that of glucose. Its metabolic pathways bypass the pentose phosphate
shunt, its synthesis of the NADPH and hence reductive biosynthesis of
fatty acids in adipocytes, cholesterol and the steroid hormones in the
liver, and other important products of reductive biosynthesis including
cytochrome P450, reduced glutathione, nitric oxide and tetrahydrofolate
all of which use ATP.
In anaerobiosis in exercising muscle phosphofructokinase is inhibited
initially by the fall in pH induced by the accompanying unreversed ATP
hydrolysis and later by the fall in [ATP] and rise in [AMP]. Concurrently
fructose-6-phosphatase is upregulated so that F-6-phosphate accumulates.
Gluconeogenesis is thus stimulated promoting a rise in blood glucose from
synthesis in the liver from the lactate, glycerol and amino acids.
Glycogenolysis may also be inhibited further preserving the glucose
generated by gluconeogenesis for consumption by the brain. Thus in
anaerobiosis of exercising muscle fatty acids become the preferred
substrate for muscle and the glucose entering the blood is preserved for
uptake and utilisation by the glial cells interposed between capillaries
and neurons. The glial cells traffic nutrient from capillaries to neurons.
Glial cells do not require insulin for their glucose uptake from
blood even in normoxic conditions. In a sense, therefore, glucose behaves
like fructose in glial cells presumably with the same purpose, increasing
the rate of substrate utlisation for ATP resynthesis. In the normal course
of events ATP resynthesis in glial cells occurs by anaerobic means. The
lactate generated by glial cells is, however, used as substrate by
adjacent and oxygenated neurons. As with lactate generated by exercising
muscle which is converted into glucose in the liver (Cori cycle)the
neurons may rely upon an adequately oxygenated and normal functioning
liver to complete their metabolic functions if also supported by anaerobic
rather than aerobic means. These circumstances may exist in some patients
with isolated head injuries or strokes.
It should be emphasised that for anaerobic metabolism to be an
efficient generator of ATP in exercising muscle any lactate, and probably
NAD, glutamate and NH4, needs to be washed into the systemic circulation
so that they can be metabolised in the liver. The lactate is converted to
glucose in the liver (Cori cycle), the NAD to NADH by the conversion of
glutamate into alpha ketoglutarate in the Krebs cycle [this may occur
primarily within the brain] and the NH4 into amino acids in the liver for
synthesis, additional fuel for the Krebs cycle or convesion into urea and
excretion in urine. The kidneys may also dispose of the NH4.
In glial cells glutamate and NH4 is converted into glutamine and
transported to the oxygenated neurons. The lactate enters the Krebs cycle
by being converted into pyruvate. The glutamine is converted back into
glutamate which is either released into the synaptic clefts and taken up
again by glial cells or used to form NADH from NAD and alpha ketoglutarate
which is consumed in the Krebs cycle. The disposal of lactate and NH4 and
replenishment of NADH are necessary for the ATP resynthesis by anaerobic
means not be inhibited to their accumulation in accordance with the law of
mass action. In the cases of regional intracerebral anaerobiosis, as may
occur with isolated head injuries and strokes, an adequately oxygenated
liver [and to a lesser degree kidneys] becomes essential if anaerobic
metabolism is to generate the ATP needed for the brain to survive.
An intravenous administration of fructose has the potential to
increase ATP resynthesis in both anaerobic tissues without interfering
with gluconeogenesis or with fatty acid utilisation by muscle. Fructose,
but not glucose if phosphofructokinase is inhibited, is metabolised to
form fructose 1,6 bisphoglycerate an intermediate metabolite within the
Embden-Meyhoff pathway. If it, instead of fructose, were to be
administered intravenously two moles of ATP would be preserved increasing
from 2 to 4 moles the net yield of ATP generated from one mole of glucose
(or for that matter fructose) in the Emden-Meyerhoff pathway. [There
would, however, be a need to replenish the NADH from NAD for the
conversion of pyruvate to lactate, a reaction that could take place in
adequately oxygenated liver if it is impaired within the glycolytic
pathway in anaerobiosis as would seem. [This may occur in the Embden-
Meyhoff pathway but befoire the synthesis of fructose 1,6 bisphoglycerate
and can be suppressed in oxidative stress, notably that induced by
cytokines].
If phosphofructokinase is inhibited and glucose is made to pass
throught the pentose phosphate shunt the phosphofructokinase step is
bypassed in glycolysis preserving one mole ATP normally used in the
metabolism of glucose. The net yield of ATP from glucose in anaerobic
metabolism may, therefore, be increased from 2 to 3 moles, but this
increase is probably off-set by the ATP consumed in the reducitve
biosynthetic pathways. In other words enough ATP may be resynthesised in
anaerobioisis from glucose alone for reductive biosynthesis to proceed and
for the basic metabolic needs for cell survival to be met.
Glycolytic turnover and hence yield of ATP by anaerobic means may
increase by four or even as much as eight times in hypoxic conditions.
This may be the product of increased extraction of nutrient from each unit
of flowing capillary blood, and increased rate of capillary blood flow and
of the 10% increase in metabolic rate that occurs with each degree of rise
in regional temperature that occurs with exercise, an increase in
metabolic activity or inflammation [the Q10 effect]. Thus the net yield of
ATP in anerobiosis, regardless of whether glucose of fructose is the
substrate, is much greater than commonly supposed. It may even be as high
as 16 moles or 24 moles for each mole of substrate utilised. As the yield
from aerobic metaolism may also be increased from 38 moles by these
influences the net yield from anaerobic metabolism in any given set of
circumstances remains much lower than that from aerobic metabolism. It is,
however, sufficient to meet the needs of highly metabolically active
physicological processes such as wound healing.
Honey has been applied to wounds for millenia. Its reduces the risk
of infection and enhances wound healing in burns, ulcers, and other
cutaneous wounds (4). As Willmore, Hunt and others have shown wounds
replenish their ATP by anaerobic means even in hyperoxic conditions. As
honey contains large amounts of fructose, fructose could be one of its
active ingredients. This deduction is consistent with frutose being the
preferred carbohydrate substrate in anaerobic metabolism and suggests that
the supplementary supplies of fructose in honey may promote wound healing
by enhancing the yield of ATP from anaerobic metabolism. In which case
spermatazoa might depend upon the high concentations of fructose in semen
and ova upon the high concentrations of fructose in follicular fluid to
survive and thrive in the hostile microaerophilic environments of the
vagina, oviduct (i.e. Fallopian tube)and uterus.
Fructose-1,6-bisphosphate, the intermediary product of fructose in
the Emden-Meyerhoff pathway, has a neuroprotective effect when
administered intravenously immediately before or after inducing
hypothermic circulatory arrest in a porcine model (5). Animals treated
with it have significantly better postoperative behavioral scores. The
administration of the fructose-1,6-bisphosphate was also associated with
lower intracranial pressures and lower venous creatine kinase isoenzyme MB
measured during rewarming (P =.01 and P =.001, respectively). Among the
treated animals, brain glucose, pyruvate and lactate levels tended to be
higher, brain glycerol levels tended to be lower, and the histopathologic
score of the brain was significantly lower (P =.04). This raises the
possibility that fructose loading and especially fructose 1,6-bisphosphate
loading might enhance the performance of marathon runners. But, apart from
oral fructose causing gastrointestinal upsets, there may be a risk.
Fructose may cause a metabolic acidosis when administered to patients
in shock (2). This is not surprising for hepatic metabolism is likely to
be impaired in shock and with it the ability to metabolise lactate and NH4
and to replenish NADH. [Hence perhaps the rise in CSF glutamine and NH4 in
liver failure]. As the gastric intramucosal pH, which falls in severe
exercise, may correlate closely with hepatic venous lactates this could
be an indication of an inadequacy of hepatic oxygenation (6). Fructose
loading might, therefore, be dangerous in the many marathon runners who
develop a gastric intramucosal acidosis.
On the other hand catalytic quantities of fructose (<_10 of="of" total="total" carbohydrate="carbohydrate" flux="flux" enhance="enhance" liver="liver" glucose="glucose" uptake="uptake" in="in" a="a" dose="dose" dependent="dependent" manner.="manner." the="the" primary="primary" fate="fate" is="is" glycogen="glycogen" synthesispossibly="synthesispossibly" because="because" fructose="fructose" may="may" inhibit="inhibit" glyogenolysis7.="glyogenolysis7." ability="ability" to="to" augment="augment" not="not" impaired="impaired" by="by" presence="presence" marked="marked" insulin="insulin" resistance="resistance" such="such" as="as" type="type" _2="_2" diabetes="diabetes" or="or" infection.="infection." this="this" surprising="surprising" since="since" upon="upon" insulin.="insulin." potent="potent" acute="acute" regulator="regulator" and="and" synthesis.="synthesis." furthermore="furthermore" inclusion="inclusion" catalytic="catalytic" quantities="quantities" meal="meal" improves="improves" tolerance.="tolerance." fructose-16-diphosphate="fructose-16-diphosphate" administration="administration" also="also" attenuates="attenuates" post-ischemic="post-ischemic" ventricular="ventricular" dysfunction="dysfunction" _8in="_8in" addition="addition" having="having" neuroprotective="neuroprotective" effect="effect" porcine="porcine" model="model" circulatory="circulatory" arrest5.="arrest5." but="but" these="these" observations="observations" appear="appear" have="have" been="been" made="made" circumstances="circumstances" which="which" adequately="adequately" oxygenated="oxygenated" those="those" shock="shock" it="it" has="has" inadequately="inadequately" oxygenated.="oxygenated." p="p"/> In the absence of inhibitory controls might an intravenous infusion
of fructose and especially of fructose-1,6-bisphosphate, which has the
potential to double the capacity for ATP resynthesis in anaerobiosis,
induce a lactic acidosis? Only if the adequacy of hepatic tissue
oxygenation is impaired or if there is preexisting hepatic disease which
compromises the ability to metabolise lactate and NH4 and replenish NADH?
The co-existing presence of renal disease can be expected to increase the
risk
There may indeed be the potential to enhance performance in marathon
runners with fructose loading by either or intravenous means. If
accompanied by bicarbionate loading to off-set the degree of any gastric
intramucosal acidosis that develops in anaerobiosis the potential to
enhance performance could be much greater. Phosphate loading to
accommmodate the increased rate of ATP resynthesis might be an additional
benefit. It is needed to prevent complications from the development of the
hypophosphataemia induced by the increase in rate of resynthesis
apparently occurring with the commensement of feeding in burned patients
and possibly malnourished children (9,10).
If it enhances performance in marathon runners fructose or fructose-
1,6-bisphosphate loading might be of partcular benefit to patients by
limiting the degree of irreversible cellular damage induced by, for
example, head injuries, strokes, and acute coronary artery occlusions.
Maintining the adequacy of hepatic tissue oxygenation and function is
likely to be an especially important determinant of benefit in these
circumstances. There will, however, be no benefit if tissue perfusion in
the region in question, be it muscle , brain or heart, and nutrient
transport to remainder of the body including the liver is not maintained.
These potentail benefits might, however, be off-set by an widening of the
intercapiiary distances that might be induced by overhydration.
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Competing interests:
None declared
Competing interests: No competing interests
The recommendations as to fluid consumption during athletic endurance
events should be welcomed by competitors at all levels.(1) However I am
concerned that there may be other serious problems relating to fluid
consumption at high level competitive sport.
Whilst taking part in a low-key endurance walking event last weekend,
on a very hot day, I overheard other walkers talking about how, last year,
a participant collapsed and had to be given intravenous fluid by the
paramedics. Those who watch ultra-long distance cycling events on obscure
satellite television stations may have noticed exhausted cyclists, who
have retired from the race, being given intravenous fluids. This put me
in mind of a Sports Medicine conference I attended last year during which
we were reliably informed that intravenous hydration, at half-time, was
not unknown in top level sport.
In hospital practice, apart from dire emergency, it is unknown to
give intravenous fluid without knowing sodium and potassium levels,
because of possibly fatal effects of hypokalaemia and hyponatraemia.
Let us suppose a professional sportsman had been suffering from
diarrhoea and vomiting prior to an event and started the match with
potassium or sodium depletion. Administration of intravenous fluids at
the end of the first half would, surely, be even more likely to cause
sudden death. This is a scenario which could easily take place in
international sport.
I can find only two references in the literature to intravenous
hydration in sport which appear to relate to Australian Rules Football.
If this procedure is taking place in international sport on a regular
basis then it is surely as dangerous as, for example anabolic steroid use
which is of course banned.
It occurs to me that half-time intravenous hydration is unlikely to
happen without the team doctor's knowledge. Maybe other reader's of this
journal may be able to offer information about how widespread this
procedure is in high level sport. Perhaps it is something the medical
profession should take up with international sporting authorities.
Should a top athlete die suddenly on the field of play, it is
submitted that the contributory role of possibly inappropriate intravenous
hydration should be considered.
(1) Noakes TD. Overcomsumption of fluids by athletes.
BMJ 2003;327:113-4.
Competing interests:
None declared
Competing interests: No competing interests
Can we keep the focus on the evidence base?
The intent of my rapid response of 13th August, 2003 was to argue
that authors, and especially writers of editorials, should make critical
evaluation of their evidence base, rather than simply paying lip service
to this need. I fear that in his response of 19th August, 2003, Dr.
Noakes may have obscured this point by parading a succession of "straw
men."
My primary concern was the uncritical statement that female runners
drink "about 15 litres of fluid" (his editorial, p. 113, where the
implication is of a generality typical of a slower female marathon runner,
rather than a single case). My purpose in testing the effect of
distributing 12-15 L into 40 litres of body fluid was simply to
demonstrate the mathematical maximum value of post-race serum sodium that
would be compatible with acceptance of such a bizarre claim (108 mMol/L).
Noakes is correct that the fluid would more likely be distributed only
through the extracellular compartment, but the maximum serum sodium would
then drop even further, to an incredible 79 mMol/L. In fact, such a
result is completely at variance with Hew et al.'s reported value of 118
mMol/L. Further, if the claim that 15 L was ingested had any validity,
body mass would necessarily increase by 12-15 kg, depending on the extent
of sweating and urination.
Plainly, a simple use of mathematics would have sufficed to show that
on several counts the statement regarding ingestion of 15 L of fluid
should not have appeared in this editorial.
Competing interests:
None declared
Competing interests: No competing interests