Anaesth Intensive Care 2008; 36: 585-588

Fatal vitamin C-associated acute renal failure

G. J. MCHUGH*, M. L. GRABER†, R. C. FREEBAIRN‡
Intensive Care Unit, Palmerston North Hospital, Palmerston North, New Zealand

SUMMARY
Although daily ingestion of high-dose vitamin C is generally regarded as largely innocuous, fatal nephrotoxicity can
occur in some rare circumstances. We report a case where the patient, who chose to forgo any advanced conventional
medical intervention (dialysis and mechanical ventilation), had failed to disclose his use of high-dose vitamin C
and subsequently died. Intra-renal oxalate crystal deposition was demonstrated at autopsy. Directed enquiry with the
family then revealed his high-dose vitamin C usage. Even though fully-informed discussion was limited by incomplete
prospective disclosure, it remains the prerogative of any competent patient to decline any treatment, including those
that may be considered life-saving.
Key Words: vitamin C, ascorbic acid, acute renal failure, mental competency, personal autonomy, autopsy, critical care

Supra-physiological vitamin C (ascorbic acid) diverticular disease. He denied any cardiorespiratory,

supplementation has been subject to considerable
debate and investigation. Popularised by the work
of Nobel Prize winner Linus Pauling in the 1970s,
vitamin C use has variously been advocated as
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ranging from the common cold through to malignancy1-5.
Subsequent studies and metanalyses have not been
DEOHWRVXEVWDQWLDWHWKHFODLPHGEHQHÀWV6-8. Although
commonly regarded as relatively innocuous, high-dose
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morbidity and mortality9-15. A fatal outcome associated
with apparent excessive vitamin C supplementation
is reported here. As well as highlighting the potential
for vitamin C toxicity and the importance of knowing
all ingested medicaments, other features include
aspects of patient competence to refuse life-preserving
therapies and the continuing importance of the post-
mortem examination.
CASE HISTORY
A 72-year-old male presented to hospital with a
two-week history of generalised malaise and lethargy,
along with unsubstantiated reports of intermittent
confusion. He had a background history of putative
pernicious anaemia and a previous hemicolectomy for
*M.B., Ch.B., F.A.N.Z.C.A., E.D.I.C., Medical Head, Intensive Care.
†M.B., B.S., M.R.C.P.(U.K.), Locum Nephrologist, Department of Renal
Medicine.
‡M.B., Ch.B., F.A.N.Z.C.A., F.J.F.I.C.M., Medical Director, Intensive Care
Services, Hawkes’ Bay Hospital, Hastings.
Address for reprints: Dr G. McHugh, Medical Head, Intensive Care,
Palmerston North Hospital, Private Bag 11036, Palmerston North, New
Zealand.
Accepted for publication on April 30, 2008.
Anaesthesia and Intensive Care, Vol. 36, No. 4, July 2008
genitourinary or gastrointestinal symptoms. He
stated that he took no regular medications and
denied substance ingestion. At times when answering
direct questions he appeared evasive, giving the
impression that certain details may have been
withheld. When directly challenged in this regard, he
was no more forthcoming. A degree of dysarthria was
noted and attributed to his very dry mouth. Despite
this he was clearly not confused or disorientated and
his executive function was deemed to be intact.
On examination, he appeared cachectic and was
dehydrated and hypothermic (tympanic temperature
32.9°C). His heart rate was 85 beats/minute with
low to normal blood pressure (SBP 95 mmHg) and
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moderate tachypnoea with a Kussmaul-type pattern
but well maintained oxygen saturations of 100% on
6 l/min supplemental oxygen by facemask. The only
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guarding or rebound tenderness. He was oliguric.
Blood chemistry revealed creatinine 1358 μmol/l,
urea 64 mmol/l, K+ 4.1 mmol/l, Na+ 140 mmol/l,
serum osmolality 353 mOsm/kg. A full blood count
result included haemoglobin 94 g/l and WCC 8.3×
109/l. Arterial blood gas analysis revealed pH 7.07,
PaO2 206 mmHg, PaCO2 8 mmHg, actual HCO3-
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arterial lactate of 0.6 mmol/l. Resuscitation with
intravenous (IV) crystalloid was commenced while
an intensivist consultation was arranged. Following
review he was transferred to the intensive care unit
(ICU) for on-going management.
Discussion with him centred upon the nature of
his problem, its possible causes and consequences,
586 G. J. MCHUGH, M. L. GRABER ET AL
and the proposed immediate management strategies.
During this discussion he made it clear that in the
interim, he did not wish to have either dialysis or,
should it become necessary, tracheal intubation and
mechanical ventilation. He stated that he wished to
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opinion the following day. It was impressed upon him
that in the event of a more immediate generalised
deterioration he would most likely be unable to offer
any revised opinion. The high likelihood of death
without advanced therapeutic measures, particularly
renal replacement therapy, was also emphasised. He
indicated that he understood and accepted this but
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contact was to be made with his immediate family
members.
In ICU, further IV crystalloid rehydration was
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hours. Given some uncertainty regarding his
‘usual’ blood pressure, it was decided to commence
titrated IV infusions of catecholamines (initially
noradrenaline with dopamine later added) with the
intent of optimising renal perfusion. Despite these
initial measures he remained oligo-anuric even
though the urea and creatinine responded favourably,
falling to 55 mmol/l and 1015 μmol/l respectively.
His acidosis worsened to a nadir of pH 6.97 and he
developed an acute confusional state with marked
agitation for which titrated IV doses of diazepam
and haloperidol were administered. An ultrasound
scan excluded obstructive nephropathy and showed
normal-sized kidneys that were unusually echogenic in
a homogenous distribution. Numerous renal tubular
epithelial cells were seen on urine microscopy. A trial
bolus-administration of frusemide was unhelpful. He
became hypoxaemic with increasing work of breathing
and a decreasing level of consciousness. In the
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overload, non-invasive ventilatory assistance (FiO2
0.5) was commenced in the belief that this did not
contravene his earlier request for limitation. Following
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changed to an isotonic bicarbonate solution.
Given his accelerated deterioration, some
consideration was given to temporarily overriding the
patient’s earlier refusal of renal replacement therapy
on the grounds that he may not have been fully
competent. At this point, his family members made
contact and provided further detail. He had long-held
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supplementation in preference to ‘conventional’
medicine. At the time, this was not recognised as
having any potential immediate causal relationship to
his acute renal failure. Further, his family members
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conventional therapeutic interventions was entirely
congruent with his character and previously expressed
beliefs. Accordingly no further consideration was
given to disregarding his initial refusal of escalation.
He had now become deeply unconscious and it was
apparent that the currently employed measures
ZHUH QRW VXIÀFLHQW WR UHYHUVH KLV GHFOLQH )ROORZLQJ
discussion with his sister and the wider family,
active management was discontinued and palliation
instituted. Death followed soon thereafter. At this
stage the cause of his acute renal failure remained
unknown and his death was referred to the coroner. An
autopsy examination was performed. Renal histology
revealed that his renal failure had been secondary to
extensive oxalate crystal deposition, with the pathologist
offering ingestion of an oxalate-containing substance
as a possible cause. Subsequent directed enquiry
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nutritional supplementation and revealed that he
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vitamin C therapy (in the order of several grams per
day). Numerous empty packages of a proprietary
vitamin C-containing preparation (whose listed
contents included both ascorbic acid and magnesium
ascorbate) had been found at his home after his death.
It appeared that he had consumed vast additional
amounts of vitamin C supplement in the period
leading up to his death. With this additional
information, a plausible clinical picture emerged.
DISCUSSION
The development of renal failure in association
with use of high-dose vitamin C has been described
previously but only one other case fatality has been
reported9-15.
Vitamin C is metabolised to oxalate and deposition
of oxalate in the kidney is a recognised cause of acute
renal failure. Some variability has been demonstrated
in the development of vitamin C-associated oxaluria
and/or nephrolithiasis but nonetheless caution has
been advised in the use of high-dose supplementation
or therapy16,17. While there is little information
available regarding the outcome from ascorbic
acid induced oxalosis and acute renal failure, renal
failure associated with primary hyperoxaluria can
be effectively managed medically and carries a
reasonable prognosis18. Although not disclosed by the
patient, his reported healthcare preferences and the
numerous empty containers of vitamin C-containing
supplements support the premise that he had
Anaesthesia and Intensive Care, Vol. 36, No. 4, July 2008
 CASE REPORT
consumed exceedingly high-dose vitamin C in his
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dosage may well have been augmented by increased
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symptoms that he had described as a prodrome to his
hospital presentation. In addition it is possible that
dehydration had contributed to the extensive intra-
renal crystallisation of oxalate salts and resulting acute
renal failure. Regardless, the presence of oxalate
deposition seen in his kidneys at autopsy supports
the theory that excessive amounts of vitamin C had
provoked his problems.
Although it may frequently be unintentional, many
patients who use complementary and alternative
medications fail to disclose their usage of such
remedies to medical practitioners17,19-21. In this case,
non-disclosure removed any possibility of identifying
the relationship between the acute renal failure and
vitamin C toxicity. It also precluded a fully informed
discussion regarding the anticipated reversibility of
oxalate-associated nephropathy and the expected
life-preserving role of short-term renal replacement
therapy. The patient was described as having been
widely read in the area of nutritional supplementation.
However it cannot be known if he was aware of the
potential toxicity of vitamin C. The physician-patient
relationship imposes duties and obligations on both
parties, and non-disclosure by a patient, whether
involuntary or not, can adversely affect the quality of
care that is provided22,23.
The relevant New Zealand legislation requires
that a patient’s competence must be assumed unless
there are reasonable grounds to believe otherwise24.
This is encompassed within the Code of Health
and Disability Services Consumers’ Rights which
stipulates the patient’s right to autonomy25. Every
patient has the right to decline any treatment, but this
patient’s interim refusal presented a challenge. He
had indicated that he wished to deliberate further, but
he proved unable to deliver his ultimate decision. The
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clearly spelt out to him and he was prepared to accept
the associated risks, including death.
Strong consideration was given to temporarily
over-riding the patient’s interim decision to refuse
dialysis on the grounds that his severe uraemia, which
can be associated with delirium and acute dementia,
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faculties and negated the validity of his response26,27.
During this deliberation, the family’s additional
SHUVSHFWLYH EHFDPH DYDLODEOH WR FRQÀUP WKDW D
decision to forgo ‘conventional’ medical intervention
Anaesthesia and Intensive Care, Vol. 36, No. 4, July 2008
587
was entirely in keeping with his expected response.
This allayed any lingering doubts that his ‘executive
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wishes were complied with and no dialysis or invasive
mechanical ventilation therapies were instituted.
At the time of death, the aetiology of his acute
UHQDOIDLOXUHZDVXQFOHDU7KHÀQGLQJVDWWKHFRURQLDO
post-mortem examination came as a surprise to the
clinical team. It was only while communicating the
autopsy result to his family that the extreme nature
of his vitamin C usage became clear. The autopsy
results were entirely compatible with the cause of
death being acute renal failure secondary to the
nephrotoxic effects of high-dose vitamin C therapy.
1RRWKHUUHOHYDQWÀQGLQJVZHUHGLVFRYHUHG+DGWKH
oxalosis not been revealed by post-mortem histology,
additional information would not have been sought
from the family and the cause of renal failure would
have remained speculative. Even though highly
selected, the autopsy still has an important role to
play in intensive care medicine28,29.
CONCLUSION
Ingestion of high-dose vitamin C can result in acute
renal failure secondary to renal oxalate deposition.
Due to an unusual and complex set of circumstances,
this has resulted in a case fatality whose occult cause
was only elucidated using additional information
gathered at autopsy. The physician-patient relationship
imposes mutual obligations, and on this occasion it
is likely that patient non-disclosure had an adverse
impact on the outcome. That notwithstanding, it
remains the prerogative of every competent patient
to decline any treatments, including those that can be
life-saving.
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Anaesthesia and Intensive Care, Vol. 36, No. 4, July 2008