Often
the benefits of vitamin C observed in randomized double-blind
placebo-controlled trials are disregarded, although at the same time
authors may exaggerate the potential harm caused by vitamin C even
when it is purely anecdotal (see for example
Olson & Hodges 1987;
Herbert 1993).
In
a casual survey of 20 physician colleagues, Goodwin and Tangum (1998)
found that all of them were aware that high-dose vitamin C ingestion
can cause kidney stones. Goodwin and Tangum were, however, interested
in where this common ‘knowledge’ comes from and
they combed the
medical literature without finding any articles in refereed journals
reporting instances of high-dose vitamin C causing kidney stones.
Review articles cited book chapters that in turn cited abstracts,
letters, and other review articles. Goodwin and Tangum concluded that
nowhere in the trail of citations was there any fundamental
information on whether or how frequently high-dose vitamin C
supplementation might lead to kidney stones. The authors simply
stated that vitamin C may cause kidney stones, and as proof they
cited other authors who had said the same thing. Thus, this
description reveals a typical urban legend; a story that is retold,
yet no-one confirms that the story is true.
The anecdote of vitamin C
and kidney stones is mentioned in a major textbook of pharmacology:
"…risks of megadose treatment ... include formation of
kidney
stones"
(Marcus
& Coulston 2001).
The statement that vitamin C may cause kidney
stones has been reiterated, e.g., in the Nordic Nutritional
Recommendations without any references (NNR 2004
p 310).
When
reviewing the health effects of vitamin C, Olson and Hodges (1987)
and Herbert (1993)
claimed that "Large intakes of vitamin C may
reduce insulin production." This statement was based on a paper
published in 1946. Levey and Suter (1946)
reported that vitamin C
potentiates the diabetogenic action of alloxan in rats, whose
blood-sugar level was determined 3 days after injecting alloxan, or
alloxan with vitamin C. Hyperglycemia was observed in 50% of the rats
treated with alloxan and vitamin C, in contrast to 17% of the rats
treated with alloxan alone. Nevertheless, the authors concluded from
their own previous work that "ascorbic acid alone does not
produce hyperglycemia" (Levey & Suter 1946).
Thus, this old
experiment with alloxan- treated rats was the basis for Olson and
Hodges (1987)
and Herbert (1993)
to state that large doses of vitamin
C alone may reduce insulin production in human subjects.
Olson
and Hodges (1987)
and Herbert (1993)
stated that "Large intakes
of vitamin C may interrupt pregnancies." This suggestion was
based on a brief Russian paper published in 1964. Twenty women whose
menstruation was delayed by 10-15 days were given 6 g/day of vitamin
C, and 16 of them started to menstruate within 3 days (Samborskaya
&
Ferdman 1966).
Pauling (1976a)
wrote a letter to the authors
inquiring whether any actual direct test of pregnancy was carried
out, but he received only a copy of the publication by way of reply.
Thus, there was no evidence that the women were pregnant to begin
with. Possibly the women just had irregular menstruation, yet this
report was valid enough for Olson and Hodges (1987)
and Herbert
(1993)
to conclude that vitamin C may cause miscarriages.
Olson
and Hodges (1987)
and Herbert (1993)
also argued that "Large
intakes of vitamin C may lower plasma vitamin B12 levels." This
claim was originally made by Herbert himself (Herbert & Jacob
1974),
however, it was shown afterwards that the apparent breakdown
of vitamin B12 was due to methodological shortcomings (Newmark et
al. 1979;
Marcus 1981),
and the vitamin B12 level was not
decreased in patients administered as much as 4 g/day of vitamin C
for 11 months or more (Afroz et
al. 1975),
or in children administered gram-doses of vitamin C for years (Ekvall
et al. 1981).
However, these papers
were not cited by Olson and Hodges (1987)
or Herbert (1993).
In
extreme cases, suggestions about vitamin C toxicity have been based
on double-speculation. Herbert (1993)
stated that (1) vitamin C might
cause elevated iron levels, and (2) elevated iron levels might cause
increased risk of coronary heart disease. However, (1) in order to
quantify the effect of vitamin C supplementation on iron status, Cook
et al. (1984)
administered 2 g/day of
vitamin C to 9 subjects for 2 years without finding indications of
iron accumulation, and (2) several studies with different types of
settings were unable to corroborate the hypothesis that raised iron
levels increase the risk of coronary heart disease (Bendich &
Langseth 1995; Hemilä & Paunio 1997).
In contrast to
ordinary people, patients suffering from actual iron overload may
derive harm from vitamin C; however, its harmful effect on these
particular patients and the rationale of treating such patients with
the combination of vitamin C and desferrioxamine has been known for a
long time (Nienhuis 1981).
Rivers
(1987) reviewed 74 publications dealing with the possible toxicity of
vitamin C and concluded that "Large quantities of ascorbic acid
will not result in calcium-oxalate stones, increased uric acid
excretion, impaired vitamin B12 status, iron overload, systemic
conditioning, or increased mutagenic activity in healthy
individuals." In another review, Marks (1989)
concluded that "A
large number of adverse reactions have been alleged to occur with the
use of large doses of ascorbic acid, but almost without exception
further study has demonstrated that the allegations are without
foundation ... an overview of all the information shows that the safe
daily level is at least 100 times the RDA." The RDA level for
vitamin C was 60 mg/day at that time. Hathcock (1997)
stated that
"Many hypothetical adverse effects of high intakes of vitamin C
have been cited for decades. Most, with the exception of mild and
transient gastrointestinal effects, seem to have little or no known
factual basis." Several other reviews have also concluded that
vitamin C is safe in doses around 1 g/day (Hanck 1982;
Bendich
&
Langseth 1995; Diplock 1995;
Hathcock et
al.
2005).
The recent US nutritional recommendations suggest
that
the safe range of vitamin C intake goes to 2 g/day for adults, but
the basis for this upper limit of ‘safe doses’ is
the appearance
of loose bowels (FNB 2000 pp
155-65), which, however, is quite a
trivial adverse effect and disappears quite quickly with a change to
lower intake levels.
There
are a few reports of severe harm caused by highdose vitamin C
administration. Nevertheless, the death of a 68-year old African
American man was not attributed to intravenous injection of 80 grams
of vitamin C on 2 consecutive days per
se,
but to his coincident glucose-6-phosphate deficiency (Campbell et
al. 1975).
Such isolated instances have no public health
relevance. In a recent pharmacokinetic study participants were
administered up to 100 grams of vitamin C within a few hours
indicating the safety of such a large dose per
se in healthy people (Padayatty et al.
2004).
There is much evidence indicating that vitamin C
metabolism changes during infections and this may affect the
relationship between doses and adverse effects (Hemilä 2006
pp 6-7; see Metabolism).
It has been reported that people with serious infections can ingest
over 50 g/day of vitamin C without gastric problems (Luberoff 1978;
Cathcart 1981).
References
NOTE:
all the links in the
main text should be freely accessible, but several of the
links
below require a permission from publisher.
Afroz M, Bhothinard B, Etzkorn JR, et al. (1975) Vitamins C and B12
[letter]. JAMA
232:246CH
Bendich A, Langseth L (1995) The health effects of vitamin C
supplementation. J
Am Coll Nutr 14:124-36, 218, 398
Campbell GD, Steinberg MH, Bower JD (1975) Ascorbic acid-induced
hemolysis in G-6-PD deficiency [letter]. Ann
Intern Med 82:810
Ekvall S, Chen IW, Bozian R (1981) The effect of supplemental ascorbic
acid on serum vitamin B12 levels in myelomeningocele patients. Am
J Clin Nutr 34:1356-61
FNB [Food and Nutrition Board, Institute of Medicine] (2000) Dietary
Reference Intakes for Vitamin C, Vitamin E, Selenium and Carotenoids.
Washington DC: National Academy Press vitamin
C pp 95-185
Goodwin JS, Tangum MR (1998) Battling quackery: attitudes about
micronutrient supplements in American Academic medicine. Arch
Intern Med 158:2187-91p
2188
Marcus R, Coulston AM (2001) The vitamin B complex and ascorbic acid.
In: Goodman & Gilman’s The Pharmacological Basis of
Therapeutics, 10th edn [Hardman JG, Limbird LE, Gilman AG, eds]. NY:
McGraw Hill. pp
1765-71