Editorial
Vitamin D—Risk vs Benefit
The important paper by Holmes and Kummerow, in this issue,
calls our attention to the need for balancing benefit against
risk when providing dietary supplements to all in forms that are
not readily recognized. In the case of vitamin D, the
prophylactic use of which prevents a former common
disease—rickets—recommendation that general
widespread supplementation be discontinued or even modified
requires careful consideration. Holmes and Kummerow have done
this, by putting into focus the evidence that we are consuming
far more vitamin D than had been suspected, and that not only the
age group most vulnerable to rickets, but those for whom less
vitamin D is needed, consume more than antirachitic doses. They
provide insight into what the hidden sources of vitamin D are and
refer to the unreliability of the assays of activity or toxicity
of the different vitamin D precursors, congeners, and breakdown
products.
It is well to remember that not all are at equal risk of
vitamin D toxicity. Taussig [1] and Beuren [2] called attention
to the great variation in the severity of exogenously caused
malformation (as in the case of thalidomide) and suggested that
the same might be true for the vitamin D-associated
abnormalities, their degree depending on the time and magnitude
of exposure to excessive intakes. They were referring,
principally, to the supravalvular aortic stenosis syndrome (SASS)
and related arterial abnormalities, such as those that resulted
from the infantile hypercalcemia that occurred in epidemic
proportions in Great Britain during the period of
oversupplementation of infant formulas and foods [3].
Administration of more than 400 I U of vitamin D—from all
sources—was never approved in the United States or Canada,
but the disorders that developed in a substantial minority of
infants subjected to overdosage are less commonly seen here. This
brings us to individual variations in response to vitamin D.
Genetic or acquired vitamin D resistance is well recognized.
Since the severe manifestations of vitamin D toxicity that are
seen in SASS are familial [2], it is plausible that
hyperreactivity to vitamin D is genetic. To those with such a
metabolic pattern, inadvertent consumption of excess vitamin D is
a particular risk. There is still another possibility that should
be investigated. Fragmentary animal studies indicate that
successive generations, given toxic doses of vitamin D, exhibit
increased vulnerability to hypervitaminosis D [4]. We are at
least in the third generation of vitamin D supplementation, that
from Holmes and Kummerow's evidence, may well be considerably
more than necessary. They present a survey of the new
developments in our knowledge of the metabolism of vitamin D that
have been made possible by the new methodology, which provides
the tools to elucidate the mechanisms of altered
responsivity.
During the era of eradication of rickets, new pediatric and
adult diseases have increased in prevalence. Hutchison [5]
observed in 1955 that over the 20 years during which rickets had
been eliminated in England, infantile hypercalcemia with and
without osteosclerosis, renal tubular acidosis, and fibrocystic
disease of the pancreas had emerged as serious diseases of
childhood. He noted that antirachitic measures had been
associated with the appearance of infantile hypercalcemia.
Lightwood [6] reported that the incidence of renal tubular
acidosis, as well as that of hypercalcemia, declined when the
amount of vitamin D added to infant formula was diminished. Since
generalized arteriosclerosis, as well as the mental retardation
and valvular damage, is part of the SASS, and juvenile
cardiovascular disease has become a serious problem [7], it is
possible that excessive vitamin D might contribute to the early
roots of arteriosclerosis in a larger segment of our population
[8] than those so hyperreactive as to develop the full-blown
toxicity. The preliminary clinical evidence of association of
only moderately high vitamin D intakes with hypercholesterolemia
[9-11] deserves further study.
The wealth of evidence adduced by Holmes and Kummerow that
intakes of vitamin D exceed the official recommendations, and far
exceed the requirements of many, emphasizes the importance of
reopening the question of how best to protect against rickets,
without placing others at risk of cardiovascular and renal
disease. Practices that result in supplying amounts of vitamin D
(directly from supplemented foods for human consumption, or from
foods derived from supplemented animals) that can be toxic to a
subset of the population require reexamination.
We recognize that this subject is controversial; we welcome
letters to the editor and submission of papers presenting other
points of view.
MILDRED S. SEELIG. MD, MPH, FACN
Editor
REFERENCES
1. Taussig HB: Possible injury to the cardiovascular system
from vitamin D. Ann Intern Med 165:1195-1200,1966.
2. Beuren AJ, Apitz J, Stoermer J, Kaiser B: Vitamin
D-hypercalcemic cardiovascular disease. Mschr Kinderheilk
114:457-470, 1966 (Ger).
3. Seelig MS: Vitamin D and cardiovascular, renal, and brain
damage in infancy and childhood. Ann NY Acad Sci 147:537-582,
1969.
4. Light RF, Miller GE, Frey CN: Studies on the effects of
overdosage of vitamin D. II. J Biol Chem 92:47-52, 1931.
5. Hutchison JH: Some new diseases in paediatrics. Brit Med J
2:339-342, 1955.
6. Lightwood R, Butler N: Decline of renal tubular acidosis:
Aetiological implications. Brit Med J 1:855-857, 1963.
7. Seelig MS: Early nutritional roots of cardiovascular
disease. In Naito HK (ed): "Nutrition and Heart Disease." New
York: SP Medical & Scientific Books, 1982, pp 31-59.
8. Seelig MS: Magnesium deficiency with phosphate and vitamin
D excesses: Role in pediatric cardiovascular disease? J
Cardiovasc Med 3:637-650. 1978.
9. Dalderup LM, Stockmann VA, Rechsteiner de Vos H, Van der
Slikke GJ: Survey on coronary heart disease in relation to diet
in physically active farmers. Voeding 26:245-275, 1965.
10. Feenstra L, Wilkens JH: Cholesterol and vitamin D: Ned T
Geneesk 109:615-619, 1965 (Dutch).
11. Linden V: Correlations of vitamin D intake to ischemic
heart disease, hypercholesterolemia, and renal calcinosis. In
Seelig MS (ed): "Mineral. Vitamin D, and Cholesterol Imbalance in
Diseases of Infants and Adults." SP Medical & Scientific
Books, 1977, pp 23-42.
Journal of the American College of Nutrition 2:109-110
(1983)
1983 Alan R. Liss, Inc.
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