THE PROPHYLACTIC REQUIREMENT AND THE TOXICITY …pediatrics.aappublications.org/content/pediatrics/31/3/... · THE PROPHYLACTIC REQUIREMENT AND THE TOXICITY OF VITAMIN D COMMITTEE

THE PROPHYLACTIC REQUIREMENT AND THETOXICITY OF VITAMIN D

COMMITTEE ON NUTRITION

512

PEDIATRICS, March 1963

I T Is NOW more than 40 years since Sir

Edward Mellanby1 demonstrated that

cod liver oil would prevent rickets. Since

this discovery, rickets due to vitamin D

deficiency, once a serious pediatric problem

in temperate climates, has become a com-

paratively rare clinical entity throughout

the civilized world. Nonetheless, cases of

deficiency rickets still occur in the United

23 Canada,4 Great Britain,5 and else-

where.

In temperate climates, sunlight cannot be

relied upon to provide year-round protec-

tion from rickets in infancy and early child-

hood, and vitamin D must be provided from

other sources. Until recently, the intakes of

vitamin D recommended by official organ-

izations in a number of countries could only

he achieved by administration of oral vita-

mm D supplements, since the normal diet

(even one including butter, milk, and egg

yolk) contained relatively little vitamin D.

Today, however, the situation is greatly

altered, at least in such countries as the

United States, Canada, and Great Britain.

Because the addition of supplemental vita-

mm D to various foods is sanctioned, mdi-

viduals of all ages now receive variable and

sometimes considerable amounts of vitamin

D from pasteurized, evaporated, on pow-

dered milk, margarine, certain ready-to-eat

cereals, and a variety of other foodstuffs. In-

deed, in the United States and Canada there

is now a reasonable likelihood that the in-

dividual, even the small infant, may receive

the total recommended allowance of vitamin

D from an average diet; in some instances

he will receive considerably more than the

recommended intake even when no vitamin

supplement is given.

It is well known tilat vitamin D produces

serious toxic effects if consumed for a period

in grossly excessive amounts. In addition,

ADDRESS: 1801 Hinman Avenue, Evanston, Illinois.

however, vitamin D, in amounts not much

greater than the recommended allowance,

has been incriminated as one of the fac-

tons in the pathogenesis of idiopathic hy-

percalcemia of infancy, and in this respect

even small excesses of vitamin D may oc-

casionally be injurious. Whereas in tile past

it was frequently the practice to administer

doses of vitamin D in excess of the recom-

mended allowance with the object of pro-

viding an extra measure of nutritional

safety, it is now evident that all those con-

cerned with the optimal nutrition of the

population must bear in mind the possible

untoward effects of vitamin D prescribed

for prophylaxis. This, in turn, demands that

closer attention be paid to the total intake

of vitamin D, a task that is becoming in-

creasingly difficult as each new “fortified”

food is introduced onto the market.

In the report that follows, the Committee

on Nutrition of the American Academy of

Pediatrics summarizes the evidence regard-

ing the prophylactic requirement and tile

toxicity of vitamin D, and presents certain

recommendations for use of the vitamin.

THE REQUIREMENT OF VITAMIN D

AT VARIOUS AGES

Vitamin D is believed to function in mi-

nute concentrations by regulating or po-

tentiating certain complex biochemical re-

actions at various sites in the body. The

amount necessary to achieve optimal phys-

iologic function in a given individual is de-

pendent upon a number of factors, among

which are believed to be age, rate of

growth, efficiency of intestinal absorption

(especially of fat), and coexisting disease,

but little is known concerning the influence

of these factors.

From the sections that follow, it will be

apparent that vitamin D is an essential fac-

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COMMITFEE ON NUTRITION 513

tor in the metabolism of the growing hu-

man being, and, indeed, probably at all

ages. For the llealthy premature and full-

term infant, fairly reliable estimates of the

minimal requirements have been made.

This has been possible in pant because the

newborn infant develops evidence of vita-

mm D deficiency relatively rapidly, and in

part because, by selecting for study infants

born in the autumn, the otherwise undefin-

able amount of vitamin D contributed by

sunlight can justifiably be neglected. The

minimal requirements during later child-

hood, adolescence, adulthood, pregnancy,

and lactation have been much more difficult

to determine because sources of vitamin D

become more accessible and more varied,

because rickets rarely develops after in-

fancy, and because other satisfactory en-

tenia of minimal vitamin D deficiency have

not yet been established.

In early years there was much disagree-

ment regarding the relative efficacies of the

various forms of vitamin D. It is now be-

lieved that, microgram for microgram, vita-

mm D2 (calciferol) and vitamin D3 (ir-

radiated 7-dehydrocholesterol) have equal

potencies in the human.6 Ordinarily, vitamin

D is almost completely absorbed by the in-

testine, and the vehicle in which the vita-

mm is administered (be it oil, aqueous sus-

pension, milk, or other food) is believed not

to affect absorption7 unless the intestinal

absorption of fat is impaired. In children

with steatorrhea, the finely dispersed, water-

miscible preparations are thought to be pref-

enable on the basis of indirect evidence ob-

tamed from vitamin A absorption u#{176}

The Normal Full-term Infant

Numerous studies, most of them con-

ducted some 20 on 30 years ago, have con-

cerned the efficacy of various amounts of

vitamin D in preventing rickets,7’ 10-12 in pro-

moting intestinal absorption of 14

and in promoting linear � 16

On the basis of the above criteria, esti-

mates of minimal vitamin D requirement

range from approximately 100 U.S.P.

711 12 to approximately 400 U.S.P. units

per day’#{176}’16(1 U.S.P. unit = 1 I.U.). Doses

of vitamin D greater than 400 I.U. per day

did not result in a greaten degree of pro-

tection against 710 11 and did not

further increase retention of 14

Although there is not complete agreement

on the minimal requirement of vitamin D

to promote maximal linear growth (or even

whether vitamin D effects linear growth),

it would appear that intakes of 250 I.U.

daily are at least as effective as greater in-

takes.12, 16

Many of these early studies are now open

to question from the standpoint of modern

experimental design. However, the observa-

tion that intakes of 300 to 500 I.U. of vita-

mm D pen day resulted in rapid healing of

severe 710 provides strong evidence

concerning the probable effectiveness of the

doses proposed for prophylaxis.

The formerly high incidence of rickets

among Negro infants living in the large

metropolitan areas of the northern United

States gave rise to the impression that sun-

shine was less effective in preventing

rickets in individuals with deeply-pig-

mented skins; however, sociologic factors

made tllis difficult to prove. On the other

hand, data in the American literature sup-

ports the opinion that the amount of in-

gested vitamin D required to �

or to cure1#{176}rickets in Negro infants does

not differ from the requirements of white

infants.

The manner in which other factors, such

as chronic infection, metabolic disease, and

rapid skeletal growth influence vitamin D

requirement is not yet accurately known. In

particular, there has been argument re-

ganding the relation between calcium intake

and vitamin D requirement. Clearly, it is

necessary to provide sufficient dietary cal-

cium to meet the requirements of the grow-

ing skeleton. Similarly, sufficient vitamin D

must be provided to prevent rickets and to

promote satisfactory calcium retention.

However, having satisfied the minimum

needs in these two respects, there is no

reason to postulate any specific relation be-

tween D requirement and calcium intake.


514 VITAMIN D

This principle is of special importance in

considering the vitamin dosage of the

breast-fed infant, since, per calorie, the cal-

cium content of human milk is approxi-

mately one-third to one-quarter that of a

cow’s milk formula.17 However, both from

theoretical considerationsl8 and practical

observation, the calcium requirements of the

normal full-term infant are satisfactorily

met by human milk, and there is no reason

to increase the prophylactic dose of vitamin

D to more than 400 I.U. per day for the

breast-fed infant.

In many parts of Europe, the custom of

giving daily vitamin supplements to babies

has never been established. In these regions,

it is the practice to administer to infants,

usually under direct medical supervision,

single large oral or intramuscular doses

(Stossen) of vitamin D at intervals. mdi-

vidual doses of 300,000 I.U. at intervals of

l,� to 3 months have been suggested.’9 The

Committee endorses the view of Lightwood

and Stapleton2#{176} that such administration of

vitamin D is unphysiologic and has no use-

ful place in countries where daily vitamin

D prophylaxis has become established prac-

tice.

The Premature Infant

Although the various techniques used to

determine the vitamin D requirement of

full-term infants have been applied to pre-

mature infants, it has been more difficult to

establish the requirement. In part at least,

this has been because of the relatively

greater requirement for calcium. The skele-

ton of tile infant born 6 weeks prematurely

contains approximately half as much cal-

cium as that of the full-term infant.21

Cleanly, it is axiomatic that the premature

infant should be given sufficient calcium to

satisfy the needs of the rapidly growing

skeleton. Since the average accretion of

calcium during the last 2 months of fetal life

has been estimated at approximately 200

mg per day,18 an intake of calcium that

will permit retention of this amount must

be provided. The relatively low calcium

content of human milk makes such reten-

tion unlikely, even when the intake of vita-

mm D is sufficient to permit maximal intes-

final absorption. Disregard of this principle

by early investigators22 may explain the

statement that premature infants frequently

developed rickets when receiving intakes of

vitamin D as great as 5,000 lU. per day.

More recent studies in which large groups

of formula-fed premature infants were ob-

served clinically, roentgenographically, and

biochemically indicate that rickets could

usually be prevented and normal calcium

and phosphorus homeostasis maintained

with vitamin D intakes as low as 100 to 200

I.U. per day.12 23 Rates of growth in body

length are reported to have been as rapid

with intakes of 100 to 200 I.U. daily as

with intakes of 400 to 1,200 I.U. 23

Recent studiesl4 ne-emphasize tile necessity

of commencing vitamin D prophylaxis with-

in the first 2 weeks of life.

The Pre-school and School Child

There is no doubt that vitamin D is re-

quired beyond infancy, since nutritional

rickets occurs occasionally in older chil-

525 However, the requirement of vita-

mm D is more difficult to ascertain at this

age than in infancy because of the slower

rate of skeletal growth, the greater oppor-

tunity to ingest foods fortified with vitamin

D, and the tendency to receive more ex-

posure to sunlight. Because clear-cut evi-

dence of rickets occurs so rarely beyond in-

fancy, this manifestation cannot be em-

ployed as a dependable index by which to

determine vitamin D requirement in this

age group. On the basis of unpublished cal-

cium retention studies, Stearns estimated

that the requirement of growing children is

of the order of 400 I.U. per day.26 There is

no question that this intake provides an am-

pie supply of vitamin D for normal children.

However, it should be recalled that before

the current trend toward widespread vita-

mm D enrichment of food, a balanced diet

and outdoor play practically always pro-

vided sufficient vitamin D to prevent de-

tectable evidence of vitamin D deficiency

even though, in a great many instances, the


TABLE I

RECOMMENDED DIETARY ALLOWANCES FOR

VITAMIN D, (1.U./DAY)

Age Group

Infants

Premature0-24 mo

Children

�-1Q yr

Adolescents (male &female)

13-19 yr

Adults

Male

Female

NonpregnantPregnancy. lot half

Pregnancy, 2nd half

Lactation

U.S.A.#{176}

400

400

400

400

400

400

Canadat

400-800

400

400

400�

400

400

Great

Britain

. . (8001)

800 (400jJ)

400

400

400

600

800

0 Total daily vitamin 1) intake to maintain good nutrition in

healthy persons (not only in the average person but in substantiallyall normal persons) in the United States under current conditions of

living. The recommendation is meant to afford a margin of sufficiencyabove minimal requirements and to provide a buffer against addedneeds of various stresses other than disease or nutrient repletion.(Food and Nutrition Board. National Academy of Sciences-National Research Council; Recommended Dietary Allowances;1958; Publication 589, Washington, D.C.)

t Recommended total daily vitamin D intake to maintain goodnutrition of healthy persons and to provide a margin of safety.(Canadian Bulletin on Nutrition; A Dietary Standard for Canada;Vol. 3, No. 2, Ottawa, August. 1938.)

� Total daily vitamin D intake “believed sufficient to establishand maintain a good nutritional state in representative individuals

of the groups concerned. It is recognized that in every group theremust be cases where the need is greater than that of the average.”(British Medical Association; Nutrition Committee; Report; 1930,London.)

I Recommendation of Medical Research Council Conference onHypercalcaemia in Infants (1936). Not published. Quoted in Refer-

ence 5.!l Recommendation of Joint Sub-committee on Welfare Foods

(1937).’

#{182}Adolescents 18-15 years.

COMMITI’EE ON NUTRITION 515

youngsters had not received any vitamin

supplements, and the computed intake of

vitamin D was considerably less than the

figure recommended above.

Obviously, additional data are needed to

delineate the minimal requirement in this

age group.

The Adolescent

The determination of the minimal vita-

mm D requirement of the adolescent pre-

sents the same problems as those met for

children. Some years ago, it was considered

that rapid skeletal growth during this period

necessitated a considerably greaten intake

of vitamin D (up to 3,900 I.U. pen day).27

However, when studies were made in

healthy adolescents under conditions of op-

timal calcium and phosphorus intake, maxi-

mal calcium retention was achieved with

intakes of 400 I.U. pen day.28

The Adult

Calcium retentions have been measured

in a number of healthy adults consuming

average unfortified diets with standardized

intakes of calcium and varying supplemental

intakes of vitamin D. In none of these

studies was a consistent difference in cal-

cium retention detected before and during

the administration of vitamin D supple-

ments.2’ For this reason it has sometimes

been implied that healthy adults do not re-

quire vitamin D, and no allowances are rec-

ommended by the various national commit-

tees (Table I).

From physiologic considerations, this is

probably not strictly correct. It is more

likely that the amount of vitamin D needed

for the maintenance of normal calcium and

phosphorus metabolism in adults is so low

that the requirement is readily met by the

average diet and by casual exposure to sun-

light. The hypothesis of a small require-

ment is strengthened by a number of re-

ports of adults with osteomalacia attributed

to vitamin D deficiency. One report men-

tions 15 nuns who developed radiographic

and clinical signs of osteomalacia during

World War II while confined to a convent

under conditions of poor nutrition.30 The

other 33 record isolated cases, in

each of which food faddism had led to ex-

tremely low intakes of vitamin D containing

foods. In one case33 the vitamin D intake

was estimated to be less than 20 I.U. pen

day. Although the bizarre diets were also

extremely low in calcium, it is probable that

vitamin D deficiency was the important fac-

ton, particularly since there is evidence that

low calcium intakes per se lead to osteoporo-

sis rather than to osteomalacia.34

The Pregnant and Lactating Woman

The reports of osteomalacia in pregnant

and lactating Chinese 536 constitute


516 VITAMIN D

evidence that these states impose physio-

logic stresses upon the normal calcium and

phosphorus metabolism of the adult. Al-

though the calcium content of the diets of

the women was poor, the osteomalacia re-

sponded to vitamin D rather than to extra

calcium. These studies have therefore been

taken to indicate that amounts of vitamin

D greater than those needed by the normal

adult are required for optimal nutrition dur-

ing the last trimester of pregnancy and dun-

ing lactation. However, data regarding the

actual requirements are lacking.

In addition, provision should be made in

tile diet for the extra calcium required by

the growing fetus (approximately 200 mg

are deposited per day during the last 2

months of pregnancy) and by lactation (ap-

proximately 200 to 300 mg are excreted per

day).18

Summary: Recommended Allowances at

Various Ages

Allowances currently recommended in

the United States, Great Britain, and Can-

ada are shown in Table I. The recommen-

dations are seen to be in reasonably close

agreement. As indicated, there are minor

differences in the terms of reference. How-

ever, it should be noted that in all instances

the figures are intended to be taken as rep-

resenting the total recommended daily in-

take of vitamin D from all ingested sources,

assuming no exposure to ultraviolet radia-

tion, assuming the consumption of adequate

(luantities of calcium and phosphorus(values about which, incidentally, there is

still much argnment�4) and incorporating a

safety factor beyond the minimum daily re-

quirement of the normal individual.

The Committee on Nutrition believes that

available data support the view that for full-

term infants fed cow’s milk formulas or

human milk a total intake of 400 I.U. vita-

mm D per day from all dietary sources is a

suitable allowance to prevent rickets and to

promote optimal calcium and phosphorus

metabolism. The same dose, perferably pro-

vided as a water miscible suspension,37 is

considered to be suitable for premature in-

fants fed commonly employed formulas of

cow’s milk. The higher recommendation of

the British authorities (Table I) is intended

to provide an additional safety factor, but

there does not appear to be scientific proof

that tile extra amount is actually more ef-

fective. For both full-term and premature

infants tile range of individual variation has

been well investigated. It may he assumed

that this dose provides a moderate safety

factor, and that few, if any, normal infants

will develop rickets while receiving such an

intake. Vitamin D prophylaxis should be

commenced within the first 2 weeks of

life.

There is no question that in certain lo-

cales and under proper conditions prophy-

lactic amounts of vitamin D can be acquired

from sunlight during the summer months.

However, to cover all contingencies, the

Committee considers that an attempt should

be made to ensure the provision of tile 400

I.U. allowance from ingestible sources on

a year-round basis.

Available data do not provide accurate es-

timates of the minimum requirement be-

yond the period of infancy. For children

and adolescents, the Committee recom-

mends a total dietary intake of 400 I.U. of

vitamin D per day from all sources as a safe

allowance. As indicated below, in the

United States such an intake will ordinarily

be acquired from fortified foods witllout

administration of a vitamin supplement. In

Canada, the same situation frequently ob-

tains in individual cases, but cannot he so

generally relied upon.

The small requirement of tile healthy

adult is satisfactorily met by casual ex-

posure to sunlight and by the consumption

of usual unenniched foods, and no vitamin

D supplementation is necessary unless spe-

cifically indicated by reason of occupation

or other unusual circumstance. A total daily

intake of 400 I.U. of vitamin D is con-

sidered adequate to provide for added de-

mands during the second half of pregnancy

and during lactation.

It is the opinion of the Committee that

there is no necessity to exceed tile recom-


COMMITTEE ON NUTRITION 517

mended allowance during convalescence

from acute infections. Similarly, for most

chronic conditions, the recommended allow-

ance is probably adequate.

THE DANGERS OF VITAMIN D

Notwithstanding lack of knowledge con-

cerning minimal requirements, the Com-

mittee believes a daily intake of 400 I.U.

of vitamin D can be expected to prevent

detectable vitamin D deficiency in the nor-

mal infant or child consuming adequate

amounts of calcium. Furthermore, there is

no evidence to indicate that larger amounts

of vitamin D would be more effective in

any way. On the other hand, because nowa-

days many infants and children un-

doubtedly receive more than 400 I.U. of

vitamin D daily, and because there is in-

controvertible evidence that prolonged in-

take of vitamin D in large doses produces

hypercalcemia with its numerous sequelae,

it has become imperative to define the safe

upper limits of vitamin D intake.

Many years ago Hess and Lewis38 demon-

strated that very large doses of vitamin D

would produce hypercalcemia. Since that

time hypervitaminosis D has been reported

in many individuals, a considerable number

of whom were infants and children. There

appears to be a fairly wide range of sus-

ceptibility to the toxic actions of vitamin D

and it has been estimated that approxi-

mately 20% of normal adults who receive

100,000 I.U. of vitamin D daily for several

weeks or months will develop hypercal-

cemia.38 Hypencalcemia is accompanied by

anorexia, nausea, weight loss, polyunia, con-

stipation, and reversible azotemia. If hyper-

calcemia continues generalized vascular cal-

cification, nephrocalcinosis and irreversible

renal insufficiency eventually supervene. In

terms of unit body weight, dosages in the

region of 1,000 to 3,000 I.U./kg/day for

several weeks or months are toxic in the

adult, and evidence suggests that this unit

dose manifests approximately the same de-

gree of toxicity in infants under 2 years of

age.1#{176}For a 1-year-old infant, this amount

of vitamin D would represent a total dose

of between 10,000 and 30,000 I.U. per

day.

The Risk of Vitamin D Toxicity

in Infancy

The dosages mentioned above are at least

25 times greater than the prophylactic re-

quirement. On the other hand, Jeans &

Stearns40 suggested in 1938 that daily in-

takes of vitamin D in the range of 1,800 to

6,300 I.U. inhibited linear growth of normal

infants and were therefore undesirable. Be-

cause the series of infants was small, and

because considerable variability was ob-

served in the individual growth patterns of

experimental and control subjects, the data

are difficult to interpret. The study has not

been confirmed by other workers, and there

has been little concern until relatively ne-

cently about administering prophylactic

doses of vitamin D in the order of 2,000

I.U. daily.

However, in 1952 reports from Great

Britain and Switzerland drew attention to

a small group of infants with unexplained

ypt2 Shortly after the initial

reports were published, cases of infantile

hypercalcemia commenced to be diagnosed

in increasing numbers throughout the

British Isles. In its rare severe form42 hy-

pencalcemia was associated with mental ne-

tardation, osteosclerosis, severe azotemia

and other bizarre features. In its relatively

more common mild form,4’ which typically

commenced between the second and tenth

month of life, there was fairly sudden onset

of anorexia, vomiting, polydipsia, weight

loss, and failure to thrive, and the serum

calcium was elevated above 12 mg/100 ml

(often to 15 mg/100 ml or higher). Mild,

usually reversible azotemia frequently de-

veloped.

Because many of the features resembled

those of hypervitaminosis D, it was logical

that attention should be focused upon the

possibility that vitamin D was implicated in

the pathogenesis of this new and important

health problem. It was found that the hy-

percalcemia was controlled when all sources

of vitamin D were withheld and a very low


518 VITAMIN D

calcium intake instituted, although tile ad-

ditional features of the severe form did not

disappear.

In 1953 and 1954 at a time when approxi-

mately 100 new cases of hypercalcemia

were being diagnosed annually in Great

Britain, an extensive survey of infant feed-

ing practices in Great Britain revealed that,

as a result of the then liberal enrichment of

national dried milk powder and infant

cereals with vitamin D, a normal infant con-

suming an average diet plus the recom-

mended daily supplement of vitamin D (at

that time 700 to 800 I.U.) might readily in-

gest 4,000 I.U. of vitamin D per day.43

On the other hand, idiopathic hypercal-

cemia cannot be explained solely on the

basis of excessive vitamin D intake. For one

thing, it was noted that not all affected in-

fants were ingesting as much as 4,000 I.U.

of vitamin D per day. For instance, in a

study of 38 cases from Glasgow, 26 (two-

thirds) had received less than 2,000 I.U.

per day, and 8 (one-fifth) had received less

than 1,000 lU. per day.44 Further, it should

he recalled that, of the large number of

British infants who during one period are

presumed to have ingested 3,000 to 4,000

lU. per day, relatively few suffered any de-

tectable ill effects.

To account for some of the contradictory

findings, it has been suggested that patients

with idiopathic hypercalcemia may be hy-

persensitive to vitamin D45 or, alternatively,

that they may have an inborn disturbance

in cholesterol metabolism�#{176} which causes

tile accumulation of vitamin D or of some

abnormal metabolite with vitamin D-like ac-

748 The fact that none of the affected

infants had been entirely breast-fed�9 sug-

gests that tile higher calcium content or

some other feature of cow’s milk may also

be a factor.

Although it is obvious that infants who

develop hypercalcemia differ in some fun-

damental way from normal infants, it is

hard to escape the still-circumstantial evi-

dence which appears to relate the condition

with vitamin D. As a result of recommenda-

tions of the British Paediatrie Association

Committee on Hypercalcaemia41 and of the

Joint Subcommittee on Welfare Foods,5

measures were taken to reduce the average

intake of vitamin D of British infants by

halving the potency of National Cod Liver

Oil and by considerably reducing the

amounts of vitamin D added to dried milk

powders and to infant cereals. It has been

estimated that the average intake of vitamin

D has probably been reduced to between

one-third and one-half the former quantity

as a result of these measures.

Obviously, careful evaluation of the pres-

ent incidence of idiopathic hypercalcemia

in Britain is essential before conclusions can

be drawn regarding the importance of vita-

mm D in the etiology of the condition. Un-

fortunately, this information is not yet ac-

curately known. However, according to an-

notations in the British Medical Journal�#{176}and in Lancet5#{176} in 1960, many pediatricians

believe that the incidence of the disease has

fallen since the recommendations regarding

vitamin D intake were carried out. It is very

tempting therefore, to suggest that vitamin

D and idiopathic hypercalcemia are caus-

ally related. On the other hand, because it

is not yet possible to weigh the many com-

plex factors, it seems unwarranted to draw

final conclusions regarding the etiologic role

of vitamin D until the results become avail-

able of a comprehensive study which is cur-

rently being undertaken by the British

Paediatric Association Committee on Hy-

percalcaemia.

ESTIMATES OF VITAMIN D INTAKES INTHE UNITED STATES AND CANADA

AT VARIOUS AGES

The large number of vitamin prepara-

tions and of commonplace commercially-for-

tified foodstuffs on the North American

market provide a variable and virtually un-

avoidable intake of vitamin D which,

though difficult to estimate, may often be

considerable. Table II gives information

concerning some of the foods currently en-

riched with vitamin D in the United States

and Canada. Because of frequent changes

by the manufacturers, this information is



TABLE hA

VITAMIN D ADDED TO FOODS IN U.S.A.

Food Product Manufacturer and Trade NameApproxnnate Vitamin D Content

.

Claimed (lU/unit nzea.ntre)

Milks Dairy Milk

Evaporated

Powdered

Fortified (approx 85% total sales)

All brands

Klim (whole) & most powdered infant for-

mulas

Skim milks (powdered)

1 U.S. quart

1 IJ.S. quart (reconstit.)

1 U.S. quart (reconstit.)

400

400

400

0

Milk flavorings Powders

Syrups

Ovaltine (plain or chocolate)

Hershey-Instant Cocoa Mix

Nestle-”Quick”

Borden’s Dutch Chocolate

Baker’s-Instant Choc. Mix

Bosco

Cocoa Marsh

I (approx. 15 gm)� (approx. 15 gas)

� (approx. �0 gm)

“� (approx. 15 gm)

(approx. �0 gm)

(approx. �0 gm)

(approx. 15 gm)

150

150

100

100

100

150

50

Margarine Parkay, Kraft

All-Sweet, Blue Bonnet, Fleishman’s, Good-

Luck, Imperial, Mazola

1 oz

I oz

�50

1�5

Breakfast (ereals Kellogg-All Bran

Cornflakes

Special K

Sugar Pops

Pep

Concentrate

General Mills-Hi-Pro

Quaker-Life

Coco-Wheats

1 serving (1 oz)

400

�00

�00

W0

�00

�00

150

80

80

\Iiscellaneous Bread

CandyBeverage

Special Sunbeam Bread (a premium prod-

uct only)

Swiss BarStuart’s Instant Vita Drink

1 slice

I bar

I glass

(1 teaspoon powder)

100

400

I ,000

only approximate. The recorded figures are

computed from the manufacturers’ label

claims and represent minimum values, since

it is customary manufacturing practice to

add an “overage” to allow for possible de-

tenioration, etc. Overage may constitute as

much as 100% or more of the label claim in

tile United States. In Canada, regulations

prescribe that a given food may contain not

less than 400 or more than 800 I.U. of vita-

mm D in a reasonable daily intake of that

food,5’ but despite the regulations, the over-

age permitted within the limits of good

manufacturing practice undoubtedly re-

mains a factor to be considered.

There are certain differences between the

United States and Canadian figures. In the

United States, vitamin D is added to virtu-

ally all evaporated milk in a concentration of

400 I.U. per reconstituted U.S. quart, and

a similar amount is added to 85% of all dairy

milk marketed in the United States (al-

though the latter figure may decrease as

a result of the recent re-introduction of

unfortified dairy milk by certain super-

markets). In Canada, all brands of evapo-

rated milk contain approximately 600 to 800

I.U. vitamin D per reconstituted Imperial

quart (i.e., 500 to 700 I.U. per reconstituted

U.S. quart). However, in contrast to custom

in the United States, less than 1% of dairy

milk on the Canadian market is enriched


520 VITAMIN D

TABLE JIB

VITAMIN D ADDED TO FOODS IN CANADA

Food Product Manufacturer and Trade NameA pprox-iiiiate J itam in D Content

, . .Claimed (IJ ./untt measure)

Milks Dairy milk

Evaporated

Powdered milk

Unfortified (approx. 99% total Cairn-

dian sales)

Irradiated or fortified (1% total sales)

All brands

Klim (whole milk powder)

Milko (skim milk powder)

(skim+chocolate)

Instant-Sweet (skim)

None

� ad(le(l

� 400

I lIlIperial quart � 600�S00

(1,� U.S. quart) �

� 800

800

700

I (approx. 13 gui) l3�

(approx. 13 gin) � Isoa (approx. 15 gIll) � 1.50� (approx. �0 gill) � �0()

M ) (approx. �0 gui) �oo“#{176} (approx. 15 gm) 150

(approx. �2() gill) �200

� (approx. 1.5 gnl) �200

�IiIk flavorings Powders

Syrups

Cadbury: “Choco”

Ovaltine: plain & chocolate

Nestle: “Quik”

Bordens: Instant Dutch

Instaiit Toddy

I.G.A. : Instant Chocolate

Bosco

Cocoa Marsh

Margarine All brands I oz �50-31()

Breakfast

cereals

Kellogg: Special K

Cornflakes

Sugar Pops

Sugar Frosted Flakes

Pep

I 01 400

400

400

400

4(8)

Biscuits Sun Wheat I biscuit 50

Beverages Happy Henri: Apple drink

Happy Henri: Breakfast drink34 oz

34 oz

�200

C200

with vitamin D. For this reason, a consider-

able number of Canadian babies will fail to

receive sufficient amounts of vitamin D in

their food, and in a certain proportion of

these, rickets may be expected to develop

unless vitamin D is given as a supplement

or by exposure to sunlight.

By constructing hypothetic menus, and

using the information contained in Table

II, an estimate has been made in Table III

of the amounts of vitamin D that might be

ingested under present-day living conditions

in the United States and Canada. Two diets

have been constructed for each of three age

groups, one selected to represent an an-

bitranily average situation, the other to rep-

resent a situation in which the intake is

unquestionably, but not unrealistically high.

In computing the total intakes of vitamin

D the amount administered as a vitamin

supplement must be included. For several

concentrated drop preparations, the daily

amount recommended by the manufacturer

contains from 800 to 1,000 I.U., but most

products now contain 400 I.U. per recom-

mended dose. Most of the candy-type multi-

pie vitamin preparations available for older

children in both the United States and Can-

ada contain 400 I.U. per lozenge. Most mul-

tiple vitamin capsules intended primarily for

adults contain 1,000 I.U. vitamin D or more

per capsule.

A glance at Table III will indicate that

the well-cared-for infant, receiving an


COMMITTEE ON NUTRITION

TABLE Ill

Age of

ChildIntake Vitamin

Supple-

ment

Amount of Vitamin D Contributed by lndiriduaJ FOOd#{176}

Milk,

1 iquid

.�fiLk, Milk,

Lrapo-Powder

vated

MargarineMilk.

Flavoring

Ilvtakfast

Cereal

Special

Breakfast

Drink

Special

Candy

Bar or

Biscuit

6 nio

S yr

8 yr

Total Intake

lU/day)

Arerage High

Average

High

Average

Iligli

Average

high

400

1 , 000

(1,000)

1 , 000

(400)

1 , 000

000

401)

400

400

400 �- - - -

400 - - - -

. - - - - . �

100

- . - - 450 850

- - � - - . . �oo

. . � --� 600 500

�O0

400

�00 ..

400 (1,000)

II. (‘hiletren in (anada

(400)

(800)

(100)

(150)

6 nio Average 400 . . 800

High 1,000 . 1,000

S yr Average (400) �3 ..

Iligh 1,000 -.

8 yr Average (-100) 23 - -

Ilighi 1,000 . - -

800

1,400

600

(1 , 600)

. q,600

(3,000)

800 ..

(I ,�00)

. 2,900

(4,700)

1,200

. 2,01)0

300(800)

. 3.230

(3,400)

700 ..

(1 , 100)

. - 4,100

(4,230)

1400 � 450

� 800 � 600

275

400

275

500

400

400

800

�oo

400 � (150)

S When values appear in parentheses, total intake of vitamin 0 has been calculated twice; ome including and once exhuding these values

evaporated milk formula and vitamin sup-

plement (as is customary in North America)

will automatically ingest two to four times

the recommended daily allowance of vita-

mill D without taking the question of over-

age into account. However, it seems un-

likely, under present circumstances, that a

significant proportion of the infant popula-

tion in either the United States or Canada

�vould obtain as much vitamin D as many

British babies were estimated to have re-

ceived before tile present restrictive meas-

tires were implemented. On the other hand,

the well-cared-for toddler in North America,

still receiving a vitamin supplement, is likely

to receive at least three times tile recom-

mended allowance and the daily intake

might reasonably exceed 2,000 or even 3,003

I.U. For the older child, even higher intakes

can he envisaged. especially if he regularly

521

receives one of the candy-like vitamin prep-

arations or has access to a vitaminized

candy bar or beverage.

Admittedly these hypothetic examples

have no validity as estimates of the national

vitamin D intake. They were selected

merely to emphasize the diversity of foods

tilat are artificially enriched, and the un-

expected ease with which vitamin D can

now be acquired in both the United States

and Canada.

COMMENT

From the foregoing discussions, it is evi-

dent that vitamin D is essential for the

maintenance of normal calcium and phos-

phorus metabolism in humans. On the basis

of present evidence, it is considered that a

total intake of 400 I.U. of vitamin D per

day provides an adequate margin of safety

HYPOTHETIC TOTAL DAILY INTAKES OF VITAMIN D

.4. (‘F,ildnn in (nited Slates


522 VITAMIN D

to protect substantially all normal growing

individuals from detectable evidence of

vitamin D deficiency.

At the same time, it is known that exces-

sive amounts of vitamin D are toxic. The

low limit of toxicity is not cleanly defined,

but British experience with the problem of

idiopathic hypercalcemia suggests that this

toxic level may, on rare occasions, be as low

as 3,000 to 4,000 I.U. per day for susceptible

individuals in tile infant age group, and

sometimes considerably lower.

Until relatively recently, the average diet

contained very little vitamin D and could

not necessarily be relied upon to prevent

vitamin D deficiency during growth, par-

ticularly during infancy. The use of vitamin

D supplements was therefore promoted, and

there was widespread acceptance of this

public health measure throughout North

America. However, when it became evident

that rickets had not been entirely eliminated

by this measure, the decision was made to

enrich commercial milks with vitamin D,

and tile outstanding success of this program

gave impetus for the addition of this and

other vitamins to a variety of foods. At the

present time, a wide range of common food-

stuffs contain added vitamin D, and it is

obvious that the oven-all vitamin D intake

of all ages of the population has risen ap-

pneciably in the United States and Canada.

Calculations indicate that the amount of

vitamin D now acquired from the diet alone

may readily exceed tile recommended daily

allowance, sometimes by a considerable

amount.

Although the exact cause of idiopathic

hypercalcemia of infancy remains to be

established, there is now a large amount of

evidence which incriminates vitamin D as

an important etiologic factor. Despite the

fact that infantile hypencalcemia has, until

now, been much less common on this conti-

nent than in Great Britain, more than 30

cases have already been reported in North

America since 1954 and existence of a num-

ben of unpublished cases is known to mem-

bens of the Committee.

Thus, in the face of existing evidence,

the Committee on Nutrition considers that

practitioners and public health authorities

should strive to ensure that the total vitamin

D intake of all infants reaches tile recom-

mended allowance of 400 I.U. per day, but

at the same time, they should make con-

certed efforts to restrict the upper limit of

intake for all sources to an amount as close

to this figure as is practicable. This de-

mands tilat cognizance be taken of the

amount of vitamin D contributed by the

formula and other components of the diet

before prescribing a vitamin D supplement,

and that attention be paid to the amount of

vitamin D provided by the supplement

chosen.

It demands, also, that efforts be intensi-

fled to dispel from the minds of parents tile

concept of vitamins as tonics, with the

hope of reducing the all-too-prevalent prac-

tice of vitamin D “over-insurance” in tile

home.�� Although there is no specific evi-

dence that daily intakes of vitamin D in tile

order of 2,000 to 3,000 I.U. produce de-

letenious effects on individuals beyond in-

fancy, it should be realized that tue present

trend in nutrition is imposing a new situa-

tion upon the children and adults of North

America, the long-term effects of which are

entirely unknown.

The addition of vitamin D to practically

all commercial milk supplies in the United

States has been amply justified by the dra-

matic reduction which it brought about in

the incidence of rickets. By inference, simi-

lan benefits would presumably be observed

in Canada by broadening tile present milk-

fortification program to include dairy milk.

On the other hand, the milk consumption

habits of North American children ensure a

uniformity and dependability of intake

which does not apply to other foodstuffs.

Hence, the enrichment of a large variety of

additional foods with vitamin D cannot be

similarly justified.

SUMMARY AND RECOMMENDATIONS

Despite inadequacies in information con-

cerning the minimum prophylactic require-

ment of vitamin D for all age groups be-



yond infancy, there is no doubt that a total

intake of 400 I.U. per day is adequate to

prevent vitamin D deficiency in substan-

tially all normal children from birth through

adolescence.

Evidence derived from the study of idio-

pathic hypercalcemia suggests that certain

infants excessively sensitive to the toxic ac-

tion of vitamin D may, on rare occasions,

be adversely affected by daily intakes of

3,000 to 4,000 I.U. and sometimes consider-

ably less. Because of the prevalent practice

of food fortification in the United States

and Canada, there is now a definite possi-

hility that the individual, even the young

infant, may ingest considerably more than

tile recommended vitamin D allowance, andintakes of 2,000 to 3,500 lU. pen day are

possible, particularly beyond infancy. Al-

though there has been no specific evidence

that intakes of this order produce deleteni-

oils effects beyond infancy, it is pointed out

that tile long-term consequences of this new

nutritional situation on older children or

adults are entirely unknown.

In view of these considerations tile Com-

mittee on Nutrition recommends that efforts

he taken to ensure a total vitamin D intake

of 400 I.U. per day by all infants and chil-

dren. At the same time, an attempt should

1)e made to restrict the intake from all

sources to an amount not greatly in excess

of tilis figure.

The value of carefully planned enrich-

ment of commercial milk supplies with vita-

mm D has been clearly demonstrated. How-

ever, the present practice of enriching foods

other than milk and infant formula prod-

ucts is not justified, and discontinuation of

this practice is to be recommended. Under

the present circumstances, cognizance

should be taken of the amount of vitamin

D acquired by tile individual from food

sources before prescribing a vitamin D sup-

plement.

In keeping with present concepts regard-

ing vitamin D requirement, commercial

vitamin D supplements should be adjusted

to contain not more than 400 I.U. per

dose.

COMMITI-EE ON Nu-nirnoN

Richard W. Blumberg, M.D.

Gilbert B. Forbes, M.D.

Donald Fraser, M.D.

Arild E. Hansen, M.D.

Charles U. Lowe, M.D.

Nathan J. Smith, M.D.

Michael J. Sweeney, M.D.

Samuel J. Fomon, M.D., Chairman

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524 VITAMIN D

12. May, E. W., and Wygant, T. M. : Rachiticstudies : III. An evaluation of methods of

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13. Houet, R. : Recherches sur le metabolisme deIa vitamine D: III. Determination du besoin

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17. Macy, I. C., Kelley, H. J., and Sloan, R. E.:

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buch der Padiatrie. Basel. Schwabe, 1958,

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cal development in utero. Arch. Dis. Child.,26:205, 1951.

22. Davidson, L. T., and Merritt, K. K. : Viosterol

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23. Glaser, K., Parmalee, A. H., and Hoffman,

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1963;31;512Pediatrics THE TOXICITY OF VITAMIN D

COMMITTEE ON NUTRITION: THE PROPHYLACTIC REQUIREMENT AND

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