Review

Vitamin D Supplementation during Lactation to Support

Infant and Mother
Sarah N. Taylor, MD, Carol L. Wagner, MD, and Bruce W. Hollis, PhD
Medical University of South Carolina Darby Childrens Research Institute, Charleston, South Carolina
Key words: human milk, lactation, infant, rickets, vitamin D
How human milk as the ideal infant nutrition lacks vitamin D activity leading to the severe bony deformities
and muscle weakness of rickets has stymied scientists and clinicians for centuries. Recent understanding of
human vitamin D requirements based on functional indicators of vitamin D activity demonstrate that the majority
of humans, including lactating mothers, subsist in a vitamin D insufficient state. In this state, human milk
provides inadequate vitamin D supply to the nursing infant. In contrast, with achieving maternal vitamin D
sufficiency, human milk attains vitamin D activity equivalent to present infant oral supplementation. Current
investigation of the role of vitamin D in diseases beyond bone health is revealing the significance of early life
vitamin D sufficiency in establishing lifelong health.
Key teaching points
With decreased UVB exposure in the modern lifestyle, oral supplementation of vitamin D is a health requirement.
Current evaluations of adult vitamin D needs based on indicators of vitamin D function in bone health and disease prevention
identify circulating 25(OH)D concentrations of 32 ng/ml as the lower limit of vitamin D sufficiency.
When a lactating mother receives 400 IU per day vitamin D supplementation, her milk contains 3368 IU/L vitamin D activity
which is far below the recommended daily vitamin D intake of 200800 IU per day for infants.
In a pilot clinical trial, maternal supplementation of 6400 IU per day vitamin D
3
for 6 months was safe and raised the milk vitamin
D content from 82 IU/L to 873 IU/L.
Current evidence points to a vitamin D dose of 400 IU/day as adequate to achieve serum 25(OH)D concentration 11 ng/ml in
nearly all infants and 20 ng/ml in many infants, although high-risk populations may need more.
The Canadian Paediatric Society recommends 2000 IU/day supplementation to a lactating mother with monitoring of her serum
25(OH)D status. This amount of supplementation or greater is likely needed for maternal vitamin D health.
INTRODUCTION
Published reports of rickets among breastfed infants have
increased over the past 20 years, raising concern about how to
best ensure an adequate intake of vitamin D by all breastfed
infants [112]. In response, The American Academy of Pedi-
atrics (AAP) now recommends that all breast fed infants be
supplemented with 400 IU of vitamin D per day beginning at
birth [13]. At the same time, our understanding of the role of
vitamin D in health and disease prevention has expanded ex-
ponentially with concern that harmful effects of hypovitamin-
osis D are appreciated with a vitamin D status previously
defined as adequate [1442]. These factors have led to the
current concern that, for a concerning proportion of the popu-
lation, vitamin D status is inadequate during lactation for both
mother and infant, and that supplementation of the mother may
achieve improved vitamin D status for both.
The current recommended intake of 200 IU vitamin D per
day for a lactating mother results in vitamin D activity of
2070 IU/L provided in her milk [4347]. This amount of
vitamin D activity is far below the dose of 400 IU/day vitamin
D defined as adequate intake for an infant and thus, with
current common maternal vitamin D inadequacy, breast milk
alone will not supply the recommended amount of vitamin D
Address correspondence to: Sarah N. Taylor, M.D., MUSC Darby Childrens Research Institute, 165 Ashley Avenue, P.O. Box 250917, Charleston, SC 29425. E-mail:
taylorse@musc.edu
Disclosure: Dr. Hollis serves as scientific advisor for Diasorin Corporation.
Journal of the American College of Nutrition, Vol. 27, No. 6, 690701 (2008)
Published by the American College of Nutrition
690
[13]. With sufficient sun exposure of the infant, oral supple-
mentation is not needed. However, the AAP recommends no
direct sun exposure in infants less than 6 months of age [48].
With the common maternal vitamin D supplementation of 400
IU/day in multi-vitamin preparations and lack of sun exposure
of infants, additional infant oral vitamin D supplementation is
required to ensure that all breastfeeding infants achieve vitamin
D sufficiency [13,4346,49].
Supplementation of the infant, however, does not address
the vitamin D needs of the mother. With recent improvement in
understanding the vitamin D needs of all adults, the 200 IU/day
recommended for a lactating woman allows hypovitaminosis D
and increases the mothers risk for decreased bone mineraliza-
tion and the numerous disease processes associated with hypo-
vitaminosis D [1442,5054]. Beyond bone health, there is
increasing evidence of the serious consequences of chronic
vitamin D deprivation, including increased risks of autoim-
mune diseases such as multiple sclerosis, rheumatoid arthritis,
periodontal disease, infections, type I and type II diabetes,
myopathy, and depression [1517,1923,28,3033,3,39,40,55]
and cancer [23,25,30,34,35]. Lactating mothers require ade-
quate vitamin D supplementation with care taken to protect
both mother and infant from vitamin D toxicity [18,46,49,56].
Identifying the maternal vitamin D supplementation that pro-
motes vitamin D sufficiency in mothers and provides adequate
breast milk vitamin D activity to the infant will yield breast
milk that supplies complete vitamin D support. This review
presents the vitamin D requirements of both the lactating
mother and her infant and examines maternal and infant sup-
plementation as methods to achieve improved vitamin D status
of women and prevention of rickets in infants.
ASSESSMENT OF VITAMIN D
STATUS
Metabolism of Vitamin D
The relationship of modern life and vitamin D metabolism
partially explains the misdirection over the past 30 years in
defining vitamin D sufficiency. Vitamin D
3
(cholecalciferol), a
27-carbon derivative of cholesterol, is produced in the skin
from pro-vitamin D
3
, 7-dehydrocholesterol (7-DHC), in re-
sponse to ultraviolet-B (UVB) light exposure [57]. UVB light
exposure triggers the photolytic conversion of 7-DHC to pre-
vitamin D
3
, which is transformed to vitamin D
3
by thermally-
induced isomerization. Vitamin D also is found naturally in a
few foods-fish oils, egg yolk, butter, and liver, in the form of
vitamin D
3
or as vitamin D
2
(ergocalciferol; from plants), a
28-carbon molecule. Of note, vitamin D
3
appears to have
greater biological availability than vitamin D
2
in some cases
but not in others [58]. Because of its extremely-low abundance
in foods, vitamin D commonly is fortified in food products, the
most common of which is milk. Infant formula also is fortified
with vitamin D.
Both vitamin D
2
and vitamin D
3
are the precursors to
25-hydroxyvitamin D [25(OH)D], which is formed in the liver
by the enzyme-catalyzed insertion of a hydroxy group at carbon
25. 25(OH)D is the best measurement of nutritive vitamin D
status in infants and adults with a half-life of approximately 3
weeks [5960]. The primary site of systemic regulation of
vitamin D metabolism is the kidney where 25(OH)D produces
1,25-dihydroxyvitamin D [1,25(OH)
2
D], the most active form
of vitamin D, and 24,25-dihydroxyvitamin D by cytochrome
P
450
-mixed function oxidases in the mitochondria of the prox-
imal tubule [61]. The 1,25(OH)
2
D formed in the kidney exerts
hormonal action at sites involved in calcium homeostasis such
as the intestine, bone, and kidney. In addition, numerous other
tissues in the body also possess the mitochondrial enzyme
systems necessary to convert 25(OH)D to 1,25(OH)
2
D [62].
This 1,25(OH)
2
D stimulates target cells in close proximity in
an autocrine and/or paracrine function [31,55]. Uncovering this
local activity of 1,25(OH)
2
D and its role in immune and anti-
inflammatory function is a recent advancement that has lead to
great expansion in knowledge of the importance of vitamin D
in disease prevention [1517,19,2123,25,28,3032,3437,
39,40,55].
Defining Normal Nutritional Vitamin D Status
At the same time as knowledge of the role of vitamin D in
health has expanded, the definition of healthy vitamin D status
has shifted as studies have shown ill-effects at low vitamin D
levels previously considered within the normal range
[14,17,24,29,31,38,41,42,55]. A study performed 30 years ago,
evaluating vitamin D status, measured 25(OH)D levels in a
population that appeared clinically healthy. The subjects cho-
sen for the studies were considered healthy in vitamin D status
because they represented the general population and not be-
cause of known vitamin D sufficiency [63]. The data were
extrapolated by others to define normal [64]. These studies
led to a definition of the lower limit of normal vitamin D status
as 1015 ng/ml [64]. More recent studies have evaluated the
effect of vitamin D deficiency and have defined normal as
the absence of markers of insufficient vitamin D status. For
example, many studies have shown a significant, inverse rela-
tionship between circulating 25(OH)D and parathyroid hor-
mone (PTH) with a vitamin D level 32 ng/ml (80 nmol/L)
inducing secondary hyperparathyroidism [24,27,41,42]. Heaney
et al. [29] have demonstrated in normal adults that intestinal
calcium absorptive performance is reduced in individuals who
exhibit circulating 25(OH)D levels of 20 ng/ml compared to
subjects with circulating levels 32 ng/ml. These studies con-
clude that individuals with circulating 25(OH)D levels at the
low end of the past reference range may not be getting the full
benefit from their calcium intake. As the evaluation of vitamin
Ds effect advances, PTH status and calcium absorption are not
the only functional markers identified. Recently, additional
retrospective and interventional studies in adults suggest that
Vitamin D during Lactation
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 691
circulating 25(OH)D must exceed 32 ng/ml to maximize skel-
etal integrity [14,38]. In addition, with realization of the role of
vitamin D in immune function and inflammatory response,
including the development of diabetes mellitus, insulin resis-
tance and pancreatic beta cell function have proven to be
additional, important markers of healthy vitamin D status [17].
Factors Affecting Nutritional Vitamin D Status
Historical inadequacies in recognizing healthy vitamin D
status partially explain the persistence of disease secondary to
vitamin D deficiency, but other factors also are involved. The
prevalence of vitamin D deficiency has increased with the
modern lifestyle [26,31]. As sun exposure has decreased with
urbanization, increased indoor activities, and use of sunscreen-
vitamin D status has decreased in humans as well [23,26,31]. In
fact, with adequate sun exposure, vitamin D is not a required
dietary nutrient as defines a vitamin, but vitamin D has
become a vitamin due to limitations in sun exposure. The
persons who are most at risk for inadequate vitamin D status
are those with dark pigmentation, those who cover themselves
outdoors for religious or cultural reasons, and those at higher
latitudes, especially in the winter.
For the skin to produce vitamin D, a threshold of 1820
mJ/cm
2
of ultraviolet B light is required [65]. Sunscreen, of
SPF 8 or higher, blocks vitamin D production [66]. Cutaneous
melanin content, the extent of which is dependent on race,
limits the production of vitamin D [67]. In addition, the thresh-
old of 1820 mJ/cm
2
is not generally reached during the winter
in northern United States above latitude 40 regardless of
pigmentation [68]. For example, in Boston (42 N latitude) in
January, a Caucasian individual in a bathing suit outside on a
sunny day would have no cutaneous production of vitamin D
[65,68]. During summer months, a Caucasian individual in a
bathing suit can produce adequate vitamin D (10,00020,000
IU vitamin D) with 1012 minutes of sun exposure [65].
However, it is estimated that an individual with dark skin
would need 6072 minutes of exposure to synthesize the same
amount of vitamin D [67]. This difference partly explains why
in the 20
th
21
st
centuries, African American infants have a far
greater risk of developing rickets [69,70].
SUPPLEMENTATION AND
REQUIREMENT FOR VITAMIN D
DURING LACTATION
The Vitamin D Content of Human Milk
The occurrence of rickets among breast fed infants is ex-
plained by the extremely low vitamin D content of human milk.
This content was first reliably measured in the early 1980s by
ligand binding analysis [7173]. Previous assays that were
adequate for serum analysis did not possess the sensitivity
required to evaluate the vitamin D activity in human milk
[7476]. Two factors increase the difficulty of identifying
vitamin D or antirachitic activity in human milk compared to
serumnative milk contains only a small percentage of the
circulating sterols that are present in serum, and milk contains
an enormous amount of lipid compared to blood. If present, this
lipid can interfere with the ligand binding assays for vitamin D
and give falsely elevated results. Therefore, the functional
assays involve alkaline removal of lipids, followed by exhaus-
tive chromatography to separate and purify these antirachitic
sterols, with high performance liquid chromatography (HPLC)
and then ligand binding assays to determine the content of
vitamin D
3
, vitamin D
2
, and their metabolites [45,7173]. The
important sources of vitamin D activity in human milk are the
parent compounds, vitamin D
3
and vitamin D
2
, and the metab-
olites, 25(OH)D
3
and 25(OH)D
2
[45,71]. Other metabolites,
including 1,25(OH)
2
D
3
and 1,25(OH)
2
D
2
, are at insufficient
concentrations to measurably increase activity [45,71,77,78].
The two essential forms of vitamin D in human milk,
vitamin D and 25(OH)D, have specific functions based on their
metabolism and their interrelation with vitamin D binding
protein, DBP. DBP is an alpha globulin that binds vitamin D
metabolites with varying affinities [79]. DBPs highest associ-
ation is with 25(OH)D, which promotes a consistent circulating
concentration of 25(OH)D with minimal day-to-day variation
due to UVB exposure or vitamin D intake [59,79]. On the other
hand, the parent compound, vitamin D, can demonstrate great
variability in circulating concentration with UVB exposure or
fluctuation in vitamin D intake. Human milk is ideally created
to benefit from the properties of both compounds. The concen-
tration of 25(OH)D in human milk, which represents approxi-
mately 1% of the maternal circulating 25(OH)D provides a
steady supply of antirachitic activity that is resistant to daily
changes in vitamin D supply. In contrast, 2030% of maternal
circulating vitamin D is expressed in human milk. This expres-
sion allows maternal variation in vitamin D metabolite due to
UVB exposure or fluctuations in intake to be transferred to the
milk [43,70,79]. The transfer of vitamin D into human milk
allows antirachitic activity seen as high as 7600 IU/L in a
mother maintained on 100,000 IU/day vitamin D
2
for treatment
of hypoparathyroidism [44]. This mothers milk contained vi-
tamin D at 30% of her circulating concentration of vitamin D
and 25(OH)D at 1% of her circulating concentration of
25(OH)D (Table 1). This case report and results from recent
clinical trials show that, for human milk to achieve vitamin D
sufficient status, the parent compound vitamin D is the respon-
sible form [44,46,47].
With knowledge that human milk concentrations of vitamin
D and 25(OH)D correspond to the maternal circulating levels
of these compounds, studies also have demonstrated that hu-
man milk vitamin D activity relies completely on maternal
vitamin D status achieved either by UV exposure or oral
supplementation [43,44,70,80]. In 1984, Greer et al. [43]
showed that lactating white women, receiving total body UVB
exposure equal to 30 minutes of sunshine at midday on a clear
Vitamin D during Lactation
692 VOL. 27, NO. 6
summer day at temperate latitudes, significantly increased the
vitamin D content of their milk with a peak at 48 hours and
with a return to baseline at 7 days. At the same time, circulating
25(OH)D concentrations also increased from 13.9 to 20.5 ng/
ml, and remained significantly elevated for at least 14 days, but
there was no significant change in the milk 25(OH)D concen-
trations. This study highlights the role of the parent compound,
vitamin D, in human milk status and the requirement of con-
sistent dosing that reflects the relatively short half-life of this
compound. Due to reliance on regular exposure and modern-
day limitations in sunlight exposure, UVB exposure is not a
realistic option for the vast majority of lactating women to
achieve vitamin D sufficient breast milk. This fact raises the
question-is there a realistic option for lactating women to
achieve vitamin D sufficient breast milk?
Meeting Maternal Vitamin D Needs
With breast milk vitamin D content depending on the vita-
min D status of the lactating mother, the first step toward
achieving vitamin D sufficient breast milk must address the
vitamin D supplementation required to achieve vitamin D suf-
ficiency in the mother. As mentioned previously, current evi-
dence suggests that adults require circulating 25(OH)D con-
centrations of at least 32 ng/ml to maintain vitamin D
sufficiency [14,17,24,29,31,38,41,42,55]. A study published by
the CDC and our laboratory [52] using the NHANES III
database revealed the prevalence of serious vitamin D defi-
ciency. Of women of childbearing years (1549), 42.4% of
African American women and 4.2% of white women exhibited
circulating 25(OH)D below 15 ng/ml. However, by todays
standards, nearly all African American subjects in this partic-
ular study would be vitamin D deficient. With new research
defining hypovitaminosis D as circulating 25(OH)D levels 32
ng/ml, 90% of African American mothers demonstrate sub-
optimal vitamin D status [19,31]. It has long been known that
the milk produced by African American mothers contains less
vitamin D activity when compared to milk from white mothers.
This difference is attributed to both variations in vitamin D
intake from diet and skin-response to UVB exposure [70].
Currently, most obstetricians recommend 400 IU/day vita-
min D
3
supplementation to pregnant women of all races and
degrees of pigmentation since this amount is included in pre-
natal multivitamins in the United States. In 2003, Heaney et al
[51] published a regression model describing the effect of
vitamin D intake on circulating 25(OH)D status. Based on this
model, 400 IU/day vitamin D
3
will increase circulating
25(OH)D by 2.8 ng/ml following 5 months of supplementation
in a healthy, nonpregnant, nonlactating adult. For women with
vitamin D insufficiency, similar prenatal intake will continue
their insufficient status through pregnancy and into lactation.
Commonly, prenatal vitamins are continued during lactation to
provide the extra vitamin intake required for a woman to
support the needs for herself and her growing infant. For
women with vitamin D insufficiency, 400 IU/day provides no
extra vitamin D during lactation. In fact, in the few clinical
studies evaluating maternal 400 IU/day vitamin D supplemen-
tation during lactation, circulating 25(OH)D decreased unless
the mother also received UVB exposure [46,47]. And for the
infant, the milk of these mothers receiving 400 IU/day vitamin
D provided 3368 IU/L antirachitic activity-far less than the
vitamin D needed to provide healthy infant vitamin D status
[4547,71,79].
Safety of Increasing Maternal Vitamin D
Supplementation
In the past 15 years, improved understanding of human
vitamin D needs based on indicators of vitamin D function and
exponential growth in the awareness of the roles of vitamin D
in human health have lead to new recommendations for the
intake of vitamin D required to achieve healthy vitamin D
status at all age groups [14,17,27,29,31,38,42,49,55,81]. This
growing insight into vitamin D health has experienced slow
integration into dietary recommendations and education of the
healthcare community and general public due to inaccuracies of
vitamin D toxicity propagated in the second half of the 20
th
century [64,81,82]. In 1997, the border of toxic was set at
vitamin D supplementation concentrations that are now shown
to be the optimal dose for many individuals to achieve healthy
vitamin D status [19,4951,54,81]. The setting of 2,000 IU, as
the tolerable upper intake limit (TUIL) and of 4,000 IU, as the
lowest observed adverse effect level (LOAEL) impeded
progress in this area [53,54,64,81]. Recently, John Hathcock et
al [81] applied the risk assessment methodology used by the
Food and Nutrition Board to define the TUIL to the current
evidence of vitamin D supplementation. In evaluation of 21
published clinical trials with safety observations for vitamin D
supplementation, he concluded that the available evidence
Table 1. Concentration of Vitamin D
2
, D
3
, 25(OH)D
2
and 25(OH)D
3
in Maternal and Neonatal Cord Serum and Mothers Milk
from a Mother Receiving 100,000 IU/day Vitamin D
2
(from [44])
Serum Type
Vitamin D
2
(ng/mL)
Vitamin D
3
(ng/mL)
25(OH)D
2
(ng/mL)
25(OH)D
3
(ng/mL)
IU/L*
Maternal [At delivery] 551 1 545 4.9
Cord 46 1 251 2.0
Breast Milk [14 days] 155 1 7.3 0.01 7,660
Vitamin D during Lactation
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 693
points to 10,000 IU/day as the level at which no adverse effect
has been observed [81].
The highest intake of vitamin D in a lactating woman with
documentation of milk antirachitic activity was a dose of
100,000 IU/day vitamin D
2
given to a mother with familial
multiple endocrine andenomatosis with history of total thyroid-
parathyroidectomy [44] (Table 1). Analysis of this mothers
milk demonstrated total vitamin D activity of 7,600 IU/L at 14
days lactation. The infants serum 25(OH)D status was 251
ng/ml at birth (mother received the pharmacologic vitamin D
dose throughout pregnancy), but was not measured after onset
of lactation. The infant did have mild elevation of serum
calcium at 11.4 mg/dl at 11 postnatal days with a decrease to a
normal value of 10.3 mg/dl by 25 postnatal days. The infant
demonstrated no symptoms of hypercalcemia.
Effect of Lack of Mother and Infant
Supplementation
With high vitamin D supplementation of a lactating mother,
no symptoms of hypercalcemia were observed, but, with no
vitamin D supplementation of a nursing infant and mother
dyad, symptoms of hypocalcemia are seen [2]. Recent studies
from around the world demonstrate the current situation
[3,9,10,8385]. In the United Arab Emirates after recognizing
38 cases of infantile vitamin D deficiency rickets requiring
hospital admission over a 30 month period [3], Dawodu and
colleagues found vitamin D deficiency, defined as serum
25(OH)D 10 ng/ml, in 92% of the rachitic children and in
97% of their mothers. In comparison, a control group demon-
strated vitamin D deficiency in 22% of children and in 52% of
their mothers [86]. The investigators further evaluated the
vitamin D status of mothers and infants in this community
where whole-body clothing of women is the common practice.
In the summer months in this sunny area in infants of Arab and
South Asian ethnicity, investigators found serum 25(OH)D
10 ng/ml in 61% of lactating mothers and in 82% of their
children demonstrating the prevalence of vitamin D deficiency
in certain populations despite the availability of sun exposure
[87]. A similar study in Australia reiterated the expectedly high
prevalence of vitamin D deficiency in mothers of infants with
rickets [84]. In sunny Greece when summer-born infants and
their mothers received no vitamin D supplementation, the in-
fants exhibited mean serum 25(OH)D of 13.3 ng/ml at 6
months of age in the winter [83]. These infants had a mean
25(OH)D concentration of 10.1 ng/ml at 1 postnatal week and
depended on sun exposure instead of supplementation thereby
demonstrating barely sufficient stores of vitamin D metabolites
to avoid vitamin D deficiency.
A study in the United States demonstrates the commonness
of vitamin D deficiency even in a country with vitamin D
fortification of milk products and recommendations for infant
and nursing mother vitamin D supplementation [85]. In this
study in Iowa, in breastfeeding infants at 9 months of age, 10%
demonstrated serum 25(OH)D level 11 ng/ml. Most vitamin
D deficient infants had serum 25(OH)D measurement in the
winter, had dark skin, and received no vitamin D supplement.
In this group of 87 breastfed infants, only 5% received vitamin
D supplementation. These studies demonstrating the pervasive-
ness of vitamin D deficiency in multiple settings reinforce the
need for vitamin D intake recommendations with consideration
of latitude, season, skin pigmentation, and clothing practices to
promote adequate vitamin D status for the health of all infants.
Defining Infant Vitamin D Requirements
A dose of 400 IU/day has a long record of reliably prevent-
ing infantile rickets, but even for that established dose the
documentation of vitamin D adequacy is scant because most of
the pertinent studies occurred before it was possible to measure
vitamin D status [88]. In addition, the new developments in
understanding of the vitamin D needs of adults raise the notion
that vitamin D sufficiency cannot be defined simply as the
absence of rickets. In evaluation of the long-term effect of
infant vitamin D status, one retrospective cohort study has
demonstrated a significant association between vitamin D sup-
plementation during infancy and bone mineral mass at specific
skeletal sites in prepubertal girls [89]. Another study brought to
light how vitamin D status during infancy may have far-
reaching effects on outcomes other than bone health. A 30-year
prospective cohort study of 10,821 infants born in Finland
demonstrated an 80% decrease in risk of diabetes mellitus type
I in infants who received at least 2,000 IU vitamin D per day in
the first year of life [32].
Contemporary studies to identify the vitamin D intake that
promotes bone mineral content [9092] have not demonstrated
a consistent relationship between infant vitamin D status and
bone mineralization. Nevertheless, vitamin D-deficient rickets
persists in infancy [2,3,513,26,49,83,84]. A review of the
reports of nutritional rickets in children in the United States
published between 1986 and 2003 revealed 166 cases of rickets
reported [11]. The vast majority of subjects were 30 months,
exhibited vitamin D deficiency, were breast-fed, and were
described as African American or black. In review of the
records, only 5% of the breast-fed subjects received vitamin D
supplementation. At least partially responsible for the lack
of vitamin D supplementation is inconsistency in vitamin D
recommendations.
In 1997, the National Academy of Sciences (NAS) recom-
mended 200 IU vitamin D per day as the adequate intake to
prevent vitamin D deficiency in normal infants, children, and
adolescents [64]. The NAS recommendations relied mainly on
data from a prospective study conducted in 4 locations in China
that demonstrated no evidence of rickets at 6 months in infants
receiving as low as 100 IU per day vitamin D supplementation
[93]. However in this study, despite the absence of overt
rickets, over 30% of the infants in the Northern locations had
circulating 25(OH)D concentrations below 11 ng/ml. Since
Vitamin D during Lactation
694 VOL. 27, NO. 6
rickets has been clinically-apparent with circulating 25(OH)D
concentrations below 11 ng/ml, this level is commonly consid-
ered to define vitamin D deficiency in infants [13].
Following the NAS recommendations, the AAP provided a
recommendation to supply a minimum intake of 200 IU per day
of vitamin D to begin in the first 2 months of life for all infants
including those who are exclusively breastfed [13]. After these
recommendations, United States formula companies continued
vitamin D supplementation to provide 400 IU/L [94], with
exclusively formula-fed infants over one month in age com-
monly taking at least a liter of formula a day. In addition, the
infant vitamin supplement readily available in the United States
continues to provide a standard dose of 400 IU/day [95].
Recently, the Canadian Paediatric Society, in response to
104 confirmed cases of rickets in Canada between 2002 and
2004 [9] and reports of pervasive vitamin D deficiency in
Canada especially in people with dark pigmentation [10], pub-
lished recommendations for vitamin D supplementation for
Canadian mothers and infants [49]. They recommend that total
vitamin D intake during the first year should be 400 IU/day in
the full-term infants, with an increase to 800 IU/day from all
sources between October and April north of the 55th parallel
(approximate latitude of Edmonton) and between the 40th and
55th parallel in individuals with risk factors for vitamin D
deficiency other than latitude alone. In addition, they recom-
mend considering 2000 IU/day vitamin D intake for pregnant
and lactating women, especially in the winter. They do recom-
mend periodic assessment of vitamin D status in these women
for effectiveness of this regimen and possible side effects. Of
note, the recommendations state that vitamin D supplementa-
tion is not only to prevent rickets, but to prevent vitamin D
deficiency-associated disease in early and later life [49].
These new recommendations emphasize the prevalence of
vitamin D deficiency especially in populations at high latitude,
during winter, and in persons of dark pigmentation. In addition,
they address the growing evidence supporting a serum
25(OH)D concentration of 32 ng/ml to achieve vitamin D
sufficiency and the long-term consequences of poor vitamin D
status in early life [4,18,28,31,32,49,5456]. The AAP recently
revised its 2003 vitamin D recommendations to supplement all
infants not on formula, children and adolescents with 400 IU
vitamin D/day [13].
With current infant formula and vitamin D supplements
providing 400 IU/day [94,95] and recent recommendations for
infants to receive 400 IU/day [49], understanding the expected
effect of 400 IU/day is essential. Table 2 presents 3 trials
providing 400 IU/day to term infants. Of note, in the study
published by Pittard et al [96] in 1991, 80% of the subjects
were black. In addition, in this study, a second group of term
infants received 800 IU/day vitamin D with resulting mean
serum 25(OH)D of 35 ng/ml at 16 weeks. In a fourth study of
vitamin D supplementation in infancy, Zeghoud et al [97]
provided 500 IU/day and 1000 IU/day vitamin D above that
received with a 426 IU/L vitamin D formula. The investigators
classified the infants into 3 groups based on vitamin D and
intact parathyroid hormone (iPTH) status at birth and evaluated
the infants at 1 and 3 months. They reported that infants with
serum 25(OH)D 12 ng/ml and iPTH 60 ng/L (vitamin D
deficient) had a mean serum 25(OH)D of 18.2 ng/ml at one
month and 22.4 ng/ml at 3 months when receiving 500 IU/day
vitamin D plus formula. For the vitamin D deficient infants
who received 1000 IU/day vitamin D plus formula, serum
25(OH)D status was 21.2 ng/ml at 1 month. In the group of
infants who demonstrated serum 25(OH)D 12 ng/ml at birth
but had normal iPTH ( 60 ng/L) and received 1000 IU/day
vitamin D plus formula, the serum 25(OH)D rose to 23.9 ng/ml
by one month. In the group of infants with serum 25(OH)D
12 ng/ml at birth who received 1000 IU/day vitamin D plus
formula, serum 25(OH)D was 23.7 ng/ml at one month. In this
study, serum calcium, iPTH, alkaline phosphatase activity, and
phosphate were monitored with no evidence of vitamin D
toxicity.
These studies demonstrate that 4001426 IU/day vitamin D
supplementation can be given to infants without toxicity and
with vitamin D status above the range associated with infantile
rickets, but a few questions persists. Is there a vitamin D dose
that is safe for a lactating mother and can provide adequate
vitamin D to the exclusively nursing infant? And if so, then
which route of supplementation is the better option?
Meeting Infant Needs with Maternal
Supplementation
Clinical trials to answer the first question are extremely
limited due to the previously-mentioned concern for vitamin D
toxicity with vitamin D intake that exceeds 2000 IU per day
[54,56,64]. A few trials have studied the effect of maternal
vitamin D supplementation on the 25(OH)D status of infants
receiving complete human milk nutrition and found no signif-
icant improvement with 5001000 IU/day vitamin D
2
intake
Table 2. Studies Evaluating a Dose of 400 IU/day Vitamin D in Early Infancy
Studies
Serum 25(OH)D
with no vitamin D
supplement
Serum 25(OH)D
with 400 IU/day
vitamin D
Length of Supplementation (all
begin in first postnatal week)
Greer et al, 1982 [91] 12.9 32.7 6 months
Greer et al, 1989 [90] 23.5 37 6 months
Pittard et al, 1991 [96] Not studied 26 16 weeks
Vitamin D during Lactation
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 695
[98101]. Only one study in Finland in 1986 comparing ma-
ternal vitamin D
3
intake of 2,000 IU/day with infant intake of
400 IU/day showed equivalent vitamin D status in the 2 infant
comparison groups [99]. In this study, maternal supplementa-
tion with 2000 IU/day vitamin D
3
for 15 weeks increased
maternal serum 25(OH)D from a mean of 11 ng/ml to a mean
serum 25(OH)D close to 40 ng/ml. In the infants being exclu-
sively breastfed during this time with no additional vitamin D
intake, the serum 25(OH)D increased from a mean of 8.5 ng/ml
at birth to a mean nearing 30 ng/ml. This result compared
favorable to the infants receiving 400 IU/day whose serum
25(OH)D increased from a mean of 8.5 ng/ml at birth to a mean
above 30 ng/ml at 15 postnatal weeks. Their mothers, who
received no supplementation, had no change in their mean
serum 25(OH)D level of 11 ng/ml. For the infants who received
no direct supplementation of vitamin D and whose mothers
received 1000 IU/day vitamin D
3
, serum 25(OH)D rose over 15
weeks from a mean of 8.5 ng/ml to 15 ng/ml but, despite this
increase, this concentration was significantly lower than that
observed for both the infants whose mothers received 2000
IU/day and the infants who directly received 400 IU/day. The
authors concluded a sufficient supply of vitamin D to the
breastfed infant is achieved only by increasing the maternal
supplementation up to 2000 IU/day. As such a dose is far
higher than the daily dietary allowance recommended for lac-
tating mothers its safety over prolonged periods is not known
and should be examined [99].
These results were ignored for two decades due to the
predicted concern of recommending the tolerable upper intake
limit of 2,000 IU/day to lactating women [56,64,99] and to the
uncertainty of the serum 25(OH)D status that denotes vitamin
D sufficiency in mothers and infants. Of note, maternal 1000
IU/day vitamin D
3
did increase serum 25(OH)D concentration
in infants to levels considered sufficient to avoid rickets (15
ng/ml), but not even this concentration of maternal supplemen-
tation was adopted [99].
With shift of vitamin D paradigm and realization of the
multiple disease processes associated with hypovitaminosis D,
investigators are discovering that even 2,000 IU/day vitamin D
does not reach adequate supplementation for some populations
[31,49,5356]. With this improved understanding of human
vitamin D needs, reexamination of the questioncan human
milk attain adequate vitamin D status, must occur.
In 2004, we published a clinical trial [46] comparing the
maternal, milk, and infant vitamin D status achieved with
supplementation with 400 IU/day vitamin D
3
with 1600 IU/day
vitamin D
2
(total supplementation of 2,000 IU/day vitamin D),
and 400 IU/day vitamin D
3
with 3600 IU/day vitamin D
2
(total
supplementation of 4,000 IU/day vitamin D). Vitamin D
2
sup-
plements were used to distinguish the effect of the study
supplementation from the effect of UVB exposure and other
dietary sources. The mothers in both the 1600 and 3600 IU/day
vitamin D
2
groups experienced significant increases in total
circulating 25(OH)D concentrations and in 25(OH)D
2
, but
demonstrated decreases in serum 25(OH)D
3
(Table 3).
The significant improvement in maternal vitamin D status
did translate to increases in the vitamin D activity in the milk,
but it did not reach 400 IU/L. The milk from mothers receiving
a total of 2000 IU/day vitamin D reached a mean antirachitic
activity of 69.7 3.0 IU/L. The milk from mother receiving a
total of 4000 IU/day vitamin D achieved a mean antirachitic
activity of 134.6 48.3 IU/L. These increases were attribut-
able to both vitamin D
2
and 25(OH)D
2
in the milk.
The improvement in vitamin D activity concentrations in
the milk was associated with improved vitamin D status in the
infant. The mothers receiving 400 IU vitamin D
3
and 1600 IU
vitamin D
2
per day nursed infants with a significant rise in total
circulating 25(OH)D concentrations from 7.9 1.1 to 27.8
3.9 ng/ml over the 3-month study period. For the infants whose
mothers received 400 IU vitamin D
3
and 3600 IU vitamin D
2
per day, the total circulating 25(OH)D levels significantly
increased from 13.4 3.3 to 30.8 5.0 ng/ml. Following these
results, the next step was to compare the effect of maternal
supplementation and direct infant supplementation on the vita-
min D status of the exclusively-breastfeeding infant.
Further study was performed with vitamin D
3
supplemen-
tation with comparison of the vitamin D status achieved in
nursing infants who received 300 IU vitamin D
3
per day
directly and those whose mothers received 6400 vitamin D
3
per day [47]. When lactating mothers received 6400 IU/day
vitamin D
3
for 6 months, their mean milk vitamin D activity
increased from 82 to 873 IU/L (Fig. 1). This increase in
vitamin D supply to the infant achieved infant vitamin D
status equal to that observed with direct infant supplemen-
tation of 300 IU/day (46 ng/ml versus 43 ng/ml, respec-
tively) (Fig. 2). In addition, mothers demonstrated signifi-
cant improvement in vitamin D status. Compared to a
maternal intake of 400 IU vitamin D
3
/day, a maternal intake
Table 3. Serum 25(OH)D Status Achieved in Infants with Maternal Supplementation at 2000 and 4000 IU/day Total Vitamin
D25(OH)D Values Are ng/ml (from [97])
1600 IU D
2
and 400 IU D
3
3600 IU D
2
and 400 IU D
3
Baseline 3 months p-value Baseline 3 months p-value
Total 25(OH)D 27.6 (3.3) 36.1 (2.3) 0.05 32.9 (2.4) 44.5 (3.9) 0.04
25(OH)D
2
0.4 (0.1) 17.4 (1) 0.0001 1.8 (1) 25.0 (2.5) 0.0001
25(OH)D
3
27.2 (3.2) 18.7 (1.7) 0.02 32.0 (2.5) 18.9 (3.0) 0.0007
Vitamin D during Lactation
696 VOL. 27, NO. 6
of 6400 IU vitamin D
3
/day was associated with a dramatic
increase in both circulating maternal vitamin D
3
and
25(OH)D with steady-state achieved by the 3
rd
month of
supplementation (Figs. 3 and 4). No toxicity was observed in
mothers or infants throughout the 6 month study period.
Serum calcium concentrations remained in the normal range,
and no hypercalcuria was observed. With steady-state
achieved by 3 months of supplementation and no trends of
increasing calcium or urinary calcium appreciated, this study
presented no evidence that longer supplementation would
lead to toxicity. The current standard dose of 400 IU/day
vitamin D contributed little to the vitamin D nutritional
status of mother and her milk, with 25(OH)D levels reflect-
ing seasonal variation. In comparison, maternal supplemen-
tation of 6400 IU/day for a period of six months appeared
safe and ensured adequate vitamin D status of both the
mother and her nursing infant independent of season. In both
groups, the milk vitamin D activity was directly related to
maternal vitamin D status.
This study demonstrates that, with adequate maternal vita-
min D supplementation, human milk can achieve vitamin D
sufficiency to equal or exceed the current infant recommenda-
tions. The next question to address iswhich is the better
option?
CONCLUSION
The discovery that with sufficient vitamin D supplementa-
tion of the mother, human milk can provide adequate vitamin D
supply to the nursing infant is referred to by human lactation
expert, Dr. Ruth Lawrence, as shifting the vitamin D para-
digm [102]. This shift supports lactating mothers who take
great pride in providing complete nutritional support to their
breastfed infants. In addition, maternal vitamin D supplemen-
tation avoids concern of development of allergy or asthma that
has been demonstrated with early multi-vitamin administration
in water-soluble form [103,104]. A strong benefit of breast-
feeding is avoidance of direct introduction of foreign sub-
stances to young infants, and maternal vitamin D supplemen-
tation supports that function.
Maternal supplementation also allows the opportunity to
support the health of mother and infant with one dose. Current
infant supplementation can leave the nursing mother with se-
vere vitamin D deficiency [46,47,86]. As the vitamin D intake
to achieve a serum 25(OH)D of at least 32 ng/ml is identified,
sufficient supplementation of mother will be crucial for her
health. The Canadian Paediatric Society currently recommends
Fig. 3. Mothers receiving 6400 IU/day had significantly greater serum
25(OH)D status when compared to mothers receiving 400 IU/day (p
0.0028). From [47].
Fig. 4. Mothers receiving 6400 IU/day had significantly greater serum
vitamin D status when compared to mothers receiving 400 IU/day (p
0.0043). From [47].
Fig. 1. Milk antirachitic activity is significantly greater for mothers
receiving 6400 IU/day vitamin D than for mothers receiving 400
IU/day vitamin D (pp 0.0003). From [47].
Fig. 2. Maternal supplementation with 6400 IU/day vitamin D pro-
duced infant serum 25(OH)D status similar to that achieved with infant
intake of 300 IU/day vitamin D. From [47].
Vitamin D during Lactation
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 697
that consideration should be given to administering 2,000 IU
of vitamin D daily to pregnant and lactation women, especially
during the winter months, to maintain vitamin D sufficiency.
The effectiveness of this regimen and possible side effects
should be checked with periodic assays for 25(OH)D and
calcium [49]. This dose is a step towards improved supple-
mentation of mother, but higher intake will be required for most
mothers to support infant vitamin D health. Currently, this
higher intake is above the TUIL of 2,000 IU/day for vitamin D.
Further evaluation of dosing is required to confidently provide
this opportunity in a manner that supports health of mother and
infant without risk for toxicity.
At present, the available option to support vitamin D health
of the infant is direct infant supplementation. A dose of 400
IU/day has consistently resulted in serum 25(OH)D status 20
ng/ml, but some populations may need more, and 1427 IU/day
(1,000 IU vitamin D and 427 IU/L formula per day) has been
given without evidence of toxicity [97]. For high risk popula-
tions, dark-pigmented skin, Northern latitudes, winter months,
whole-body covering of mother; measurement of mother and
infant serum 25(OH)D status with vitamin D intake individu-
ally tailored to achieve sufficiency is currently the best option.
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