Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 234
TABLE 1 Dietary Reference Intakes for Vitamin E
(a -Tocopherol a) by Life Stage Group
DRI values (mga/day)
EARb RDAc AId ULe,f
Life stage groupg
NDh
0 through 6 mo 4
7 through 12 mo 5 ND
1 through 3 y 5 6 200
4 through 8 y 6 7 300
9 through 13 y 9 11 600
14 through 18 y 12 15 800
19 through 30 y 12 15 1,000
31 through 50 y 12 15 1,000
51 through 70 y 12 15 1,000
> 70 y 12 15 1,000
Pregnancy
£ 18 y 12 15 800
19 through 50 y 12 15 1,000
Lactation
£ 18 y 16 19 800
19 through 50 y 16 19 1,000
a For the EAR, RDA, and AI: a-Tocopherol includes RRR-a-tocopherol, the only
form of a-tocopherol that occurs naturally in foods, and the 2R-stereoisomeric forms
of a-tocopherol (RRR-, RSR-, RRS-, and RSS-a-tocopherol) that occur in fortified
foods and supplements. This does not include the 2S-stereoisomeric forms of a-
tocopherol (SRR-, SSR-, SRS-, and SSS-a-tocopherol), also found in fortified foods
and supplements. The 2S-stereoisomers are not stored in the body.
b EAR = Estimated Average Requirement.
c RDA = Recommended Dietary Allowance.
d AI = Adequate Intake.
e UL = Tolerable Upper Intake Level. Unless otherwise specified, the UL represents
total intake from food, water, and supplements.
f As a-tocopherol; applies to any form of supplemental a-tocopherol since all are
absorbed and can potentially contribute to vitamin E toxicity. The UL applies to synthetic
forms obtained from supplements, fortified foods, or a combination of the two. Little
information exists on the adverse effects that might result from ingestion of other
forms.
g All groups except Pregnancy and Lactation represent males and females.
h ND = Not determinable. This value is not determinable due to the lack of data of
adverse effects in this age group and concern regarding the lack of ability to handle
excess amounts. Source of intake should only be from food to prevent high levels of
intake.
OCR for page 235
PART III: VITAMIN E 235
VITAMIN E
V
itamin E is a fat-soluble nutrient that functions as a chain-breaking
antioxidant in the body by preventing the spread of free-radical reac-
tions. Of the eight naturally occurring forms of vitamin E only the
a-tocopherol form of the vitamin is maintained in the plasma.
The requirements for vitamin E are based on the prevention of hydrogen
peroxide–induced hemolysis. The Estimated Average Requirement (EAR), Rec-
ommended Dietary Allowance (RDA), and Adequate Intake (AI) values for vita-
min E only apply to intake of the 2R-stereoisomeric forms of a-tocopherol from
food, fortified foods, and supplements. Other naturally occurring forms of vita-
min E do not meet the vitamin E requirement because they are not converted to
a-tocopherol in humans and are poorly recognized by the a-tocopherol trans-
fer protein in the liver.
The Tolerable Upper Intake Level (UL) is based on the adverse effect of
increased tendency to hemorrhage. The UL for vitamin E applies to any forms
of supplemental a-tocopherol because all are absorbed; these forms of syn-
thetic vitamin E are almost exclusively used in supplements, food fortification,
and pharmacological agents. Little information exists on the adverse effects that
might result from the ingestion of other forms of vitamin E. DRI values are
listed by life stage group in Table 1.
Food sources of vitamin E include vegetable oils and spreads, unprocessed
cereal grains, nuts, fruits, vegetables, and meats (especially the fatty portion).
Overt deficiency of vitamin E in the United States and Canada is rare and is
generally only seen in people who are unable to absorb the vitamin or who have
inherited conditions that prevent the maintenance of normal blood concentra-
tions. There is no evidence of adverse effects from the consumption of vitamin
E naturally occurring from foods. The possible chronic effects of lifetime expo-
sures to high supplemental levels of a-tocopherol remain uncertain.
VITAMIN E AND THE BODY
Function
Unlike most nutrients, vitamin E does not appear to play a specific role in
certain metabolic pathways. Its major function seems to be as a nonspecific
chain-breaking antioxidant that prevents the spread of free-radical reactions. It
scavenges peroxyl radicals and protects polyunsaturated fatty acids within mem-
brane phospholipids and in plasma lipoproteins.
OCR for page 236
DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS
236
On the molecular level, vitamin E (a-tocopherol form) inhibits protein ki-
nase C activity (involved in cell proliferation and differentiation) in smooth
muscle cells, platelets, and monocytes. It may also improve vasodilation and
inhibit platelet aggregation by enhancing the release of prostacyclin.
Absorption, Metabolism, Storage, and Excretion
Vitamin E is absorbed in the intestine, although the precise rate of absorption is
not known. All of the forms of vitamin E appear to have similar low absorption
efficiency. Absorbed vitamin E in the form of chylomicron remnants is taken up
by the liver, and then only one form of vitamin E, a-tocopherol, is preferentially
secreted in very low density lipoproteins. Thus, it is the liver, not the intestine,
that discriminates between tocopherols. Tissues take up vitamin E from the
plasma. Vitamin E rapidly transfers between various lipoproteins and also be-
tween lipoproteins and membranes, which may enrich membranes with vita-
min E. Vitamin E is excreted in both the urine and feces, with fecal elimination
being the major mode of excretion.
DETERMINING DRIS
There are eight naturally occurring forms, or isomers, of vitamin E: four toco-
pherols (a-, b-, g-, and d-tocopherols) and four tocotrienols (a-, b-, g-, and
d-tocotrienols). These various forms of vitamin E are not interconvertible in
humans, and thus do not behave the same metabolically. Of the eight, only a-
tocopherol is maintained in the plasma.
The isomer a-tocopherol has eight possible stereoisomers: four in the 2R-
stereoisomeric form (RRR-, RSR-, RRS-, and RSS-a-tocopherol) and four in the
2S-stereoisomeric form (SRR-, SSR-, SRS-, and SSS-a-tocopherol). Of these, only
one—the RRR form—naturally occurs in foods. All eight stereoisomers are rep-
resented by synthetic forms (together called all-rac-a-tocopherol) and are present
in fortified foods and in vitamin supplements.
Of the eight stereoisomers of a-tocopherol, the only forms that are main-
tained in the plasma are naturally occurring RRR-a-tocopherol and the 2R-ste-
reoisomeric forms present in synthetic forms. Since the 2S-stereoisomers are
not maintained in the plasma or tissues, they are not included in the definition
of active components for vitamin E activity in humans.
For the purpose of establishing the requirements, vitamin E activity is de-
fined here as being limited to the 2R-stereoisomeric forms of a-tocopherol. How-
ever, all eight stereoisomeric forms of supplemental a-tocopherol are used as
the basis for establishing the UL for vitamin E. This is because all eight forms
are absorbed. These recommended intakes and ULs vary from past definitions
and recommendations for vitamin E.
OCR for page 237
PART III: VITAMIN E 237
Determining Requirements
The adult requirements for vitamin E are based largely on induced vitamin E
deficiency in humans and the intake that correlated with in vitro hydrogen
peroxide–induced red blood cell hemolysis and plasma a-tocopherol concen-
trations. Although some studies have reported a possible protective effect of
vitamin E on conditions such as cardiovascular and neurological diseases, can-
cer, cataracts, and diseases of the immune system, the data are inadequate to
support population-wide dietary recommendations that are specifically based
on preventing these diseases.
The EAR, RDA, and AI values for vitamin E apply only to intake of the 2R-
stereoisomeric forms of a-tocopherol from food, fortified foods, and supple-
ments. The other naturally occurring isomers of vitamin E (b-, g-, and d-toco-
pherols and a-, b-, g-, and d-tocotrienols) do not contribute to meeting the
vitamin E requirement because they are not converted to a-tocopherol in hu-
mans; these forms of synthetic vitamin E are almost exclusively used in supple-
ments, food fortification, and pharmacological agents. Little information exists
on the adverse effects that might result from ingestion of excess amounts of
other isomeric forms (such as g- and b-tocopherol).
Currently, most nutrient databases, as well as nutrition labels, do not dis-
tinguish among all the different forms of vitamin E found in food. These data-
bases often present the data as a-tocopherol equivalents (a-TE), and thus in-
clude the contributions of all eight naturally occurring forms of vitamin E, after
adjustment for bioavailability using previously determined equivalencies. It is
recommended that the use of a-TE be abandoned due to the lack of evidence of
bioavailability via transport in the plasma or tissues. Because these other forms
of vitamin E occur in foods, the intake of a-TE is greater than the intake of a-
tocopherol alone. The values above were converted from a-TE to a-tocopherol
using a factor of 0.8 as described later in this chapter (see “Dietary Sources”).
Criteria for Determining Vitamin E Requirements,
by Life Stage Group
Life stage group Criterion
0 through 6 mo Human milk content
7 through 12 mo Extropolation from 0 to 5.9 mo
1 through 18 y Extrapolation from adult
19 through 30 y Prevention of hydrogen peroxide–induced hemolysis
31 through > 70 y Extrapolation of hydrogen peroxide–induced hemolysis
from 19 through 30 y
OCR for page 238
DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS
238
Pregnancy
£ 18 y through 50 y Age-specific requirement + plasma concentration
Lactation
£ 18 y through 50 y Age-specific requirement + vitamin E secreted in milk
The UL
The Tolerable Upper Intake Level (UL) is the highest level of daily nutrient
intake that is likely to pose no risk of adverse effects for almost all people.
Members of the general population should not routinely consume more than
the UL. The UL for vitamin E is based on the adverse effect of increased ten-
dency to hemorrhage. The UL applies to all supplemental a-tocopherol forms
of vitamin E (RRR-a-tocopherol and all-rac-a-tocopherol), since all are absorbed
and can thus potentially contribute to vitamin E toxicity.
Sources of vitamin E available as supplements are usually labeled as inter-
national units (IUs) of natural vitamin E and its esters or as synthetic vitamin E
and its esters. Table 2 shows the IUs of various sources of supplemental vitamin
E that are equivalent to the UL for adults of 1,000 mg/day of any form of supple-
mental a-tocopherol.
Based on the Third National Health and Nutrition Examination Survey
(NHANES III, 1988–1994) data, the highest mean reported intake of vitamin E
from food and supplements for all life stage and gender groups was approxi-
mately 45 mg/day of a-tocopherol equivalents (reported by women aged 51 to
70 years). This group also had the highest reported intake at the 99th percen-
tile, at 508 mg/day of a-tocopherol equivalents, which is well below the UL of
1,000 mg/day for any form of a-tocopherol. Vitamin E supplement use is high
in the U.S. population. In the 1986 National Health Interview Survey (NHIS),
supplements containing vitamin E were used by 23 percent of men, 29 percent
of women, and 37 percent of young children in the United States. The risk of
adverse effects resulting from excess intake of a-tocopherol from food and supple-
ments appears to be very low based on this information.
Special Considerations
Vitamin K deficiency or anticoagulant therapy: The UL for vitamin E pertains
to individuals in the general population with adequate vitamin K intake. Indi-
viduals who are deficient in vitamin K or who are on anticoagulant therapy are
at increased risk of coagulation defects and should be monitored when taking
vitamin E supplements.
OCR for page 239
PART III: VITAMIN E 239
TABLE 2 Amounts in International Units (IU) of Any Forms of
a -Tocopherola Contained in Vitamin Eb Supplements Equivalent to
the UL for Adultsc
UL for Adults
Total a-Tocopherol
Sources of Vitamin E IU from Source
Available as Supplements (mg/day) Providing Adult UL
Synthetic Vitamin E and Esters
dl-a-Tocopheryl acetate 1,000 1,100
dl-a-Tocopheryl succinate 1,000 1,100
dl-a-Tocopherol 1.000 1,100
Natural Vitamin E and Esters
d-a-Tocopheryl acetate 1,000 1,500
d-a-Tocopheryl succinate 1,000 1,500
d-a-Tocopherol 1,000 1,500
a All forms of supplemental a-tocopherol include all eight stereoisomers of a-tocopherol. The UL is
based on animal studies feeding either all racemic- or RRR-a-tocopherol, both of which resulted in equivalent
adverse effects.
b Vitamin E supplements have been historically, although incorrectly, labeled d- or dl-a-tocopherol.
Sources of vitamin E include the a ll racemic- ( dl - a-tocopherol [ RRR-, RRS-, RSR-, RSS-,
SSS-, SRS-, SSR-, and SRR-] or synthetic) form and its esters. All of these forms of vitamin E may be
present in supplements.
c The conversion factors used in this table are based on 2S-forms contributing to the adverse effects
DIETARY SOURCES
Foods
The main dietary sources of vitamin E are vegetable oils, such as wheat-germ
oil, sunflower oil, cottonseed oil, safflower oil, canola oil, olive oil, palm oil,
and rice-bran oil. Fats and oils in the form of spreads often contribute to vita-
min E intake. Other sources of vitamin E include unprocessed cereal grains,
nuts, fruits, vegetables, and meats (especially the fatty portion). As previously
stated, only the natural form of a-tocopherol (RRR-a-tocopherol) found in these
unfortified foods counts toward meeting the RDA. Other non-a-tocopherol forms
of vitamin E present in food do not.
It is important to note that because vitamin E is generally found in fat-
containing foods and is more easily absorbed from fat-containing meals, in-
takes of vitamin E by people who consume low-fat diets may be less than opti-
mal unless food choices are carefully made to enhance vitamin E intake.
OCR for page 240
DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS
240
Estimating a-tocopherol content of foods and diets: As discussed, many data-
bases of nutrient content and many food-intake surveys list vitamin E in the
form of a-tocopherol equivalents (a-TE) rather than a-tocopherol. To estimate
a-tocopherol content, multiply the number of a-tocopherol equivalents by a
factor of 0.8:
mg of a-tocopherol in a meal = mg of a-TEs in a meal ¥ 0.8
Dietary Supplements
Vitamin E supplement use appears to be high in the U.S. population. Data from
the Boston Nutritional Status Survey (1981–1984) on adults aged 60 years and
older found that 38 percent of men took dietary supplements and, of them, 68
percent took a vitamin E supplement. Of the women surveyed, 49 percent used
supplements, and 73 percent of them took a vitamin E supplement. In the
1986 NHIS, 26 percent of all adults reported using supplements that contained
vitamin E.
Converting IUs to mg of a-tocopherol: To determine the milligrams of a-toco-
pherol in a dietary supplement labeled in international units (IUs), one of two
conversion factors may be used:
• If the form of the supplemental vitamin E is naturally occurring or RRR-
a-tocopherol (which has been historically and incorrectly labeled as d-
a-tocopherol), the correct factor is 0.67 mg/IU. Thus, 30 IUs of RRR-a-
tocopherol (labeled as d-a-tocopherol) in a multivitamin supplement
would equate to 20 mg of a-tocopherol (30 ¥ 0.67). The same factor is
used for 30 IUs of either RRR-a-tocopherol acetate or RRR-a-tocopherol
succinate because the amount in grams of these forms in a capsule has
been adjusted based on their molecular weight.
Mg of a-tocopherol in food, fortified food, or multivitamin = IU of
the RRR-a-tocopherol compound ¥ 0.67
• If the form of the supplement is all-rac-a-tocopherol (historically and
incorrectly labeled as dl-a-tocopherol), the appropriate factor is 0.45
mg/IU. (This reflects the inactivity of the 2S-stereoisomers.) Thus, 30
IU of all-rac-a-tocopherol (labeled as dl-a-tocopherol) in a multivita-
min supplement would equate to 13.5 mg of a-tocopherol (30 ¥ 0.45).
The same factor is used for the all-rac-a-tocopherol acetate and succi-
nate forms.
Mg of a-tocopherol in food, fortified food, or multivitamin = IU of
the all-rac-a-tocopherol compound ¥ 0.45
OCR for page 241
PART III: VITAMIN E 241
See Appendix F on conversion factors on converting IUs of vitamin E to
a-tocopherol.
Bioavailability
Because vitamin E is a fat-soluble nutrient, its absorption is enhanced when it is
consumed in a meal that contains fat; however, the optimal amount of fat to
enhance absorption has not been reported. This is probably more of a consider-
ation for people who take vitamin E in supplement form, rather than for those
who consume it from foods, since most dietary vitamin E is found in foods that
contain fat.
Dietary Interactions
There is evidence that vitamin E may interact with certain dietary substances
(see Table 3).
TABLE 3 Potential Interactions with Other Dietary Substances
Substance Potential Interaction Notes
SUBSTANCES THAT AFFECT VITAMIN E
Polyunsaturated Vitamin E requirements may High PUFA intakes should be accompanied
fatty acids (PUFAs) increase when intakes of by increased vitamin E intakes.
PUFAs are increased.
INADEQUATE INTAKE AND DEFICIENCY
Vitamin E deficiency is very rare; overt symptoms of deficiency in healthy indi-
viduals consuming diets low in vitamin E have never been described. Vitamin E
deficiency occurs only as a result of genetic abnormalities of vitamin E metabo-
lism, fat malabsorption syndromes, or protein-energy malnutrition. The signs
and symptoms of deficiency include the following:
• Peripheral neuropathy (primary symptom)
• Spinocerebellar ataxia
• Skeletal myopathy
• Pigmented retinopathy
• Increased erythrocyte fragility
• Increased ethane and pentane production
OCR for page 242
DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS
242
EXCESS INTAKE
There is no evidence of adverse effects from the excess consumption of vita-
min E naturally occurring in foods. With regard to supplemental vitamin E
intake in the form of synthetic α-tocopherol (as a supplement, food fortificant,
or pharmacological agent), most studies in humans showing the safety of vita-
min E were conducted in small groups of individuals who received supple-
mental amounts of 3,200 mg/day or less (usually less than 2,000 mg/day) of
α-tocopherol for periods of a few weeks to a few months Thus, the possible
chronic effects of longer exposure to high supplemental levels of α-tocopherol
remain uncertain and some caution must be exercised in judgments regarding
the safety of supplemental doses of α-tocopherol over multiyear periods. The
potential adverse effects of excess vitamin E intake include hemorrhagic toxic-
ity and diminished blood coagulation in individuals who are deficient in vita-
min K or on anticoagulant therapy.
Special Considerations
Premature infants: Hemolytic anemia due to vitamin E deficiency is of frequent
concern in premature infants. However, its management via vitamin E supple-
mentation must be carefully controlled because small premature infants are
particularly vulnerable to the toxic effects of α-tocopherol.
OCR for page 243
PART III: VITAMIN E 243
KEY POINTS FOR VITAMIN E
Vitamin E (a-tocopherol) is a fat-soluble nutrient that functions
3
as a chain-breaking antioxidant in the body by preventing the
spread of free-radical reactions.
The adult requirements for vitamin E are based on prevention
3
of hydrogen peroxide–induced hemolysis. The UL is based on
the adverse effect of increased tendency to hemorrhage.
The EAR, RDA, and AI values for vitamin E apply only to intake
3
of the 2R-stereoisomeric forms of a-tocopherol from food,
fortified foods, and supplements. The UL applies to any form of
supplemental a-tocopherol because all are absorbed; these
forms of synthetic vitamin E are almost exclusively used in
supplements, food fortification, and pharmacological agents.
Food sources of vitamin E include vegetable oils and spreads,
3
unprocessed cereal grains, nuts, fruits, vegetables, and meats
(especially the fatty portion).
Vitamin E deficiency is very rare in the United States and
3
Canada, generally occurring only as the result of genetic
abnormalities of vitamin E metabolism, fat malabsorption
syndromes, or protein-energy malnutrition. The primary effect
of vitamin E deficiency is peripheral neuropathy.
There is no evidence of adverse effects from the consumption
3
of vitamin E naturally occurring in foods.
The primary known adverse effect resulting from excessive
3
supplemental vitamin E intake is hemorrhagic toxicity.
