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OCR for page 414
TABLE 1 Dietary Reference Intakes for Boron, Nickel, and
Vanadium by Life Stage Groupa
DRI values (mg/day)
Vanadiumc
Boron Nickel
ULb UL UL
Life stage groupd
NDe
0 through 6 mo ND ND
7 through 12 mo ND ND ND
1 through 3 y 3 0.2 ND
4 through 8 y 6 0.3 ND
9 through 13 y 11 0.6 ND
14 through 18 y 17 1.0 ND
19 through 30 y 20 1.0 1.8
31 through 50 y 20 1.0 1.8
51 through 70 y 20 1.0 1.8
> 70 y 20 1.0 1.8
Pregnancy
£ 18 y 17 1.0 ND
19 through 50 y 20 1.0 ND
Lactation
£ 18 y 17 1.0 ND
19 through 50 y 20 1.0 ND
a Data were insufficient to set a UL for arsenic and for silicon. Although a UL was
not determined for arsenic, there is no justification for adding it to food or supplements.
In addition, although silicon has not been shown to cause adverse effects in humans,
there is no justification for adding it to supplements.
b UL = Tolerable Upper Intake Level. Unless otherwise specified, the UL represents
total intake from food, water, and supplements.
c Although vanadium in food has not been shown to cause adverse effects in
humans, there is no justification for adding it to food, and vanadium supplements
should be used with caution. The UL is based on adverse effects in laboratory animals
and these data could be used to set a UL for adults, but not for children or adolescents.
d All groups except for Pregnancy and Lactation represent males and females.
e 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.
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PART III: ARSENIC, BORON, NICKEL, SILICON, AND VANADIUM 415
ARSENIC, BORON, NICKEL,
SILICON, AND VANADIUM
T
here is evidence that the minerals arsenic, boron, nickel, silicon, and
vanadium play a beneficial role in some physiological processes of cer-
tain animal species. For boron, silicon, and vanadium, measurable re-
sponses by human subjects to dietary intake variations have also been demon-
strated. However, the available data were not as extensive and the responses
were not as consistently observed as with vitamins and other minerals. There-
fore, data were insufficient to determine Estimated Average Requirements (EARs),
and thus Recommended Dietary Allowances (RDAs), for these minerals.
Estimates of dietary intakes of arsenic, boron, nickel, silicon, and vana-
dium by the North American adult population were available and could have
been used to establish Adequate Intakes (AIs). However, establishing an AI also
requires a clearly defined, reproducible indicator in humans who are sensitive
to a range of intakes. Indicators that meet this criterion for establishing an AI
were not available for any of these minerals, and therefore no AIs were set.
ULs were set for boron, nickel, and vanadium based on animal data. DRI
values are listed by life stage group in Table 1. There were insufficient data to set
Tolerable Upper Intake Levels (ULs) for arsenic and silicon.
Observations of deficiency effects (e.g., on growth and development) in
multiple animal species and data from limited human studies suggest beneficial
roles for arsenic, boron, nickel, silicon, and vanadium in human health. How-
ever, the data indicate a need for continued study of these elements to deter-
mine their metabolic role, identify sensitive indicators, and more fully charac-
terize their specific functions in human health.
ARSENIC, BORON, NICKEL, SILICON, AND
VANADIUM AND THE BODY
Function
Arsenic: There have been no studies performed to determine the nutritional
importance of arsenic for humans. Animal studies suggest a role for arsenic in
the metabolism of methionine, in growth and reproduction, and in gene
expression.
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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS
416
Boron: A collective body of evidence has yet to establish a clear biological func-
tion for boron in humans. Although some evidence does suggest a role in the
metabolism of vitamin D and estrogen, further research is necessary.
Nickel: The possible nutritional importance or biochemical function of nickel
in humans has not been established. Nickel may serve as a cofactor or struc-
tural component of specific metalloenzymes of various functions, including hy-
drolysis and redox reactions and gene expression. Nickel may also serve as a
cofactor facilitating iron absorption or metabolism.
Silicon: A functional role for silicon in humans has not yet been identified,
although animal studies show that silicon may be involved in the formation of
bone.
Vanadium: A functional role for vanadium in humans has not been identified.
There are some reports that vanadium may increase the action of insulin, but
the potential mechanism of action is uncertain. Vanadium also stimulates cell
proliferation and differentiation and inhibits various ATPases, phosphatases,
and phosphoryl-transfer enzymes.
Absorption, Metabolism, Storage, and Excretion
Arsenic: Approximately 90 percent of inorganic arsenic from water is absorbed
by the body; the amount absorbed of dietary arsenic is approximately 60–70
percent. Once absorbed, inorganic arsenic is transported to the liver, where it is
reduced to arsenite and then methylated. Most ingested arsenic is rapidly ex-
creted in the urine.
Boron: With normal intakes, about 90 percent of dietary boron is absorbed.
The mechanism of absorption has not been confirmed, but a passive
(nonmediated) diffusion process is likely. The excretory form of boron has not
been studied.
Nickel: The absorption of dietary nickel is less than 10 percent and is affected
by certain foods, including milk, coffee, tea, orange juice, and ascorbic acid.
Nickel is transported through the blood bound primarily to albumin. Most
organs and tissues do not accumulate nickel, but in humans the thyroid and
adrenal glands have relatively high concentrations. Because of the poor absorp-
tion of nickel, most ingested nickel is excreted in the feces. Absorbed nickel is
excreted in the urine, with minor amounts secreted in the sweat and bile.
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PART III: ARSENIC, BORON, NICKEL, SILICON, AND VANADIUM 417
Silicon: Findings indicating that as much as 50 percent of ingested silicon is
excreted in the urine suggest that some dietary forms of silicon are well ab-
sorbed. Silicon in the blood exists almost entirely as silicic acid and is not bound
to proteins. Most body silicon is found in the various connective tissues includ-
ing the aorta, trachea, bone, tendons, and skin. Excretion is primarily through
the urine.
Vanadium: Less than 5 percent of ingested vanadium is absorbed. Absorbed
vanadate is converted to the vanadyl cation, which can complex with ferritin
and transferrin in plasma and body fluids. Very little absorbed vanadium re-
mains in the body; whatever does remain is found primarily in the liver, kid-
neys, and bone. Because of the low absorption of ingested vanadium, most
excretion occurs through the feces.
DETERMINING DRIS
Determining Requirements
Data were insufficient to estimate EARs, RDAs, or AIs for arsenic, boron, nickel,
silicon, and vanadium.
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 health effects for almost all indi-
viduals. Although members of the general healthy population should be ad-
vised not to routinely exceed the UL, intake above the UL may be appropriate
for investigation within well-controlled clinical trials. The UL is not meant to
apply to individuals receiving any of these elements under medical supervision.
Arsenic: Data were insufficient to set a UL for arsenic. Although a UL was
not determined for arsenic, there is no justification for adding it to food or
supplements.
Although no UL was set for arsenic, there may be a risk of adverse effects
with the consumption of organic arsenic in food or with the intake of inor-
ganic arsenic in water supplies at the current maximum contamination level of
50 mg/L, set in the United States.
Boron: The UL for boron is based on reproductive and developmental effects in
animals as the critical endpoint and represents intake from food, water, and
supplements.
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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS
418
According to data from the Third National Health and Nutrition Examina-
tion Survey (NHANES III, 1988–1994) at the 95th percentile, intake of boron
from the diet and supplements was approximately 2.8 mg/day. Adding to that a
maximum intake from water of 2 mg/day provides a total intake of less then 5
mg/day of boron at this percentile. At the 95th percentile intake, no segment of
the U.S. population had a total (dietary, water, and supplemental) intake greater
than 5 mg/day, according to NHANES III and the Continuing Survey of Food
Intakes by Individuals (CSFII, 1994–1996) data. Those who take body-build-
ing supplements could consume an additional 1.5–20 mg/day. Therefore, this
supplemental intake may exceed the UL of 20 mg/day.
Nickel: The UL for nickel is based on general systemic toxicity (in the form of
decreased body-weight gain reported in rat studies) as the critical endpoint.
Because there were no data on the adverse effects of nickel consumption from a
normal diet, the UL for nickel applies to excess nickel intake as soluble nickel
salts.
Individuals with preexisting nickel hypersensitivity (from previous dermal
exposure) and kidney dysfunction are distinctly susceptible to the adverse ef-
fects of excess nickel intake and may not be protected by the UL set for the
general population.
Based on the Food and Drug Administration’s (FDA’s) Total Diet Study
(1991–1997), 0.5 mg/day was the highest intake at the 99th percentile of nickel
(from food) reported for any life stage and gender group; this was also the
reported intake for pregnant females. Nickel intake from supplements provided
only 9.6–15 mg/day at the 99th percentile for all age and gender groups, accord-
ing to NHANES III. The risk of adverse effects resulting from excess intake of
nickel from food and supplements appears to be very low at the highest intakes
noted above. Increased risks are likely to occur from environmental exposures
or from the consumption of contaminated water.
Silicon: Data were insufficient to set a UL for silicon. Although silicon has not
been shown to cause adverse effects in humans, there is no justification for
adding it to supplements.
Vanadium: The UL for vanadium is based on renal toxicity in animals as the
critical adverse effect. Since the forms of vanadium found in food and supple-
ments are the same, the UL applies to total vanadium intake from food, water,
and supplements. Due to insufficient data, no UL was set for pregnant and
lactating women, children, and infants. Caution should be exercised regarding
the consumption of vanadium supplements by these individuals.
Because of the widespread use of high-dose (60 mg/day) supplemental va-
nadium by athletes and other subgroups (e.g., borderline diabetics) that are
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PART III: ARSENIC, BORON, NICKEL, SILICON, AND VANADIUM 419
considered part of the apparently healthy general population, further research
on vanadium toxicity is needed.
Vanadium in the forms of vanadyl sulfate (100 mg/day) and sodium
metavanadate (125 mg/day) has been used as a supplement for diabetic pa-
tients. Although insulin requirements were decreased in patients with Type I
diabetes, the doses of vanadium used in the supplements were about 100 times
the usual intakes and greatly exceeded the UL for vanadium.
Although percentile data were not available for dietary vanadium intakes
from U.S. surveys, the highest mean intake of vanadium for the U.S. population
was 18 mg/day. The average intake of supplemental vanadium at the 99th per-
centile by adults was 20 mg/day, which is significantly lower than the adult UL.
The risk of adverse effects resulting from excess intake of vanadium from food
is very unlikely. Because of the high doses of vanadium present in some supple-
ments, increased risks are likely to result from excess intake.
DIETARY SOURCES
Foods
Arsenic: Dairy products contribute as much as 31 percent of dietary arsenic;
meat, poultry, fish, grains, and cereal products collectively contribute approxi-
mately 56 percent. Based on a national survey conducted in six Canadian cities
from 1985 to 1988, the foods that contained the highest concentrations of ar-
senic were fish, meat and poultry, bakery goods and cereals, and fats and oils.
Most of the arsenic found in fish is in the organic form. Major contributors of
inorganic arsenic are raw rice, flour, grape juice, and cooked spinach.
Boron: Fruit-based beverages and products, tubers, and legumes have been
found to have the highest concentrations of boron. Other studies have reported
that the top ten foods with the highest concentration of boron were avocado,
peanut butter, peanuts, prune and grape juices, chocolate powder, wine, pe-
cans, and granola-raisin and raisin-bran cereals. When both content and total
food consumption (amount and frequency) were considered, the five major
contributors were found to be coffee, milk, apples, dried beans, and potatoes,
which collectively accounted for 27 percent of the dietary boron consumption.
Coffee and milk are generally low in boron, but they tend to be high dietary
contributors because of the volume at which they are consumed.
Nickel: Nuts and legumes have the highest concentrations of nickel, followed
by sweeteners, including chocolate powder and chocolate candy. Major con-
tributors to nickel intake are mixed dishes and soups (19–30 percent), grains
and grain products (12–30 percent), vegetables (10–24 percent), legumes (3–
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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS
420
16 percent), and desserts (4–18 percent). Major contributors of nickel to the
Canadian diet include meat and poultry (37 percent), bakery goods and cereals
(19 percent), soups (15 percent), and vegetables (11 percent). Cooking acidic
foods in stainless-steel cookware can increase the nickel content of these foods.
Silicon: Plant-based foods contain higher concentrations of silicon than do
animal-based foods. Beer, coffee, and water appear to be the major contributors
of silicon to the diet, followed by grains and vegetables. Silicate additives that
have been increasingly used as antifoaming and anticaking agents in foods can
raise the silicon content of foods, but the bioavailability of these additives
is low.
Vanadium: Foods rich in vanadium include mushrooms, shellfish, black pep-
per, parsley, dill seed, and certain prepared foods. Processed foods contain more
vanadium than unprocessed foods. Beer and wine may also contribute appre-
ciable amounts to the diet. The Total Diet Study showed grains and grain prod-
ucts contributed 13–30 percent of the vanadium in adult diets; beverages, which
contributed 26–57 percent, were an important source for adults and elderly
men. Canned apple juice and cereals have been shown to be major contributors
to vanadium intake in infants and toddlers.
Dietary Supplements
Arsenic: This information was not provided at the time the DRI values for this
nutrient were set.
Boron: In NHANES III, the adult median intake of boron from supplements
was approximately 0.14 mg/day.
Nickel: In NHANES III, the adult median intake of nickel from supplements
was approximately 5 µg/day.
Silicon: In NHANES III, the adult median intake of silicon from supplements
was approximately 2 mg/day.
Vanadium: In NHANES III, the adult median intake of vanadium from supple-
ments was approximately 9 µg/day.
Bioavailablility
This information was not provided at the time the DRI values for these nutri-
ents were set.
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PART III: ARSENIC, BORON, NICKEL, SILICON, AND VANADIUM 421
INADEQUATE INTAKE AND DEFICIENCY
This information was not provided at the time the DRI values for these nutri-
ents were set.
EXCESS INTAKE
Arsenic: Arsenic occurs in both inorganic and organic forms, with the inor-
ganic forms that contain trivalent arsenite (III) or pentavalent arsenate (V) hav-
ing the greatest toxicological significance. No data were found on the possible
adverse effects, including cancer, of organic arsenic compounds from food. Be-
cause organic forms of arsenic are less toxic than inorganic forms, any increased
health risks from the intake of organic arsenic from food is unlikely.
In contrast, inorganic arsenic is an established human poison, and acute
adverse effects such as anemia and hepatotoxicity can occur in doses of 1 mg/
kg/day or greater. The ingestion of acute doses greater than 10 mg/kg/day leads
to encephalopathy and gastrointestinal symptoms. Chronic intake of 10 mg /kg/
day or greater of inorganic arsenic produces arsenicism, a condition character-
ized by keratosis and the alteration of skin pigmentation. Intermediate and
chronic exposures of arsenic up to levels of 11 mg/L of water are associated
with symmetrical peripheral neuropathy.
The ingestion of inorganic arsenic is also associated with the risk of skin,
bladder, and lung cancers. Most studies indicating a positive association with
cancer involved intakes of inorganic arsenic from drinking water, as reported in
areas of Taiwan, Japan, Argentina, and Chile. Studies of U.S. populations ex-
posed to arsenic in drinking water have not identified cancer increases. Occu-
pational exposure to inorganic forms of arsenic, in environments such as smelt-
ers and chemical plants, occurs primarily by inhalation (where the predominate
form is arsenic trioxide dust).
Boron: No data were available on adverse health effects from ingestion of large
amounts of boron from food and water. However, animal data suggest that re-
productive and developmental effects may occur.
Nickel: There is no evidence in humans of adverse effects associated with expo-
sure to nickel through a normal diet. The acute effects of ingesting large doses
of soluble nickel salts include nausea, abdominal pain, diarrhea, vomiting, and
shortness of breath. In animal studies, the signs and symptoms of general sys-
temic toxicity include lethargy, ataxia, irregular breathing, hypothermia, and
salivation, as well as decreased body-weight gain and impaired reproduction.
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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS
422
Silicon: There is no evidence that naturally occurring silicon in food and water
produces adverse health effects. Limited reports indicate that magnesium
trisilicate (6.5 mg of elemental silicon per tablet) used as an antacid in large
amounts for long periods (i.e., several years) may be associated with the devel-
opment of silicon-containing kidney stones.
Vanadium: There is no evidence of adverse effects associated with vanadium
intake from food, which is the major source of exposure for the general popula-
tion; no special subpopulations are distinctly susceptible. In animal studies,
renal toxicity has occurred. Most vanadium toxicity reports involve industrial
exposure to high levels of airborne vanadium. Vanadyl sulfate supplements are
used by some weight-training athletes to increase performance; in addition,
vanadium supplements have been studied for the treatment of diabetes. For
these reasons, further research on vanadium toxicity is necessary.
KEY POINTS FOR ARSENIC, BORON,
NICKEL, SILICON, AND VANADIUM
Data were insufficient to set EARs, RDAs, or AIs for arsenic,
3
boron, nickel, silicon, and vanadium.
There were insufficient data to set ULs for arsenic and silicon.
3
However, ULs based on animal data were set for boron, nickel,
and vanadium.
Although a UL was not determined for arsenic, there is no
3
justification for adding it to food or supplements.
Although silicon has not been shown to cause adverse effects
3
in humans, there is no justification for adding it to supplements.
Observations of deficiency effects (e.g., on growth and
3
development) in multiple animal species and data from limited
human studies suggest that there are beneficial roles for
arsenic, boron, nickel, silicon, and vanadium in human health.
However, the data indicate a need for continued study of these
elements to determine their metabolic role, identify sensitive
indicators, and more fully characterize their specific functions
in human health.
