Download Dietary Reference Intakes for Bone Metabolism Related Nutrients

Review of the Dietary Reference Intake for Calcium: Where
Do We Go From Here?
Susan Meacham1, Darlene Grayscott2, Jau-Jiin Chen3, Christine Bergman4
Susan Meacham1 and Christine Bergman4 are Associate Professors in the School of Life
Sciences1 and the Department of Food and Beverage Management, Jau-Jiin Chen3 is an Assistant
Professor in the Department of Nutrition Sciences, and Darlene Grayscott2 is a Master’s degree
candidate in the Department of Health Promotion, all at the University of Nevada Las Vegas.
Address correspondence to: Susan L. Meacham, Ph.D., R.D., 4505 Maryland Parkway, Box
454004, Las Vegas, NV 89154-4004, phone 702-895-1169, fax 702-895-2616, email
[email protected]
Abstract
In this article the science relied on to establish the Dietary Reference Intakes (DRI)
specifically for calcium was examined. The latest dietary recommendations for the essential
nutrients significant with respect to their roles in bone metabolism and health were reported in
the Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride
(1997)1. For calcium an adequate intake was recommended because insufficient data were
available at the time to determine specific Recommended Dietary Allowances (RDA). Dietary
intake data and the controversies regarding the role calcium may play in other chronic diseases
have also been discussed. Advances and continued dilemmas regarding these topics reported
since the publication of the DRI were also addressed in this review. A recent Dietary Reference
Intake Research Synthesis Workshop report identified an extensive range of suggested future
research directions needed to improve our understanding of calcium and bone and health.
Key words not in title: Recommended Dietary Allowances, Adequate Intakes, Tolerable Upper
Intake Levels, and Bone Nutrients
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Introduction
Dietary Reference Intakes
The daily dietary intake recommendations reported in the Dietary Reference Intakes for
Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride 1 were values calculated with the
goal of maintaining health and avoiding potential risks from nutrient toxicity. A panel of
scientists and nutrition experts from the United States and Canada developed the dietary
recommendations for calcium, along with other essential nutrients, based on analysis of the
currently available scientific literature. The latest revisions of the Dietary Reference Intakes
(DRI) expand upon and replace the 10th edition (1989) of the United States Recommended
Dietary Allowances (RDA) that the National Academy of Sciences first established in 1941.
Canada also used this latest DRI report to update their Recommended Nutrient Intakes (RNI).
DRI reference categories defined in Figure 1 are now used for diet evaluation and planning.
The science-based evidence used to establish the DRIs for calcium, as well as the other
bone related nutrients, examined the role of these nutrients in the development and maintenance
of bones and teeth. At the time some consideration was also given to the data describing the
potential biological role of these nutrients in the prevention of other chronic diseases. But
relatively little emphasis was given to these data since the Food and Nutrition Board (FNB) were
unable to develop conclusions that could be agreed upon. This was not surprising since chronic
disease is known to result from complex interactions among genetic, dietary, and other
environmental factors. This review on dietary calcium requirements includes brief comments
regarding what has been learned about this essential nutrient since the FNB report was published.
Since Adequate Intakes (AI) and not Recommended Dietary Allowances were set for
calcium in 1997 it is time to revisit, ten years later, the controversies that surrounded the original
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“second” tier recommendation for calcium. What science based evidence is needed? What have
we learned since making our last recommendation? Also, considering the economic, marketing,
pharmacological and educational effort invested in calcium there are many entities that have a
“stake” in knowing which way a committee might go with the next revisions? Up? Down? Or
stay the same? Potential changes may impact many, including school lunch budgets, menus,
hospital menus, and educational materials.
Calcium Overview
Calcium, the most abundant element in the body, makes up only 1 to 2 percent of total
body weight, yet more than 99% of it is found in teeth and bones. Calcium in hard tissue is
primarily in the form of hydroxyapatite. The remainder is found in the blood, extracellular fluid,
muscle, and other tissues critical to the functioning in vascular contraction and vasodilation,
muscle contraction, nerve transmission, and glandular secretion. With the help of 1, 25dihydroxyvitamin D, calcium is absorbed by active transport and can be absorbed by passive
diffusion when calcium intakes are high. Calcium absorption, known to vary inversely with
intake, is still insufficient in meeting body requirements when calcium is low2. Calcium
absorption varies throughout the lifespan, highest in infancy3 and then declining with advancing
age4. Some dietary factors hypothesized to play a role in calcium absorption rates include:
prebiotic oligosaccharides, dietary fiber, phytate, oxalate, lactose, phosvitin peptides, and other
dietary minerals5,6,7,8. Determining the actual effects of these compounds on calcium
bioavailability will continue to be an arduous task considering some are proposed to act as
absorption enhancers and some as inhibitors, and some may interact with others.
Calcium and Disease
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Chronic calcium deficiency due to poor dietary intake or absorption is considered by
many to be a contributing factor in the loss of bone mass and development of osteoporosis9.
Peak bone mass occurs somewhere between the ages of 19 and 30 years. At this point, growth of
the long bones has ceased but bone remodeling continues throughout life. This remodeling
necessitates that an adequate calcium intake occurs throughout the life cycle to meet the needs of
bone, a dynamic tissue. At the time the committee met this need was well established; however,
what an adequate intake of calcium was throughout the stages of the lifecycle was not as firmly
supported by the research literature.
Calcium and Bone Mineral Density
The DRI for calcium was primarily influenced by the belief that adequate calcium intake
promotes high bone mineral density (BMD) and thus reduces risk of osteoporotic fracture.
Recent studies have raised questions about the appropriateness of using the DRI for calcium to
prevent osteoporosis the biomarker, the endpoint assessment, for all populations. This is due to
reports that some populations have very low calcium intakes, low BMD and low rates of fracture
risk10, 11. Also, the association between low BMD and increased risk of osteoporotic fracture was
reportedly not as strong across the general population as it was within ethnic groups12. That
means that BMD was correlated with fracture risk within an ethnic group, but when several
ethnic groups were analyzed together this correlation was not as strong. For example, black
women in the U.S. had a lower fracture risk than white women at every level of BMD and this
population was also reported to have a lower calcium intake11. Some of the lowest intakes of
calcium and the lowest incidence of hip fracture have been estimated to be in China and India11.
Prentice13 suggests some of the confusion in this area may be due to the inappropriate use of
BMD to define osteoporosis risk in a world-wide context rather than using fragility fracture as
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the disease endpoint. Others have written that the ability to sustain bone health with lower
calcium intakes was due to genetic differences, increased levels of exercise, greater soy
consumption, differences in bone architecture and their interaction14, 15, 16. Whatever the reasons
for these reported differences the DRI committee and many medical related organizations
currently recommend that all populations, no matter their ethnic or racial background, intake
more calcium than they are currently17. However, significant barriers exist which prevent the
achievement of this dietary recommendation for many people; education, lactose intolerance and
limited financial resources to name just a few.
Calcium and Hypertension
The relationship between calcium and hypertension has been examined to a lesser extent
than the impact of calcium on bone health. One review of 22 intervention trials reported that
calcium supplementation moderately decreased systolic blood pressure and had no significant
effect on diastolic blood pressure in hypertensive adults. There appeared to be no effect of
calcium on blood pressure in normotensive individuals18. The Dietary Approaches to Stop
Hypertension (DASH) trials reported a lowering of blood pressure through dietary modification.
The DASH diet, compared to the average Western intake, emphasized fruits, vegetables, and
low-fat dairy foods, included whole grains, poultry, fish, and nuts, and was reduced in fats, red
meat, sweets, and sugar-containing beverages19,20. Moore et al.21 found a greater lowering of
blood pressure using the DASH diet as compared to a control and a diet high in fruits and
vegetables. This trial suggested that increasing calcium intake from the low levels found in the
average western diet to those levels suggested by the current AI may help to reduce blood
pressure in those that are hypertensive. Lin et al. also reported that the DASH diet improved
markers of bone health in adults no matter their age, sex, race or blood pressure status.
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However, this hypothesis needs testing since levels of many other dietary components besides
calcium are different in the DASH diet22. The DASH diet is quite different from the typical
Westerner’s food intake: specifically, it is lower in total fat, saturated fat, and cholesterol, and
higher in potassium, calcium, magnesium, dietary fiber, protein and many other phytochemicals.
Calcium and Colon Cancer
The influence of dietary calcium on colon cancer risk was not clear at the time of the DRI
publication. Data was inconsistent regarding tumor growth with calcium supplementation.
Clinical trials examining the effects of calcium intake or additional calcium supplementation on
the risk of colon cancer were unavailable. Since then studies have used an array of calcium
supplements that contribute 1.2 to 2.0 g of elemental calcium daily, however, no dose response
data is available at this time. Multiple controlled research trials have found calcium
supplementation to reduce the risk of adenoma recurrence which is considered to be a precursor
to colorectal cancer23, 24. The effect of calcium supplementation was proposed to aid in
preventing the reoccurrence of adenoma in one of two ways; by binding with bile and fatty acids
in the colon or by reducing the growth of colon epithelial cells25. Research to date thus indicates
that calcium supplementation may be of benefit to people with a previous history of
adenomatous polyps, but a link with actual prevention of colorectal cancer has not been
established26.
Calcium Recommendations
For most men and women in Canada and the US the daily recommendation for calcium
intake, the AI, was determined to be 1,000 mg per day, an intake level achievable through a well
planned diet (Tables 1 and 2). The ideal method for determining dietary calcium
recommendations for the public would be to find calcium intakes associated with the fewest
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osteoporotic fractures, but well designed, large-scale, long term studies are not yet able to
provide this information. The methodologies employed to date to determine calcium
requirements were based on measurements of calcium retention from balance studies, factorial
estimates of requirements, and more limited data on bone mass or bone mineral content changes.
The DRI panel concluded that there was insufficient data to determine an EAR and therefore
calculated an AI for calcium. The AI for calcium represents an approximation of the intake that
appears to be sufficient to maintain adequate calcium status for various life-stage and gender
populations. AIs were set as opposed to RDAs due to uncertainties in balance methodology, lack
of agreement with observational and experimental data regarding intake, and lack of longitudinal
data on calcium intake, calcium retention, and long-term bone loss and the interdependence
assumed between these factors. For most adult life-stage groups, the current DRI is higher than
previous recommendations; however, for infants and children through the age of three years the
new AI is actually lower than the previous RDA1, 27.
Although calcium is essential in the diet, a tolerable upper intake level was set by the
committee (Table 1). For most individuals intake of calcium exceeding 2,500 mg a day is
difficult to achieve, unless dietary supplements are being consumed. Though there is concern
that very high intakes of calcium may cause nephrolithiasis, i.e., kidney stones, well-controlled
clinical studies supporting this causal relationship in healthy individuals were not convincing
when the AI and UL for calcium intake were established1. Epidemiological studies and a feeding
trial have suggested that age, race and sex may influence this relationship28, 29, 30. Specifically,
calcium supplementation usage has been reported to not be associated with increased risk of
kidney stones in a twin study31.
Factors Affecting Calcium Requirement
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There is sufficient evidence to support the role of exercise in increasing bone mass
throughout adolescence and early adulthood and at least preventing bone loss in post-menopausal
women32, 33. Likewise, the lack of exercise, as seen in lengthy immobilization or exposure to an
antigravity environment, has resulted in bone mass loss despite what was considered to be an
adequate calcium intake. At the time the FNB set the AI there was insufficient evidence to
suggest that physically active individuals have different calcium requirements than more
sedentary persons. Studies since the committee met indicated that both very short- and longterm immobilization resulted in increased bone resorption and decreased bone formation even
with adequate or elevated calcium intakes34, 35, 36.
Some have hypothesized that greater activity levels result in an adaptation to lower
intakes of calcium37. If found to be true this may help explain why women in Asia have lower
calcium intakes than their counterparts in the United States and Europe, but lower risk of bone
fracture10, 38. Murphy and Carroll39 reviewed the literature on the effect of physical activity and
calcium intake and found evidence, though limited, that these two lifestyle factors may act
synergistically on bone health. Additional research is needed to examine this hypothesis.
Additional dietary factors may also influence calcium adequacy and ultimately bone
health. High sodium intakes have been reported to result in an increased calcium loss through
the urine40, presumed to affect calcium in bone over an extended period of time. Similarly,
protein increased the urinary loss of calcium, and, conversely, low or poor protein intakes were
associated with reduced recovery from osteoporotic hip fractures41. Currently, there is no
evidence to suggest making separate calcium recommendations based on dietary sodium, protein
or any other nutrient intakes13, 42.
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Caffeine has been reported to have a modest effect on calcium excretion; however, the
Institute of Medicine1 did not make a specific recommendation for calcium intake in relationship
to coffee and tea consumption. The FNB thought that any perturbation in calcium intake with
caffeine consumption could be compensated for by additional dietary calcium. A recent review
of this topic by Nawrot et al.43 suggested that 1 to 2 cups of coffee a day (< 400 mg of caffeine)
do not significantly affect bone status or calcium balance as long as they are consuming at least
800 mg calcium a day. Since many U.S. and Canadian females ingest less than this amount of
calcium from their daily diets this interaction is likely to receive continued review.
Women with low levels of estrogen often have altered calcium metabolism. For
example, amenorrheic women (women without menstrual cycles) had reduced absorption,
increased excretion, and lower bone mass when compared to eumenorrheic, or normally cycling
women44. These effects on calcium balance have frequently been demonstrated in
postmenopausal women also. The accelerated bone loss that occurred during menopause was not
solely due to insufficient dietary calcium. Estrogen loss appeared to reduce the efficiency of
calcium absorption. Likewise, evidence suggested that increasing calcium intake during this
period did not necessarily prevent bone loss that occurred with menopause1.
Another subpopulation reviewed with regard to calcium nutriture was vegans. A recent
literature review concluded that lacto-ovo vegetarians have normal bone mass45. Studies
evaluating bone mass and calcium consumption in vegans compared to their meat-eating
counterparts are still lacking. Additionally, the actual risk of osteoporosis in the various types of
vegetarians needs study.
Dietary Intake and Sources of Calcium
10
When usual calcium consumption patterns were analyzed most groups consumed less
than the recommended AI of 1000-1200 mg/day for adults and intakes tended to decline with
advancing age. The richest sources of calcium come from milk and dairy products. Many plant
foods are good sources of calcium but contain oxalic acid or phytic acid which interferes with
calcium absorption (Table 2). Since it is often difficult for some individuals to get the AI for
calcium from foods, supplementation may be beneficial. Supplement solubility is not as
important as tablet disintegration. It appeared that calcium absorption from tablets providing
calcium citrate, malate, carbonate, and tricalcium phosphate were similar to that of milk.
However, the relationship of solubility to absorbability was weak46. The absorption from
supplements seemed to be greatest in doses of 500 mg or less47. Since the committee reviewed
this area mounting evidence has been published suggesting that intake of fermented vegetables,
prebiotics (e.g., inulin), and probiotics increases the bioavailability of calcium from plant sources
and thus recommendations may someday advocate greater consumption of such foods5.
Research Recommendations
The research recommendations for calcium reported in the 1997 DRI report stated a need for
more definitive data on the effect of calcium intake on mineral metabolism and peak bone mass,
genetics and calcium intake interactions, the status of adult calcium intakes and skeletal, and
nonskeletal, end point assessments, such as blood pressure, cancer risk, and diabetes, and the
impact of calcium intake on the risk of developing kidney stones and recurrent stone
development1.
These research recommendations suggested continuing to use balance studies, but urged
the use of tracers to estimate changes in calcium balance through defined markers such as
fractional absorption, bone calcium content and turnover rates. The adaptation to changes in
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calcium intakes should be followed both short term and long term studies with comprehensive
evaluation of biochemical measures of bone mineral content and metabolism. The influence of
genetic and ethnic factors on bone needs to be studied in relation to such factors as varying
dietary intakes, physical activity, and hormonal changes. The committee also acknowledged
interactions between calcium and other minerals, as well as the likelihood that calcium intake
may exert influence over other nutritional risk factors, i.e. fat intake. Likewise, calcium excesses
may exacerbate these relationships or, increase the likelihood of unhealthy imbalances. A recent
workshop offered an opportunity for experts to review the DRI for calcium and the related bone
nutrients and the research published during that ten year period. They defined a new research
agenda needed to refine our dietary recommendations for calcium48. They supported the
continuing need for research emphasizing science based data on calcium and calcium’s
interactions with other nutrients and the cumulative effects on bone health and other indicators of
optimal health. Thus, better methodologies need to be developed for studying nutrients
impacting calcium nutriture throughout the life cycle. For example, improved methods for
determining and standardizing concentrations of vitamin D are needed to improve food
composition data for vitamin D. Also, improving our understanding of the impact of low
phosphorus intakes on calcium metabolism, particularly in the elderly, is needed and the effect of
increasing calcium through supplementation on the bioavailability of phosphorus is unknown.
Likewise, our understanding of the effect of phosphorus intakes on the effectiveness of anabolic
agents used in the treatment of osteoporosis will need to be studied. These advances will provide
more information regarding the role of calcium and related nutrients on other affected disease
states as well48.
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Yet, a few fundamental questions still remain. As stated by Dr. Catherine Woteki at the recent
workshop, we still may not know if the DRI paradigm, intended to improve the effectiveness of
conveying nutrient intake adequacy to the US and Canadian populations, is the “right one"?
Others attending the recent workshop asked if the rapid move to genomics will impact nutrient
recommendations when we identify drastic changes in individuals’ nutrient metabolism or
requirement. Also, questioned was the accuracy of the current use of extrapolation when
adjusting calcium intakes for development in the young? And, are there new noninvasive
methods yet to be developed that will improve our understanding of how to establish calcium
recommendations for future populations? These questions and more have been made available
to researchers as potential areas of study through an electronic database48.
Conclusion
This review focused on the research supporting the DRI for calcium, a bone-health associated
essential nutrient, along with a discussion of recent related findings. The DRI panel concluded
that there was insufficient data at that time to determine an EAR and therefore calculate an RDA
for calcium. The AI established for calcium represented an approximation of the intake that
appears to be sufficient to maintain calcium nutriture. The discussion of recent related findings
reflects the expanding research taking the prior focus on amounts needed to eliminate deficiency
diseases forward to include the amount required to minimize the onset and impact of chronic
diseases. For calcium, establishment of specific optimal intakes may become increasingly harder
to define. Some of this difficulty will likely come from our expanding knowledge of the role
nonnutritive compounds play in preventing chronic diseases such as osteoporosis and the
synergistic actions between essential nutrients (such as calcium), and nonessential nutrients (such
as soy isoflavones). Bone health involves not just calcium but many other nutrients and
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hormones to work in concert. A balanced and healthy diet like DASH has shown improvements
in markers of bone health in adults regardless of other factors. Determining the individual and
synergistic activity of and between these essential nutrients and nonessential compounds in
maintaining bone health will be a great challenge. In addition we are becoming increasingly
aware that differences between individual’s genetic make-up impacts the effect of essential and
nonessential dietary compounds on health. Therefore, by the time the DRIs for bone-related
nutrients are revisited the FNB task will likely be even more difficult than that which the
previous panel faced.
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44. Abrams, S. A., Silber, T. J., Esteban, N. V., Vieira, N. E., Stuff, J. E., Meyers, R., Majd,
M., and Yergey, A. L. (1993). Mineral balance and bone turnover in adolescents with
anorexia nervosa. J. Pediatr., 123:326-331.
45. New, S. A. (2004). Do vegetarians have a normal bone mass? Osteo. Internat., 15(9):679688.
46. Heaney, R. P., Recker, R. R., and Weaver, C. M. (1990). Absorbability of calcium
sources: The limited role of solubility. Calcif. Tissue Int., 46(5):300-304.
47. Heaney, R. P., Recker, R. R., and Hinders, S. M. (1988). Variability of calcium
absorption. Am. J. Clin. Nutr., 47(2):262-264.
48. Food and Nutrition Board, Carol West Suitor, Linda D. Meyers, Rapporteurs. (2006)
Dietary Reference Intakes Research Synthesis: Workshop Summary. Institute of
Medicine of the National Academies, Washington, D.C. http://fermat.nap.edu/
books/0309103223/html/R1.html. Accessed November 12, 2006.
49. U.S. Department of Agriculture, Agricultural Research Service. (2006). USDA National
Nutrient Database for Standard Reference, Release 19. Nutrient Data Laboratory Home
Page, http://www.ars.usda.gov/main/site_main.htm. ?modecode=12354500. Accessed
November 12, 2006.
20
∗
Estimated Average Requirement (EAR) – is the average daily intake value for a particular
nutrient for a given life stage and gender group. It is estimated to satisfy the nutrient intakes
of approximately 50% of the persons in that particular life stage and gender group.
∗
Recommended Dietary Allowance (RDA) – The average daily intake level has not changed
in definition from previous years. It is the intake level of a specific nutrient that will provide
approximately all (97 to 98%) of the persons in a life stage and gender group with sufficient
daily quantities to meet body needs.
∗
Adequate Intake (AI) – When data are not available to determine a specific EAR, needed to
determine the RDA, the AI is set as the average amount of a nutrient expected to be sufficient
to maintain health.
∗
Tolerable Upper Intake Level (UL) – To avoid nutrient toxicities, the highest amount of a
nutrient that can be expected to be ingested safely, daily and not cause health risks or adverse
reactions to almost all individuals in the general population is known as the UL.
Figure 1. Dietary Reference Intakes Reference Categories. Dietary intake recommendation
categories developed for the purpose of setting estimated average intakes, recommended intakes,
adequate intakes, tolerable upper limits for various populations on the basis of age, gender and
physiological state in the United States and Canada1.
21
Table 1. Dietary Reference Intakes (DRI) for Calcium, Adequate Intakes (AI) and Tolerable
Upper Levels (UL) for U.S. and Canadian Populations by Life stage and Gender.
DRI Life stage
AI mg/d UL mg/d
Infant
0-6 mo 210
NE*
7-12 mo 270
NE
Children
1-3 y
500
2500
4-8 y
800
2500
Boys
9-13 y
1300
2500
14-18 y 1300
2500
Girls
9-13 y
1300
2500
14-18 y 1300
2500
Men
19-30 y 1000
2500
Women
19-30 y 1000
2500
Men
31-50 y 1000
2500
Women
31-50
1000
2500
Men
51-70 y 1200
2500
Women
51-70 y 1200
2500
Men
>70 y
1200
2500
Women
>70 y
1200
2500
Pregnancy 14-18 y 1300
2500
19-30 y 1000
2500
31-50 y 1000
2500
Lactation 14-18 y 1300
2500
19-30 y 1000
2500
31-50 y 1000
2500
*NE = Not established
1
Food and Nutrition Board. (1997). Standing Committee on the Scientific Evaluation of Dietary
Reference Intake, Institute of Medicine, Dietary Reference Intakes for Calcium, Phosphorus,
Magnesium, Vitamin D, and Fluoride. Washington D.C.: National Academy Press.
22
Table 2. Calcium Content of Selected Foods Commonly Consumed in the U.S. in Common
Serving Sizes.
NDB No. Description
Measure Calcium (mg)
08077
Cereals, ready-to-eat, GENERAL MILLS, Whole Grain ¾ cup
1104
TOTAL
01111
Milk shakes, thick vanilla
11 fl oz
457
11164
Collards, frozen, chopped, cooked, boiled, drained,
1 cup
357
without salt
01085
Milk, nonfat, fluid, with added vitamin A (fat free or
1 cup
306
skim)
01077
Milk, whole, 3.25% milkfat
1cup
276
01036
Cheese, ricotta, whole milk
1 cup
509
11458
Spinach, cooked, boiled, drained, without salt
1 cup
245
01009
Cheese, cheddar
1 oz
204
16126
Tofu, firm, prepared with calcium sulfate and
¼ block
163
magnesium chloride (nigari)
20046
Rice, white, long-grain, parboiled, enriched, dry
1 cup
102
16120
Soy milk, fluid
1 cup
93
16043
Beans, pinto, mature seeds, cooked, boiled, without salt 1 cup
79
U.S. Department of Agriculture, Agricultural Research Service. 2006. USDA National Nutrient
Database for Standard Reference, Release 18. Nutrient Data Laboratory
http://www.nal.usda.gov/fnic/foodcomp/Data/SR18/nutrlist/sr18w301.pdf49, access as of Nov 10,
2006.
23