Fractional Zinc Absorption for Men, Women, and Adolescents Is Overestimated in the Current Dietary Reference Intakes 1,2

Transcription

1 The Journal of Nutrition Methodology and Mathematical Modeling Fractional Zinc Absorption for,, and Adolescents Is Overestimated in the Current Dietary Reference Intakes 1,2 Seth M Armah* Department of Nutrition Science, Purdue University, West Lafayette, IN Abstract Background: The fractional zinc absorption values used in the current Dietary Reference Intakes (DRIs) for zinc were based on data from published studies. However, the inhibitory effect of phytate was underestimated because of the low phytate content of the diets in the studies used. Objective: The objective of this study was to estimate the fractional absorption of dietary zinc from the US diet by using 2 published algorithms. Methods: Nutrient intake data were obtained from the NHANES and the corresponding Food Patterns Equivalents Database. Data were analyzed with the use of R software by taking into account the complex survey design. The International Zinc Nutrition Consultative Group (IZiNCG; Brown et al. Food Nutr Bull 2004;25:S99 203) and Miller et al. (Br J Nutr 2013;109: ) models were used to estimate zinc absorption. Results: Geometric means (95% CIs) of zinc absorption for all subjects were 30.1% (29.9%, 30.2%) or 31.3% (30.9%, 31.6%) with the use of the IZiNCG model and Miller et al. model, respectively. For men, women, and adolescents, absorption values obtained in this study with the use of the 2 models were 27.2%, 31.4%, and 30.1%, respectively, for the IZiNCG model and 28.0%, 33.0%, and 31.6%, respectively, for the Miller et al. model, compared with the 41%, 48%, and 40%, respectively, used in the current DRIs. For preadolescents, estimated absorption values (31.1% and 32.8% for the IZiNCG model and Miller et al. model, respectively) compare well with the conservative estimate of 30% used in the DRIs. When the new estimates of zinc absorption were applied to the current DRI values for men and women, the results suggest that the Estimated Average Requirement (EAR) and RDA for these groups need to be increased by nearly one-half of the current values in order to meet their requirements for absorbed zinc. Conclusions: These data suggest that zinc absorption is overestimated for men, women, and adolescents in the current DRI. Upward adjustments of the DRI for these groups are recommended. J Nutr 2016;146: Keywords: zinc, absorption, phytate, Dietary Reference Intakes, US diet Introduction Zinc is an essential micronutrient in human nutrition that is needed as a catalyst for several enzymes and also as a structural component of many proteins, and is necessary for normal growth and development (1). Absorption of zinc from the diet is affected mainly by dietary zinc and phytate. Other dietary factors that can possibly influence zinc absorption include animal protein, calcium, and iron intake, although for some of these nutrients results are mixed (2 4). Phytate is found in a high amount in grains, legumes, nuts, and oil seeds, and serves as the main storage form of phosphorus (5). Apart from the absorption of zinc, phytate also inhibits the absorption of minerals such as iron 1 The author reported no funding received for this study. 2 Author disclosures: SM Armah, no conflicts of interest. *To whom correspondence should be addressed. sarmah@purdue.edu. and calcium by binding to these minerals with the use of the negatively charged phosphorus group in the phytic acid structure and forming insoluble complexes that cannot be absorbed at the intestinal ph (5, 6). Particularly for zinc, the phytate-to-zinc (PZ) 3 molar ratio in a diet is known to affect the percentage of zinc absorbed. The WHO classifies dietary zinc bioavailability as high (50%), moderate (30%), or low (15%) based on a PZ molar ratio of <5, 5 15, and >15, respectively (7). The International Zinc Nutrition Consultative Group (IZiNCG) estimated zinc bioavailability 3 Abbreviations used: AR, Average Requirement; EAR, Estimated Average Requirement; EFSA, European Food Safety Authority; FPED, Food Patterns Equivalents Database; IOM, Institute of Medicine; IZiNCG, International Zinc Nutrition Consultative Group; PRI, Population Reference Intake; PZ, phytate-to-zinc; WWEA, What We Eat in America. ã 2016 American Society for Nutrition Manuscript received October 13, Initial review completed December 3, Revision accepted March 15, First published online May 4, 2016; doi: /jn

2 to be 26% in men and 34% in women for diets containing a PZ molar ratio of 4 15 and 18% in men and 25% in women for diets containing a PZ molar ratio >18 (8). In the United States, the current Estimated Average Requirement (EAR) for zinc set by the Institute of Medicine (IOM) used a fractional zinc absorption value of 30% for preadolescent children based on data from 2 published studies (9 11). In men and women aged $19 y, fractional absorption values were 41% and 48%, respectively, based on data from multiple studies on dietary zinc absorption (11 18). For adolescents (14- to 18-y-old males and females) a value similar to that for men (40%) was used. However, for many of the studies used to determine the relation between dietary zinc intake and absorption in men and women, the tested diets, including semipurified diets, were very low in phytate. Assuming that the average adult in the United States consumes nearly 750 mg phytate/d (19), it is very likely that the inhibitory effect of phytate was underestimated in the current DRI (3). The consequence is an overestimation of zinc absorption and concomitant underestimation of the DRI. When Hunt et al. (12) measured zinc absorption from the typical US diet consumed by 14 men and 14 women aged y, they found that women and men absorbed 29% and 22% of zinc, respectively, from the diet. Turnlund et al. (15) showed that zinc absorption from a diet containing 2.34 g phytate was 17.5% compared with 34% from a semipurified diet. Considering the important role of phytate on zinc absorption, there is a need to re-evaluate the current recommendations for zinc intake, taking into account the inhibitory effect of phytate on fractional zinc absorption. The objective of this study was to estimate the absorption of dietary zinc from the US diet by using nationally representative data from the NHANES (20) and 2 algorithms published by the IZiNCG (8) and Miller et al. (21). Methods Data were analyzed with the use of R software version (22). Day 1 total nutrient intake data from the NHANES survey cycle (20) and the corresponding Food Patterns Equivalents Database (FPED) data (23) were used in this analysis. Because the NHANES data do not include estimates of phytate intake and phytate content of foods, phytate intake was estimated with the use of the published values of phytate content of foods and food groups reported by the IZiNCG (8) and the FPED data for the survey cycle of the What We Eat in America (WWEA) survey (23, 24). The FPED provides information on how many ounce- or cup-equivalents of different food groups are present in each food consumed as reported in the WWEA survey. To calculate phytate intake, phytate contents were assigned to various food groups (dark green vegetables, potatoes, other starchy vegetables, beans and peas, whole grains, refined grains, soy products, and nuts and seeds) in the FPED data based on the IZiNCG values (8). The FPED file, fped_dr1iff_0910.sas7bdat, includes the amount of each of the food groups in individual foods reported by each respondent on day 1 of the WWEA survey. It was therefore possible to estimate how much phytate was consumed from each food reported by participants based on the amount of the different food groups present in that food. The daily phytate intake for each subject was estimated as the sum of phytate intake from all foods consumed in the day by the subject. Estimating zinc absorption with the use of the IZINCG model (8) required the PZ molar ratio, which was estimated as follows: PZ ¼ ½phytateðmg=dÞ=660Š=½zincðmg=dÞ=65:4Š ð1þ The following equations were then used to estimate zinc absorption. LogitðFAZÞ ¼ 1:136520:61293lnðmg zincþ20:31643lnðpzþ ð2þ where FAZ is fraction of absorbed zinc and PZ is the phytate:zinc molar ratio. The FAZ was then estimated as follows: FAZð%Þ 5 fexp½logitðfazþš 3 100g=f1 1 exp½logitðfazþšg To estimate the zinc absorption with the use of the Miller et al. model (21), the intake of phytate, zinc, and calcium were expressed in mmol/d, whereas protein intake was expressed in g/d, as follows: TDP ¼ phytateðmg=dþ=660 ð4þ TDC ¼ calciumðmg=dþ=40 TDZ ¼ zincðmg=dþ=65:4 TDPr ¼ proteinðg=dþ where TDP is total daily phytate, TDC is total daily calcium, TDZ is total daily zinc, and TDPr is total daily protein. Total absorbed zinc (TAZ) was then estimated with the use of the following equation (21): " TDP ð1 2 BCa TDCÞ TAZ 5 0:5 KT AMAX 1 TDZð1 1 BPr TDPrÞ Kp s ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi 2 # TDP ð1 2 BCa TDCÞ 2 KT AMAX 1 TDZð1 1 BPr TDPrÞ 2 4AMAX TDZð1 1 BPr TDPrÞ Kp where A MAX = 0.084, K T = 0.069, K P = 0.44, B Ca = 0.017, and B Pr = The FAZ was then calculated with the use of the following equation: FAZ ð%þ ¼ TAZ3100=TDZ ð9þ Means, medians and geometric means were estimated with the use of the Survey package in R software, taking into account the appropriate sampling weight, strata, and primary sampling unit. Data for pregnant and lactating women and individuals lacking data needed for the estimation of the PZ molar ratio were excluded from the analysis. The medians and means and their 95% CIs were reported for the intake of phytate, zinc, protein, and calcium and the PZ molar ratio. Percentage zinc absorption values obtained from the 2 models were log-transformed to approximate normality, and the geometric means (95% CIs) were reported. Summaries for the different variables were presented for different age categories, and values were compared with those for men y of age as a reference group. An independent-samples t test was used to compare zinc absorption values in the log scale between age groups, whereas a Mann-Whitney U test was used to compare dietary intake between groups. Statistical significance was set at P # 0.05, and a Bonferroni correction for 6 comparisons was applied. Thus, differences were considered to be significant only at P # To demonstrate the effect of the newly estimated absorption values on the current DRI for zinc, the EAR and RDA were estimated for selected age groups from the required absorbed zinc used by the IOM. The EAR values were estimated as the required absorbed zinc divided by the percentage absorption for the respective age groups. The RDA was estimated as the EAR plus twice the CV. The IOM used a CV of 10%; thus, RDA was estimated as 120% of the EAR (11). Results The original data included 9754 subjects who provided complete dietary intake data for day 1 of the survey cycle of the WWEA survey. After excluding pregnant and lactating women, children <1 y of age, and individuals with an undefined PZ molar ratio, the final sample size was reduced to The mean daily intake of phytate, zinc, calcium, and protein and the PZ molar ratio are shown in Table 1. Because of skewness in the distribution of the intake of these nutrients, the medians were also reported and intake was compared with the use of a nonparametric test. Median phytate intake ranged from 423 mg/d in children 1 8 y of age to 726 mg/d in men y of age, and median zinc intake ranged from 8.0 to 13.0 mg/d in the same respective age groups. The median PZ molar ratio ranged from 5.5 in children 1 8 y of age and boys 9 18 y of age to 6.8 in ð3þ ð5þ ð6þ ð7þ ð8þ Fractional zinc absorption from the US diet 1277

3 TABLE 1 Intake of selected nutrients and PZ molar ratio by age and sex in subjects from the NHANES Median (95% CI) Mean (95% CI) Phytate, mg/d Zinc, mg/d PZ molar ratio Protein, g/d Calcium, g/d Phytate, mg/d Zinc, mg/d PZ molar ratio Protein, g/d Calcium, g/d Group n Children (1 8 y) (405, 450)* 7.97 (7.62, 8.40)* 5.5 (5.1, 5.8) 53.5 (52.1, 55.6)* 0.94 (0.91, 0.97)* 523 (488, 558) 8.80 (8.58, 9.02) 6.5 (6.1, 6.9) 57.8 (56.1, 59.6) 1.0 (0.99, 1.1) Boys (9 18 y) (596, 710)* 11.2 (10.0, 12.5)* 5.5 (5.2, 5.8) 80.6 (75.2, 85.1)* 1.1 (1.0, 1.2) 767 (727, 807) 12.9 (12.1, 13.7) 7.1 (6.6, 7.6) 87.0 (81.5, 92.4) 1.2 (1.1, 1.3) Girls (9 18 y) (481, 547)* 8.47 (8.13, 8.83)* 6.5 (6.0, 7.1)* 60.0 (56.8, 63.9)* 0.85 (0.80, 0.89)* 628 (596, 661) 9.36 (8.84, 9.89) 7.6 (7.1, 8.1) 63.8 (61.1, 66.6) 0.93 (0.90, 0.97) y (696, 781) 13.0 (12.6, 13.5) 5.6 (5.2, 6.0) 97.3 (94.5, 99.8) 1.1 (1.0, 1.1) 919 (863, 975) 14.8 (14.1, 15.5) 6.9 (6.6, 7.2) 105 (101, 109) 1.2 (1.2, 1.3).50 y (648, 735) 11.4 (10.9, 11.8)* 6.1 (5.6, 6.5) 83.1 (79.8, 86.2)* 0.89 (0.84, 0.95)* 856 (809, 904) 13.4 (13.0, 13.8) 7.5 (7.1, 7.9) 93.5 (90.9, 96.2) 1.2 (1.2, 1.2) y (531, 573)* 8.74 (8.38, 9.15)* 6.3 (6.1, 6.4)* 65.0 (63.9, 66.7)* 0.82 (0.79, 0.86)* 676 (635, 717) 9.98 (9.63, 10.3) 7.4 (7.2, 7.7) 69.5 (68.0, 71.0) 0.92 (0.88, 0.95).50 y (554, 626)* 8.48 (8.12, 8.89)* 6.8 (6.6, 7.2)* 61.4 (58.9, 64.0)* 0.75 (0.73, 0.80)* 741 (697, 785) 9.68 (9.21, 10.2) 8.2 (7.8, 8.6) 67.7 (64.5, 70.9) 0.87 (0.84, 0.90) Total (581, 610) 9.74 (9.63, 9.88) 6.1 (5.8, 6.3) 71.6 (70.1, 72.7) 0.89 (0.88, 0.90) 748 (727, 768) 11.5 (11.3, 11.7) 7.3 (7.2, 7.5) 79.1 (77.8, 80.6) 1.0 (1.0, 1.0) 1 Pregnant and lactating women and children,1 y of age were excluded from analysis. *Significantly different from values for men aged y, P # (Bonferroni correction for 6 comparisons). Only medians were compared; means were not compared because data were skewed. PZ, phytate-to-zinc. postmenopausal women. Compared with intake in men y of age, the median phytate intake in all other groups was lower (P < ), except in men >50 y old (P = 0.11). The median zinc intake was lower in all groups than in men y of age (P < ). The median PZ molar ratio in the diets of children 1 8 y of age, boys 9 18 y of age, and men >50 y of age was not significantly different from that of men y of age (P > ). However, girls 9 18 y of age, women y of age, and postmenopausal women had significantly higher median PZ molar ratio values than did men y old (P < ). Zinc absorption estimated with the use of the 2 different models followed a similar pattern, with slightly higher values for the Miller et al. model than for the IZiNCG model (Table 2) y of age had significantly lower zinc absorption than all the other groups based on the IZiNCG model (P < ). With the use of the Miller et al. model, zinc absorption in men y of age was significantly lower than in all other groups (P < ) except men >50 y old (P = 0.42). For the purpose of comparing with the value used in the current DRI, zinc absorption was estimated separately for adolescents y of age, and preadolescents 9 13 y. The estimated values for adolescents were 30.1% (29.5%, 30.7%) and 31.6% (30.9%, 32.4%) for the IZiNCG model and Miller et al. model, respectively. For preadolescents, the estimated values were 31.1% (30.6%, 31.6%) and 32.8% (32.1%, 33.5%) for the IZiNCG model and Miller et al. model, respectively (data not shown in tables). When the EAR and RDA for men and women were estimated with the use of the new absorption values, both models suggested that the DRI needs to be increased by nearly one-half of the current values in order to meet the requirements for absorbed zinc (Table 3). Discussion Micronutrient deficiencies, including zinc and iron deficiencies, affect >2 billion people around the globe (25). One of the main causes of micronutrient deficiencies is poor absorption. In this study, zinc absorption from the US diet was estimated with the use of 2 published models that take into account the dietary factors that influence zinc absorption. Mean intake of protein, zinc, and calcium for all subjects were 79 g/d, 11.5 mg/d, and 1.03 g/d, respectively, identical to estimates by the USDA (26) of 80 g/d, 11.5 mg/d, and 1.03 g/d. Mean phytate intake in the US population was 748 mg/d, similar to the value suggested by Harland and Peterson (19) of 750 mg/d. The estimated mean PZ molar ratio was 7.3. This compares favorably with the findings of Ellis et al. (27), who reported a range of 4 to 12 for the omnivorous US diet. Zinc absorption was consistently higher in women than men, even though women had a higher PZ molar ratio. To further demonstrate this difference, zinc absorption was estimated for each sex group. Whereas absorption (mean for the 2 models) for men was 28.8%, that for women was 32.5%. This disparity in sex in zinc absorption may be due to the lower intake of zinc by women. It is well known that with higher zinc intake, fractional absorption tends to decrease. Wada et al. (13) showed that consumption of a diet containing 16.5 mg Zn resulted in an absorption of 25%, whereas when the diet was modified to contain 5.5 mg Zn, the absorption increased to 49% after 42 d. Possible reasons for this relation between zinc intake and absorption include saturation of the transport mechanisms and increased intestinal zinc excretion at a high intake (4). The effect of the PZ molar ratio on zinc absorption has been quantified differently by different authors. According to the 1278 Armah

4 TABLE 2 Fractional zinc absorption (percentage) estimated with the use of IZiNCG and Miller et al. models 1 Age group n IZiNCG (8) Miller et al. (21) Children (1 8 y) (33.3, 34.3)* 35.9 (35.5, 36.3)* Boys (9 18 y) (28.2, 29.7)* 30.3 (29.4, 31.2)* Girls (9 18 y) (31.8, 32.6)* 33.9 (33.2, 34.6)* y (26.8, 27.7) 28.0 (27.3, 28.7).50 y (27.9, 28.6)* 28.8 (28.3, 29.4) y (30.8, 32.1)* 33.0 (32.2, 33.7)*.50 y (30.8, 31.7)* 32.4 (31.7, 33.1)* Total (29.9, 30.2) 31.3 (30.9, 31.6) 1 Values are geometric means (95% CIs). Pregnant and lactating women and children,1 y of age were excluded from analysis. *Significantly different from values for men aged y, P # (Bonferroni correction for 6 comparisons). IZiNCG, International Zinc Nutrition Consultative Group. WHO, ;30% of zinc is absorbed from diets with a PZ molar ratio in the range of 5 15 (7). This compares well with the estimates from this study (30.1% or 31.3%, depending upon which model was used), although the WHO estimation was based mostly on single-meal data (28). Similarly, the IZiNCG estimates of 26% and 34% for men and women when the diet has a PZ molar ratio of 4 15 (8) compare favorably with our estimates for men and women reported above (28.8% and 32.5%). In the current DRI, the absorption of zinc was 41%, 48%, and 40% for men, women, and adolescents. The disparity between the values used in the DRI and those obtained in this study for these age groups (27.2% or 28.0%, 31.4% or 33.0%, and 30.1% or 31.6%, respectively) can be attributed to the low phytate content of the diets used in the studies in determining the relation between zinc intake and absorption in the DRI. Based on this observation, an upward adjustment of the current DRI is suggested to account for the inhibitory effect of phytate. This view is shared by Hambridge et al. (3), who have suggested that 1000 mg phytate/d in the US diet could double the current EAR and 2000 mg/d could triple it. To estimate zinc absorption, 2 different models developed by the IZiNCG (8) and Miller et al. (21) were used. Data used by the IZiNCG group were based on radio- or stable-isotope studies in which true absorption was estimated from the total diet, and were not restricted by geographic location (8, 29). In addition to these criteria, the IZiNCG excluded studies that used semipurified formula diets or diets with exogenous zinc salts added (8). Similarly, in their original model, Miller et al. (29) used radio- or stable-isotope study data in which true absorption was estimated from total diets. Unlike the IZiNCG model, however, they included a study with a liquid formula diet (29). Since the original Miller et al. model was published, it has undergone continuous evaluation and development, with the inclusion of additional data and improvement of model variables (3, 21, 30). In this study, their most recent model that included the effect of protein and calcium intake on zinc absorption was used (21). The 2 models differ in that the IZiNCG model accounts for only phytate and zinc intake, wheras the Miller et al. model accounts for protein and calcium, in addition to zinc and phytate intake. Moreover, the IZiNCG model is purely mathematical, whereas the Miller et al. model is a saturation model based on the transporter-mediated process of zinc absorption. In addition, whereas the IZiNCG model explained 41% of the variability in zinc absorption, according to the authors, the Miller et al. model TABLE 3 Comparison of current EAR and RDA for zinc and estimates based on new absorption values 1 Age group Required absorbed zinc, mg/d IOM (11) current values, mg/d EAR RDA New estimate, 2 mg/d IZiNCG (8) Miller et al. (21) EAR RDA EAR RDA y y y y y y y y Pregnant and lactating women were excluded from analysis. EAR, Estimated Average Requirement; IOM, Institute of Medicine; IZiNCG, International Zinc Nutrition Consultative Group. 2 New estimates for EAR values were obtained by dividing the required absorbed zinc values by the fractional zinc absorption (percentage) reported in Table 2. RDA was calculated as the EAR CV, where CV = 10%. explained 88% of variability in zinc absorption (8, 21). When the 2 models were independently tested by Hunt (31), the IZiNCG model was outperformed by the original Miller et al. model. The Miller et al. model explained 82% or 44% of variance in zinc absorption depending on whether mean values or individual values were used. The IZiNCG model, however, underestimated saturation in zinc absorption with increasing zinc intake. These differences notwithstanding, the estimates of zinc absorption that used the 2 models were quite comparable, with a strong positive correlation between the 2 sets of values (r =0.86;P < ). To demonstrate the effect of overestimated absorption values on the DRI, the EAR and the RDA for men and women were estimated with the use of the new absorption values. The results suggested that the current EAR and RDA for zinc (men and women) need to be adjusted upward by nearly one-half of the current values to be able to meet their absorbed zinc requirements. Compared with the Dietary Reference Values recently published by the European Food Safety Authority (EFSA) (32), the estimates from this manuscript are higher. The EFSA values require that men consuming 900 mg phytate/d have an Average Requirement (AR) of 11 mg/d and Population Reference Intake (PRI) of 14 mg/d compared with the 14 mg/d and 17 mg/d, respectively, estimated in this article. However, the EFSA AR for men is based on a physiologic zinc requirement of 3.2 mg/d [when assuming a BMI (in kg/m 2 ) of 22], whereas the IOM used a physiologic requirement of 3.84 mg/d. When the same physiologic zinc requirement as EFSA (3.2 mg/d) is used, the new estimates of zinc absorption suggested in this manuscript for men (28%) will lead to a similar estimate of EAR/AR (11.4 mg/d), whereas the current absorption value used for men (41%) will yield an EAR of 7.8 mg/d. Similarly, the physiologic requirement used by the 2 institutions for women were different because of the use of an assumed BMI of 22 by EFSA. Moreover, the IOM and EFSA used different approaches in estimating the RDA/PRI, contributing to the disparity in the estimates of these values. Whereas the IOM estimated the RDA as the EAR plus twice the CV, the EFSA estimated the PRI as the zinc intake that meets the physiologic zinc requirement for individuals at the 97.5th percentile of weight, assuming a BMI of 22. Fractional zinc absorption from the US diet 1279

5 The absorption value of 30% used for preadolescent children (9 13 y of age) by the IOM, however, compares well with our estimates. This is most likely because the test meals in the studies used by the IOM may have phytate, zinc, and PZ molar ratio contents similar to the intake of this age group. The limitations of this study include the use of models to estimate zinc absorption instead of directly measuring true absorption. These models are limited by current understanding of the factors that influence zinc absorption. Moreover, the models were developed from data that were not limited to the United States geographically. Also, phytate intake was not reported in the NHANES data, and therefore were estimated by using the phytate content of foods and food groups reported by the IZiNCG (8). In conclusion, this study suggests that zinc absorption from the US diet is overestimated in the current DRI for men, women, and adolescents, implying the need to reevaluate the current DRI for zinc to adequately adjust for the inhibitory effect of phytate on fractional zinc absorption. Acknowledgments I thank Leland Miller (University of Colorado, Denver) for his contributions in shaping the content of the manuscript. The sole author had responsibility for all parts of the manuscript. References 1. Institute of Medicine. Dietary Reference Intakes: the essential guide to nutrient requirements. Washington (DC): National Academies Press; Krebs NF. Overview of zinc absorption and excretion in the human gastrointestinal tract. J Nutr 2000;130:1374S 7S. 3. Hambidge KM, Miller LV, Westcott JE, Krebs NF. Dietary reference intakes for zinc may require adjustment for phytate intake based upon model predictions. J Nutr 2008;138: Lönnerdal B. Dietary factors influencing zinc absorption. J Nutr 2000;130:1378S 83S. 5. Bohn L, Meyer AS, Rasmussen SK. Phytate: impact on environment and human nutrition. A challenge for molecular breeding. J Zhejiang Univ Sci B 2008;9: Hurrell R, Egli I. Iron bioavailability and dietary reference values. Am J Clin Nutr 2010;91:1461S 7S. 7. WHO/FAO. Vitamin and mineral requirements in human nutrition. 2nd edition. Geneva (Switzerland): WHO and FAO of the United Nations; Brown KH, Rivera JA, Bhutta Z, Gibson RS, King JC, Lönnerdal B, Ruel MT, Sandtröm B, Wasantwisut E, Hotz C. International Zinc Nutrition Consultative Group (IZiNCG) technical document #1. Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull 2004;25:S Davidsson L, Mackenzie J, Kastenmayer P, Aggett PJ, Hurrell RF. Zinc and calcium apparent absorption from an infant cereal: a stable isotope study in healthy infants. Br J Nutr 1996;75: Fairweather-Tait SJ, Wharf SG, Fox TE. Zinc absorption in infants fed iron-fortified weaning food. Am J Clin Nutr 1995;62: Institute of Medicine. Panel on micronutrients. Dietary Reference Intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc: a report of the Panel on Micronutrients and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Washington (DC): National Academy Press; Hunt JR, Mullen LK, Lykken GI. Zinc retention from an experimental diet based on the U.S.F.D.A total diet study. Nutr Res 1992;12: Wada L, Turnlund JR, King JC. Zinc utilization in young men fed adequate and low zinc intakes. J Nutr 1985;115: Turnlund JR, Durkin N, Costa F, Margen S. Stable isotope studies of zinc absorption and retention in young and elderly men. J Nutr 1986;116: Turnlund JR, King JC, Keyes WR, Gong B, Michel MC. A stable isotope study of zinc absorption in young men: effects of phytate and alphacellulose. Am J Clin Nutr 1984;40: Taylor CM, Bacon JR, Aggett PJ, Bremner I. Homeostatic regulation of zinc absorption and endogenous losses in zinc-deprived men. Am J Clin Nutr 1991;53: Jackson MJ, Jones DA, Edwards RH, Swainbank IG, Coleman ML. Zinc homeostasis in man: studies using a new stable isotope-dilution technique. Br J Nutr 1984;51: Lee DY, Prasad AS, Hydrickadair C, Brewer G, Johnson PE. Homeostasis of zinc in marginal human zinc-deficiency role of absorption and endogenous excretion of zinc. J Lab Clin Med 1993;122: Harland BF, Peterson M. Nutritional status of lacto-ovo vegetarian Trappist monks. J Am Diet Assoc 1978;72: CDC. National Center for Health Statistics [Internet] National Health and Nutrition Examination Survey (NHANES) [cited 2015 Jun 8]. Available from: nhanes09_10.aspx. 21. Miller LV, Krebs NF, Hambidge KM. Mathematical model of zinc absorption: effects of dietary calcium, protein and iron on zinc absorption. Br J Nutr 2013;109: R Core Team [Internet]. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2014 [cited 2015 Jun 8]. Available from: USDA. Food patterns equivalents database [Internet]. USDA food patterns equivalents data for analyzing dietary data, [cited 2015 Jun 8]. Available from: htm?docid= Bowman SACJ, Thoerig RC, Friday JE, Shimizu M, Moshfegh AJ. Food patterns equivalents database : methodology and user guide [online]. Food Surveys Research Group, Beltsville Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Beltsville, Maryland; Available from: ars.usda.gov/ba/bhnrc/fsrg. 25. WHO/WFP/UNICEF. Preventing and controlling micronutrient deficiencies in populations affected by an emergency. Joint statement by the WHO, WFP and UNICEF; USDA ARS [Internet]. Nutrient intakes from food: mean amounts consumed per individual, by gender and age, What We Eat in America (WWEA), National Health and Nutrition Examination Survey (NHANES) [cited 2015 Jun 6]. Available from: SP2UserFiles/Place/ /pdf/0910/Table_1_NIN_GEN_09.pdf. 27. Ellis R, Kelsay JL, Reynolds RD, Morris ER, Moser PB, Frazier CW. Phytate:zinc and phytate X calcium:zinc millimolar ratios in selfselected diets of Americans, Asian Indians, and Nepalese. J Am Diet Assoc 1987;87: WHO. Trace elements in human nutrition and health. Geneva (Switzerland): WHO; Miller LV, Krebs NF, Hambidge KM. A mathematical model of zinc absorption in humans as a function of dietary zinc and phytate. J Nutr 2007;137: Hambidge KM, Miller LV, Westcott JE, Sheng X, Krebs NF. Zinc bioavailability and homeostasis. Am J Clin Nutr 2010;91:1478S 83S. 31. Hunt JR. Algorithms for iron and zinc bioavailability: are they accurate? Int J Vitam Nutr Res 2010;80: European Food Safety Authority (EFSA). Scientific opinion on Dietary Reference Values for zinc. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). EFSA Journal 2014;12: Armah