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Journal of the American College of Nutrition, Vol. 26, No. 1, 1-9 (2007)
Published by the American College of Nutrition

Effect of Dietary Phytate on Zinc Homeostasis in Young and Elderly Korean Women

Jihye Kim, PhD, Hee Young Paik, ScD, Hyojee Joung, PhD, Leslie R. Woodhouse, PhD, Shanji Li, PhD and Janet C. King, PhD

Department of Food and Nutrition, Seoul National University, Seoul, KOREA (K.K., H.Y.K., S.L)
The School of Public Health, Seoul National University, Seoul, KOREA (H.J.)
USDA/ARS Western Human Nutrition Research Center, Davis, CA (L.R.W.)
Children's Hospital Oakland Research Institute, Oakland, CA (J.C.K.)

Address correspondence to: Janet C. King, PhD, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609. E-mail: jking{at}chori.org


   ABSTRACT
TOP
 FOOTNOTES
 ABSTRACT
INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 CONCLUSIONS
 ACKNOWLEDGMENTS
 REFERENCES
 
Background: Previous studies suggest that consumption of predominantly plant-based diets with high phytate content contribute to zinc deficiency by inhibiting zinc absorption. Age of the individual may also affect the ability to maintain zinc homeostasis.

Objective: This study was designed to determine the effect of dietary phytate on zinc homeostasis and to evaluate the effect of age on the capacity to maintain the zinc homeostasis with changes in dietary phytate in young and elderly Korean women.

Design and Methods: Seven healthy young women (22–24 yr) and 10 healthy elderly women (66–75 yr) were studied consecutively for 3 months in 2 metabolic periods (MP) in two different metabolic units. During MP1 the women consumed a high phytate (HP) diet (P:Zn molar ratio = 23) for 9 days. After a 10 d wash-out period at home eating their usual diets, a lower phytate diet (LP) (P:Zn molar ratio = 10) was fed in MP2 for 9 d. Phytase was added to selected foods in the high phytate diet to reduce the phytate content of the meals in the LP period. The zinc content of both diets was about 6.5 mg/d. Stable isotopes of Zn (70Zn) were administered intravenously on d 5 of MP 1 and 2 for measuring endogenous fecal zinc excretion. Plasma samples were also collected on d 5 for measuring plasma zinc concentrations by Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). 24 hr urine samples were collected for 5 d and complete fecal samples were collected for 9 d after isotope administration. Fractional zinc absorption (FZA) was calculated from mass balance corrected for endogenous fecal zinc (EFZ) excretion and EFZ was determined by using an isotopic dilution technique. Isotopic ratios for FZA and EFZ were measured by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Statistical analyses were done using ANOVA.

Results: Both the young and elderly women were in negative zinc balance during the HP period. This was due to a significant decrease in FZA and total absorbed zinc (TAZ) with a HP diet (43 vs 22% in young women, 34 vs 20% in elderly women, p < 0.001). EFZ excretion did not differ in the young and elderly women during the LP and HP periods. Dietary phytate did not alter plasma zinc concentrations or and urinary zinc excretion in either group.

Conclusions: Adjustments in zinc homeostasis with an increase in dietary phytate did not differ between young and elderly women in this study.

Key words: dietary phytate, zinc homeostasis, zinc absorption, endogenous zinc excretion, isotope dilution technique


   INTRODUCTION
TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
SUBJECTS AND METHODS
 RESULTS
 CONCLUSIONS
 ACKNOWLEDGMENTS
 REFERENCES
 
Marginal zinc deficiency and suboptimal zinc status have been recognized in populations in both less developed and industrialized countries. Zinc deficiency in humans reduces growth, sexual maturity, and the immune defense system [1]. Maintaining a constant state of cellular zinc nutrition, or homeostasis, is essential for normal physiological function. Although an inadequate zinc intake may cause zinc depletion, inhibitors of zinc absorption, such as dietary phytate, along with a marginal intake are more likely to induce a poor zinc status [2].

Zinc homeostasis appears to be maintained by adjustments in gastrointestinal zinc absorption and endogenous excretion [3]. Phytic acid is the most potent inhibitor of zinc absorption in animal and humans, particularly when the molar ratio of phytate to zinc is >15, because it can form insoluble complexes with zinc in the gastrointestinal tract [4]. In addition, substantial quantities of endogenous zinc enter the lumen of the small intestine via pancreatic secretions postprandially; the reabsorption of this secreted zinc is necessary to maintain homeostasis. Dietary phytate may also form complexes with this endogenous secreted zinc and inhibit its reabsorption [5]. Fractional zinc absorption from low phytate maize was 78% greater than that from high phytate maize suggesting phytate can play a major role in zinc homeostasis [6].

Elderly individuals are thought to be at greater risk of zinc depletion than younger adults [6] due to a lower intake of zinc and/or a reduced efficiency of zinc absorption with aging [7, 8]. It may also indicate higher endogenous fecal or urinary zinc losses with aging [9]. Several investigators have measured zinc balance in elderly [10–12]. Burke et al [12] showed that zinc retention in elderly was not improved by feeding a high zinc diet. The effect of dietary phytate on whole body zinc homeostasis has not been addressed in elderly individuals.

The high prevalence of low zinc intakes and lower plasma zinc concentrations among Koreans suggests that their zinc status may be marginal [13, 14]. Also, zinc intakes and plasma zinc concentrations are lower among the elderly in Korea than that of younger adults [15]. Consuming a traditional Korean diet largely based on grains and vegetables may contribute to the risk of marginal zinc deficiency in Korea. Rural adults had lower zinc intakes and higher phytate/zinc molar ratios than adults in urban area [16]. Zinc intakes average 5.2 mg/d for women and 7.3 mg/d for men living in rural areas where about 60–70% of the zinc is provided by plant foods that are high in phytate [13].

The purpose of this study was to determine the effect of dietary phytate on zinc homeostasis and to test the effect of age on maintaining zinc homeostasis with the changes of dietary phytate in Korean population.


   SUBJECTS AND METHODS
TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
RESULTS
 CONCLUSIONS
 ACKNOWLEDGMENTS
 REFERENCES
 
Subjects
Ten healthy young women (22–24 years) and 10 elderly women (66–75 years) were recruited for the study by word-of-mouth and flyers on the campus of Seoul National University and in neighboring areas. Exclusion criteria included a body mass index of less than 17 or greater than 28 kg/m2; cigarette smoking; chronic use of alcohol or prescription drugs; use of oral contraceptives or vitamin or mineral supplements; a hemoglobin level <105 g/L; the presence of acute disease or chronic disease such as diabetes, gastrointestinal disorder, hyperlipidemia; pregnancy and lactation; and a usual dietary zinc intake <5 mg/d or >15 mg/d. Data from three of the 10 young women were excluded due to incomplete sample collection. One of the elderly women took medication for hypertension during study.

All subjects gave their informed consent to participate in the study. The study protocol was reviewed and approved by the Committee on Human Research at the College of Human Ecology at Seoul National University and the Office of Human Research Protection at the University of California, Davis.

Study Design
The study was divided into two 9-d metabolic periods, MP1 and MP2, during which the women were housed in metabolic units created to do this study. The young women were housed at the Faculty House of Seoul National University and the elderly stayed in an apartment near Seoul National University. The metabolic studies were completed in the young women first, and then the elderly women were studied. All women started with MP 1 and then completed MP 2 after returning home and eating their usual diets for a 10-day washout period between the two metabolic periods. Diet records were completed prior to MP 1 for estimating usual zinc intakes.

On the 5th day of each metabolic period, a fasting blood sample was collected and then the women were infused with 0.3 mg of 70Zn, as ZnCl2, by a registered nurse after the women received 1 mg of 67Zn in orange juice, which was used as a fecal marker, immediately following breakfast meal. Baseline spot urine and fecal samples were collected prior to the isotope infusion. Complete 24-h urine and all fecal output were collected for 5 or 9 days, respectively, following isotope administration. Endogenous fecal zinc losses were estimated from the isotopic tracer ratios in the feces relative to urinary ratios [17]. Total zinc retention or loss was estimated using the mass balance technique. Zinc absorption was estimated from the difference between total and endogenous fecal zinc losses.

Diets
A two-day cycle menu of common Korean foods was used for the two controlled metabolic diets (Table 1). The high phytate diet (phytate:zinc molar ratio = 23) was fed in MP 1; the lower phytate diet (phytate:zinc molar ratio = 10) was fed in MP 2. To lower the phytate content of the diet for MP 2 without changing the food sources, a phytase enzyme from Aspergillus Niger (5000 U/g, BASF, Mount Olive, NJ) was added to the brown rice gruel served at breakfast on menu day 1 and the soybean curd served for lunch on menu day 1 [18]. On menu day 2, brown rice was replaced with white rice at lunch and dinner to reduce the phytate content of the total day's diet. Two mg of phytase was added to 100 g brown rice and incubated at 4°C for 6 h; 4 mg phytase was added to 100 g soybean curd residue and incubated at 4°C for 3 h. The iron content of menu day 2 of the low phytate diet was lower than that of menu day 2 of the high phytate diet due to the substitution of white rice for brown rice with soybean (2.7 versus 5.3 mg iron/d). To balance the iron content of the two study diets, 2.6 mg iron, as a liquid of ferrous sulphate (Alphama, Baltimore) was dissolved in water and served with lunch meals on menu day 2 of the low phytate diet period.


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  		Table 1. Menus for Controlled Diets for Young Women

 
To accommodate the food preferences of the elderly women, we made several substitutions in the menus designed for the young women. Beef and vegetable gruel and grilled seaweed replaced the ham and cheese sandwich for elderly women at breakfast on day 2. Milk for lunch on days 1 and 2 was replaced with soymilk, and tangerines were substituted for water melon at dinner on days 1 and 2. These substitutions did not significantly change the energy, protein, calcium, and iron content of the menus or the zinc or phytate content. Meals were served 3 times daily at 7–9 am, 12–2 pm, and 6–8 pm.

All food was prepared, weighed, and packaged in the metabolic kitchen, which is located at the Food and Nutrition Department in Seoul National University. The women either ate their meals in the metabolic kitchen, at living room in the metabolic unit, or their workplace with members of our staff. All water consumed was provided. Diet samples of each meal were prepared for the two study diets and analyzed for minerals and phytate. The energy, protein, calcium, and iron content of the study diets were determined by the estimated values from a nutrient database developed by the Korean Nutrition Society (Table 2) [19, 20].


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  		Table 2. Composition of the Diets Consumed for 9 Days by the Women during High Phytate Diets and Low Phytate Diets1

 
The usual dietary intakes of the women were estimated from either a 3-day diet record collected from the young women or a 24 h dietary recall from the elderly women during screening for participation in the study (Table 3). We initially used 3-day diet records to determine the food intakes of both young and elderly women. However, the elderly women were unable to complete their diet records accurately. Thus, our research staff interviewed the elderly women and recorded their intakes using a 24-hr recall method. A study of nutrient intakes in Korea using the same two methods showed that there was no significant difference in mean nutrient intakes between two methods [21]. Intakes of energy, protein, and zinc were estimated from a nutrient database developed by the Korean Nutrition Society and phytate intake was estimated from a phytate database developed by Human Nutrition Laboratory at Food and Nutrition Department in Seoul National University [20].


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  		Table 3. Characteristics of Study Participants1

 
Isotope Preparation and Administration
A stable isotope label of zinc, highly enriched in 70Zn (95.56% abundance), was purchased as zinc oxide from Trace Sciences Inc., Toronto, Canada. The chloride salt of the isotope was prepared using concentrated HCl. Solutions of 70Zn were diluted to 0.3 mg Zn/mL with triply deionized water at pH2 and sent to the Parenteral Solution Laboratory at the University of California, San Francisco, for sterile preparation, testing, and packaging into vials. The stable isotope solutions were stored at 4°C until use.

On the morning of the 5th day of each metabolic period, an indwelling catheter was placed in the antecubital vein from which baseline (fasting) blood samples were drawn using Monovette syringes (Sarstedt 8-mL monovette syringes, Newton, North Carolina, USA) that contained ammonium heparin-coated beads. The subjects then received a standard breakfast consisting of typical Korean foods. Immediately after breakfast, 0.3 mg of the 70Zn (1.0 mL) was infused over 1 min into the antecubital vein of the arm opposite that used for blood sampling, using a "butterfly" infusion set. The butterfly tubing was flushed with 5 ml sterile saline solution to ensure that the entire tracer dose was infused. The exact amount of the tracer solution infused was determined by weighing the syringe before and after the infusion. The isotope infusion was done by a registered nurse.

Sample Collection and Analyses
Composites of each meal in the two study diets were prepared twice during each metabolic study. Aliquots were taken and stored at 4°C for subsequent zinc and phytate analysis. Blood samples for plasma zinc analysis were collected in plastic syringes and were kept on ice for a maximum of 2 h before centrifugation at 3000 rpm (4°C, 10 min, Hanil micro 17R Plus, Incheon, Korea). After centrifugation, the plasma was transferred to polypropylene tubes using transfer pipettes and stored at –70°C. Hemoglobin was measured at each visit using a HemoCue (HemoCue AB, Angelholm, Sweden). All urine and fecal samples were collected in polypropylene containers. After collection, the 24-hr urine collections were mixed by shaking vigorously, weighed, acidified with 0.4 mL concentrated HCl/100 g urine (Trace metal grade; Merck, Germany), and aliquots were stored at –20°C until zinc analysis. All fecal samples were weighed and stored at –20°C until analysis for zinc. Precautions against environmental zinc contamination were taken for all diet, blood, urine, and fecal collections and analyses by using only new polypropylene containers, triply deionized water, and ultra high-purity reagents. All glassware was acid-washed in 10% HNO3 and rinsed 3 times with triply deionized water.

Diet, plasma, urinary, and fecal zinc content were determined by Inductively Coupled Plasma-Atomic Emission Spectrophotometry (ICP-AES, Vista, Varian Inc., Walnut Creek, CA). Diet and fecal samples were freeze-dried (Bondyro, Ilsin Inc., Seoul, Korea) and ground to homogeneity. Weighed aliquots for diet (0.2–0.4 g) and fecal samples (0.1–0.2 g) were digested by microwave digestion (MARS 5, CEM Corp., Matthews, NC) using concentrated HNO3 (Optima grade; Fisher Scientific; Pittsburgh, PA) prior to analysis. Diet and fecal samples were diluted with 1% HNO3 (Optima grade; Fisher Scientific; Pittsburgh, PA) prior to analysis. Plasma samples were prepared for analysis by diluting the plasma with 6% HNO3 (Optima grade; Fisher Scientific; Pittsburgh, PA) and centrifuging at 3200 rpm (2200 x g, 4°C, 15 min). Urinary samples were centrifuged at 1000 rpm (230 x g, 4°C, 10 min) using Allegra 6R (Beckman Coulter Inc., Palo Alto, CA) to remove any solid material and then diluted with 1% HNO3 (Optima grade; Fisher Scientific; Pittsburgh, PA) for ICP-AES analysis. Bovine liver serum (BLS) and internal standards were used as quality controls for ICP-AES analysis. The BLS zinc measurements compared well to standard values: 0.121 µg/mL ± 0.010 vs 0.123 µg/mL ± 0.008.

Myo-Inositol 1, 3, 4, 5, 6-pentakis-phosphate (IP5) and myo-inositol 1, 2, 3, 4, 5, 6-hexakis-phosphate (IP6) forms of dietary phytate were determined by Dionex Liquid Chromatograph System (Dionex Corp., Sunnyvale, CA, USA) after extracting IP6, IP5, and phosphate ion (PO4–3) from each sample using a modification of the procedure from J. Lehrfeld [22]. Ten mL of 1.25% (v/v) H2SO4 was added to freeze-dried diet composites (0.25 g) weighed into disposable 15 mL centrifuge tubes. After vortexing, tubes were placed horizontally on a shaker for 2 hours, then centrifuged at 1800 x g for 10 min. One ml of supernatant was then diluted to a final volume of 10 mL with deionized water. Phosphate, IP5, and IP6 contained in this sample were separated and quantified against appropriate standards via HPLC. Aliquots (25 µL) were injected into a Dionex (Dionex Corp., Sunnyvale, CA, USA) IonPac AS11 4 x 250 mm column preceded by an IonPac AG11 4 x 50 mm guard column (DX600 Dionex Liquid Chromatograph System equipped with an AS50 Autosampler, a GS50 gradient pump, an ED50 conductivity detector, and an AMMS III 4 mm Suppressor, with external 50 mM H2SO4 suppressant). The sample was eluted using a carbonate-free 200 mM NaOH solution and deionized water gradient. The flow rate was 1 ml/min starting at 13% 200 mM NaOH and 87% deionized water for 3 min followed by 8 min of a linear gradient up to 50% of the NaOH solution. A four min re-equilibration was used to return the column to initial conditions (modification of Dionex Application Note 65). All measurements were done in triplicate. The total phytate content of the meals was determined from the analyzed value multiplied by dry weight.

Isotopic ratios of 70Zn:66Zn, as well as 68Zn:66Zn and 67Zn:66Zn, were determined in urine and fecal samples using a Sciex ELAN 6000 ICP-MS instrument (Perkin-Elmer, Norwalk, CT) equipped with a U-6000AT+ ultrasonic nebulizer (Cetac Technologies Inc, Omaha, NE) and a model AS 93+ autosampler (Perkin-Elmer, Norwalk, CT). A detailed description of sample preparation for ICP-MS analysis is described elsewhere [23]. In brief, urine samples were centrifuged at 1000 rpm (230 x g, 4°C, 10 min) using Allegra 6R (Beckman Instruments, Inc., Palo Alto, CA) and the inorganic salts were removed using a chelating resin (Chelex 100 resin; Bio-Rad Laboratories, Hercules, CA). Freeze-dried fecal samples were weighed (0.1–0.2 g) and digested by microwave digestion (MARS 5, CEM Corp., Matthews, NC) prior to ion exchange chromatography. Zinc in urine and fecal samples were separated from the eluent by ion exchange chromatography (type AG1X-8 ion exchange resin; Bio-Rad Laboratories, Hercules, CA). Tracer-to-tracee ratios were calculated using the natural abundances of the various zinc isotopes and the tracer mass (in mg) [23, 24].

Calculations
Zinc balance was calculated using the following equation: Zinc balance (mg/d) = (Dietary Zinc – (Fecal zinc + Urinary zinc))/day.

We modified the method of Yergey [25] for measuring endogenous fecal zinc excretion [17]. Endogenous fecal zinc excretion (EFZ), can be measured after intravenous administration of a stable isotopic tracer dose of zinc highly enriched in 70Zn (70Zntr) by the following equation: EFZ (mg) = [(total 70Zntr in feces)/total 70Zntr in urine)] Vu where Vu is the rate of urinary zinc tracee excretion (in mg/d). We measured the cumulative excretion of 70Zntr in the urine and feces for 5 d after isotopic tracer administration. Daily endogenous fecal zinc excretion was measured by dividing the total EFZ loss over the 5 day period by the length of the collection period (5 d). Fig. 1 shows the cumulative fecal and urinary 70Zntr over the 5 d collection period. The relative standard deviation for the lowest level of enrichment, i.e., 70Zntr in the urine on day 5, was 0.6; this is 3-fold higher than the detection limit of the ICP-MS.


Figure 1
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  		Fig. 1. The accumulation of 70Zn tracer in feces and urine over 5 days following isotope administration.

 
Fractional zinc absorption (FZA) was estimated from the dietary and fecal zinc and EFZ as follows [23]: FZA (%) = (Diet zinc, mg/d – (Total fecal zinc, mg/d – EFZ, mg/d)) 100/Diet zinc.

Total absorbed zinc (TAZ) was determined from the analyzed zinc content of the diets and FZA: TAZ (mg/d) = Diet Zinc (mg/d) x FZA.

Statistical Analysis
Results are expressed as means ± standard deviations (SDs). Statistical analyses were conducted with Stata 8.0 (StataCorp LP, College Station, TX). Differences in subject baseline characteristics by age group were determined using two-sample t-tests. Changes in zinc homeostasis measures over the two metabolic periods and for two age groups were determined using repeated measures analysis of variance (ANOVA). Each ANOVA included the zinc measure as the dependent variable, the metabolic period as the repeated measure factor, and factors for age group and for age group by metabolic period interaction. Residual versus fitted plots, box plots, and Q-norm plots of the standardized residuals were tested and Shapiro-Wilk tests of the residuals were examined to test the assumptions of normality and constant variance in this ANOVA model. The data were normally distributed. Associations between various zinc homeostatic measurements were examined using Pearson correlations. Statistical significance was defined as p < 0.05.


   RESULTS
TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
CONCLUSIONS
 ACKNOWLEDGMENTS
 REFERENCES
 
The characteristics of the young and elderly women in the study are described in (Table 3). All of the women were of normal weight-for-height and had normal hemoglobin values at the beginning of the study. Their usual intakes of energy, protein, phytate, and zinc did not differ significantly. Phytate intakes of the elderly women were about 20% higher than that of the younger women, but this difference was not significant. Zinc intakes averaged about 6.5 mg/d in both groups.

Plasma zinc concentrations were about 33% higher in the elderly than younger women in both metabolic periods (p < 0.001) (Table 4). Plasma zinc concentrations tended to be higher during the low phytate period in both groups, but this did not reach significance (p < 0.077).


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  		Table 4. Zinc Homeostasis in Young and Elderly Korean Women Consuming High or Low Phytate Diets1

 
Total urinary zinc excretion did not change significantly with dietary phytate, but it tended to be higher in the elderly women than that of younger women (p < 0.081) (Table 4). Fecal zinc losses increased by about 20% during the high phytate period (p < 0.001) in both groups. This increase in fecal zinc losses lead to a net loss of about 0.4 mg zinc/d in the young women and 0.9 mg zinc/d in the elderly women during the high phytate MP (p < 0.01); the difference due to age was not significant.

EFZ losses did not vary with dietary phytate or age; it remained constant at 1.8 mg/d throughout the study representing about 25% of the total fecal zinc excretion during the high phytate period and about 30% in the low phytate period (Table 4). Since total fecal zinc losses increased with high dietary phytate and EFZ did not, the FZA, estimated as the difference between total fecal zinc and EFZ, decreased by about 50% during the high compared to the low phytate periods in the young women and by about 40% in the older women (p < 0.001). Differences due to age were not significant. The decline in FZA during the high phytate period was associated with a significant reduction in TAZ in both age groups (p < 0.001). As expected, TAZ was negatively correlated with fecal zinc in both groups on each of the diets: r = –0.96 (p < 0.001) in the high and r = –0.76 (p < 0.05) in the low phytate period among the young women, and r = –0.73 (p < 0.05) in the high and r = –0.84 (p < 0.01) in low phytate period among the elderly women. There was no correlation between TAZ and plasma zinc, urinary zinc or EFZ in either age group.


   DISCUSSION
 
A high phytate diet increased total fecal zinc excretion and reduced the amount of total absorbed zinc in both young women and elderly women. Plasma zinc concentrations tended to be lower during the high phytate period when the women were in negative zinc balance, but this did not reach significance (p < 0.077). Endogenous fecal and urinary zinc losses were not reduced during the high phytate metabolic period. It appears that in the short-term, higher intakes of phytate primarily affects the intestinal uptake of dietary zinc rather than altering the secretion or reabsorption of endogenous zinc.

Others have reported that dietary phytate reduces zinc absorption [26, 27]. In a study of young and elderly subjects [26], zinc absorption averaged about 35% when both groups were fed dephytinized diets (phytate/zinc molar ratio equals 0), but it declined to about 20% when the phytate/zinc molar ratio was increased to 20. Turnlund and co-workers [28] showed that zinc absorption declined by 50% in young men when 2.34 g of phytate (phytate:zinc molar ratio = 15) was added as sodium phytate to a semi-purified diet. Our results are similar. We found that age did not affect the response to a two-fold increase in the phytate:zinc molar ratio from about 10 to 20; fractional zinc absorption dropped about 40–50% in both groups.

Although the amount of zinc absorbed decreased during 9-day high phytate diet period, there was no compensatory reduction in gastrointestinal or urinary zinc losses, and a negative zinc balance occurred. Plasma zinc concentrations tended to decline suggesting that the high phytate diets impaired zinc status. Others have reported that a high intake of phytate reduces zinc status in humans. Certain populations, such as children and pregnant women, subsisting on cereal-based diets are particularly vulnerable. For example, Malawian children and pregnant women consuming diets with phytate:zinc molar ratios greater than 15 tend to have plasma and hair zinc concentrations below acceptable cut-off values [18, 27, 29–31]. Subsistence on high phytate:zinc diets may account for the high prevalence of stunting among Malawian children; about two-thirds of the children studied had height-for-age Z scores below 2 SD of the National Center for Health Statistics reference [29]. Studies of Swedish infants also show that high intakes of phytate-containing foods lowered the zinc status of 1-year-old infants [32–34]; 36 percent of the infants fed weaning foods with high amounts of phytate ({approx}30 µmol/100 g) had low serum zinc concentrations even though their zinc intakes appeared to be adequate [34].

Since the high-phytate diet was only fed for 9 days in this study and since we were not studying a growing population with increased zinc needs, the tendency for plasma zinc concentrations to decline during the high-phytate period was unexpected. None of the women developed low plasma zinc levels, i.e., <10.7 µmol/L, however. The decline in plasma zinc concentrations may be related to the net loss of about 0.4 or 0.9 mg zinc/d in the young and elderly women, respectively, or a total of about 3.6 or 8.1 mg zinc during the high-phytate period. Although plasma zinc represents less than 0.1% of the whole body zinc, its high turnover rate, about 150 times per day, may make it sensitive to marked short-term changes in zinc homeostasis [3]. The 3.5 to 8 mg of zinc net loss during the high-phytate period is greater than the total amount of plasma zinc suggesting that zinc was mobilized from other tissues in sustain circulating levels.

As stated above, total endogenous fecal zinc excretion did not decline during the high phytate period. The process of secretion and reabsorption or excretion of intestinal endogenous zinc has not been well characterized in humans [35]. In general, endogenous fecal zinc excretion declines with low zinc intakes and with increases in physiologic need as occurs in growing infants [35]. The quantity of endogenous zinc secreted into the gastrointestinal tract after a meal is likely to exceed the usual amount of zinc in a meal [35, 36]. Thus, maintenance of zinc balance requires efficient reabsorption of endogenous zinc as well as some fraction of exogenous zinc. Studies in rats have shown that dietary phytate inhibits the reabsorption of endogenous zinc from the gastrointestinal tract [37]. Our subjects developed a negative zinc balance and an overall decline in the absorption of exogenous, dietary zinc. Possibly, phytate also reduced the reabsorption of endogenous zinc during the high-phytate period [38]. This could have occurred without any change in total endogenous fecal zinc losses if the total amount of zinc secreted into the gastrointestinal tract was lower during high phytate period than the low phytate period. If endogenous zinc secretion is reduced by the same amount as the reabsorption from the gut, endogenous fecal zinc excretion would be the same in both diet periods. Further studies are needed to determine if dietary phytate alters gastro-intestinal endogenous zinc secretion as well as reabsorption.

Alternatively, the source of pancreatic zinc secreted into the gut during this short high-phytate period may have come from a source that is not labile to forming complexes with phytate. Oberleas [39] found that endogenous zinc secreted from the pancreas in rats comes from two pools: a stable pool not affected by dietary phytate and a labile pool readily available for phytate-zinc complexes. The primary pool forms stable zinc complexes with zinc-dependent enzymes and other large molecular weight compounds. These zinc complexes are not bound to phytate in the gastrointestinal tract and are excreted in the feces. The secondary pool contains zinc in labile complexes. These complexes are thought to be dissociated in the duodenum and are vulnerable to complexation by phytate or other chelating agents. If the labile zinc is complexed with soluble compounds, it is available for resorption. If it is complexed to phytate or other nonabsorbable organic complexes that are less soluble, it is less available for absorption and excreted in the feces. In the rat study [36], endogenous pancreatic zinc came mostly from the stable pool during the first seven days following initiation of a high phytate diet (phytate:zinc molar ratio >30). Between day 7 and 14 when pancreatic zinc came primarily from a labile pool, total fecal zinc excretion increased nearly 4 times that measured during feeding of a nonphytate-containing diet. Since our diet period was only 9 days in length, possibly pancreatic endogenous zinc secretion was primarily in a stable form and not susceptible to binding with phytate in the gut. No changes in endogenous fecal zinc were seen in Malawian children when fed either a reduced hytate corn-plus-soy diet with a phytate:zinc ratio of 30 or a high phytate diet (phytate:zinc ratio of 7) for 7 days [18]. Studies that examine the longer-term effects of dietary phytate on endogenous fecal zinc losses are needed.

The gastrointestinal response to the high phytate diet was similar in both young and elderly women; total zinc absorption was reduced by the high phytate diet and fecal zinc excretion increased. Even though the gastrointestinal response to dietary phytate did not differ due to age, the plasma zinc concentrations of the elderly were significantly higher than that of the young women during both the high and low dietary phytate periods, suggesting that the distribution of absorbed zinc might change with age [40]. Urinary zinc excretion tended to be higher in the elderly compared to young women during both diet periods. Possibly, aging reduces the tubular reabsorption of zinc in conjunction with the usual decline in glomerular filtration rate and renal blood flow with age [41]. Wastney et al [9] found that the urinary zinc excretion increased significantly with age during zinc loading in humans. It is not known if a difference in urinary zinc excretion alters the zinc requirements of the elderly.


   CONCLUSIONS
TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 CONCLUSIONS
ACKNOWLEDGMENTS
 REFERENCES
 
Fecal zinc losses increased in both young and elderly women with a high phytate diet (phytate/zinc molar ratio >20). This increase in fecal zinc excretion was associated with a negative zinc balance since compensatory adjustments in endogenous fecal zinc losses and urinary zinc excretion did not occur during the 9-day high phytate period. Plasma zinc concentrations declined by about 8%, but this drop was not significant. Age did not alter the zinc homeostatic response to the high phytate diet. However, plasma and urinary zinc concentrations tended to be higher in elderly women than those of young women during both diet periods.


   ACKNOWLEDGMENTS
TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 CONCLUSIONS
 ACKNOWLEDGMENTS
REFERENCES
 
We are grateful to study participants and all staff in the Human Nutrition Laboratory at Seoul National University in Seoul, Korea, Tuan Q. Nguyen at Children's Hospital Oakland Research Institute, Oakland, CA, Erik R. Gertz at USDA/ARS Western Human Nutrition Research Center, Davis, CA, Dr. Ross Welch for phytate analysis, at Cornell University, and Meredith Milet at Children's Hospital Oakland for statistical analyses. This research was supported by the Korea Research Foundation and USDA/ARS Western Human Nutrition Research Center at the University of California at Davis.


   FOOTNOTES
TOP
 FOOTNOTES
ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 CONCLUSIONS
 ACKNOWLEDGMENTS
 REFERENCES
 
Supported by Korea Research Foundation (KRF-2000-042-D00103) and USDA/ARS Western Human Nutrition Research Center.

Received November 8, 2005. Accepted April 12, 2006.


   REFERENCES
TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 CONCLUSIONS
 ACKNOWLEDGMENTS
 REFERENCES
 

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