Effect of phytic acid on postprandial serum uric acid level in healthy volunteers: a randomized, double-blind, crossover study.

Phytic acid, a constituent of various plants, has been related to health benefits. Phytic acid has been shown to inhibit purine nucleotide metabolism in vitro and suppress elevation of plasma uric acid levels after purine administration in animal models. This study investigated the effect of phytic acid on postprandial serum uric acid (SUA) in humans. This randomized, double-blind, crossover design study included 48 healthy subjects with normal fasting SUA. Subjects consumed a control drink and a phytic acid drink with purine-rich food, and serum and urine uric acid levels were measured for 360 min after purine loading. Phytic acid lowered the incremental area under the curve (0-360 min) and incremental maximum concentration of SUA after purine loading (p < 0.05); tended to lower cumulative urinary uric acid excretion (0-360 min) after purine loading (p < 0.10); and suppressed postprandial SUA in this clinical study. Altogether, our findings suggest that phytic acid may play a beneficial role in controlling postprandial SUA.

Effect of exogenous phytase added to small-quantity lipid-based nutrient supplements (SQ-LNS) on the fractional and total absorption of zinc from a millet-based porridge consumed with SQ-LNS in young Gambian children: a randomized controlled trial.

BACKGROUND: Dietary phytate inhibits zinc absorption from composite meals in adults. OBJECTIVE: The objective of this study was to investigate the effect of adding exogenous phytase to a small-quantity lipid-based nutrient supplement (SQ-LNS) on zinc absorption among young children. METHODS: In a double-blind randomized controlled trial, intraindividual differences in fractional and total absorption of zinc (FAZ and TAZ, respectively) from a millet-based porridge containing SQ-LNS with and without phytase were measured in 30 asymptomatic children 18-23 mo of age in the Kiang West district of The Gambia. Using a crossover design, children received for 1 d each porridge test meals with 20 g SQ-LNS containing 8 mg zinc and either 1) exogenous phytase or 2) no exogenous phytase. The test meals were provided on consecutive days in randomized order. FAZ was measured using a triple stable isotope tracer ratio technique with Zn-67 and Zn-70 as oral tracers and Zn-68 as the intravenous tracer. RESULTS: Twenty-six participants completed the study. The prevalence of stunting and wasting were 20% and 13%, respectively; no children had low plasma zinc concentrations (<65 µg/dL). Total mean ± SD dietary zinc intake from the test meals was 7.3 ± 2.2 mg (phytate:zinc molar ratio = 3.1 ± 0.3, not accounting for phytase activity). Mean FAZ increased from 8.6% ± 1.3% to 16.0% ± 1.3% when exogenous phytase was added to the SQ-LNS product (P < 0.001). Mean TAZ from test meals containing SQ-LNS with phytase was more than double that from test meals containing SQ-LNS without phytase (1.1 ± 0.1 mg and 0.5 ± 0.1 mg, respectively; P < 0.001). CONCLUSIONS: The addition of exogenous phytase to SQ-LNS increased both FAZ and TAZ. These results suggest that phytate reduction may be an important strategy to increase zinc absorption among young children. This trial was registered at clinicaltrials.gov as NCT02668133.

Low-phytate wholegrain bread instead of high-phytate wholegrain bread in a total diet context did not improve iron status of healthy Swedish females: a 12-week, randomized, parallel-design intervention study.

PURPOSE: To investigate the effects of eating wholegrain rye bread with high or low amounts of phytate on iron status in women under free-living conditions. METHODS: In this 12-week, randomized, parallel-design intervention study, 102 females were allocated into two groups, a high-phytate-bread group or a low-phytate-bread group. These two groups were administered: 200 g of blanched wholegrain rye bread/day, or 200 g dephytinized wholegrain rye bread/day. The bread was administered in addition to their habitual daily diet. Iron status biomarkers and plasma alkylresorcinols were analyzed at baseline and post-intervention. RESULTS: Fifty-five females completed the study. There was a significant difference in change over time in total body iron stores between the two groups (p < 0.035). In the low-phytate bread group (n = 24) there were significant within-group decreases in both ferritin (mean 12%; from 32 ± 7 to 27 ± 6 µg/L, geometric mean ± SEM, p < 0.018) and total body iron (mean 12%; from 6.9 ± 1.4 to 5.4 ± 1.1 mg/kg, p < 0.035). Plasma alkylresorcinols indicated that most subjects complied with the intervention CONCLUSIONS: In Swedish females of reproductive age, no statistically significant difference in iron status was detected after 12 weeks of high-phytate wholegrain bread consumption. However, consumption of low-phytate wholegrain bread for 12 weeks resulted in a reduction of markers of iron status. Although single-meal studies clearly show an increase in iron bioavailability from dephytinization of cereals, medium-term consumption of reduced phytate bread under free-living conditions suggests that this strategy does not work to improve iron status in healthy women of reproductive age.

SNF472, a novel inhibitor of vascular calcification, could be administered during hemodialysis to attain potentially therapeutic phytate levels.

BACKGROUND: Cardiovascular calcification (CVC) is a major concern in hemodialysis (HD) and the loss of endogenous modulators of calcification seems involved in the process. Phytate is an endogenous crystallization inhibitor and its low molecular mass and high water solubility make it potentially dialyzable. SNF472 (the hexasodium salt of phytate) is being developed for the treatment of calciphylaxis and CVC in HD patients. We aimed to verify if phytate is lost during dialysis, and evaluate SNF472's behaviour during dialysis. METHODS: Dialyzability was assessed in vitro using online-hemodiafiltration and high-flux HD systems in blood and saline. SNF472 was infused for 20 min and quantified at different time points. RESULTS: Phytate completely dialyzed in 1 h at low concentrations (10 mg/l) but not when added at 30 or 66.67 mg/l SNF472. In bypass conditions, calcium was slightly chelated during SNF472 infusion but when the system was switched to dialysis mode the calcium in the bath compensated this chelation. CONCLUSION: Phytate dialyses with a low clearance. The administration of SNF472 as an exogenous source of phytate allows to attain supra-physiological levels required for its potential therapeutic properties. As SNF472 is infused during the whole dialysis session, the low clearance would not affect the drug's systemic exposure.

Zinc status, dietary zinc intake and metabolic risk in Australian children and adolescents; Nepean Longitudinal Study.

PURPOSE: Zinc is essential for normal growth and metabolism. We aimed to characterise the total and bioavailable dietary zinc intake and plasma zinc concentrations in healthy children, longitudinally, and to examine the association between plasma zinc concentrations, dietary zinc intake and cardiometabolic markers in the same cohort. METHODS: A secondary data analysis of a prospective cohort study, the Nepean Longitudinal Study, which followed an Australian birth cohort at ages 8 (n = 436) and 15 years (n = 290) collecting dietary, anthropometry and biochemistry data (plasma zinc, fasting glucose, insulin and lipid profile). Diet was assessed by a 3-day food record and a food frequency questionnaire at 8 and 15 years, respectively. Zinc bioavailability was determined by the phytate/zinc molar ratio. RESULTS: At 8 years, the median zinc intake was 7.84 mg (interquartile range 6.57-9.35) for boys and 7.06 mg (5.98-8.30) for girls. Three of 345 children reported inadequate absorbable zinc intake, and none reported inadequate total zinc intake. At 15 years, median zinc intake was 11.8 mg (9.41-14.8) for boys and 8.54 mg (6.76-10.7) for girls. The prevalence of inadequate intakes of absorbable zinc and total zinc was 19 and 29 %, respectively. Plasma zinc concentration was not correlated with dietary zinc intake, adiposity nor lipids at either time point, but it was inversely correlated with fasting glucose at 8 year and with insulin at 15 years. CONCLUSIONS: Australian children had an overall adequate zinc status. However, adolescents who reported suboptimal dietary zinc intakes were more likely to have raised insulin concentrations.

A moderate increase in dietary zinc reduces DNA strand breaks in leukocytes and alters plasma proteins without changing plasma zinc concentrations.

BACKGROUND: Food fortification has been recommended to improve a population's micronutrient status. Biofortification techniques modestly elevate the zinc content of cereals, but few studies have reported a positive impact on functional indicators of zinc status. OBJECTIVE: We determined the impact of a modest increase in dietary zinc that was similar to that provided by biofortification programs on whole-body and cellular indicators of zinc status. DESIGN: Eighteen men participated in a 6-wk controlled consumption study of a low-zinc, rice-based diet. The diet contained 6 mg Zn/d for 2 wk and was followed by 10 mg Zn/d for 4 wk. To reduce zinc absorption, phytate was added to the diet during the initial period. Indicators of zinc homeostasis, including total absorbed zinc (TAZ), the exchangeable zinc pool (EZP), plasma and cellular zinc concentrations, zinc transporter gene expression, and other metabolic indicators (i.e., DNA damage, inflammation, and oxidative stress), were measured before and after each dietary-zinc period. RESULTS: TAZ increased with increased dietary zinc, but plasma zinc concentrations and EZP size were unchanged. Erythrocyte and leukocyte zinc concentrations and zinc transporter expressions were not altered. However, leukocyte DNA strand breaks decreased with increased dietary zinc, and the level of proteins involved in DNA repair and antioxidant and immune functions were restored after the dietary-zinc increase. CONCLUSIONS: A moderate 4-mg/d increase in dietary zinc, similar to that which would be expected from zinc-biofortified crops, improves zinc absorption but does not alter plasma zinc. The repair of DNA strand breaks improves, as do serum protein concentrations that are associated with the DNA repair process. This trial was registered at clinicaltrials.gov as NCT02861352.

Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability.

The oral bioavailability (BA) of risedronate sodium (RS), an antiresorptive agent, is less than 1% due to its low membrane permeability as well as the formation of non-absorbable complexes with multivalent cations such as calcium ion (Ca(2+)) in the gastrointestinal tract. In the present study, to increase oral BA of the bisphosphonate, a novel enteric-coated tablet (ECT) dosage form of RS in combination with phytic acid (IP6), a natural chelating agent recognized as safe, was formulated. The chelating behavior of IP6 against Ca(2+), including a stability constant for complex formulation was characterized using the continuous variation method. Subsequently, in vitro dissolution profile and in vivo pharmacokinetic profile of the novel ECT were evaluated comparatively with that of the marketed product (Altevia, Sanofi, US), an ECT containing ethylenediaminetetraacetic acid (EDTA) as a chelating agent, in beagle dogs. The logarithm of stability constant for Ca(2+)-IP6 complex, an equilibrium constant approximating the strength of the interaction between two chemicals to form complex, was 19.05, which was 3.9-fold (p<0.05) and 1.7-fold (p<0.05) higher than those of Ca(2+)-RS and Ca(2+)-EDTA complexes. The release profile of RS from both enteric-coated dosage forms was equivalent, regardless of the type of chelating agent. An in vivo absorption study in beagle dogs revealed that the maximum plasma concentration and area under the curve of RS after oral administration of IP6-containing ECT were approximately 7.9- (p<0.05) and 5.0-fold (p<0.05) higher than those of the marketed product at the same dose (35mg as RS). Therefore, our study demonstrates the potential usefulness of the ECT system in combination with IP6 for an oral therapy with the bisphosphonate for improved BA.

Rural Beninese Children Are at Risk of Zinc Deficiency According to Stunting Prevalence and Plasma Zinc Concentration but Not Dietary Zinc Intakes.

BACKGROUND: Three commonly recommended indicators for risk assessment of population zinc deficiency are stunting rates among children aged <5 y, prevalence of inadequate dietary zinc intake, and prevalence of low plasma zinc (PZn). Data on zinc status in Benin are mainly drawn from stunting rates and data on PZn and dietary zinc intake are lacking. OBJECTIVES: The aims of this study were 1) to assess the risk of zinc deficiency in preschool and school-age children from rural communities in northern Benin by means of the 3 indicators for population assessment, 2) to evaluate their level of agreement, and 3) to identify predictors of PZn and height-for-age z scores (HAZ). METHODS: We analyzed preintervention data collected during 2 efficacy trials and cross-sectionally assessed the risk of zinc deficiency in preschool (1-5 y, n = 326) and school-age children (5-10 y, n = 272) by 1) conducting a 3-d weighed food record survey, coupled with direct zinc and phytic acid analysis of consumed foodstuffs, and calculating usual dietary zinc intakes in a subsample of school-age children (n = 36); 2) analyzing PZn in all children (n = 598); and 3) measuring anthropometry indexes for assessment of stunting (HAZ <-2 SD) in all children (n = 594) and in <5-y-old children only (n = 273). We derived predictors of PZn and HAZ by using multivariate regression with mixed-effect models. RESULTS: Prevalence of inadequate intakes of zinc ranged from 11% to 80% depending on whether the estimated average requirements (EARs) by the International Zinc Nutrition Consultative Group or the EARs derived from the WHO's recommended nutrient intakes were used. Prevalence of low PZn adjusted for acute-phase protein status was 45.7%, with higher rates among preschoolers than school-age children (P = 0.002). The stunting rate in <5-y-old children was 51.3%. PZn was predicted by age, methodologic factors, and socioeconomic status, whereas HAZ was predicted by age, sex, hemoglobin, and socioeconomic status. CONCLUSIONS: The prevalence of <5-y stunting and the prevalence of low PZn indicate that the risk of zinc deficiency is elevated in this population. Risk estimates based on the prevalence of inadequacy of zinc intakes varied depending on the EARs used, and a consensus would facilitate nutrition survey evaluations. These trials were registered at clinicaltrials.gov as NCT01472211 and NCT01790321.

Conundrum of IP6.

Here are comments on the recent paper on the determination of inositol hexaphosphate (IP6) in human plasma and on its efficacy.

There is no 'Conundrum' of InsP6.

Indirect assays have claimed to quantify phytate (InsP6) levels in human biofluids, but these have been based on the initial assumption that InsP6 is there, an assumption that our more direct assays disprove. We have shown that InsP6 does not and cannot (because of the presence of an active InsP6 phosphatase in serum) exist in mammalian serum or urine. Therefore, any physiological effects of dietary InsP6 can only be due either to its actions in the gut as a polyvalent cation chelator, or to inositol generated by its dephosphorylation by gut microflora.

Total Iron Bioavailability from the US Diet Is Lower Than the Current Estimate.

BACKGROUND: Total (heme and nonheme) iron bioavailability from the US diet has been estimated to be 18% based on a single human absorption study. New data, however, suggest that it may be time to revisit this estimate. OBJECTIVE: We estimated total iron bioavailability from the US diet with the use of our recently reported algorithm that estimates nonheme iron absorption and a conservative value for heme iron absorption. METHODS: We used dietary intake and biomarker information from the NHANES 2001-2002, MyPyramid Equivalents Database, and Food and Nutrient Database for Dietary Studies. The survey package in R software was used to estimate means and CIs, taking into account the strata, primary sampling units, and appropriate survey weight. We implemented 2 different approaches to estimate total iron absorption. In the first approach, we included all survey participants but adjusted the geometric mean of nonheme iron absorption to 15 µg ferritin/L serum to mimic values of individuals with no iron stores; in the second approach, absorption was estimated for only nonanemic subjects with no iron stores. A total sample size of 6631 was used based on availability of dietary and iron status biomarker data and C-reactive protein concentration ≤ 6 mg/L. RESULTS: The geometric mean (95% CI) of unadjusted nonheme iron absorption for all subjects was 3.7% (3.6%, 3.8%), higher in female subjects [5.6% (5.4%, 5.7%)] than male subjects [2.6% (2.5%, 2.7%)] (P < 0.0001). Nonheme iron absorption was lower in non-Hispanic whites [3.5% (3.4%, 3.6%)] than Mexican Americans [4.5% (4.2%, 4.8%)] and non-Hispanic blacks [4.4% (4.1%, 4.7%)]. Estimated total iron absorption was 15.5% or 15.1%, depending on which approach was used to carry out the calculations. CONCLUSION: This study provides useful data for evaluating the current value of iron bioavailability from the US diet.

A novel method for the purification of inositol phosphates from biological samples reveals that no phytate is present in human plasma or urine.

Inositol phosphates are a large and diverse family of signalling molecules. While genetic studies have discovered important functions for them, the biochemistry behind these roles is often not fully characterized. A key obstacle in inositol phosphate research in mammalian cells has been the lack of straightforward techniques for their purification and analysis. Here we describe the ability of titanium dioxide (TiO2) beads to bind inositol phosphates. This discovery allowed the development of a new purification protocol that, coupled with gel analysis, permitted easy identification and quantification of InsP6 (phytate), its pyrophosphate derivatives InsP7 and InsP8, and the nucleotides ATP and GTP from cell or tissue extracts. Using this approach, InsP6, InsP7 and InsP8 were visualized in Dictyostelium extracts and a variety of mammalian cell lines and tissues, and the effects of metabolic perturbation on these were explored. TiO2 bead purification also enabled us to quantify InsP6 in human plasma and urine, which led to two distinct but related observations. Firstly, there is an active InsP6 phosphatase in human plasma, and secondly, InsP6 is undetectable in either fluid. These observations seriously question reports that InsP6 is present in human biofluids and the advisability of using InsP6 as a dietary supplement.

Influence of Annona muricata (soursop) on biodistribution of radiopharmaceuticals in rats.

PURPOSE: To evaluate the effect of hydroalcoholic extract of A. muricata on biodistribution of two radiopharmaceuticals: sodium phytate and dimercaptosuccinic acid (DMSA), both labeled with 99mtechnetium. METHODS: Twenty four Wistar rats were divided into two treated groups and two controls groups. The controls received water and the treated received 25mg/kg/day of A. muricata by gavage for ten days. One hour after the last dose, the first treated group received 99mTc-DMSA and the second sodium 99mTc-phytate (0.66MBq each group), both via orbital plexus. Controls followed the same protocol. Forty min later, all groups were sacrificed and the blood, kidney and bladder were isolated from the first treated group and the blood, spleen and liver isolated from the second treated group. The percentage of radioactivity per gram of tissue (%ATI/g) was calculated using a gamma counter. RESULTS: The statistical analysis showed that there was a statistically significant decrease (p<0.05) in the uptake of %ATI/g in bladder (0.11±0.01and1.60±0.08), kidney (3.52±0.51and11.84±1.57) and blood (0.15±0.01and 0.54±0.05) between the treated group and control group, respectively. CONCLUSION: The A. muricata hydroalcoholic extract negatively influenced the uptake of 99mTc-DMSA in bladder, kidney and blood of rats.

Absence of detectable inositol hexakisphosphate (phytate) in plasma.

A critical evaluation of a recent attempt to measure inositol hexakisphosphate (IP6) in mammalian plasma by mass spectroscopy leads to the conclusion that as yet there is no unambiguous evidence that plasma contains any IP6.

Validation of an LC-MS bioanalytical method for quantification of phytate levels in rat, dog and human plasma.

Myo-inositol hexakisphosphate (phytate, IP6) is a naturally occuring compound whose determination in biological matrices is chanllenging. Several benefitial properties have been attributed to IP6 in parallel with the development of suitable analytical methodologies for its analytical determination in urine and some tissues. However, there is a lack of appropriate tools for its determination in plasma samples. In this paper, a direct, sensitive and selective bioanalytical method for the determination of IP6 based on LC-MS is presented. It is the first method published to quantify IP6 in plasma matrices directly through its molecular weight, being consequently a highly specific methodology. The method has been validated in rat, dog and human plasma, according to the acceptance criteria laid down in the FDA guidance Bioanalytical Method Validation. Accuracy and precision were not greater than 15% at medium and high concentrations and not greater than 20% at the LLOQ concentration. The mean absolute recovery obtained ranged from 78.74 to 102.44%, 62.10 to 87.21% and 61.61 to 86.99% for rat, dog and human plasma respectively. The LLOQ was 500ngmL(-1) due to the presence of endogenous IP6 in blank plasma samples and the limit of detection was within the range 30-80ngmL(-1).

Dietary fiber intake increases the risk of zinc deficiency in healthy and diabetic women.

Phytic acid is a major determinant of zinc bioavailability. Little is known about phytic acid intakes or indices of zinc bioavailability in type 2 diabetes mellitus (DM), a condition that predisposes to zinc deficiency. The aim of this cross-sectional study was to measure and explore the relationships among phytic acid intake, zinc bioavailability, and molecular markers of zinc homeostasis in 20 women with DM compared to 20 healthy women. The phytate/zinc, (calcium)(phytate)/zinc, and (calcium + magnesium)(phytate)/zinc molar ratios were used to indicate zinc bioavailability. Plasma zinc concentrations and zinc transporter (ZnT1, ZnT8, and Zip1) gene expression in mononuclear cells were measured. Participants with DM consumed 1,194 ± 824 mg/day (mean ± SD) phytic acid, an amount similar to the intake of healthy women (1,316 ± 708 mg/day). Bread products and breakfast cereals contributed more than 40 % of the phytic acid intake in each group. A positive relationship was observed in all participants between phytic acid and dietary fiber (r = 0.6, P < 0.001) and between dietary fiber and the (calcium)(phytate)/zinc ratio (r = 0.5, P < 0.001). Compared to the healthy group, the messenger RNA ratio of ZnT1 (zinc export) to Zip1 (zinc import) was lower in participants with DM, which may indicate perturbed zinc homeostasis in the disorder. The plasma zinc concentration was not predicted by age, body mass index, health status, zinc bioavailability, or zinc transporter expression. Healthy and diabetic women consume phytic acid in amounts that are likely to decrease the bioavailability of dietary zinc. Recommendations to consume greater amounts of dietary fiber, much of which is associated with phytate, increase the risk of zinc deficiency.

A randomized controlled study to evaluate the depigmenting activity of L-ascorbic acid plus phytic acid-serum vs. placebo on solar lentigines.

BACKGROUND: Solar lentigines (SL) are benign signs of sun damage that many people find distressing. AIM: To assess the efficacy and safety of L-ascorbic acid 10% + phytic acid 2% for treating SL. PATIENTS/METHODS: A double-blind, vehicle-controlled trial in 30 healthy subjects with ≥2 SL. Subjects were randomly assigned to apply product to one side of the body and vehicle to the other twice daily for 3 months with follow-up of 2 months. RESULTS: The pigmentation index for product-treated SL was reduced (maximum reduction 1.3 at 3 months [M3]), while that for vehicle-treated lesions remained stable. These differences were statistically significant for M1-M4 (P ≤ 0.003). Dermoscopy detected significant intergroup differences in pigmentation at M5 (P=0.011). Colorimetry results indicated a statistically significant improvement in brightness (L*) between study drug and vehicle at M5. Fifteen subjects experienced 23 adverse events; six (mostly halo depigmentation) were judged possibly related to the study drug. There were six instances of mild-to-moderate intolerance in the study drug group and five in the vehicle-treated group. CONCLUSIONS: Study treatment was significantly more efficacious than vehicle in many respects and was well tolerated. Future, larger studies are needed to confirm these results and to compare the product with gold standard treatments.

Influence of an iron intervention on the zinc status of young adult New Zealand women with mild iron deficiency.

Interventions to combat mild Fe deficiency in women of childbearing age may affect Zn nutriture. We used dietary and laboratory indices to assess change in Zn status during a 4-month partially blinded placebo-controlled Fe intervention in women with low Fe stores (serum ferritin < 20 microg/l and Hb > or = 120 g/l) from Dunedin, New Zealand. Subjects aged 18-40 years were randomly assigned to three groups: dietary advice (diet group; DG; n 29), daily Fe supplement with meals (supplement group; SG; n 23; 50 mg Fe as amino acid chelate) and placebo (placebo group; PG, n 26). A validated semi-quantitative FFQ (SFFQ) was administered at baseline, and at 4, 8 and 15 weeks; fasting morning blood samples were assayed for serum Zn, alkaline phosphatase (ALP) and C-reactive protein at baseline, and at 4, 8, 12 and 16 weeks; hair Zn and taste detection thresholds by electrogustometry were measured at baseline and at 16 weeks. Intakes of flesh foods and vitamin C but not Zn or Fe increased, whereas phytate and phytate:Zn molar ratios decreased (all P < or = 0.01) in the DG compared with the PG and SG, based on three SFFQ. Serum Zn increased in both the DG and PG (adjusted, P < or = 0.002), so the between-group difference was not significant; the lack of a parallel rise in the SG was significant when compared with the PG (P = 0.02). ALP activity (but not hair Zn or taste acuity) followed a similar trend. In conclusion, Zn status was not improved compared with placebo by an Fe-based dietary intervention. However, a daily moderate-dose Fe supplement with meals appeared to lower Zn status in these young adult women.

Algorithms for iron and zinc bioavailability: are they accurate?

Several bioavailability algorithms have been proposed for iron and zinc, confirming the need for these tools while emphasizing the challenge of deriving algorithms with accepted accuracy. This manuscript briefly reviews current evidence on the accuracy of proposed algorithms. Iron absorption is strongly influenced by both body iron status and dietary availability, and most evidence suggests that these do not interact. There is considerable evidence of a logarithmic relationship between percent iron absorption and serum ferritin that allows a simple and accurate computation of how human iron status affects absorption (in the absence of inflammation). Computing the effect of dietary variation on nonheme iron absorption has been challenging because of multiple influential dietary factors and incomplete knowledge of their chemical characteristics, food composition, interactions, and dose-response relationships. At present there is no fully validated algorithm for dietary iron bioavailability. Predicting zinc absorption is less complex. Fractional zinc absorption is substantially influenced by the amount of zinc consumed, and this factor, together with ingested phytic acid, account for a considerable degree of the variance. A multivariate saturation model based on these two variables has been derived using data from multiple studies and independently validated with a single large data set.