An Ex-Ante Analysis of the Impact of Biofortified Zinc Rice on Dietary Zinc Inadequacy: Evidence from Bangladesh, Indonesia, and the Philippines.

BACKGROUND: South, East and Southeast Asia are among regions of the world with the highest estimated prevalence of inadequate zinc intake. Because populations in those regions eat rice as their main staple, zinc biofortification of rice has the potential to improve zinc intake especially among the most vulnerable OBJECTIVE: We modeled the impact of consumption of zinc-biofortified rice on zinc intake and inadequacy among women of childbearing age and young children nationally in Indonesia, and the Philippines, and at a sub-national level in Bangladesh METHODS: We conducted an ex-ante analysis by applying increments of zinc content in rice, from a baseline level of 16 parts per million (ppm) to 100 ppm, and based on rice consumption data to substitute levels of conventional rice with zinc-biofortified rice varying between 10% and 70% RESULTS: Among all datasets evaluated from these three countries, the prevalence of dietary zinc inadequacy at baseline was 94 to 99% among women of childbearing age, 77 to 100% among children 4-5 years old and 27 to 78% among children 1-3 years old. At the current breeding target of 28 ppm, zinc-biofortified rice has the potential to decrease zinc inadequacy by up to 50 percent among women and children in rural Bangladesh and among children in the Philippines where consumption of rice is higher compared to Indonesia CONCLUSIONS: Our analysis shows that increasing zinc content in rice up to 45 ppm reduces the burden of zinc inadequacy substantially, after which we encourage programs to increase coverage to reach the highest number of beneficiaries.

Biofortified ß-carotene rice improves vitamin A intake and reduces the prevalence of inadequacy among women and young children in a simulated analysis in Bangladesh, Indonesia, and the Philippines.

BACKGROUND: Vitamin A deficiency continues to be a major public health problem affecting developing countries where people eat mostly rice as a staple food. In Asia, rice provides up to 80% of the total daily energy intake. OBJECTIVE: We used existing data sets from Bangladesh, Indonesia, and the Philippines, where dietary intakes have been quantified at the individual level to 1) determine the rice and vitamin A intake in nonpregnant, nonlactating women of reproductive age and in nonbreastfed children 1-3 y old and 2) simulate the amount of change that could be achieved in the prevalence of inadequate intake of vitamin A if rice biofortified with ß-carotene were consumed instead of the rice consumed at present. DESIGN: We considered a range of 4-20 parts per million (ppm) of ß-carotene content and 10-70% substitution levels for the biofortified rice. Software was used to estimate usual rice and vitamin A intake for the simulation analyses. RESULTS: In an analysis by country, the substitution of biofortified rice for white rice in the optimistic scenario (20 ppm and 70% substitution) decreased the prevalence of vitamin A inadequacy from baseline 78% in women and 71% in children in Bangladesh. In Indonesia and the Philippines, the prevalence of inadequacy fell by 55-60% in women and dropped by nearly 30% in children from baseline. CONCLUSIONS: The results of the simulation analysis were striking in that even low substitution levels and modest increases in the ß-carotene of rice produced a meaningful decrease in the prevalence of inadequate intake of vitamin A. Increasing the substitution levels had a greater impact than increasing the ß-carotene content by >12 ppm.

Biological Status and Dietary Intakes of Iron, Zinc and Vitamin A among Women and Preschool Children in Rural Burkina Faso.

BACKGROUND: Food-based approaches such as biofortification are meant to sustainably address micronutrient deficiencies in poor settings. Knowing more about micronutrient intakes and deficiencies is a prerequisite to designing and evaluating interventions. OBJECTIVE: The objectives of the study were to assess biological status and dietary intakes of iron, zinc and vitamin A among women and children aged 36-59 months in rural Burkina Faso and to study relationships between intake and status to better inform future food-based interventions. DESIGN: A cross-sectional survey was carried out in two rural provinces of Burkina Faso on a random cluster sample of 480 mother-child pairs. Dietary data was obtained by 24-hour recalls repeated on a random sub-selection of 37.5% of subjects to allow calculation of nutrient's probability of adequacy (PA). Biomarkers were measured on a sub-sample of 180 mother-child pairs. Blood samples were analyzed for hemoglobin, serum ferritin, soluble transferrin receptors (sTfR), C-reactive protein, alpha-1-glycoprotein, serum zinc concentration (SZnC) and retinol. For each micronutrient the relationship between biomarker and dietary intake was investigated by multiple linear regression models accounting for inflammatory biomarkers. RESULTS: Mean PA for iron, zinc and vitamin A was 0.49, 0.87 and 0.21 among women and 0.61, 0.95 and 0.33 among children, respectively. Prevalence of anemia, corrected low serum ferritin and high sTfR was 37.6%, 4.0% and 77.5% among women and 72.1%, 1.5% and 87.6% among children, respectively. Prevalence of low SZnC and corrected low serum retinol was 39.4% and 12.0% among women and 63.7% and 24.8% among children, respectively. There was a tendency for a positive relationship between vitamin A intakes and serum retinol among women (ß = 0.0003, P = 0.06). Otherwise, no link was found between micronutrients biomarkers and intakes. CONCLUSION: Our study depicted different images of micronutrient deficiencies when based on dietary intakes or biomarkers results, thus highlighting the need for more suitable biomarkers and more precise measures of absorbable micronutrient intakes at the individual level. It thus points to challenges in the design and evaluation of future biofortification or other food-based interventions in rural areas of Burkina Faso.

Cassava Intake and Vitamin A Status among Women and Preschool Children in Akwa-Ibom, Nigeria.

BACKGROUND: As part of the HarvestPlus provitamin A-biofortified cassava program in Nigeria we conducted a survey to determine the cassava intake and prevalence of vitamin A deficiency among children 6-59 months and women of childbearing age in the state of Akwa Ibom. METHODS: A cluster-randomized cross-sectional survey was conducted in 2011 in Akwa Ibom, Nigeria. The usual food and nutrient intakes were estimated using a multi-pass 24-hour recall with repeated recall on a subsample. Blood samples of children and women were collected to analyze for serum retinol, serum ferritin, and acute phase proteins as indicators of infection. Vitamin A deficiency was defined as serum retinol <0.70 µmol/L adjusted for infection. RESULTS: A total of 587 households of a mother-child dyad participated in the dietary intake assessment. Cassava was very widely consumed in Akwa Ibom, mainly as gari or foofoo. Daily cassava consumption frequency was 92% and 95% among children and women, respectively. Mean (±SD) cassava intake (expressed as raw fresh weight) was 348 ± 317 grams/day among children and 940 ± 777 grams/day among women. Intakes of most micronutrients appeared to be adequate with the exception of calcium. Median vitamin A intake was very high both for children (1038 µg RAE/day) and women (2441 µg RAE/day). Red palm oil and dark green leafy vegetables were the main sources of vitamin A in the diet, with red palm oil alone contributing almost 60% of vitamin A intake in women and children. Prevalence of vitamin A deficiency ranged from moderate (16.9 %) among children to virtually non-existent (3.4 %) among women. CONCLUSION: Consumption of cassava and vitamin A intake was high among women and children in Akwa Ibom with a prevalence of vitamin A deficiency ranging from moderate in children to non-existent among women. The provitamin A biofortified cassava and other vitamin A interventions should focus dissemination in states where red palm oil is not widely consumed.

Iron absorption in raw and cooked bananas: a field study using stable isotopes in women.

BACKGROUND: Banana is a staple food in many regions with high iron deficiency and may be a potential vehicle for iron fortification. However, iron absorption from bananas is not known. OBJECTIVE: The objective of this study was to evaluate total iron absorption from raw and cooked bananas. DESIGN: Thirty women (34.9±6.6 years) from rural Mexico were randomly assigned to one of two groups each consuming: 1) 480 g/day of raw banana for 6 days, or 2) 500 g/day of cooked banana for 4 days. Iron absorption was measured after extrinsically labeling with 2 mg of (58)Fe and a reference dose of 6 mg (57)Fe; analysis was done using ICP-MS. RESULTS: Iron content in cooked bananas was significantly higher than raw bananas (0.53 mg/100 g bananas vs. 0.33 mg/100 mg bananas, respectively) (p<0.001). Percent iron absorption was significantly higher in raw bananas (49.3±21.3%) compared with cooked banana (33.9±16.2%) (p=0.035). Total amount of iron absorbed from raw and cooked bananas was similar (0.77±0.33 mg vs. 0.86±0.41 mg, respectively). CONCLUSION: Total amount of absorbed iron is similar between cooked and raw bananas. The banana matrix does not affect iron absorption and is therefore a potential effective target for genetic modification for iron biofortification.

Comparison of content and in vitro bioaccessibility of provitamin A carotenoids in home cooked and commercially processed orange fleshed sweet potato (Ipomea batatas Lam).

Vitamin A deficiency (VAD) remains a public health problem in some regions of Brazil. Increased use of orange-fleshed sweet potato (OFSP) as a source of pro-vitamin A represents a potential strategy for prevention of VAD. We compared the pro-vitamin A content, vitamin A equivalency and bioaccessibility of ß-carotene (ßC) of two varieties of home cooked OFSP and two commercial sources of processed OFSP. Pro-vitamin A carotenoid content in home cooked, Beauregard variety of OFSP exceeded that in Amelia variety and commercial products for babies. All-trans-ßC was the most abundant carotenoid in raw, cooked and commercial OFSP. Boiling and frying OFSP generally decreased total ßC. A serving of 100 g FW Beauregard variety of cooked OFSP contained greater than 100% of the estimated average requirement (EAR) for children and women, and up to 92% EAR for lactating women. Although the efficiency of micellarization of all-trans-ßC during simulated digestion of OFSP was relatively low (4-8%) and significantly less than for cis-isomers, the quantities of trans-ßC incorporated into micelles from boiled Beauregard and fried Amelia varieties exceeded that in micelles generated by digesting commercial OFSP. The bioaccessibility of pro-vitamin A carotenoids in the micelle fraction of digested OFSP was confirmed with differentiated cultures of Caco-2 human intestinal cells. Continued development of OFSP such as the Amelia and Beauregard varieties that are rich in trans-ßC and dissemination of best practices for home cooking are encouraged to increase consumption of this food to decrease the risk of vitamin A deficiency in Brazil.

Retention of provitamin a carotenoids in staple crops targeted for biofortification in Africa: cassava, maize and sweet potato.

HarvestPlus, part of the Consultative Group on Internation Agriculture research (CGIAR) Program on Agriculture for Nutrition and Health (A4NH) uses conventional plant breeding techniques to develop staple food crops that are rich in micronutrients, a food-based approach to reduce micronutrient malnutrition known as biofortification. The nutritional breeding targets are established based on the food intake of target populations, nutrient losses during storage and processing and bioavailability. This review collates the evidence on the retention of provitamin A carotenoid (pVAC) after processing, cooking, and storing of the staple crops targeted for pVAC biofortification: cassava, maize, and sweet potato. Sun drying was more detrimental to the pVAC levels (27-56% retention) in cassava than shade (59%) or oven (55-91%) drying, while the pVAC retention levels (66-96%) in sweet potato were not significantly different among the various drying methods. Overall, boiling and steaming had higher pVAC retention (80-98%) compared to baking (30-70%) and frying (18-54%). Gari, the most frequently consumed form of cassava in West Africa had the lowest pVAC retention (10-30%). The pVAC retention of maize grain and cassava and sweet potato flour reached levels as low as 20% after 1-4 months of storage and was highly dependent on genotype. Therefore, we recommend that an evaluation of the pVAC degradation rate among different genotypes be performed before a high pVAC crop is promoted.

Are biofortified staple food crops improving vitamin A and iron status in women and children? New evidence from efficacy trials.

Biofortification is the breeding of crops to increase their nutritional value, including increased contents of micronutrients or their precursors. Biofortification aims to increase nutrient levels in crops during plant growth rather than during processing of the crops into foods. Emerging research from 8 human trials conducted in the past decade with staple food crops that have been biofortified by traditional plant breeding methods were presented in this symposium. Specifically, data from 6 efficacy and 2 effectiveness trials were discussed to assess the effects of regular consumption of these enhanced staple crops on improving population vitamin A and iron status and reducing the burden of micronutrient deficiencies in targeted populations living in South Asia, Sub-Saharan Africa, and Latin America. Biofortified food crops appear to have a positive impact on nutritional and functional health outcomes, as the results from the trials suggest. Additional implementation research will be needed to ensure maximization of the beneficial impact of this intervention and a smooth scaling up to make biofortification a sustainable intervention in public health. The challenge for the global health community remains how to take this efficacious intervention and implement at large scale in the real world.

Impact of genotype and cooking style on the content, retention, and bioacessibility of ß-carotene in biofortified cassava (Manihot esculenta Crantz) conventionally bred in Brazil.

Biofortification is a strategy for decreasing micronutrient deficiencies in vulnerable populations by increasing nutrient density in staple food crops. Roots from five varieties of cassava biofortified with ß-carotene (ßC), three parental accessions, and one variety of commonly consumed white cassava from Brazil were investigated. Roots from biofortified varieties contained up to 23-fold higher ßC than white cassava, and the additional complement of ßC was primarily the all-trans isomer. At least 68% of ßC per gram fresh weight was retained after boiling or boiling and briefly frying. Micellarization of ßC during simulated digestion of fried root exceeded that of boiled root. Apical uptake of all-trans-ßC from mixed micelles by Caco-2 cells was affected by an interaction between variety and cooking style. These results suggest that Brazilian cassava biofortified with ßC has the potential to reduce vitamin A deficiency without requiring major changes in local and ethnic styles of home cooking.

Carotenoid retention of biofortified provitamin A maize (Zea mays L.) after Zambian traditional methods of milling, cooking and storage.

Provitamin A biofortified maize hybrids were developed to target vitamin A deficient populations in Africa. The purpose of this study was to evaluate the degradation of carotenoids after milling, cooking, and storage among biofortified varieties released in Zambia. The biofortified maize hybrids contained 7.5 to 10.3 µg/g dry weight (DW) of provitamin A as measured by ß-carotene equivalents (BCE). There was virtually no degradation due to milling. The BCE retention was also high (>100%) for most genotypes when the maize was cooked into thick (nshima) and thin porridge, but showed a lower BCE retention (53-98%) when cooked into samp (dehulled kernels). Most of the degradation occurred in the first 15 days of storage of the maize as kernels and ears (BCE retention 52-56%) which then stabilized, remaining between 30% and 33% of BCE after six months of storage. In conclusion, most of the provitamin A degradation in biofortified maize hybrids occurred during storage compared with cooking and the magnitude of this effect varied among genotypes.

Bioavailability of iron, zinc, and provitamin A carotenoids in biofortified staple crops.

International research efforts, including those funded by HarvestPlus, a Challenge Program of the Consultative Group on International Agricultural Research (CGIAR), are focusing on conventional plant breeding to biofortify staple crops such as maize, rice, cassava, beans, wheat, sweet potatoes, and pearl millet to increase the concentrations of micronutrients that are commonly deficient in specific population groups of developing countries. The bioavailability of micronutrients in unfortified staple crops in developing regions is typically low, which raises questions about the efficacy of these crops to improve population micronutrient status. This review of recent studies of biofortified crops aims to assess the micronutrient bioavailability of biofortified staple crops in order to derive lessons that may help direct plant breeding and to infer the potential efficacy of food-based nutrition interventions. Although reducing the amounts of antinutrients and the conduction of food processing generally increases the bioavailability of micronutrients, antinutrients still possess important benefits, and food processing results in micronutrient loss. In general, biofortified foods with relatively higher micronutrient density have higher total absorption rates than nonbiofortified varieties. Thus, evidence supports the focus on efforts to breed plants with increased micronutrient concentrations in order to decrease the influence of inhibitors and to offset losses from processing.

Seasonal differences in food and nutrient intakes among young children and their mothers in rural Burkina Faso.

It is important to understand and account for seasonal variation in food and nutrient intakes when planning interventions to combat micronutrient deficiencies in resource-poor settings. The objective of the present study was to quantify food and nutrient intakes and assess the adequacy of micronutrient intakes among young children and their mothers during the lean and post-harvest (PH) seasons in rural Burkina Faso. We quantified food intakes by 24-h recall in a representative sample of 480 children aged 36-59 months and their mothers in two provinces in Western Burkina Faso. We calculated the probability of adequacy (PA) of usual intakes of ten micronutrients and an overall mean PA (MPA). Seasonal changes in nutrient intakes and PA were assessed by mixed linear regression and non-parametric tests, respectively. Energy intakes did not differ significantly between seasons for women or children, although the women's intakes were slightly higher in the PH season. Most of the micronutrient intakes were significantly higher in the PH season, with the exception of vitamin A which was lower and vitamin B12 and Zn which were similar across seasons. MPA increased significantly across seasons, from 0·26 to 0·37 for women and from 0·43 to 0·52 for children. PA of Ca, vitamin C, folate and vitamin B12 were very low. Staple grains and vegetables were major sources of micronutrients but intakes were not sufficient to meet nutrient needs for the majority of the subjects. Food-based strategies are needed to increase micronutrient intakes of women and children in Burkina Faso.

Effect of phytate reduction of sorghum, through genetic modification, on iron and zinc availability as assessed by an in vitro dialysability bioaccessibility assay, Caco-2 cell uptake assay, and suckling rat pup absorption model.

Improved iron and zinc availability from sorghum, a commonly consumed staple, will benefit many malnourished communities in rural Africa burdened with high prevalence of iron and zinc deficiency. This research compared the effect of genetic phytate reduction in sorghum on iron and zinc bioaccessibility and uptake measured by in vitro dialysability and Caco-2 cell uptake assays to that of iron and zinc absorption measured by a suckling rat pup model. The phytate reduction (80-86%) in these sorghums significantly increased zinc availability. The Caco-2 cell method, but not the dialysability assay, proved useful in estimating zinc absorption. The measured increase in iron availability differed between the methods, possibly due to the effect of varying mineral (Ca, Fe, Zn, P) contents of the sorghums. This effect was most prominent in the iron uptake results. More research is needed to determine the effect of naturally occurring variations in mineral contents of sorghum on the iron uptake by Caco-2 cells.

Bioaccessibility of carotenoids from transgenic provitamin A biofortified sorghum.

Biofortified sorghum (Sorghum bicolor (L.) Moench) lines are being developed to target vitamin A deficiency in Sub-Saharan Africa, but the delivery of provitamin A carotenoids from such diverse germplasms has not been evaluated. The purpose of this study was to screen vectors and independent transgenic events for the bioaccessibility of provitamin A carotenoids using an in vitro digestion model. The germplasm background and transgenic sorghum contained 1.0-1.5 and 3.3-14.0 µg/g ß-carotene equivalents on a dry weight basis (DW), respectively. Test porridges made from milled transgenic sorghum contained up to 250 µg of ß-carotene equivalents per 100 g of porridge on a fresh weight basis (FW). Micellarization efficiency of all-trans-ß-carotene was lower (p < 0.05) from transgenic sorghum (1-5%) than from null/nontransgenic sorghum (6-11%) but not different between vector constructs. Carotenoid bioaccessibility was significantly improved (p < 0.05) by increasing the amount of coformulated lipid in test porridges from 5% w/w to 10% w/w. Transgenic sorghum event Homo188-A contained the greatest bioaccessible ß-carotene content, with a 4-8-fold increase from null/nontransgenic sorghum. While the bioavailability and bioconversion of provitamin A carotenoids from these grains must be confirmed in vivo, these data support the notion that biofortification of sorghum can enhance total and bioaccessible provitamin A carotenoid levels.

Cooking enhances but the degree of ripeness does not affect provitamin A carotenoid bioavailability from bananas in Mongolian gerbils.

Banana is a staple crop in many regions where vitamin A deficiency is prevalent, making it a target for provitamin A biofortification. However, matrix effects may limit provitamin A bioavailability from bananas. The retinol bioefficacies of unripe and ripe bananas (study 1A), unripe high-provitamin A bananas (study 1B), and raw and cooked bananas (study 2) were determined in retinol-depleted Mongolian gerbils (n = 97/study) using positive and negative controls. After feeding a retinol-deficient diet for 6 and 4 wk in studies 1 and 2, respectively, customized diets containing 60, 30, or 15% banana were fed for 17 and 13 d, respectively. In study 1A, the hepatic retinol of the 60% ripe Cavendish group (0.52 ± 0.13 µmol retinol/liver) differed from baseline (0.65 ± 0.15 µmol retinol/liver) and was higher than the negative control group (0.39 ± 0.16 µmol retinol/liver; P < 0.0065). In study 1B, no groups differed from baseline (0.65 ± 0.15 µmol retinol/liver; P = 0.20). In study 2, the 60% raw Butobe group (0.68 ± 0.17 µmol retinol/liver) differed from the 60% cooked Butobe group (0.87 ± 0.24 µmol retinol/liver); neither group differed from baseline (0.80 ± 0.27 µmol retinol/liver; P < 0.0001). Total liver retinol was higher in the groups fed cooked bananas than in those fed raw (P = 0.0027). Body weights did not differ even though gerbils ate more green, ripe, and raw bananas than cooked, suggesting a greater indigestible component. In conclusion, thermal processing, but not ripening, improves the retinol bioefficacy of bananas. Food matrix modification affects carotenoid bioavailability from provitamin A biofortification targets.

Retention during processing and bioaccessibility of ß-carotene in high ß-carotene transgenic cassava root.

Cassava is a root crop that serves as a primary caloric source for many African communities despite its low content of ß-carotene (ßC). Carotenoid content of roots from wild type (WT) and three transgenic lines with high ßC were compared after cooking and preparation of nonfermented and fermented flours according to traditional African methods. The various methods of processing all decreased ßC content per gram dry weight regardless of genotype. The greatest loss of ßC occurred during preparation of gari (dry fermentation followed by roasting) from WT and transgenic lines. The quantities of ßC in cooked transgenic cassava root that partitioned into mixed micelles during in vitro digestion and transported into Caco-2 cells were significantly greater than those for identically processed WT root. These results suggest that transgenic high ßC cassava will provide individuals with greater quantities of bioaccessible ßC.

Applying the FDA definition of whole grains to the evidence for cardiovascular disease health claims.

The U.S. FDA defines whole grains as consisting of the intact, ground, cracked, or flaked fruit of the grains whose principal components, the starchy endosperm, germ, and bran, are present in the same relative proportions as they exist in the intact grain. We evaluated the effect of applying the FDA definition of whole grains to the strength of scientific evidence in support of claims for risk reduction of cardiovascular disease (CVD). We concluded that using the FDA definition for whole grains as a selection criterion is limiting, because the majority of existing studies often use a broader meaning to define whole grains. When considering only whole grain studies that met the FDA definition, we found insufficient scientific evidence to support a claim that whole grain intake reduces the risk of CVD. However, a whole grain and reduced risk of CVD health claim is supported when using a broader concept of whole grain to include studies that considered intake of fiber-rich bran and germ as well as whole grain. This type of analysis is complicated by diversity in nutrients and bioactive components among different types of whole grains.

A minute dose of 14C-{beta}-carotene is absorbed and converted to retinoids in humans.

Our objective was to quantify the absorption and conversion to retinoids of a 1.01-nmol, 3.7-kBq oral dose of (14)C-beta-carotene in 8 healthy adults. The approach was to quantify, using AMS, the elimination of (14)C in feces for up to 16 d after dosing and in urine for up to 30 d after dosing. The levels of total (14)C in undiluted serial plasma samples were measured for up to 166 d after dosing. Also, the levels of (14)C in the retinyl ester (RE), retinol (ROH), and beta-carotene fractions that were isolated from undiluted plasma using HPLC were measured. The apparent digestibility of the (14)C was 53 +/- 13% (mean +/- SD), based on the mass balance data, and was generally consistent with the area under the curve for zero to infinite period of (14)C that was eliminated in the feces collections made up to 7.5 d after dosing. Metabolic fecal elimination, calculated as the slope per day (% (14)C-dose/collection from d 7.5 to the final day), was only 0.05 +/- 0.02%. The portion of the (14)C dose eliminated via urine was variable (6.5 +/- 5.2%). Participants [except participant 6 (P6)] had a distinct plasma peak of (14)C at 0.25 d post-dose, preceded by a shoulder at approximately 0.1 d, and followed by a broad (14)C peak that became indistinguishable from baseline at approximately 40 d. Plasma (14)C-RE accounted for most of the absorbed (14)C early after dosing and P1 had the longest delay in the first appearance of (14)C-RE in plasma. The data suggest that plasma RE should be considered in estimating the ROH activity equivalent of ingested beta-carotene.

Excentral cleavage of beta-carotene in vivo in a healthy man.

BACKGROUND: Excentral cleavage of beta-carotene to retinoids and apocarotenoids occurs in vitro and in animal models. Whether it occurs in humans is unclear. OBJECTIVE: We tested the hypothesis of whether humans can cleave beta-carotene excentrally. DESIGN: A healthy man was given an oral dose of all-trans [10,10',11,11'-(14)C]-beta-carotene (1.01 nmol; 100 nCi). Its fate and that of its metabolites were measured in serial plasma samples. Its fate in feces and urine was also measured over time. Selected plasma samples were spiked with reference standards of retinol, beta-apo-12'-carotenal, beta-apo-8'-carotenal, 13-cis-retinoic acid, all-trans-retinoic acid, beta-carotene-5,6-epoxide, all-trans-beta-carotene, and retinyl palmitate and subjected to reverse-phase HPLC fractionation. The plasma, plasma fractions, urine, and feces were measured for (14)C with the use of accelerator mass spectrometry. RESULTS: Sixty-five percent of administered (14)C was absorbed, and 15.7% was eliminated in urine during the first 21 d after dosing. (14)C-beta-carotene and (14)C-retinyl palmitate appeared in plasma 0.25 d after the dose. (14)C-beta-carotene and (14)C-retinol both appeared at 0.5 d only. On day 3 after the dose, 2 large (14)C peaks appeared in plasma: one matched the retention time of beta-apo-8'-carotenal, and the other did not match any of the reference standards used. The delayed appearance of (14)C-beta-apo-8'-carotenal in plasma suggests that the excentral cleavage occurred after the (14)C-beta-apo-8'-carotene was absorbed into the body. CONCLUSION: These data suggest that excentral cleavage of ingested beta-carotene occurs in vivo in humans. Confirmation of that possibility and further study to identify and characterize additional metabolites are needed.

A feasibility study quantifying in vivo human alpha-tocopherol metabolism.

BACKGROUND: Quantitation of human vitamin E metabolism is incomplete, so we quantified RRR- and all-rac-alpha-tocopherol metabolism in an adult. OBJECTIVE: The objective of the study was to quantify and interpret in vivo human vitamin E metabolism. DESIGN: A man was given an oral dose of 0.001821 micromol [5-14CH3]RRR-alpha-tocopheryl acetate (with 101.5 nCi 14C), and its fate in plasma, plasma lipoproteins, urine, and feces was measured over time. Data were analyzed and interpreted by using kinetic modeling. The protocol was repeated later with 0.001667 micromol [5-14CH3]all-rac-alpha-tocopheryl acetate (with 99.98 nCi 14C). RESULTS: RRR-alpha-tocopheryl acetate and all-rac-alpha-tocopheryl acetate were absorbed equally well (fractional absorption: approximately 0.775). The main route of elimination was urine, and approximately 90% of the absorbed dose was alpha-2(2'-carboxyethyl)-6-hydroxychroman. Whereas 93.8% of RRR-alpha-tocopherol flow to liver kinetic pool B from plasma was returned to plasma, only 80% of the flow of all-rac-alpha-tocopherol returned to plasma; the difference (14%) was degraded and eliminated. Thus, for newly digested alpha-tocopherol, the all-rac form is preferentially degraded and eliminated over the RRR form. Respective residence times in liver kinetic pool A and plasma for RRR-alpha-tocopherol were 1.16 and 2.19 times as long as those for all-rac-alpha-tocopherol. Model-estimated distributions of plasma alpha-tocopherol, extrahepatic tissue alpha-tocopherol, and liver kinetic pool B for RRR-alpha-tocopherol were, respectively, 6.77, 2.71, and 3.91 times as great as those for all-rac-alpha-tocopherol. Of the lipoproteins, HDL had the lowest 14C enrichment. Liver had 2 kinetically distinct alpha-tocopherol pools. CONCLUSIONS: Both isomers were well absorbed; all-rac-alpha-tocopherol was preferentially degraded and eliminated in urine, the major route. RRR-alpha-tocopherol had a longer residence time and larger distribution than did all-rac-alpha-tocopherol. Liver had 2 distinct alpha-tocopherol pools. The model is a hypothesis, its estimates are model-dependent, and it encourages further testing.