Serum and macular response to carotenoid-enriched egg supplementation in human subjects: the Egg Xanthophyll Intervention clinical Trial (EXIT).

The macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the macula, where they are collectively referred to as macular pigment (MP). Augmentation of this pigment, typically achieved through diet and supplementation, enhances visual function and protects against progression of age-related macular degeneration. However, it is known that eggs are a rich dietary source of L and Z, in a highly bioavailable matrix. In this single-blind placebo-controlled study, L- and MZ-enriched eggs and control non-enriched eggs were fed to human subjects (mean age 41 and 35 years, respectively) over an 8-week period, and outcome measures included MP, visual function and serum concentrations of carotenoids and cholesterol. Serum carotenoid concentrations increased significantly in control and enriched egg groups, but to a significantly greater extent in the enriched egg group (P<0·001 for L, Z and MZ). There was no significant increase in MP in either study group post intervention, and we saw no significant improvement in visual performance in either group. Total cholesterol increased significantly in each group, but it did not exceed the upper limit of the normative range (6·5 mmol/l). Therefore, carotenoid-enriched eggs may represent an effective dietary source of L, Z and MZ, reflected in significantly raised serum concentrations of these carotenoids, and consequentially improved bioavailability for capture by target tissues. However, benefits in terms of MP augmentation and /or improved visual performance were not realised over the 8-week study period, and a study of greater duration will be required to address these questions.

Inflammation and biomarkers of micronutrient status.

PURPOSE OF REVIEW: Investigations to discover new biomarkers of nutrition highlighted the fact that inflammation and infection were cross-cutting issues complicating interpretation of status. Collaborative groups of nutritionists, immunologists, clinicians and statisticians were set up to investigate the issues, and some are now reporting their findings. RECENT FINDINGS: Recent work on the vitamins A, D, E and C and the elements iron, zinc and selenium are reported in this review. In clinical settings, experts emphasize the unreliability of nutritional biomarkers to reflect status, but some advocate the use of albumin to assist interpretation. In apparently healthy people with subclinical inflammation, one method to correct data on vitamin A and iron stores using C-reactive protein and alpha-1-acid glycoprotein is available, and two studies report on its use; others methods are currently being investigated. SUMMARY: Biomarkers of most micronutrients are the plasma concentrations of the respective vitamins or minerals and, irrespective of nutritional status, many are reduced by inflammation; the main exception is ferritin which is increased. Different methods are being investigated to better interpret nutritional data in the presence of infection or inflammation, and nutritionists who work with apparently healthy people need to be aware of subclinical inflammation to avoid exaggerating or underreporting nutritional results.

Folate and vitamin B12 status and dietary intake of anaemic adolescent schoolgirls in the delta region of Myanmar.

The aim of the present study was to assess the prevalence of deficiency of folate and vitamin B12 and, simultaneously, the nutrient intake adequacy of folate, vitamin B12, iron, vitamin A, vitamin C, vitamin B6 and calcium in 391 adolescent anaemic (Hb<120 g/l) schoolgirls living in the delta region of Myanmar (Burma). Dietary intakes were assessed using a 3 d estimated food record. The distribution of observed intakes calculated from the food records were adjusted for usual intakes, and the prevalence of inadequacy was estimated using the estimated average requirement cut-point method. Median (first, third quartile) serum folate and vitamin B12 concentrations were 6·5 (4·6, 8·5) nmol/l and 612·8 (443·2, 795·2) pmol/l, respectively. The prevalence of folate deficiency defined as <6·8 nmol/l was 54 %; however, vitamin B12 deficiency defined as <148 pmol/l was negligible (<1 %). The prevalence of inadequate intake of folate was high (100 %) as was the prevalence of inadequate intakes of vitamin A, vitamin C, vitamin B6 and calcium, ranging from 60 to 100 %. Red meat or poultry was rarely consumed, but fish was consumed on a daily basis. Green leafy vegetables were also consumed frequently but consumption of dairy products was uncommon. Folate deficiency was high, and the prevalence of inadequate intake of folate among other key micronutrients was relatively common in this sample of anaemic adolescent schoolgirls. Appropriate strategies such as food fortification and dietary diversification are needed to improve the micronutrient status of these young women to ensure optimal health and future reproductive success.

The use of adjustment factors to address the impact of inflammation on vitamin A and iron status in humans.

Many nutrient biomarkers are altered by inflammation. We calculated adjustment factors for retinol and ferritin by using meta-analyses of studies containing the respective biomarker and 2 acute phase proteins in serum, C-reactive protein (CRP), and α1-acid glycoprotein (AGP). With the use of CRP and AGP we identified 4 groups in each study: reference (CRP ≤5 mg/L, AGP ≤1 g/L), incubation (CRP >5 mg/L, AGP ≤1 g/L), early convalescence (CRP >5 mg/L, AGP >1 g/L), and late convalescence (CRP ≤5 mg/L, AGP >1 g/L). For each biomarker, ratios of the geometric means of the reference to each inflammation group concentration were used to calculate adjustment factors for retinol (1.13, 1.24, and 1.11) and ferritin (0.77, 0.53, and 0.75) for the incubation, early, and late convalescent groups, respectively. The application of the meta-analysis factors in more recent studies compares well with study-specific factors. The same method was used to calculate adjustment factors for soluble transferrin receptor (sTfR) and body iron stores (BISs) in Lao children. We found no advantage in adjusting sTfR for inflammation; in fact, adjustment decreased iron deficiency. Neither adjusted (10% <0 mg/kg) nor nonadjusted (12% <0 mg/kg) BISs detected as much iron deficiency as did ferritin (18% <12 µg/L) and adjusted ferritin (21% <12 µg/L) unless the cutoff for BISs was increased from 0 to <3 mg/kg. However, we could find no evidence that the larger number of children identified as having BISs <3 mg/kg had risks of anemia comparable to those identified by using ferritin <12 µg/L. In conclusion, both corrected and uncorrected ferritin concentrations <12 µg/L are associated with more iron deficiency and anemia than either sTfR >8.3 mg/L or BISs <0 mg/kg in Lao children.

Macular response to supplementation with differing xanthophyll formulations in subjects with and without age-related macular degeneration.

PURPOSE: Our aim was to investigate the macular response to three different supplements containing lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) in normal subjects and those with age-related macular degeneration (AMD). MATERIALS AND METHODS: Macular pigment optical density (MPOD) and serum xanthophyll concentrations were measured in normal (n = 31) and AMD subjects (n = 32), randomly assigned to: group 1 (20 mg L, 2 mg Z, 0.3 mg MZ), group 2 (10 mg L, 2 mg Z, 10 mg MZ) or group 3 (3 mg L, 2 mg Z, 17 mg MZ). MPOD was measured at baseline, 2, 4, 6 and 8 weeks and at 0.25°, 0.5°, 1.0° and 1.75° of eccentricity using customised heterochromatic flicker photometry and serum xanthophylls by HPLC. RESULTS: MPOD increased significantly at all eccentricities in each group (p < 0.05), except at 1.75° in group 3 (p = 0.242). There was no difference in MPOD measurements between AMD and normal subjects, except for group 2, where AMD subjects exhibited a greater response at 1.75° (p = 0.012). Final serum concentrations of MZ were positively and significantly related to final MPOD values at each eccentricity in all subjects. Targeted analysis of those subjects receiving the MZ-containing supplements exhibited stronger relationships between serum MZ concentrations and MPOD at 0.25° in group 3 than group 2; in group 2 all associations were positive, but only significant at 1.75°. CONCLUSIONS: Serum concentrations of MZ were strongly correlated with MPOD after 8 weeks of supplementation with the group 3 formulation, but the inclusion of L in the group 2 formulation may result in greater MPOD augmentation across the spatial profile.

Inflammation and Vitamin A.

BACKGROUND: Serum retinol concentrations are homeostatically controlled and only fall when liver stores of vitamin A are very low. Nevertheless, low concentrations of serum retinol occur in apparently healthy people where there is no evidence of vitamin A deficiency (VAD). OBJECTIVE: To determine the reason for low serum vitamin A concentrations where there is no VAD. METHODS: We observed that elevated acute-phase protein (APP) concentrations often accompanied low retinol concentrations, and we developed a model of the inflammatory response to categorize 4 groups of participants termed reference (no raised APP), incubation (raised acute APP only), early convalescence (both acute and chronic APP raised), and late convalescence (raised chronic APP only). We identified 7 studies with participants who could be allocated to the 4 groups, and using meta-analysis methods we calculated correction (ie, multiplication) factors 1.13, 1.24, and 1.11 to remove the influence of inflammation from the incubation, early, and late convalescent groups, respectively. CONCLUSION: In nutrition surveys or intervention studies to measure vitamin A status, workers should measure APP and correct retinol concentrations using the multiplication factors where inflammation is found.

The influence of vitamin A status on iron-deficiency anaemia in anaemic adolescent schoolgirls in Myanmar.

OBJECTIVE: The present study was conducted to investigate reasons for the high prevalence of anaemia among adolescent schoolgirls and to elucidate the role of vitamin A in contributing to Fe-deficiency anaemia (IDA). DESIGN: Among 1269 schoolgirls who were previously screened for anaemia (Hb < 120 g/l), 391 anaemic girls were further assessed for Fe, vitamin A and subclinical inflammation status. Fe and vitamin A indicators were corrected for inflammation and were compared in the Fe-deficient and non-deficient groups as well as between those with and without inflammation. Logistic regression was done to determine whether vitamin A status and subclinical inflammation were risk factors for Fe deficiency. The differences in Fe status among tertiles of vitamin A concentrations were assessed using ANOVA. SETTING: Myanmar. SUBJECTS: Adolescent schoolgirls (n 391). RESULTS: One-third of the anaemia (30·4%) was IDA. Prevalence of low vitamin A status (serum retinol <1·05 µmol/l) was 31·5%. Fe and vitamin A status were significantly different between the IDA and non-IDA groups and also based on their inflammation status. Logistic regression showed that low vitamin A status was a significant predictor for being Fe deficient (OR = 1·81; 95% CI 1·03, 3·19 and OR = 2·31; 1·31, 4·07 in the middle (1·056-1·298 µmol/l) and low (≤1·056 µmol/l) vitamin A tertiles, respectively). ANOVA showed that better Fe status was associated with a higher concentration of serum retinol but only in IDA. CONCLUSIONS: Fe deficiency was not the main cause of anaemia in the present population. The role of vitamin A as well as other micronutrients should be taken into account in addressing the problem of anaemia.

Hepcidin profile of anemic adolescent schoolgirls in Indonesia at the end of 12 weeks of iron supplementation.

BACKGROUND: Iron deficiency is still the major nutritional problem in the developing world, and iron supplementation remains one of the most effective intervention strategies. Hepcidin, a newly discovered iron regulatory hormone, is an acute phase protein, and its role in iron supplementation has not been well explored. OBJECTIVE: To investigate the hepcidin profiles of anemic adolescent girls who had received weekly iron supplementation. METHODS: A cross-sectional study was conducted at the end of iron supplementation among adolescent schoolgirls (n = 83) in Pramuka Island, Indonesia. All the girls were anemic at the beginning and received 60 mg of elemental iron twice weekly for 12 weeks. Hemoglobin, hepcidin, serum ferritin, and red cell parameters were measured, together with inflammation markers. RESULTS: At the end of the 12-week supplementation, 65.1% (n = 64) of the girls were no longer anemic, but 43.4% (n = 36) were still iron deficient. The rate of subclinical inflammation, measured by C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP), was 38.6% (n = 32). Hepcidin was not correlated with either ferritin or red cell parameters. There was no association between hepcidin and the inflammatory markers CRP and AGP. The mean hepcidin concentration was 42.9 +/- 17.9 ng/mL and was not significantly different between anemic and nonanemic girls (44.2 +/- 14.9 and 42.3 +/- 19.2 ng/mL, respectively; p = .708). However, hepcidin concentration was slightly higher in the iron replete-group than in the iron-deficient group (45.2 +/- 20.0 and 39.3 +/- 13.5 ng/mL, respectively), a suggestive trend that did not reach statistical significance (p = .218). CONCLUSIONS: Hepcidin concentrations tended to be higher among the subset of girls who responded poorly to iron supplementation as a consequence of increased subclinical inflammation. A longitudinal study should be conducted to explore the role of hepcidin in iron supplementation.

Impact of inflammation on the biomarkers of iron status in a cross-sectional survey of Lao women and children.

Anaemia is prevalent in South East Asia and Fe deficiency (ID) is considered to be the main cause, but the role of subclinical inflammation in the aetiology is uncertain. In the present study, we determined the influence of inflammation on the biomarkers of Fe status in women and children, and herein, we discuss the proportion of anaemia associated with ID. As part of the 2006 Lao People's Democratic Republic (The Lao PDR) National Nutrition Survey, blood collected from 482 young children and 816 non-pregnant women was analysed. Plasma ferritin, transferrin receptor (sTfR), Hb, C-reactive protein (CRP) and α-1-acid glycoprotein (AGP) concentrations were measured. ID was assessed using ferritin concentrations ( < 12 (children) or < 15 (adults) µg/l), sTfR concentrations (>8.3 mg/l) and body Fe stores (BIS < 0). Elevated CRP (>5 mg/l) and/or AGP (>1 g/l) concentrations were used to categorise inflammation status in order to correct the Fe biomarkers for inflammation. Inflammation was present in 14% of adults and 43% of children. Anaemia was present in 37.6% of both women (Hb concentrations < 120 g/l) and children (Hb concentrations < 110 g/l). Correcting ferritin concentrations for inflammation increased the prevalence of ID from 24.3 to 26% for women and from 18 to 21% for children (P< 0.001 for both). Ferritin concentrations were more helpful in detecting ID than sTfR concentrations or BIS, but regression analysis found that sTfr concentrations explained more of the variance in Hb concentrations in both women (20%) and children (17%) than ferritin concentrations (5 and 1.4%, respectively). Nevertheless, the total variance in Hb concentrations explained was only 26 and 18 % in women and children, respectively, and other factors may be more important than ID in contributing to anaemia in The Lao PDR.

Serum response to supplemental macular carotenoids in subjects with and without age-related macular degeneration.

Macular pigment (MP) is composed of lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ). The present study reports on serum response to three different MP supplements in normal subjects (n 27) and in subjects with age-related macular degeneration (AMD) (n 27). Subjects were randomly assigned to: Group 1 (20 mg L and 2 mg Z), Group 2 (10 mg L, 2 mg Z and 10 mg MZ) or Group 3 (3 mg L, 2 mg Z and 17 mg MZ). Serum carotenoids were quantified at baseline, and at 4 and 8 weeks using HPLC. Response data for normal and AMD subjects were comparable and therefore combined for analysis. We report response as the average of the 4- and 8-week concentrations (saturation plateau). Serum L increased significantly in Group 1 (0·036 µmol/l per mg (269 %); P< 0·001) and Group 2 (0·079 µmol/l per mg (340 %); P< 0·001), with no significant change in Group 3 (0·006 µmol/l per mg (7 %); P= 0·466). Serum Z increased significantly in Group 1 (0·037 µmol/l per mg (69 %); P= 0·001) and Group 2 (0·015 µmol/l per mg (75 %); P< 0·001), with no significant change in Group 3 ( − 0·0002 µmol/l per mg ( − 6 %); P= 0·384). Serum MZ increased significantly in Group 1 (0·0094 µmol/l (absolute value); P= 0·015), Group 2 (0·005 µmol/l per mg; P< 0·001) and Group 3 (0·004 µmol/l per mg; P< 0·001). The formulation containing all three macular carotenoids (Group 2 supplement) was the most efficacious in terms of achieving the highest combined concentration of the three MP constituent carotenoids in serum, thereby potentially optimising the bioavailability of these compounds for capture by the target tissue (retina).

The discovery and characterization of riboflavin.

The first observation of a pigment in milk with yellow-green fluorescence can be traced to the English chemist Alexander Wynter Blyth in 1872, but it was not until the early 1930s that the substance was characterized as riboflavin. Interest in accessory food factors began in the latter half of the 19th century with the discovery of the first vitamin, thiamin. Thiamin was water soluble and given the name vitamin B(1). However, researchers realized that there were one or more additional water-soluble factors and these were called the vitamin B-2 complex. The search to identify these accessory food factors in milk, whole wheat, yeast, and liver began in the early 1900s. As there is no classical nutritional disease attributable to riboflavin deficiency, it was the growth-stimulating properties of the food extracts given to young rats that provided the tool with which to investigate and eventually extract riboflavin. Riboflavin was the second vitamin to be isolated and the first from the vitamin B-2 complex; the essential nature of the vitamin as a food constituent for man was shown in 1939.

Is Iron Supplementation Influenced by Sub-Clinical Inflammation?: A Randomized Controlled Trial Among Adolescent Schoolgirls in Myanmar.

Iron absorption was impaired in the presence of sub-clinical inflammation (SCI) and might hamper the effect of iron supplementation. The purpose of the study was to identify the influence of SCI on iron supplementation. A randomized, double-blinded, placebo-controlled experimental study was conducted among anaemic adolescent schoolgirls in Ayeyarwady region, Myanmar. A total of 402 schoolgirls were recruited from six schools screened from 1269 girls who were assigned into one of four groups: Folate group (2.5 mg of folate), Vitamin A group (15,000 IU of vitamin), Iron folate group (60 mg elemental iron and folate) and Iron, and vitamin A and folate group. Supplementation was done once a week for 12 weeks. Iron, vitamin A and inflammation were measured at the baseline, middle and endline. Changes in serum ferritin and body iron were significantly higher in the IFA and IFA + vitA among those without SCI. There was interaction between vitamin A and SCI on Hb changes. Analysis of GLM repeated measure showed interactions between treatment and SCI for hemoglobin and serum transferrin receptor. Those treated with vitamin A had better outcomes when there was SCI. Inflammation accompanied a negative effect on iron supplementation and vitamin A improved efficacy of iron supplementation in the presence of SCI.

Effectiveness of an early supplementation scheme of high-dose vitamin A versus standard WHO protocol in Gambian mothers and infants: a randomised controlled trial.

BACKGROUND: Most developing countries have adopted a standard WHO dosing schedule for vitamin A supplementation. However, in 2002 the International Vitamin A Consultative Group (IVACG) Annecy Accord recommended a new high-dose regimen for mothers and infants. Our aim was to test whether the new high-dose regimen of vitamin A supplementation would increase maternal and infant plasma vitamin A, reduce infant Helicobacter pylori infection and nasopharyngeal pneumococcal carriage, and improve infant gut epithelial integrity. METHODS: In an area of moderate vitamin A deficiency in rural Gambia, 220 mother-infant pairs were enrolled in a randomised double-blind trial between September, 2001, and October, 2004, that compared the IVACG high dose with the WHO dose. The primary endpoints were levels of maternal and infant plasma vitamin A, H pylori infection, pneumococcal carriage, and gut epithelial integrity. The trial is registered as ISRCTN 98554309. FINDINGS: 197 infants completed follow-up to 12 months (99 high dose and 98 WHO dose). There were no adverse events at dosing. No differences were found in the primary outcomes for high-dose versus WHO schedule: maternal vitamin A concentration at 2 months +0.02 micromol/L (95% CI -0.10 to 0.15); infant vitamin A at 5 months +0.01 micromol/L (-0.06 to 0.08); H pylori infection at 12 months -0.3% (-14.7 to 14.2); maternal pneumococcal carriage at 12 months -2.0% (-13.7 to 9.7); infant pneumococcal carriage at 12 months -4.1% (-15.8 to 7.6); infant gut mucosal damage at 12 months 5.2% (-8.7 to 19.2). There were more clinic attendances by the high-dose group in the first 6 months of life (p=0.018). INTERPRETATION: Our results do not lend support to the proposal to increase the existing WHO standard dosing schedule for vitamin A in areas of moderate vitamin A deficiency. Caution is urged for future studies because trials have shown possible adverse effects of higher doses of vitamin A, and potential negative interactions with the expanded programme on immunisation (EPI) vaccines.

The influence and benefits of controlling for inflammation on plasma ferritin and hemoglobin responses following a multi-micronutrient supplement in apparently healthy, HIV+ Kenyan adults.

Hemoglobin and ferritin are important biomarkers of iron status but are both altered by inflammation. We used the inflammation biomarkers C-reactive protein (CRP) and alpha1-acid glycoprotein (AGP) to adjust hemoglobin and ferritin concentrations to clarify interpretation of iron status. Apparently healthy adults who tested positive twice for HIV but who had not reached stage IV or clinical AIDS were randomly allocated to receive a food supplement (n = 17 and 21) or the food plus a micronutrient capsule (MN; 10 men and 34 women, respectively) containing 30 mg iron/d. Hemoglobin, ferritin, CRP, and AGP concentrations were measured at baseline and 3 mo and subjects were divided into 4 groups (reference, no inflammation; incubating, raised CRP; early convalescence, raised AGP and CRP; and late convalescence, raised AGP). Correction factors (the ratios of the median for the reference group over each inflammatory group) improved the consistency of the ferritin but not the hemoglobin results. After correction, ferritin (but not hemoglobin) increased in both men (48 microg/L; P = 0.02) and women (12 microg/L; P = 0.04) who received MN but not in the food-only group. However, hemoglobin did improve in subjects who showed no inflammation both at baseline and mo 3 (P = 0.019), but ferritin did not increase in this group. In conclusion, ferritin concentrations were more closely linked to current inflammation than hemoglobin; hence, correction by inflammation biomarkers improved data consistency. However, low hemoglobin concentrations were the consequence of long-term chronic inflammation and improvements in response to MN supplements were only detected in subjects with no inflammation.

A supplementation study in human subjects with a combination of meso-zeaxanthin, (3R,3'R)-zeaxanthin and (3R,3'R,6'R)-lutein.

We measured the blood uptake of meso-zeaxanthin (MZ) from a mixture of macular pigments since its bioavailability in man has not been studied. Volunteers (ten men and nine women) were recruited and received one capsule of Lutein Plus/d. Blood was taken at baseline, day 10 and day 22. One capsule contained 10.8 mg lutein, 1.2 mg (3R,3'R)-zeaxanthin and 8.0 mg MZ. Plasma lutein and total zeaxanthin concentrations were quantified using isocratic liquid chromatography and the eluting xanthophyll fractions were collected and re-chromatographed on a chiral column to assess the proportion of MZ. Plasma concentrations per mg dose at day 22 suggested that (3R,3'R)-zeaxanthin (0.088 micromol/l per mg) was about 50 % more actively retained by the body than lutein (0.056 micromol/l per mg) (although the difference was not significant in women) and 2.5-3.0 times more than MZ (0.026 micromol/l per mg). Concentrations of MZ at day 22 were 2.5 times higher in women than men. The plasma responses from lutein and (3R,3'R)-zeaxanthin in the Lutein Plus were lower than literature values for the pure substances. That is, their uptake into plasma appeared to be slightly depressed by the presence of MZ. Plasma concentrations of beta-carotene were depressed by about 50 % at day 10 and about 35 % at day 22. In conclusion, the lower plasma response to MZ compared with (3R,3'R)-zeaxanthin probably indicates that MZ is less well absorbed than (3R,3'R)-zeaxanthin but work with pure MZ will be needed to confirm that the lower plasma response was not due to the large amount of lutein in the Lutein Plus.

Using plasma acute-phase protein concentrations to interpret nutritional biomarkers in apparently healthy HIV-1-seropositive Kenyan adults.

Inflammation influences the assessment of nutritional status. For example, inflammation reduces plasma retinol concentrations and vitamin A deficiency is overestimated. Conversely inflammation increases plasma ferritin concentrations and Fe deficiency is underestimated. Blood samples were obtained from 163 free-living HIV-1-infected adults, not on continuous medication, anti-retroviral drugs or micronutrients, not unwell and who had not reached WHO stage IV of HIV/AIDS. We used four markers of inflammation, C-reactive protein (CRP), alpha1-acid glycoprotein (AGP), alpha1-antichymotrypsin and erythrocyte sedimentation rate but mainly CRP and AGP were used to separate the subjects into four groups: 'healthy' where both CRP and AGP were normal; 'incubation phase' where CRP was elevated; 'early convalescence' where AGP and CRP were elevated and 'late convalescence' where only AGP was elevated. Correction factors were calculated to remove the influence of inflammation from each biomarker and group where inflammation was present and the data are shown before and after recalculation. The correction increased median plasma retinol concentrations of the whole group from 1.16 to 1.33 micromol/l, comparable with values (mean 1.29 micromol/l) in HIV-negative Kenyan women. Median ferritin concentrations fell by about 50% in both sexes and the number of women with plasma ferritin concentrations < or = 12 microg/l increased from eleven to twenty. The correction also increased plasma carotenoids and Hb but not alpha-tocopherol concentrations. We suggest that the method described to remove the influence of inflammation from nutritional biomarkers should be generally applicable in apparently healthy people and prevents discarding valuable data because of mild inflammation. The method does now need to be tested in other populations.

Monitoring micronutrients in cigarette smokers.

Smoking is associated with oxidative stress and increased risks of many chronic diseases that both shorten life and impair its quality. Low concentrations of several micronutrients, especially the antioxidants vitamin C and beta-carotene, are also associated with smoking, and there has been much interest in determining whether deficiencies in micronutrients are involved etiologically in smoking-related diseases. The objective of this review was to bring together reports on dietary intakes, biochemical indicators of micronutrient status, and results of some intervention studies on micronutrients where authors had compared outcomes in smokers and non-smokers. The micronutrients discussed are vitamins A, E, and C; the carotenoids; some of the B-vitamin group; and the minerals selenium, zinc, copper, and iron. The data were then examined to determine whether effects on the biochemical markers of micronutrient status were due to differences in dietary intakes between smokers and non-smokers or to the consequences of inflammatory changes caused by the oxidative stress of smoking. It was concluded that although smoking is associated with reduced dietary intake of vitamin C and carotenoid-containing foods, inflammatory changes increase turnover of these micronutrients so that blood concentrations are still lower in smokers than non-smokers even when there is control for dietary differences. In the case of vitamin E, there is some evidence for increased turnover of this nutrient in smokers, but this has little to no influence on blood concentrations, and there are no differences in dietary intake of vitamin E between smokers and non-smokers. Serum concentrations of vitamin A, folate, and vitamin B12 and B6 markers do not appear to be influenced by smoking, although there is some influence of dietary intake on concentrations of these nutrients in the body. In the case of the minerals examined, the main effects on biochemical markers of mineral status were attributed to inflammation and were therefore greater in heavy or long-term smokers. Serum concentrations of selenium and erythrocyte GPx activity were lower in smokers. Erythrocyte CuZn-SOD activity and serum ceruloplasmin concentrations were elevated, while serum zinc concentrations were depressed only in heavy smokers. Lastly, smoking appears to affect iron homeostasis mainly by changing hemoglobin concentrations, which were in general increased. Serum iron, TfR, and ferritin were mostly unaffected by smoking, except in pregnancy where there is evidence of increased erythropoiesis causing lower saturation of plasma transferrin and some evidence of lowering of iron stores.

Macular zeaxanthins and lutein -- a review of dietary sources and bioavailability and some relationships with macular pigment optical density and age-related macular disease.

The retina is unique in the human body in containing three xanthophyll carotenoids; 3R,3'R-zeaxanthin, meso-zeaxanthin (MZ) and lutein. Humans consume 1 to 3 mg lutein per d and the lutein:zeaxanthin ratio in the diet is about 5:1.Xanthophyll pigments occur widely in vegetables and fruits but MZ is found in only a few foods such as the shrimp carapace and fish skin. In spite of the amounts of the different xanthophylls in the diet, zeaxanthin and MZ occur in approximately equal amounts in the eye, and their combined concentration can exceed that of lutein. In the present review the bioavailablity of zeaxanthin and lutein is assessed using the plasma xanthophyll response to dietary intervention. A number of studies have used single and mixed sources of the pure xanthophylls to achieve steady-state plasma responses. Mostly these have been with lutein and zeaxanthin but two using MZ are also described. Responses following the intervention with the pure xanthophylls are compared with those following food intervention. Vegetables are the richest source of dietary lutein and several vegetable-feeding studies are discussed. Intervention studies with eggs, which are a good source of zeaxanthin, suggest that the xanthophyll carotenoids in egg yolk may be more bioavailable than those in other foods and are described separately. MZ has been a component of a xanthophyll supplement added to chicken feed in Mexico in the last 10 years. Egg consumption in Mexico is approximately one egg/person per d and the potential contribution of this food source of MZ to Mexican dietary intakes is described. Very limited information from human feeding studies of MZ-containing supplements suggests that MZ is less well absorbed than zeaxanthin. However, MZ is unusual in the diet and not reported in the plasma. Thus plasma responses may not reflect true absorption if it takes MZ longer to equilibrate with body tissues than the other xanthophylls and competition with zeaxanthin may lower the relative concentrations of MZ in plasma. Lastly, the effects of long-term feeding with both pure and food sources of the xanthophyll pigments on macular pigment optical density is compared and the importance of previous dietary intake on the effects of intervention is discussed.