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.
The World Health Organization recommends serum ferritin concentrations as the best indicator of iron deficiency (ID). Unfortunately, ferritin increases with infections; hence, the prevalence of ID is ...underestimated.
The objective was to estimate the increase in ferritin in 32 studies of apparently healthy persons by using 2 acute-phase proteins (APPs), C-reactive protein (CRP) and alpha(1)-acid glycoprotein (AGP), individually and in combination, and to calculate factors to remove the influence of inflammation from ferritin concentrations.
We estimated the increase in ferritin associated with inflammation (ie, CRP gt 5 mg/L and/or AGP gt 1 g/L). The 32 studies comprised infants (5 studies), children (7 studies), men (4 studies), and women (16 studies) (n = 8796 subjects). In 2-group analyses (either CRP or AGP), we compared the ratios of log ferritin with or without inflammation in 30 studies. In addition, in 22 studies, the data allowed a comparison of ratios of log ferritin between 4 subgroups: reference (no elevated APP), incubation (elevated CRP only), early convalescence (both APP and CRP elevated), and late convalescence (elevated AGP only).
In the 2-group analysis, inflammation increased ferritin by 49.6% (CRP) or 38.2% (AGP; both P lt 0.001). Elevated AGP was more common than CRP in young persons than in adults. In the 4-group analysis, ferritin was 30%, 90%, and 36% (all P lt 0.001) higher in the incubation, early convalescence, and late convalescence subgroups, respectively, with corresponding correction factors of 0.77, 0.53, and 0.75. Overall, inflammation increased ferritin by ap 30% and was associated with a 14% (CI: 7%, 21%) underestimation of ID.
Measures of both APP and CRP are needed to estimate the full effect of inflammation and can be used to correct ferritin concentrations. Few differences were observed between age and sex subgroups.
Wieringa et al discuss the study by Suri et al on associations between inflammation and total body and liver stores of vitamin A. The study fits well in a series of papers appearing in the last ...couple of years examining the impact of inflammation on the biomarkers of micronutrient status. Studies have examined the associations between inflammation and ferritin, soluble transferrin receptor, retinol-binding protein, and zinc, to name a few. The importance of the article lies not in demonstrating that the retinol isotope dilution method is rather unaffected by inflammation or in arguing that we should switch to the retinol dilution method to determine vitamin A status in populations with a high prevalence of inflammation.
The immune response promotes a complex series of reactions by the host in an effort to prevent ongoing tissue damage, isolate and destroy the infective organism and activate the repair processes that ...are necessary for restoring normal function. The homoeostatic process is known as inflammation and the early set of reactions that are induced are known as the acute phase response (APR). The APR has marked effects on the circulation, metabolism in the liver and the plasma concentration of many nutrients. The changes in nutrient concentrations follow a cyclic pattern; occurring before any clinical evidence of disease, being at their most pronounced during the disease and remaining in convalescence when all evidence of disease or trauma has disappeared. Therefore, where susceptibility to disease is high as in people who are HIV+ but still apparently healthy, obtaining an accurate measurement of nutritional status may not be possible. Accurate measurements of status are important for national statistics to plan for the proper utilisation of government resources and they are especially important to evaluate the effectiveness of nutritional interventions. Many acute phase proteins (APP) are synthesised during inflammation and they are used to monitor the progress of disease and recovery but, individually, none of their lifecycles compare well with those of the nutritional biomarkers. Nevertheless, recognising the presence of inflammation can help interpret data and, using two APP, this review paper will illustrate the methods we have developed to assist interpretation of plasma retinol, ferritin and zinc concentrations in apparently healthy, HIV+, Kenyan adults.
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 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.
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.
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.
Inflammation and Vitamin A Thurnham, David I.
Food and nutrition bulletin,
09/2015, Volume:
36, Issue:
3
Journal Article
Peer reviewed
Open access
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 macula (central retina) contains a yellow pigment, comprising the dietary carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin, known as macular pigment (MP). The concentrations of MP's ...constituent carotenoids in retina and brain tissue correlate, and there is a biologically-plausible rationale, supported by emerging evidence, that MP's constituent carotenoids are also important for cognitive function.
To investigate if patients with Alzheimer's disease (AD) are comparable to controls in terms of MP and visual function.
36 patients with moderate AD and 33 controls with the same age range participated. MP was measured using dual-wavelength autofluorescence (Heidelberg Spectralis®); cognitive function was assessed using a battery of cognition tests (including Cambridge Neuropsychological Test Automated Battery). Visual function was recorded by measuring best corrected visual acuity (BCVA) and contrast sensitivity (CS). Serum L and Z concentrations (by HPLC) and age-related macular degeneration (AMD, by retinal examination) status were also assessed.
In the AD group, central MP (i.e., at 0.23°) and MP volume were significantly lower than the control group (p < 0.001 for both), as were measures of BCVA, CS, and serum L and Z concentrations (p < 0.05, for all).
AD patients were observed to exhibit significantly less MP, lower serum concentrations of L and Z, poorer vision, and a higher occurrence of AMD when compared to control subjects. A clinical trial in AD patients designed to investigate the impact of macular carotenoid supplementation with respect to MP, visual function, and cognitive function is merited.
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 β-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.
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