Charles B Stephensen, Grace S Marquis, Robert A Jacob, Laurie A Kruzich, Steven D Douglas, Craig M Wilson, Nutritional vitamins C and E in adolescents and younger adults with HIV an infection, The American Journal of Medical Vitamin, Quantity 83, Challenge 4, April 2006, Pages 870–879, https://doi.org/10.1093/ajcn/83.4.870
ABSTRACT
INTRODUCTION
Nutritional vitamins C and E are antioxidant vitamins that defend cells and tissues in opposition to harm by reactive oxygen and nitrogen species. The manufacturing of such species will increase throughout episodes of infectious illness, when the immune system is activated to get rid of pathogenic organisms. Continual infections, resembling HIV an infection, place a long-term pressure on antioxidant defenses, which can improve dietary antioxidant necessities. The intakes of nutritional vitamins C and E advisable for wholesome topics could thus be lower than sufficient to cope with the elevated oxidative stress of HIV an infection. This stress can harm cells and tissues of the immune system and result in elevated severity of illness (1). Infections may have an effect on the absorption, tissue distribution, and excretion of vitamins (2). It’s thus not shocking that each a low consumption of vitamin C (3) and low plasma concentrations of vitamin E (4) have been related to a better threat of development to AIDS in HIV-infected US topics.
Research of HIV an infection and dietary standing in the US usually haven’t included adolescents or younger adults. Nevertheless, as a result of adolescents and younger adults are at excessive threat of HIV an infection in the US and different nations, we selected to look at the affiliation of antioxidant dietary standing with HIV an infection on this age group. To take action, we studied topics from the Reaching for Excellence in Adolescent Well being (REACH) Research, which recruited topics aged 14–18 y from 13 US cities. Most topics had been feminine and African American, and ≈20% had been Hispanic (5). The demographic traits of this inhabitants are distinctive amongst main HIV research in the US, and thus the present research offers a novel alternative to look at the relation of dietary standing to HIV an infection. The dietary consumption patterns and concentrations of immune activation and oxidative harm markers in these topics have been described beforehand (5–7).
Within the present observational research, we examined the relation of vitamin C and E intakes, HIV standing, and immune activation to biochemical indicators of antioxidant standing, together with plasma α-tocopherol, γ-tocopherol, ascorbate, and urate concentrations and complete antioxidant standing (TAS). In flip, we assessed the affiliation of those variables with indicators of oxidative harm (ie, plasma malondialdehyde and protein carbonyl concentrations). Our objectives had been to evaluate the antioxidant standing of those topics, verify whether or not HIV an infection was related to decrease plasma concentrations of those key antioxidant vitamins, determine markers of immune activation which may be related to low plasma concentrations of those vitamins (and, by inference, with better utilization), and verify whether or not plasma concentrations of those vitamins had been related to safety in opposition to oxidative harm (ie, decrease concentrations of plasma oxidative harm markers).
SUBJECTS AND METHODS
Research inhabitants
The REACH Research was a potential, observational research of HIV an infection in adolescents performed at 15 US scientific websites (8, 9). A standardized protocol was developed by way of the Adolescent Drugs HIV/AIDS Analysis Community. Between March 1996 and November 1999, 325 adolescents aged 12–18 y who had acquired HIV an infection by way of sexual exercise or intravenous drug use had been recruited. As well as, 171 HIV-negative adolescents had been recruited from the identical websites by utilizing choice standards to make the HIV-negative and HIV-positive teams comparable with regard to risk-behavior profiles and demographic traits (together with age, intercourse, race, and ethnicity). This report describes a supplemental research performed throughout one research go to between January and October 2000. One website didn’t take part within the present research due to logistical difficulties. Of the 436 contributors who had been lively within the 14 REACH Research community websites, 391 (264 HIV-positive and 127 HIV-negative) agreed to take part on this substudy. The 14 scientific websites had been positioned in Miami, Fort Lauderdale, New Orleans, Birmingham, Los Angeles, Memphis, Washington (DC), Baltimore, Philadelphia, Newark, New York Metropolis (3 websites), and Chicago.
All contributors supplied written knowledgeable consent. The research was accredited by human topics analysis assessment boards on the College of California, Davis; Iowa State College; the College of Alabama at Birmingham; and every clinic website.
Information collected by the REACH Research
Within the REACH Research, knowledge had been collected with face-to-face interviews, interactive pc interviews, medical document abstractions, and bodily and laboratory examinations. HIV-positive topics had been seen each 3 mo, and HIV-negative topics had been seen each 6 mo. Contributors had been gowned and weighed at every go to by utilizing digital scales that had been correct to 0.1 kg. Top was measured by utilizing calibrated stadiometers that had been put in at every research website. Physique mass index (BMI; in kg/m2) was calculated for every participant.
Laboratory exams had been carried out at native clinic websites based on the REACH Research protocol described elsewhere (8–11). Activated CD8+ T cells had been measured as described beforehand by utilizing CD38 and HLA-DR as markers of activation (12). Absolute CD4+ T cell counts for HIV-positive contributors had been stratified on the premise of Facilities for Illness Management and Prevention standards for HIV/AIDS classification: > 499, 200–499, and < 200 cells/mm3. The quantitative HIV-1 RNA viral load in plasma was measured in a centralized laboratory on frozen specimens by utilizing both nucleic acid sequence–primarily based amplification or NucliSens assays (Organon Teknika, Durham, NC) as described elsewhere (13). Antiretroviral remedy was coded as a dichotomous variable (receiving or not receiving remedy), and descriptive knowledge on the usage of and compliance with antiretroviral remedy had been reported beforehand (6). Variables collected for the present research Within the present research, nonfasting blood was collected at a usually scheduled REACH Research go to. Website-to-site variation inside biochemical variables was minimized by offering all websites with the identical blood-collection and -processing tubes from a central supply and by processing and analyzing all samples collected for the present research in batches at a central laboratory. Plasma C-reactive protein (CRP), ceruloplasmin, neopterin, malondialdehyde, and protein carbonyls had been measured as described (6). The Block Meals-Frequency Questionnaire [(Block FFQ) version 98.2; Block Dietary Data Systems, Berkeley, CA] was used to estimate regular dietary consumption patterns and the usage of vitamin dietary supplements over the previous 12 months as described elsewhere (7). The Block FFQ was administered in an interview format by educated clinic workers a imply (±SD) ≤1.4 ± 0.4 d after the clinic go to when blood was drawn. Serving-size footage and plates and cups had been used to assist estimate portion sizes. A registered dietitian reviewed the questionnaires, and, earlier than knowledge entry, interviewers had been contacted about lacking data, uncommon responses, or discrepancies. Nutrient consumption was measured by utilizing SYSTAT dietary evaluation software program for the Block Dietary Information Programs (model 10.0; SPSS Inc, Chicago, IL). Ascorbate and urate had been measured in plasma by utilizing HPLC with electrochemical detection, as described elsewhere (14). Plasma TAS was measured on a Hitachi 902 Autoanalyzer (Roche Molecular Programs, Alameda, CA) by utilizing reagents from Randox (San Diego, CA). Plasma α- and γ-tocopherol concentrations had been measured with isocratic reverse-phase HPLC by utilizing a C18 column and a photodiode array detector, primarily as described elsewhere (15).
Statistical evaluation Software program All analyses had been carried out by utilizing SIGMASTAT for WINDOWS (variations 2.03 and three.01; Jandel Scientific, San Rafael, CA). Until in any other case indicated, knowledge are introduced as means ± SEs, and P < 0.05 was thought of to point statistical significance. Transformations A complete of 356 topics had full knowledge for all 5 principal antioxidant variables: ascorbate, urate, TAS, α-tocopherol, and γ-tocopherol (Desk 1). Information from these topics had been used within the present evaluation. Some variables required transformation to realize normality and fixed variance. For urate, sq. root and log10 transformations had been required for bivariate and a number of regression evaluation, respectively. Log10 transformation was required for bivariate evaluation of TAS. The tocopherol values, the ratio of α-tocopherol to γ-tocopherol, and protein carbonyl values weren't normalized by a number of transformations, and bivariate evaluation was performed by utilizing nonparametric strategies. Rank-order transformation of those variables achieved normality and fixed variance for regression evaluation, aside from γ-tocopherol values for HIV-positive topics (P = 0.018 for the normality take a look at). Nevertheless, this lack of normality of the γ-tocopherol values of HIV-positive topics was ignored as a result of the elimination of topics to normalize the untransformed γ-tocopherol distribution resulted within the identification of the identical unbiased variable in stepwise regression evaluation as did the usage of rank order. Bivariate evaluation of protein carbonyl knowledge was carried out by utilizing nonparametric strategies. Log10 transformation was used for all analyses of malondialdehyde knowledge. Bivariate evaluation Bivariate evaluation was carried out by utilizing Pupil’s t exams and 1-way and 2-way analyses of variance. The rank-sum take a look at or 1-way evaluation of variance on ranks was used for group comparability of variables with out regular distributions. Proportions had been in contrast by utilizing the chi-square or Fisher’s precise take a look at. For these analyses, topics had been grouped by HIV standing, stage of HIV illness as indicated by CD4+ T lymphocyte rely (<200, 200–499, and ≥500 mm−1), use of antiretroviral remedy, and intercourse. Regression evaluation A number of linear regression evaluation was used initially to find out whether or not HIV standing was a big predictor of the antioxidant variables by utilizing HIV standing, intercourse, nutrient consumption from eating regimen, nutrient consumption from dietary supplements (for ascorbate, α-tocopherol, γ-tocopherol, and α-tocopherol:γ-tocopherol), and research website because the unbiased variables (Desk 2). Tocopherol consumption from dietary supplements was presumed to be completely α-tocopherol and was utilized in all tocopherol regression fashions. Whole tocopherol consumption from meals was used for regression evaluation of plasma γ-tocopherol and α-tocopherol:γ-tocopherol, whereas α-tocopherol consumption from meals was used for evaluation of plasma α-tocopherol. Backwards stepwise linear regression evaluation was used to determine important predictors of the plasma antioxidant measures (ascorbate, urate, TAS, α-tocopherol, γ-tocopherol, and α-tocopherol:γ-tocopherol) from among the many following unbiased variables (Desk 3): demographic variables—age, intercourse, BMI, race, ethnicity, and smoking; consumption variables—consumption of nutritional vitamins C and E from meals and dietary supplements; HIV variables—HIV standing, CD4+ T cell rely, plasma virus load, and use of antiretroviral remedy; and immune activation variables—activated CD8+ T cells, neutrophil rely, plasma neopterin, plasma CRP, and plasma ceruloplasmin. This evaluation was carried out on all topics, HIV-negative topics and HIV-positive topics independently, with variables for HIV standing, intercourse, and nutrient consumption (for the vitamin C and E fashions) from meals and dietary supplements compelled into the mannequin. Variables included within the closing mannequin (Desk 3) had been important (P < 0.05) in 1 of the three groupings of topics. If a variable was not important within the mannequin with all topics, it was included provided that the coefficients differed at P < 0.10 between the HIV-positive and HIV-negative topics, as assessed by Pupil’s t take a look at. As a result of important variations within the markers of oxidative harm had been seen between the totally different scientific research websites (6), dummy variables had been included in all fashions to symbolize the totally different research websites, however coefficients weren't reported. Evaluation of α-tocopherol:γ-tocopherol recognized primarily the identical unbiased variables that had been recognized when γ-tocopherol and α-tocopherol concentrations had been analyzed individually, and the outcomes of the previous mixed evaluation should not introduced right here. The entire variables talked about above (besides vitamin consumption) had been additionally used as described in backward stepwise regression evaluation to foretell oxidative harm (plasma protein carbonyl, knowledge not proven; plasma malondialdehyde, Desk 4). Equations predicting oxidative harm by utilizing these demographic, HIV, and immune variables have been reported elsewhere (6).RESULTS
Topic traits
Topics from the REACH Research had been predominately feminine and African American. Twenty-one % reported their ethnicity as Hispanic, and BMI for females was better than that for males (Desk 1). The prevalence of weight problems was excessive within the REACH Research topics, as was reported beforehand in better element (5, 6).
Antioxidant standing
Vitamin C
Plasma ascorbate was considerably (P = 0.005) better in males (45 ± 2.0 μmol/L) than in females (39 ± 2.0 μmol/L) and marginally (P = 0.064) decrease in HIV-positive (40 ± 1.2 μmol/L) than in HIV-negative (44 ± 1.9 μmol/L) topics (Determine 1). HIV standing was a big detrimental predictor of plasma ascorbate when a number of regression evaluation was used to regulate for intercourse, vitamin C consumption, and research website (Desk 2). Plasma ascorbate in HIV-positive topics didn’t differ by stage of HIV illness (knowledge not proven; P = 0.90). When divided into quartiles primarily based on age- and sex-specific knowledge from the third Nationwide Well being and Vitamin Examination Survey (NHANES III; 16), a considerably (P = 0.002) decrease proportion of feminine topics than anticipated was within the highest quartile, however the reverse pattern was seen in males, of whom a considerably (P = 0.043) better proportion than anticipated was within the highest quartile (Determine 2). The general prevalence of low and poor plasma ascorbate (<17 μmol/L; 17) was 8.7% (31/356). The prevalence was marginally larger in females than in males [10.4% (28/270) and 3.5% (3/86); P = 0.080]. No distinction was seen by HIV standing (P = 0.31). When stepwise a number of regression evaluation was used to determine important predictors of plasma ascorbate, solely plasma CRP was recognized as a big, detrimental predictor (Desk 3). Urate Plasma urate was considerably (P < 0.001) better in males (359 ± 11 μmol/L) than in females (277 ± 5.4 μmol/L), as anticipated (18), and it didn't differ considerably (P = 0.79) between HIV-positive (316 ± 5.9 μmol/L) and HIV-negative (319 ± 10 μmol/L) topics (Determine 1 and Desk 2). Plasma urate in HIV-positive topics didn't differ by stage of illness (knowledge not proven; P = 0.40). The general imply values for REACH Research topics (296 μmol/L) is much like the imply worth reported from NHANES I for topics < 45 y previous (316 μmol/L; 18). Vitamin E Plasma α-tocopherol concentrations didn't differ considerably (P = 0.19) between females (median: 18.3 μmol/L; twenty fifth/seventy fifth percentiles: 15.4/22.1 μmol/L; n = 270) and males (17.2 μmol/L; 14.4/20.8 μmol/L; n = 86) or between HIV-positive (18.0 μmol/L; 15.2/21.8 μmol/L; n = 241; P = 0.80) and HIV-negative (18.4 μmol/L; 15.2/22.0 μmol/L; n = 115) topics (Determine 1 and Desk 2). Nor did concentrations in HIV-positive topics differ considerably by stage of illness (knowledge not proven; P = 0.79). When divided into quartiles primarily based on age- and sex-specific nationwide reference knowledge (NHANES III), a better proportion of topics than anticipated was within the lowest quartile (Determine 2). The distribution for females and males analyzed collectively was considerably (P ≤ 0.001) totally different from that anticipated based on the nationwide normal. The distributions of female and male REACH Research topics didn't differ considerably (P = 0.79). With the usage of a cutoff of 12 μmol/L (18), the prevalence of vitamin E deficiency was 7.0% (25/356). The prevalence in males (11.6%, 10/86) was twice that in females (5.6%, 15/270), however the distinction was not important (P = 0.094). No important distinction was seen by HIV standing (P = 0.79).
A number of regression evaluation discovered that BMI was negatively related to plasma α-tocopherol (Desk 3). As well as, the usage of vitamin E dietary supplements was positively related to plasma α-tocopherol in HIV-negative however not HIV-positive topics (Desk 3). This affiliation was additionally seen in bivariate regression evaluation for HIV-positive topics, though, with out adjustment for different variables, the affiliation didn't differ considerably from that seen in HIV-negative topics (Determine 3). Two markers of immune activation, the acute part protein ceruloplasmin and the neutrophil rely, additionally had been positively related to α-tocopherol in HIV-positive however not HIV-negative topics (Desk 3). Plasma γ-tocopherol was considerably (P = 0.003) larger in females (median: 4.35; twenty fifth/seventy fifth percentiles: 3.05/5.68 μmol/L; n = 270) than in males (3.45; 2.28/4.96 μmol/L; n = 86), nevertheless it didn't differ considerably between HIV-positive (4.18; 2.88/5.68 μmol/L; n = 241, P = 0.19) and HIV-negative (3.88; 2.59/5.42 μmol/L; n = 115) topics (Determine 1). A number of regression evaluation after adjustment for intercourse, research website, and vitamin E consumption did discover a important constructive affiliation of HIV standing with plasma γ-tocopherol focus (Desk 2). Plasma γ-tocopherol concentrations didn't differ considerably (P = 0.14) by stage of illness in HIV-positive topics. Imply plasma α-tocopherol:α-tocopherol was marginally (P = 0.056) larger in females (median: 0.231; twenty fifth/seventy fifth percentiles: 0.159/0.318 μmol/L; n = 270) than in males (0.196; 0.126/0.299 μmol/L; n = 86), nevertheless it didn't differ considerably between HIV-positive (0.229; 0.157/0.314 μmol/L; n = 241, P = 0.28) and HIV-negative (0.213; 0.148/0.318 μmol/L; n = 115) topics (Determine 1). Adjustment for intercourse and research website confirmed a constructive affiliation of HIV standing with α-tocopherol:γ-tocopherol, however the distinction was not statistically important (Desk 2). The ratio didn't differ by stage of illness amongst HIV-positive topics (P = 0.18). A number of regression evaluation discovered that consumption of vitamin E from dietary supplements was negatively related to plasma γ-tocopherol concentrations (Desk 3). In settlement with this commentary, plasma γ-tocopherol was considerably (P = 0.004) decrease in topics who had been utilizing vitamin E dietary supplements (median: 3.60; twenty fifth/seventy fifth percentiles: 2.28/5.26 μmol/L, n = 121) than in topics who weren't utilizing dietary supplements (4.36; 3.11/5.80 μmol/L, n = 234). In distinction to the detrimental affiliation that was seen between BMI and plasma α-tocopherol, BMI had a constructive affiliation with γ-tocopherol (Desk 3). Whole antioxidant standing Plasma TAS values had been considerably (P < 0.001) larger in males (1.70 ± 0.017 mmol/L) than in females (1.58 ± 0.0089 mmol/L). Values in HIV-positive topics (1.65 ± 0.010 mmol/L) didn't differ considerably (P = 0.10) from these in HIV-negative topics (1.62 ± 0.016 mmol/L; Determine 1). Nevertheless, a number of regression evaluation after adjustment for intercourse and research website discovered a big, constructive affiliation of HIV standing with TAS (Desk 2). TAS values for HIV-positive topics didn't differ by stage of illness (P = 0.49). Plasma antioxidants had been included within the stepwise regression evaluation to foretell TAS values as a result of they contribute on to the entire antioxidant capability of plasma. As anticipated, urate and α-tocopherol confirmed constructive associations with TAS (Desk 3). Ceruloplasmin, however, confirmed a detrimental affiliation with TAS in HIV-positive however not HIV-negative topics (Desk 3). Oxidative harm We (6) beforehand confirmed that the usage of antiretroviral remedy and the markers of immune activation (seeTable 4) are related to oxidative harm within the REACH Research topics. Within the present research, we analyzed the affiliation of ascorbate, urate, TAS, α-tocopherol, and γ-tocopherol with the markers plasma malondialdehyde and plasma protein carbonyls. We anticipated that safety in opposition to oxidative harm by one among these antioxidants would end in a detrimental affiliation between the antioxidant and the oxidative harm variables. Nevertheless, each α- and γ-tocopherol had a constructive affiliation with malondialdehyde (Desk 4). No important affiliation was discovered between antioxidant variables and plasma protein carbonyls. In a earlier report (6), we used each of those oxidative harm variables to categorize topics as with or with out oxidative harm (by utilizing the ninetieth percentile for every variable as a threshold to determine these with oxidative harm). Utilizing these classes, we in contrast plasma tocopherol values in these with and people with out oxidative harm and located that the median γ-tocopherol focus was 25% larger (P < 0.001) in these with oxidative harm than in these with out (Determine 4). Equally, median γ-tocopherol:α-tocopherol was 20% better (P = 0.003) in topics with oxidative harm than in these with out oxidative harm. A big distinction was not seen for α-tocopherol independently.DISCUSSION – “vitamin c hiv”
Vitamin C
Plasma ascorbate was decrease in topics with HIV an infection, which means that such topics have better vitamin C necessities than do individuals with out HIV an infection. Though oxidized ascorbate may be recycled, elevated oxidative stress is presumed to extend ascorbate depletion (19). Thus, plasma ascorbate could also be decreased by the persistent immune activation of HIV an infection even when dietary consumption is at a degree judged to be sufficient for wholesome individuals, as was true for the REACH Research topics (7). Nevertheless, plasma ascorbate was decrease in HIV-positive than in HIV-negative REACH Research topics. Earlier research have made related observations (20–23) however didn’t management for eating regimen. Thus our outcomes counsel that vitamin C utilization is elevated by HIV an infection. Larger intakes throughout HIV an infection ought to assist stop oxidative harm and preserve regular immune operate.
Allard et al (24) discovered that vitamin C and E dietary supplements decreased oxidative harm and tended to lower illness severity in HIV-positive Canadian adults. Excessive intakes of vitamin C additionally had been related to a decrease threat of development to AIDS in an observational research of US males (3). Trials in Africa of multinutrient dietary supplements containing nutritional vitamins C and E discovered a decrease threat of demise as a consequence of HIV an infection in Tanzanian girls (25) and a small improve in CD4 T lymphocyte counts in Kenyan girls (26), though a rise in vaginal HIV shedding was additionally seen within the latter research. Whereas the outcomes of those intervention trials can’t be attributed solely to the antioxidant elements of the dietary supplements, the research do present that multinutrient dietary supplements designed to handle underlying deficiencies in antioxidant vitamins can diminish the severity of HIV illness. Dangers may end result from such dietary supplements, as seen by the elevated virus shedding within the Kenyan research.
Vitamin E
α-Tocopherol
Virtually 40% of REACH Research topics have vitamin E intakes beneath the estimated common requirement (7). It thus seems that low dietary consumption of vitamin E is a principal explanation for the comparatively poor vitamin E standing of the REACH Research topics. Evaluation of dietary consumption by utilizing an FFQ has limitations. For instance, topics with HIV an infection could change their intakes in the course of the recall interval lined by the questionnaire, and thus the questionnaire could be extra more likely to mirror present intakes than the intakes initially of the research interval. Such an instance raises questions of validity and reverse causality. Nonetheless, the settlement of those dietary knowledge with plasma α-tocopherol concentrations helps the validity of their use within the present research.
Plasma α-tocopherol was not related to HIV an infection within the REACH Research topics. This lack of affiliation means that dietary intakes of vitamin E, though low general, was sufficient to keep up plasma α-tocopherol regardless of the oxidative stress of HIV an infection. In help of this view, we beforehand reported that vitamin E intakes in REACH Research topics had been larger in HIV-positive than in HIV-negative males (7). Nevertheless, solely 24% of REACH Research topics within the present evaluation had been male. Thus, larger dietary consumption of vitamin E in these with HIV an infection will not be the principal cause for the upkeep of plasma α-tocopherol concentrations. A extra essential issue will be the exercise of α-tocopherol switch protein (ATTP), which regulates the transport of α-tocopherol from the liver into the plasma (27). It’s doable that ATTP exercise maintained plasma α-tocopherol concentrations in these HIV-positive topics regardless of the elevated oxidative stress ensuing from irritation brought on by HIV an infection.
Outcomes of the present research are according to the speculation that HIV an infection will increase vitamin E necessities. For instance, the constructive affiliation of vitamin E complement use with plasma α-tocopherol that was seen in HIV-negative REACH Research topics was not seen in HIV-positive topics, which suggests better want for or much less absorption of vitamin E throughout HIV an infection. Thus, HIV an infection could improve vitamin E necessities.
Earlier research confirmed decrease plasma α-tocopherol concentrations in topics with HIV an infection or AIDS than in wholesome controls (28–30), however we didn’t see such a distinction within the present research. A principal cause for this discrepancy could also be that the REACH Research topics had been studied earlier within the illness than had been topics in earlier research, and thus they had been comparatively wholesome. For instance, solely 13% of the REACH Research topics have CD4 T lymphocyte counts < 200/μL (6). This interpretation can be according to the report that plasma α-tocopherol concentrations lower with time throughout HIV an infection (31). A number of regression evaluation discovered apparently paradoxical constructive associations between 2 markers of immune activation, ceruloplasmin and neutrophil rely, and α-tocopherol. Ceruloplasmin is an acute part protein that additionally has antioxidant exercise (32). The latter exercise could clarify its constructive affiliation with α-tocopherol if related components regulate each ceruloplasmin and α-tocopherol concentrations to keep up antioxidant safety. The constructive affiliation of neutrophil counts with α-tocopherol is tougher to interpret however could also be as a consequence of reverse causality. For instance, topics with larger plasma α-tocopherol could have much less extreme tissue irritation as a consequence of higher antioxidant safety. This might lower extravasation of neutrophils and assist preserve larger blood neutrophil counts. γ-Tocopherol Though an age- and sex-appropriate US reference inhabitants was not accessible for comparability, the median γ-tocopherol focus in REACH Research topics (4.1 μmol/L; n = 356) was much like that in male US physicians aged 40–84 y who had been at low threat of heart problems (4.2 μmol/L) (33) and to that of wholesome, postmenopausal US girls (5.0 μmol/L) (34). In distinction, the imply for REACH Research topics (4.5 μmol/L) was 2.8-fold the imply for a pattern of apparently wholesome Greek women and men aged 30–82 y (1.8 μmol/L) (35). α-Tocopherol:γ-tocopherol was additionally larger than anticipated in British adolescents and younger adults (36). Poor eating regimen high quality (eg, excessive complete vitality intakes and low fruit and vegetable intakes; 34) and excessive intakes of γ-tocopherol-rich meals (eg, vegetable oils and nuts; 37) could account for the excessive γ-tocopherol concentrations seen within the REACH Research topics. A hanging discovering of the present research was the elevation of plasma γ-tocopherol in topics underneath physiologic stress, together with HIV an infection, oxidative harm, and excessive BMI. This affiliation with BMI was reported beforehand (34, 36). It's tempting to invest that elevated oxidative stress is the frequent issue that leads to the elevation of plasma γ-tocopherol in these conditions. Nevertheless, that is counterintuitive, as a result of disposal of γ-tocopherol happens through oxidation by liver cytochrome P450 enzymes (27). Disposal of γ-tocopherol is comparatively speedy: a latest tracer research reported the half-life of plasma γ-tocopherol as 13 h, whereas that for α-tocopherol is 57 h (38). To account for the observations of the present research, one must speculate that the exercise of those enzymes is decreased by HIV an infection or oxidative stress. Nevertheless, it was just lately reported that liver α-tocopherol concentrations are positively correlated with cytochrome P450 (particularly, Cyp3a) exercise and the γ-tocopherol oxidation product γ-carboxyethyl hydroxychroman (39). On the premise of this affiliation, one might speculate that, if liver α-tocopherol concentrations are decreased by oxidative stress (on the similar time that plasma concentrations are maintained by ATTP), that might scale back Cyp3a exercise, thus reducing γ-tocopherol degradation and rising plasma γ-tocopherol concentrations. ATTP exercise additionally could clarify the constructive affiliation of plasma α-tocopherol with oxidative harm seen within the present research. Thus, it might be fascinating to look at tissue α-tocopherol concentrations in topics present process oxidative stress. The detrimental affiliation of vitamin E consumption from dietary supplements with plasma γ-tocopherol has been reported beforehand (40, 41). Whereas the two types of vitamin E are equivalently absorbed and transported to the liver, ATTP preferentially binds and re-secretes α-tocopherol from the liver into the plasma. Thus, larger liver concentrations of α-tocopherol could additional scale back the secretion of γ-tocopherol from the liver, in addition to rising its catabolism, as mentioned above. Whole antioxidant standing TAS is an mixture measure of the power of plasma to forestall the oxidation of a water-soluble indicator by a peroxidase (metmyoglobin) and hydrogen peroxide (42). Thus, the constructive affiliation of the plasma antioxidants urate and α-tocopherol with TAS was anticipated. Nevertheless, ceruloplasmin, which additionally has antioxidant properties, was negatively related to TAS, which can be as a result of capacity of ascorbate plus copper (which can be launched from ceruloplasmin in the course of the assay by oxidation) to generate hydroxyl radicals from the hydrogen peroxide that's current within the TAS assay system (19). This prooxidant exercise might improve the oxidation of the indicator and thereby scale back the TAS values of topics with elevated ceruloplasmin. Nevertheless, this detrimental affiliation was seen solely in HIV-positive topics, which suggests {that a} physiologic distinction as a consequence of HIV an infection, reasonably than an artifact of the assay technique that might have an effect on all topics, underlies this distinction.
SUMMARY
Information from the present research help the conclusion that HIV an infection will increase the necessities for each vitamin C and vitamin E. Plasma ascorbate concentrations had been decrease in topics with HIV an infection regardless of sufficient consumption and comparatively excessive general plasma ascorbate concentrations. Alternatively, vitamin E consumption was low in lots of REACH Research topics, however plasma α-tocopherol concentrations weren’t decreased by HIV an infection, maybe due to compensatory mechanisms resembling ATTP exercise that assist preserve plasma concentrations and the transport of α-tocopherol from the liver to peripheral tissues. Such a compensatory mechanism may clarify the elevation of γ-tocopherol within the REACH Research topics underneath situations of better oxidative stress, together with HIV an infection.
We acknowledge the contributions of the investigators and workers of the Adolescent Drugs HIV/AIDS Analysis Community (1994–2001) and of the youths who participated within the analysis. Collaborating investigators and workers are listed in J Adolesc Well being 2001;29(suppl):5–6. We acknowledge Alina Wettstein and Giovanna Aiello for performing assays, Leslie Woodhouse for supervising assays, and Ginny Gildengorin for help with regression evaluation.
CBS, GSM, SDD, and CMW all participated within the design and implementation of this research. LAK educated clinic workers to carry out dietary consumption and carried out high quality management on dietary knowledge assortment and evaluation. RAJ helped design and implement the gathering of samples for ascorbate evaluation and supervised that evaluation. Not one of the authors had any private or monetary battle of curiosity.
FOOTNOTES
“vitamin c hiv”