Effect of Statin Therapy on the Plasma Concentrations of Retinol, Alpha-Tocopherol and Coenzyme Q10 in Children with Familial Hypercholesterolemia.

PURPOSE: Familial hypercholesterolemia (FH) requires early treatment. However, statins, which are regarded the first-line therapy, have an influence on redox balance. Antioxidant vitamins are important for many metabolic processes in the developing body. There are few data available on the long-term safety of statin use in children. The aim of this study was to evaluate the influence of statin treatment in children with FH on plasma concentrations of antioxidant vitamins: retinol, alpha-tocopherol and coenzyme Q10. METHODS: The first study group consisted of 13 children aged 10-18 years treated with simvastatin for at least 6 months, and the second group comprised 13 age- and sex-matched children with hypercholesterolemia, in whom pharmacological treatment had not been applied yet. Analyses were performed using a high-performance liquid chromatograph coupled with a MS detector. RESULTS: The analysis did not reveal significant differences in the concentration of retinol, alpha-tocopherol or coenzyme Q10 between the studied groups. The adjustment of the concentrations of the vitamins to the cholesterol level also indicated no significant differences. We found no deficits in antioxidant vitamins in patients treated with statins, or any risk of adverse effects associated with an increase in their concentration. CONCLUSION: There is no rationale for additional supplementation using antioxidant vitamins or modification of low-fat and low-cholesterol diet in pediatric patients treated with statins.

Associations of metabolomic profiles with circulating vitamin E and urinary vitamin E metabolites in middle-aged individuals.

Vitamin E (α-tocopherol [α-TOH]) is transported in lipoprotein particles in blood, but little is known about the transportation of its oxidized metabolites. In the Netherlands Epidemiology of Obesity Study, we aimed to investigate the associations of 147 circulating metabolomic measures obtained through targeted nuclear magnetic resonance with serum α-TOH and its urinary enzymatic (α-CEHC) and oxidized (α-TLHQ) metabolites from 24-h urine quantified by liquid chromatography with tandem mass spectrometry. Multivariable linear regression analyses, in which multiple testing was taken into account, were performed to assess associations between metabolomic measures (determinants; standardized to mean = 0, SD = 1) and vitamin E metabolites (outcomes), adjusted for demographic factors. We analyzed 474 individuals (55% women, 45% men) with a mean (SD) age of 55.7 (6.0) y. Out of 147 metabolomic measures, 106 were associated (P < 1.34 × 10-3) with serum α-TOH (median ß [interquartile range] = 0.416 [0.383-0.466]), predominantly lipoproteins associated with higher α-TOH. The associations of metabolomic measures with urinary α-CEHC have directions similar to those with α-TOH, but effect sizes were smaller and non-significant (median ß [interquartile range] = 0.065 [0.047-0.084]). However, associations of metabolomic measures with urinary α-TLHQ were markedly different from those with both serum α-TOH and urinary α-CEHC, with negative and small-to-null relations to most very-low-density lipoproteins and amino acids. Therefore, our results highlight the differences in the lipoproteins involved in the transportation of circulating α-TOH and oxidized vitamin E metabolites. This indicates that circulating α-TOH may be representative of the enzymatic but not the antioxidative function of vitamin E.

Association between serum retinol and overall and cause-specific mortality in a 30-year prospective cohort study.

How retinol as a clinical indicator of vitamin A status is related to long-term mortality is unknown. Here we report the results of a prospective analysis examining associations between serum retinol and risk of overall and cause-specific mortality. During a 30-year cohort follow-up, 23,797 deaths were identified among 29,104 men. Participants with higher serum retinol experienced significantly lower overall, CVD, heart disease, and respiratory disease mortality compared to men with the lowest retinol concentrations, reflecting 17-32% lower mortality risk (Ptrend < 0.0001). The retinol-overall mortality association is similar across subgroups of smoking intensity, alcohol consumption, body mass index, trial supplementation, serum alpha-tocopherol and beta-carotene concentrations, and follow-up time. Mediation analysis indicated that <3% of the effects of smoking duration and diabetes mellitus on mortality were mediated through retinol concentration. These findings indicate higher serum retinol is associated with lower overall mortality, including death from cardiovascular, heart, and respiratory diseases.

The plasma antioxidant vitamin status of the INTAPP cohort examined: The unsuspected importance of ß-carotene and γ-tocopherol in preeclampsia.

OBJECTIVE: Examine the levels of plasma antioxidant vitamins before and during a treatment with placebo or vitamin E + C supplement to prevent preeclampsia (PE). STUDY DESIGN: Per-protocol analysis of a subset group of pregnant women (n = 295) from the International Trial of Antioxidants for the Prevention of PE (INTAPP) randomized case-control study. Normotensive receiving placebo or vitamins (n = 115 and 87 respectively) were compared to gestational hypertension (GH) without proteinuria (n = 30 and 27) and PE (n = 21 and 15). Vitamin quantification was performed at 12-18, 24-26 and 32-34 weeks of gestation. MAIN OUTCOME MEASURES: Coenzyme (Co) Q10, ß-carotene and vitamins E (α and γ forms) plasma levels. RESULTS: Vitamin E + C supplementation was found to increase the α-tocopherol levels by 40% but was associated with a 57% decrease in the γ-tocopherol isoform for all study groups (p < 0.001). The ß -carotene was lower in the PE than in the normotensive and GH groups (p < 0.001) while the level of CoQ10 remained unaffected. CONCLUSIONS: A more personalized approach that target the suboptimal levels of specific antioxidants without disturbing the α/γ-tocopherol ratio could be a more successful approach to counteract oxidative stress in PE.

Circulating Alpha-Tocopherol Levels, Bone Mineral Density, and Fracture: Mendelian Randomization Study.

Recent cohort studies indicate a potential role of the antioxidant α-tocopherol in reducing bone loss and risk of fractures, especially hip fractures. We performed a Mendelian randomization investigation of the associations of circulating α-tocopherol with estimated bone mineral density (eBMD) using heel ultrasound and fractures, identified from hospital records or by self-reports and excluding minor fractures. Circulating α-tocopherol was instrumented by three genetic variants associated with α-tocopherol levels at p < 5 × 10-8 in a genome-wide association meta-analysis of 7781 participants of European ancestry. Summary-level data for the genetic associations with eBMD in 426,824 individuals and with fracture (53,184 cases and 373,611 non-cases) were acquired from the UK Biobank. Two of the three genetic variants were strongly associated with eBMD. In inverse-variance weighted analysis, a genetically predicted one-standard-deviation increase of circulating α-tocopherol was associated with 0.07 (95% confidence interval, 0.05 to 0.09) g/cm2 increase in BMD, which corresponds to a >10% higher BMD. Genetically predicted circulating α-tocopherol was not associated with odds of any fracture (odds ratio 0.97, 95% confidence interval, 0.91 to 1.05). In conclusion, our results strongly strengthen a causal link between increased circulating α-tocopherol and greater BMD. Both an intervention study in those with a low dietary intake of α-tocopherol is warranted and a Mendelian randomization study with fragility fractures as an outcome.

Association of measures of body fat with serum alpha-tocopherol and its metabolites in middle-aged individuals.

BACKGROUND AND AIMS: The accumulation of fat increases the formation of lipid peroxides, which are partly scavenged by alpha-tocopherol (α-TOH). Here, we aimed to investigate the associations between different measures of (abdominal) fat and levels of urinary α-TOH metabolites in middle-aged individuals. METHODS AND RESULTS: In this cross-sectional analysis in the Netherlands Epidemiology of Obesity study (N = 511, 53% women; mean [SD] age of 55 [6.1] years), serum α-TOH and α-TOH metabolites from 24-h urine were measured as alpha-tocopheronolactone hydroquinone (α-TLHQ, oxidized) and alpha-carboxymethyl-hydroxychroman (α-CEHC, enzymatically converted) using liquid-chromatography-tandem mass spectrometry. Body mass index and total body fat were measured, and abdominal subcutaneous and visceral adipose tissue (aSAT and VAT) were assessed using magnetic resonance imaging. Using multivariable-adjusted linear regression analyses, we analysed the associations of BMI, TBF, aSAT and VAT with levels of urinary α-TOH metabolites, adjusted for confounders. We observed no evidence for associations between body fat measures and serum α-TOH. Higher BMI and TBF were associated with lower urinary levels of TLHQ (0.95 [95%CI: 0.90, 1.00] and 0.94 [0.88, 1.01] times per SD, respectively) and with lower TLHQ relative to CEHC (0.93 [0.90, 0.98] and 0.93 [0.87, 0.98] times per SD, respectively). We observed similar associations for VAT (TLHQ: 0.94 [0.89, 0.99] times per SD), but not for aSAT. CONCLUSIONS: Opposite to our research hypothesis, higher abdominal adiposity was moderately associated with lower levels of oxidized α-TOH metabolites, which might reflect lower vitamin E antioxidative activity in individuals with higher abdominal fat instead.

Dynamics of Serum Retinol and Alpha-Tocopherol Levels According to Non-Alcoholic Fatty Liver Disease Status.

The available data on the association between micronutrients in the blood and non-alcoholic fatty liver disease (NAFLD) are limited. To investigate the clinical implications of this relationship, we sought to identify the difference in the serum levels of vitamins A and E according to NAFLD status using data from the seventh Korea National Health and Nutrition Examination Survey. In this cross-sectional study of the Korean population, NAFLD and its severity were defined using prediction models. Differences in the prevalence and severity of NAFLD were analyzed according to serum retinol (vitamin A) and alpha (α)-tocopherol (vitamin E) levels. Serum levels of retinol and α-tocopherol were positively correlated with the prevalence of NAFLD. In most prediction models of the NAFLD subjects, serum retinol deficiency was significantly correlated with advanced fibrosis, while serum α-tocopherol levels did not differ between individuals with or without advanced fibrosis. Similar trends were also noted with cholesterol-adjusted levels of α-tocopherol. In summary, while circulating concentrations of retinol and α-tocopherol were positively associated with the presence of NAFLD, advanced liver fibrosis was only correlated with serum retinol levels. Our findings could provide insight into NAFLD patient care at a micronutrient level.

Serum retinol, ß-carotene, and α-tocopherol as biomarkers for disease risk and milk production in periparturient dairy cows.

The effectiveness of using serum vitamin concentrations as biomarkers to predict diseases in dairy cows during the periparturient period is not well known. The objective of this study was to evaluate the association between serum ß-carotene, retinol, and α-tocopherol concentrations and periparturient cow diseases in commercial dairies. We measured serum concentrations of these vitamin-active compounds at dry-off and during close-up (approximately 3 wk before calving) and early lactation (approximately 7 d post-calving), and we examined their association with clinical diseases in the first 30 d in milk. Diseases were diagnosed by trained personnel and recorded using database software. Blood samples were taken from 353 cows from 5 different farms over a 3-yr period. Blood samples were analyzed for ß-carotene, retinol, α-tocopherol, and cholesterol. We built separate mixed logistic regression models for each disease outcome: hyperketonuria, lameness, mastitis, uterine diseases (retained placenta or metritis), and an aggregate outcome. For the aggregate outcome, a cow was considered positive if she had one or more of the following: hyperketonuria, lameness, mastitis, uterine disease, pneumonia, milk fever, or displaced abomasum. Concentrations of all 3 fat-soluble vitamins decreased significantly in early lactation relative to the 2 prepartum sampling times. Serum retinol concentrations at close-up and early lactation were negatively associated with odds of developing postpartum hyperketonuria. At early lactation, cows with uterine disease had lower serum retinol concentrations than cows without uterine disease. Similarly, lower serum retinol concentrations were associated with greater odds of having any one disease in the aggregate outcome. First-test 305-d mature-equivalent milk yield was positively correlated with increased serum α-tocopherol and negatively correlated with ß-carotene concentrations. This study demonstrates the potential for serum ß-carotene, retinol, and α-tocopherol to serve as biomarkers for disease risk.

Effects of 2,4-thiazolidinedione (TZD) on milk fatty acid profile and serum vitamins in dairy goats challenged with intramammary infusion of Streptococcus uberis.

The study included two experiments. In the first, 24 lactating Saanen dairy goats received low-energy diet without vitamin supplements. Twelve goats received a daily IV injection of 2,4- thiazolidinedione (TZD), others received saline injection. A week later, 6 goats from each treatment were challenged with intramammary infusion (IMI) of saline (CTRL) or Streptococcus uberis. In the second experiment, 12 Saanen lactating dairy goats received supplemental vitamins to reach NRC recommendation level. Six goats in each group were injected with TZD or saline daily, and 14 d later received Streptococcus uberis IMI in the right half of the udder. The hypotheses were (1) TZD does not affect the level of retinol in blood, and (2) the fatty acid profile is affected by the interaction between mammary infection and TZD in dairy goats. In the first experiment blood samples were collected on d -7, -2, 1, 2, 12 and milk samples were collected on d -8, 1, 4, 7, and 12, both relative to IMI. In the second experiment, blood samples were collected on d -15, 0, 1, and 10 relative to IMI. Milk and serum samples were analyzed for retinol, α-tocopherol and fatty acid profile. Serum retinol and ß-carotene concentrations were higher in the second experiment compared to the first. Serum ß-carotene and α-tocopherol were greater in TZD than CTRL and there was a TZD × time interaction in the first experiment. In addition, the TZD × time interaction showed that the milk fatty acid were reduced in C16 : 0 while C18 : 3 n3 while total omega 3 fatty acids were increased, as well as with minor effect on preventing a transient increase in α-tocopherol in milk. Overall, the TZD may affect the lipid-soluble vitamins and fatty acid profile, potentially altering immune responses, during mastitis in dairy goats.

An elevated 8-isoprostaglandin F2 alpha (8-iso-PGF2α) in COVID-19 subjects co-infected with malaria.

INTRODUCTION: the most recently discovered severe acute respiratory syndrome Coronavirus 2 (SARS-COV-2) that causes COVID-19, subjected the entire world in turmoil health-wise and economically. With higher burden of malaria in Nigeria and other sub-Saharan African countries coupled with fragile healthcare system and delivery, these may pose a threat in the diagnosis and management of COVID-19 patients co-infected with malaria. Free radicals have been implicated in the progression and pathogenesis of malaria and COVID-19 through Fenton's reaction and cytokine storm respectively. METHODS: the current research comprises of seventy-four (74) participants; 20 apparently healthy controls and 54 COVID-19 patients (34 among which were co-infected with malaria). Serum levels of 8-iso PGF2α and Alphatocopherol were determined among the study participants using ELISA technique and colorimetric assay, respectively. RESULTS: results revealed statistically significant elevation of 8-iso PGF2α in COVID-19 patients co-infected with malaria compared to COVID-19 patients only, and this may be due to increase production of free radicals. Furthermore, a significant decrease of Alphatocopherol was observed in COVID-19 co-infected with malaria compared to COVID-19 patients due to increase utilization of antioxidants in counterbalancing the negative effect of free radicals generated. CONCLUSION: conclusively, SARS-COV-2 patients co-infected with malaria might be predisposed to oxidative stress and low Alphatocopherol. The increase in oxidative stress is proportional to malaria parasite density and inversely related to Alphatocopherol levels. This implies that oxidative stress is notably higher and such patients may have a severer form of the COVID-19. Increased 8-iso-PGF2α in co-infection and decreased alphatocopherol levels can reflect the severity and adverse outcomes compared to COVID-19 naïve because of their tremendous involvement in the pathogenesis and progression of diseases.

Interrelation between Plasma Concentrations of Vitamins C and E along the Trajectory of Ageing in Consideration of Lifestyle and Body Composition: A Longitudinal Study over Two Decades.

Although the interrelation between vitamins C and E has been demonstrated on an experimental level, its impact on biomarkers in community-dwelling subjects along the trajectory of ageing has not yet been shown. The present longitudinal study investigates the determinants and interrelation of vitamins C and E plasma concentrations in 399 subjects aged ≥60 years with a median follow-up time of 12 years. Linear mixed-effects models were used to analyze the influence of age, sex, body composition, dietary intake, physical activity, smoking and supplement/drug use on plasma vitamin C, plasma α-tocopherol and α-tocopherol/total cholesterol ratio. At baseline, median plasma concentrations of vitamin C and α-tocopherol were 74 and 35 µmol/L. Absolute fat-free mass, physical activity, use of supplements, and plasma α-tocopherol were main determinants of plasma vitamin C in the course of ageing. For the α-tocopherol/total cholesterol ratio, age, use of supplements, use of lipid-modifying drugs, and plasma vitamin C were main determinants. The results reveal a stable positive interrelation between plasma concentrations of vitamins C and E along the trajectory of ageing independent of the other identified determinants. The possible regulatory mechanisms that could explain this robust positive interrelation remain to be elucidated.

Relationship between Serum Antioxidative Vitamin Concentrations and Type 2 Diabetes in Japanese Subjects.

A high intake of green leafy vegetables rich in antioxidative nutrients such as vitamin C and ß-carotene may protect against the risk of type 2 diabetes. Measurement of the circulating nutrient concentrations can indicate the nutrient status more directly, and vitamin C and carotenoids are recognized as good biomarkers for the intake of fruits and vegetables. The aim of this study was to investigate the relationships between serum antioxidative vitamin concentrations and type 2 diabetes in Japanese subjects. The study subjects comprised 506 men and 493 women who first underwent anti-aging health checks at Tokai University Tokyo Hospital. Serum concentration of vitamin (V) A, VC, α-tocoferol, ß-carotene, VB12, folate, ferritin and homocysteine, and fasting plasma glucose and HbA1c were used for analysis. Low levels of ß-carotene and VC were significantly associated with dysglycemia. Diabetic subjects showed significantly decreased ß-carotene and VC levels, and multivariate analyses suggested that low levels of ß-carotene and VC were factors related to diabetes. Low levels of ß-carotene and VC are significantly related to dysglycemia/type 2 diabetes, and encouraging people at a higher risk of diabetes to take more green vegetables may be useful as a dietary intervention to improve the antioxidative vitamin status and dysglycemia.

Infant Rhesus Macaque Brain α-Tocopherol Stereoisomer Profile Is Differentially Impacted by the Source of α-Tocopherol in Infant Formula.

BACKGROUND: α-Tocopherol (αT) in its natural form [2'R, 4'R, 8'R αT (RRR-αT)] is more bioactive than synthetic α-tocopherol (all rac-αT). All rac-αT is widely used in infant formulas, but its accretion in formula-fed infant brain is unknown. OBJECTIVE: We sought to compare αT and stereoisomer status in infant rhesus macaques (Macaca mulatta) fed infant formula (RRR-αT or all rac-αT) with a reference group fed a mixed diet of breast milk and maternal diet. METHODS: From 1 d after birth until 6 mo of age, infants (n = 23) were either nursery reared and exclusively fed 1 of 2 formulas by staff personnel or were community housed with their mothers and consumed a mixed reference diet of breast milk (69 mL/d at 6 mo) transitioning to monkey diet at ∼2 mo (MF; n = 8). Formulas contained either 21 µmol RRR-αT/L (NAT-F; n = 8) or 30 µmol all rac-αT/L (SYN-F; n = 7). Total αT and αT stereoisomers were analyzed in breast milk at 2, 4, and 6 mo and in monkey plasma and liver and 6 brain regions at 6 mo of age. α-Tocopherol transfer protein (α-TTP), lipoprotein αT, and urinary α-carboxyethyl-hydroxychroman (α-CEHC) were measured. One-way ANOVA with Tukey's post-hoc test was used for analysis. RESULTS: At study termination, plasma, liver, lipoprotein, and brain total αT did not differ between groups. However, the NAT-F-fed group had higher RRR-αT than the SYN-F-fed group (P < 0.01) and the MF group (P < 0.0001) in plasma (1.7- and 2.7-fold) and brain (1.5- and 2.5-fold). Synthetic αT 2R stereoisomers (SYNTH-2R) were generally 3- and 7-fold lower in brain regions of the NAT-F group compared with those of the SYN-F and MF groups (P < 0.05). SYNTH-2R stereoisomers were 2-fold higher in MF than SYN-F (P < 0.0001). The plasma percentage of SYNTH-2R was negatively correlated with the brain percentage of RRR-αT (r = -0.99, P < 0.0001). Brain αT profiles were not explained by α-TTP mRNA or protein expression. Urine α-CEHC was 3 times higher in the NAT-F than in the MF group (P < 0.01). CONCLUSIONS: Consumption of infant formulas with natural (NAT-F) compared with synthetic (SYN-F) αT differentially impacted brain αT stereoisomer profiles in infant rhesus macaques. Future studies should assess the functional implications of αT stereoisomer profiles on brain health.

The Relationship between Serum Vitamin E Level and Risk Factors for Arteriosclerosis in Japanese Postmenopausal Women.

Since vitamin E is one of the most potent antioxidant and anti-inflammatory agents, vitamin E can play a role against arteriosclerosis through various actions. Then, we have studied the relationship between serum vitamin E status and risk factors for arteriosclerosis in Japanese postmenopausal women. One hundred and seven subjects (70.0±7.7 y) were evaluated for vitamin E status by measuring serum α- and γ-tocopherol (αT and γT) levels. The number of arteriosclerosis risk factors was defined by the existence of high blood pressure, hyperglycemia, and dyslipidemia. Median serum αT and γT concentrations were 24.32 and 2.79 µmol/L, respectively. In none of the subjects, serum αT level was below the cutoff value (<12 µmol/L) for vitamin E deficiency which causes fragile erythrocyte and hemolysis. While no significant differences were found in serum levels of αT and γT between the groups categorized by the number of arteriosclerosis risks, serum levels of αT adjusted by serum total cholesterol (TC) and triglyceride (TG) decreased with an increasing number of arteriosclerotic risk factors (p=0.074). Serum αT level adjusted by serum TC and TG was also a negative significant predictor for the number of arteriosclerosis risk factors controlled by covariates associated with arteriosclerosis. The present study described that serum vitamin E level was positively associated with a lower number of arteriosclerotic risks, and its role for preventing noncommunicable diseases was suggested.

Associations of Serum Retinol and α-Tocopherol Levels with Uric Acid Concentrations: Analysis of a Population-Based, Nationally Representative Sample.

The effects of serum retinol and α-tocopherol on serum uric acid levels have not been established, especially in Asian people. This study evaluated the independent associations of retinol and α-tocopherol with serum uric acid levels in the Korean population. We included 6023 participants aged ≥ 19 years from the Korean National Health and Nutrition Examination Survey (KNHANES). Serum retinol and α-tocopherol levels were divided into quintiles, and a multivariate linear regression model was used to evaluate the association of serum retinol and α-tocopherol levels with uric acid concentration. Additionally, we used multivariate logistic regression to examine the relationships between the levels of these micronutrients and hyperuricemia. Serum retinol levels were positively associated with uric acid concentrations in a dose-dependent fashion in both sexes (ptrend < 0.001); the difference in serum uric acid levels between the highest and lowest quintiles of retinol levels was 0.57 mg/dL in men and 0.54 mg/dL in women. In the multivariable logistic model, the hyperuricemia risk increased linearly with the increase in serum retinol level, regardless of sex (ptrend < 0.001). Although the serum α-tocopherol level appeared to be significantly associated with increased uric acid levels, this association was nullified after adjusting for serum retinol levels. Serum retinol levels were positively associated with serum uric acid levels and hyperuricemia in a dose-response fashion. Maintaining serum retinol concentrations under sub-toxic levels might be necessary to prevent hyperuricemia-related adverse health outcomes.

Association Between Serum Retinol and α-Tocopherol Levels and Metabolic Syndrome in Korean General Population: Analysis of Population-based Nationally Representative Data.

This study aimed to evaluate the association between serum retinol and α-tocopherol levels and metabolic syndrome (MetS) using data from the Korea National Health and Nutrition Examination Survey. Of the 24,269 individuals, 5885 adults (2672 men and 3213 women) were included. The prevalence of MetS and its components according to quartiles of serum retinol and α-tocopherol levels was calculated. Multivariate linear regression model was used to calculate the number of metabolic components according to serum vitamin levels. The association between serum vitamin levels and MetS with its components was assessed using multivariate logistic regression model. The prevalence of MetS was highest in Q4 and lowest in Q1 for both vitamins, regardless of sex. A dose-dependent association between serum retinol and α-tocopherol levels and MetS was observed. After adjustment for covariates, the odds ratio (OR) for MetS in Q4 compared to Q1 was 2.351 (95% CI: 1.748-3.163, Ptrend < 0.001) in the retinol group and 2.559 (95% CI: 1.953-3.353, Ptrend < 0.001) in α-tocopherol group. Among metabolic components, hypertriglyceridemia, high fasting glucose, and high blood pressure was positively associated with serum retinol and α-tocopherol levels. In conclusion, high serum retinol and α-tocopherol levels were associated with increased risk of MetS.

The Impact of Glucose-Based or Lipid-Based Total Parenteral Nutrition on the Free Fatty Acids Profile in Critically Ill Patients.

INTRODUCTION: Our study aim was to assess how the macronutrient intake during total parenteral nutrition (TPN) modulates plasma total free fatty acids (FFAs) levels and individual fatty acids in critically ill patients. METHOD: Adult patients aged 18-80, admitted to the intensive care unit (ICU), who were indicated for TPN, with an expected duration of more than three days, were included in the study. Isoenergetic and isonitrogenous TPN solutions were given with a major non-protein energy source, which was glucose (group G) or glucose and lipid emulsions (Smof lipid; group L). Blood samples were collected on days 0, 1, 3, 6, 9, 14, and 28. RESULTS: A significant decrease (p < 0.001) in total FFAs occurred in both groups with a bigger decrease in group G (p < 0.001) from day 0 (0.41 ± 0.19 mmol∙L-1) to day 28 (0.10 ± 0.07 mmol∙L-1). Increased palmitooleic acid and decreased linoleic and docosahexaenoic acids, with a trend of increased mead acid to arachidonic acid ratio, on day 28 were observed in group G in comparison with group L. Group G had an insignificant increase in leptin with no differences in the concentrations of vitamin E, triacylglycerides, and plasminogen activator inhibitor-1. CONCLUSION: Decreased plasma FFA in critically ill patients who receive TPN may result from increased insulin sensitivity with a better effect in group G, owing to higher insulin and glucose dosing and no lipid emulsions. It is advisable to include a lipid emulsion at the latest from three weeks of TPN to prevent essential fatty acid deficiency.

Nodular panniculitis in a cat with high alpha tocopherol concentration in serum.

A 5-year-old male neutered domestic shorthair cat suffered from recurrent solitary nodules in different subcutaneous body regions. Nodules were surgically removed and each time histopathological diagnosis was fat necrosis and fibrosing to pyogranulomatous panniculitis. After the second surgery the alpha (α)-tocopherol concentration in serum of the cat was examined and the result (21 mg/L) exceeded the upper limit of the reference interval (3-11 mg/L). Vitamin E amount in diet fed solely in the past was checked as studies have shown that vitamin E amounts in food significantly influence vitamin E concentrations in serum. For comparative purposes, α-tocopherol concentrations were determined in sera of healthy control cats. Additionally, vitamin E amount in wet food from different manufacturers was analysed using gas chromatography coupled to mass spectrometry (GC-MS). The results showed that the diet did not have higher vitamin E amounts compared to other diets. All control cats had similar high serum α-tocopherol concentrations. We conclude that panniculitis can occur despite high serum α-tocopherol concentrations in cats. Further studies are needed to redefine reference values of α-tocopherol in serum of cats.

Associations of α- and γ-tocopherol during early life with lung function in childhood.

BACKGROUND: Tocopherol isoforms may regulate child lung growth and spirometric measures. OBJECTIVE: Our aim was to determine the extent to which plasma α-tocopherol (α-T) or γ-tocopherol (γ-T) isoform levels in early childhood or in utero are associated with childhood lung function. METHODS: We included 622 participants in the Project Viva cohort who had lung function at a mid-childhood visit (age 6-10 years). Maternal and child tocopherol isoform levels were measured by HPLC at the second trimester and 3 years of age, respectively. Multivariable linear regression models (adjusted for mid-childhood body mass index z scores, maternal education, smoking in pregnancy, and prenatal particulate matter with diameter of <2.5 micrometers (PM2.5) particulate exposure) stratified by tertiles of child γ-T level were used to assess the association of α-T levels with FEV1 and forced vital capacity (FVC) percent predicted. Similarly, models stratified by child α-T tertile evaluated associations of γ-T levels with lung function. We performed similar analyses with maternal second trimester tocopherol isoform levels. RESULTS: The median maternal second trimester α-T level was 63 µM (interquartile range = 47-82). The median early-childhood level was 25 µM (interquartile range = 20-33 µM). In the lowest tertile of early-childhood γ-T, children with a higher α-T level (per 10 µM) had a higher mid-childhood FEV1 percent predicted (ß = 3.09; 95% CI = 0.58-5.59 and a higher FVC percent predicted (ß = 2.77; 95% CI = 0.47-5.06). This protective association of α-T was lost at higher γ-T levels. We did not see any consistent associations of second trimester levels of either α-T or γ-T with mid-childhood FEV1 or FVC. CONCLUSION: When γ-T levels were in the lowest tertile, a higher early-childhood α-T level was associated with better lung function at mid-childhood. Second trimester maternal plasma α-T concentration was 3-fold higher than in the adult nonpregnant female population.

The modifying effect of nutritional factors on the association between IL1-ß single nucleotide polymorphism and serum CXCL10 levels in young Canadian adults.

BACKGROUND: Genetic and nutritional factors play an important role in inflammatory response and diseases. CXCL10 is a critical biomarker that is involved in multiple inflammatory diseases, and elevated levels of CXCL10 have been associated with the development of several chronic and infectious diseases. In contrast, micronutrients can attenuate inflammatory responses. Single nucleotide polymorphisms in the pro-inflammatory cytokine genes such as IL-1ß at rs16944 contributed to a number of inflammatory disorders and may substantiate the convergance between chronic and infectious diseases. AIM: This study aims to identify the modifying effect of nutritional factors on the association between IL-1ß genotypes and CXCL10 levels. METHODS: Participants (N = 386) were healthy males and females from the Toronto Nutrigenomics and Health study recruited from the University of Toronto. Levels of micronutrients and inflammatory markers were measured in plasma. IL-1ß genotypes were extracted from the Affymetrix 6.0 SNP chip. RESULTS: CXCL10 levels were not different across different IL-1ß genotypes. Among those with the GA genotype, elevated CXCL10 levels were observed with higher than median ascorbic acid (ß = 0.004 ± 0.002, P = 0.047) or higher than median vitamin D status (ß = 0.003 ± 0.002, P = 0.044). Among participants with the AA genotype, subjects with low α-tocopherol status had elevated levels of CXCL10 (ß = -0.016 ± 0.007, P = 0.012). CONCLUSION: The association between IL-1ß rs16944 genotype and CXCL10 levels was modified by the levels of ascorbic acid, α-tocopherol and vitamin D. These findings may aid in understanding the combined effect of genetic and dietary factors in the development of various infectious and chronic diseases in which IL-1ß and CXCL10 may play an etiological role.