1.
Estimating Vitamin C Status in Critically Ill Patients with a Novel Point-of-Care Oxidation-Reduction Potential Measurement.
Rozemeijer, S, Spoelstra-de Man, AME, Coenen, S, Smit, B, Elbers, PWG, de Grooth, HJ, Girbes, ARJ, Oudemans-van Straaten, HM
Nutrients. 2019;11(5)
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This cohort study examines Vitamin C status as a functional measure in critically ill ICU patients with those of healthy volunteers. Vitamin C deficiency is common in critically ill patients and so establishing vitC status in everyday clinical practise may help quickly identify patients who might benefit from vitamin C supplementation. Common practise is to measure plasma concentrations using timely and expensive high-pressure liquid chromatography. A new point-of-care device enables clinicians to measure the static oxidation-reduction potential (sORP), reflecting oxidative stress, and antioxidant capacity (AOC) as functional indicators of vitC status. This cohort study measured sORP and AOC in 211 samples taken from 103 subjects in stored plasma samples taken from two 2015 studies; an observational vitamin C status study and a randomized pharmacokinetics study. Normal plasma vitC concentrations were defined as 23 to 100 µmol/L whilst deficiency is defined as <11 µmol/L. The results showed that VitC concentrations were negatively associated with sORP (R2 = 0.816) and positively associated with AOC (R2 = 0.842) indicating oxidative stress and vitamin C deficiency. This novel device may help facilitate speedy measurement of vitC status to identify critically ill patients who could benefit from vitC therapy.
Abstract
Vitamin C deficiency is common in critically ill patients. Vitamin C, the most important antioxidant, is likely consumed during oxidative stress and deficiency is associated with organ dysfunction and mortality. Assessment of vitamin C status may be important to identify patients who might benefit from vitamin C administration. Up to now, vitamin C concentrations are not available in daily clinical practice. Recently, a point-of-care device has been developed that measures the static oxidation-reduction potential (sORP), reflecting oxidative stress, and antioxidant capacity (AOC). The aim of this study was to determine whether plasma vitamin C concentrations were associated with plasma sORP and AOC. Plasma vitamin C concentration, sORP and AOC were measured in three groups: healthy volunteers, critically ill patients, and critically ill patients receiving 2- or 10-g vitamin C infusion. Its association was analyzed using regression models and by assessment of concordance. We measured 211 samples obtained from 103 subjects. Vitamin C concentrations were negatively associated with sORP (R2 = 0.816) and positively associated with AOC (R2 = 0.842). A high concordance of 94-100% was found between vitamin C concentration and sORP/AOC. Thus, plasma vitamin C concentrations are strongly associated with plasma sORP and AOC, as measured with a novel point-of-care device. Therefore, measuring sORP and AOC at the bedside has the potential to identify and monitor patients with oxidative stress and vitamin C deficiency.
2.
Antioxidant intervention in rheumatoid arthritis: results of an open pilot study.
van Vugt, RM, Rijken, PJ, Rietveld, AG, van Vugt, AC, Dijkmans, BA
Clinical rheumatology. 2008;27(6):771-5
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While the aetiology of rheumatoid arthritis (RA) is largely unknown, oxidative stress triggered by immune activation is well described. Oxidative stress is thought to play a causal role in the inflammation of RA. Hence, this study attempts to add to the evidence of using antioxidants as therapeutic agents, alongside drug treatment. The study was a small, open study involving eight female participants with steady disease state and drug regimes. The intervention was a an antioxidant enriched margarine (mixture of a-tocopherol, lycopene, palm oil carotenoids (mainly α-carotene) and lutein) plus vitamin C supplement, consumed daily over ten weeks. After the intervention blood samples did not show a significant change in laboratory markers of inflammation. However, the number of painful joints decreased, as shown by a significant decrease in disease activity score (DAS). The author suggested alternative markers for measuring antioxidant status and oxidative damage. Whilst these results indicate promise for using a mixture of antioxidants to help relieve symptoms of RA, this was a small, open pilot study. Double blinded, placebo controlled human trials are required to establish effect and causality.
Abstract
There is evidence that reactive oxygen species play a causal role in auto-immune diseases, such as rheumatoid arthritis (RA). Despite the supporting evidence for a beneficial effect of antioxidants on clinical characteristics of RA, the right balance for optimal effectiveness of antioxidants is largely unknown. To determine the potential beneficial effects of an antioxidant intervention on clinical parameters for RA, an open pilot study was designed. Eight non-smoking female patients with rheumatoid factor + RA and a Disease Activity Score (DAS 28) higher than 2.5 were enrolled in the study. Patients had to be receiving stable non-steroidal anti-inflammatory drug treatment and/or 'second line' medication for at least 3 months. The pilot group consumed 20 g of antioxidant-enriched spread daily during a period of 10 weeks. The intervention was stopped after 10 weeks and was followed by a 'wash-out' period of 4 weeks. At t = 0, t = 10 weeks and t = 14 weeks, patients' condition was assessed by means of DAS. In addition, standard laboratory analyses were performed, and blood-samples for antioxidants were taken. The antioxidant-enriched spread was well tolerated. All laboratory measures of inflammatory activity and oxidative modification were generally unchanged. However, the number of swollen and painful joints were significantly decreased and general health significantly increased, as reflected by a significantly improved (1.6) DAS at t = 10 weeks. The antioxidant effect was considered beneficial as, compared to the scores at t = 0, the DAS significantly reduced at t = 10 weeks. Increase of the DAS (0.7) after the "wash-out period" at t = 14 confirmed a causal relation between changes in clinical condition and antioxidants. This open pilot study aimed to assess the clinical relevance of an antioxidant intervention as a first step in assessing potential beneficial effects of antioxidants on rheumatoid arthritis. These conclusions need to be validated in a larger controlled study population.
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Metabolism of phytanic acid and 3-methyl-adipic acid excretion in patients with adult Refsum disease.
Wierzbicki, AS, Mayne, PD, Lloyd, MD, Burston, D, Mei, G, Sidey, MC, Feher, MD, Gibberd, FB
Journal of lipid research. 2003;44(8):1481-8
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Phytanic acid (PA) is a branched-chain fatty acid, found in many animal products, that, unlike most fatty acids, cannot be metabolised by beta-oxidation. Instead, it undergoes alpha-oxidation in the peroxisome. Adult Refsum Disease is a genetic neurological disease, in which alpha-oxidation is impaired, resulting in the accumulation of PA in nerves and fat tissues. Other pathways for the metabolism of PA are not fully understood, such as omega-oxidation, which results in the production of 3-methyl-organic acids (3-MAA). This study assessed the contribution of the omega-oxidation pathway to the metabolism of PA by measuring 3-MAA excretion in patients with ARD. Eleven patients with ARD were put on a low-PA diet for 12 weeks. Blood, urine and tissue samples were taken at the start and end of the 12-week period to assess levels of PA and its metabolites. The low-PA diet led to an average 21% fall in blood PA levels over 12 weeks. The capacity of the omega-oxidation pathway was 6.9mg PA/day. The authors concluded that the omega-oxidation pathway can metabolise PA ingested by patients with ARD. Therefore, omega-oxidation is a potential target for therapeutic intervention to reduce PA levels in ARD patients.
Abstract
Adult Refsum disease (ARD) is associated with defective alpha-oxidation of phytanic acid (PA). omega-Oxidation of PA to 3-methyl-adipic acid (3-MAA) occurs although its clinical significance is unclear. In a 40 day study of a new ARD patient, where the plasma half-life of PA was 22.4 days, omega-oxidation accounted for 30% initially and later all PA excretion. Plasma and adipose tissue PA and 3-MAA excretion were measured in a cross-sectional study of 11 patients. The capacity of the omega-oxidation pathway was 6.9 (2.8-19.4) mg [20.4 (8.3-57.4) micromol] PA/day. 3-MAA excretion correlated with plasma PA levels (r = 0.61; P = 0.03) but not adipose tissue PA content. omega-Oxidation during a 56 h fast was studied in five patients. 3-MAA excretion increased by 208 +/- 58% in parallel with the 158 (125-603)% rise in plasma PA. Plasma PA doubled every 29 h, while 3-MAA excretion followed second-order kinetics. Acute sequelae of ARD were noted in three patients (60%) after fasting. The omega-oxidation pathway can metabolise PA ingested by patients with ARD, but this activity is dependent on plasma PA concentration. omega-Oxidation forms a functional reserve capacity that enables patients with ARD undergoing acute stress to cope with limited increases in plasma PA levels.
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Gastrointestinal permeability during exercise: effects of aspirin and energy-containing beverages.
Lambert, GP, Broussard, LJ, Mason, BL, Mauermann, WJ, Gisolfi, CV
Journal of applied physiology (Bethesda, Md. : 1985). 2001;90(6):2075-80
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Many athletes use aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) for analgesia. This study of 17 subjects aimed to assess whether the use of aspirin with prolonged exercise could increase gastrointestinal permeability. It also aimed to examine whether consumption of a carbohydrate-containing or a carbohydrate and glutamine-containing beverage could reduce this effect. Authors concluded that acute aspirin consumption before prolonged exercise could increase gastroduodenal and intestinal permeability. They also indicated that gastroduodenal permeability was significantly decreased by the ingestion of carbohydrate-containing beverages and that consumption of carbohydrate containing glutamine beverage provided no additional benefits than the carbohydrate alone beverage.
Abstract
The purpose of this study was to determine whether aspirin (A) ingestion combined with prolonged exercise increases gastrointestinal permeability and whether consumption of a carbohydrate-containing (CHO) or a CHO + glutamine-containing (CHO+G) beverage would reduce this effect. Seventeen subjects completed six experiments. They ingested A (1,300 mg) or placebo (P) pills the evening before and before running 60 min at 70% maximal oxygen uptake. Also, before running they ingested a solution containing 5 g lactulose (L), 5 g sucrose (S), and 2 g rhamnose (R). During each trial, either a 6% CHO beverage, a 6% CHO+G (0.6%; 41 mM) beverage, or a water placebo (WP) was consumed. For 4 h after a run, all urine was collected to measure urinary excretion of L, R, and S. S excretion (percentage of dose ingested; measure of gastroduodenal permeability) was significantly greater (P < 0.05) during the A trial while the subjects drank the WP compared with all other trials. Administration of A also significantly increased L/R (measure of intestinal permeability) for the CHO and WP trials compared with all P trials. Ingestion the CHO or CHO+G beverages significantly reduced S excretion and L excretion when A was administered, but it did not reduce L/R. These results indicate that gastroduodenal and intestinal permeability increase after A ingestion during prolonged running and that ingestion of a CHO beverage attenuates the gastroduodenal effect but not the intestinal effect. Furthermore, addition of G to the CHO beverage provided no additional benefit in reducing gastroduodenal or intestinal permeability.