Vitamin C (ascorbic acid) is a water-soluble vitamin with an array of biological functions. A number of proposed factors contribute to the vitamin’s plasma bioavailability and ability to exert optimal functionality. The aim of this review was to systematically assess plasma vitamin C levels post-surgery compared with pre-surgery/the magnitude and time frame of potential changes in concentration. We searched the PUBMED, SCOPUS, SciSearch and the Cochrane Library databases between 1970 and April 2020 for relevant research papers. Prospective studies, control groups and true placebo groups derived from controlled trials that reported means and standard deviations of plasma vitamin C concentrations pre- and postoperatively were included into the meta-analysis. Data were grouped into short-term (≤7 d) and long-term (>7 d) postoperative follow-up. Twenty-three of thirty-one studies involving 642 patients included in the systematic review were suitable for meta-analysis. Pooled data from the meta-analysis revealed a mean depletion of plasma vitamin C concentration of −17·99 µmol/l (39 % depletion) (CI −22·81, −13·17) (trial arms = 25, n 565, P < 0·001) during the first postoperative week and −18·80 µmol/l (21 % depletion) (CI −25·04, −12·56) (trial arms = 6, n 166, P < 0·001) 2–3 months postoperatively. Subgroup analyses revealed that these depletions occurred following different types of surgery; however, high heterogeneity was observed amongst trials assessing concentration change during the first postoperative week. Overall, our results warrant larger, long-term investigations of changes in postoperative plasma vitamin C concentrations and their potential effects on clinical symptomology.

Enhanced intakes of fruit and vegetables have been associated with improved psychological well-being. We investigated the potential mood-enhancing effects of kiwifruit, a fruit rich in vitamin C and a number of other important micronutrients. Young adult males (n 35) were supplemented with either half or two kiwifruit/d for 6 weeks. Profile of Mood States questionnaires were completed at baseline and following the intervention. No effect on overall mood was observed in the half a kiwifruit/d group; however, a 35 % (P = 0·06) trend towards a decrease in total mood disturbance and a 32 % (P = 0·063) trend towards a decrease in depression were observed in the two kiwifruit/d group. Subgroup analysis indicated that participants with higher baseline mood disturbance exhibited a significant 38 % (P = 0·029) decrease in total mood disturbance, as well as a 38 % (P = 0·048) decrease in fatigue, 31 % (P = 0·024) increase in vigour and a 34 % (P = 0·075) trend towards a decrease in depression, following supplementation with two kiwifruit/d. There was no effect of two kiwifruit/d on the mood scores of participants with lower baseline mood disturbance. Dietary intakes and body status of specific micronutrients indicated a significant increase in the participants' vitamin C intakes and corresponding plasma levels of the vitamin. The results indicate that enhanced intake of kiwifruit by individuals with moderate mood disturbance can improve overall mood.

Intraerythrocytic malaria parasites ingest the cytosol of their host cell and digest it inside their acid food vacuoles. Acidified (pH 4–5·5, 37 °C) human red blood cell lysates were used to simulate this process, measuring the denaturation of haemoglobin (Hb) and the release of iron, in the absence or presence of exogenous protease. Spontaneous Hb denaturation and appearance of non-heme iron were observed upon lysate acidification, their rates decreasing with increasing pH, and increasing in the presence of protease. Both processes were inhibited by the quinoline-containing anti-malarial drugs (QCDs) chloroquine, quinine, mefloquine and amodiaquine at concentrations well below those expected in the acidic food vacuole of the parasite. Spectrophotometric analysis indicated that chloroquine complexes with heme in acid-denatured haemoglobin. Other weak bases as well as verapamil and diltiazem, known to reverse the resistance of malarial parasites to chloroquine, were without efifect indicating that the action of QCDs is specific. Based on our previous results and the present report, we suggest that iron release in acidified lysates is mediated through the formation of ferryl (Fe(IV)) radicals. QCDs possibly complex with this radical, as they do with heme, and prevent its contact with an adjacent heme molecule which is required for ring opening and iron release. These results may suggest that one of the anti-malarial effects of QCDs is to deprive the parasite of an adequate iron supply. Addition of iron to cultures of Plasmodium falciparum was expected to circumvent the deprivation of iron and reduce the anti-malarial eflfect of QCDs. However, adding iron as penetrating fructose or nitrilotriacetate complexes did not alter the parasite's susceptibility to chloroquine. Ascorbate markedly increased the release of iron in acidified lysates, and this effect was not reduced by chloroquine. Ascorbate was found to decrease parasite susceptibility to chloroquine, suggesting that iron deprivation may be an important factor in the anti-malarial action of QCDs.

Dietary bioactive compounds (vitamin E, carotenoids, polyphenols, vitamin C, Se and Zn) have beneficial effects on skin health. The classical route of administration of active compounds is by topical application direct to the skin, and manufacturers have substantial experience of formulating ingredients in this field. However, the use of functional foods and oral supplements for improving skin condition is increasing. For oral consumption, some dietary components could have an indirect effect on the skin via, for example, secondary messengers. However, in the case of the dietary bioactive compounds considered here, we assume that they must pass down the gastrointestinal tract, cross the intestinal barrier, reach the blood circulation, and then be distributed to the different tissues of the body including the skin. The advantages of this route of administration are that the dietary bioactive compounds are metabolized and then presented to the entire tissue, potentially in an active form. Also, the blood continuously replenishes the skin with these bioactive compounds, which can then be distributed to all skin compartments (i.e. epidermis, dermis, subcutaneous fat and also to sebum). Where known, the distribution and mechanisms of transport of dietary bioactive compounds in skin are presented. Even for compounds that have been studied well in other organs, information on skin is relatively sparse. Gaps in knowledge are identified and suggestions made for future research.

Previous studies of vitamin C absorption in man using stable isotope probes have given results which cannot easily be reconciled with those obtained using non-isotope measurement. In order to investigate some of the apparent paradoxes we have conducted a study using two consecutive doses of vitamin C, one labelled and one unlabelled, given 90 min apart. Compatibility of the experimental results with two feasible models was investigated. In Model 1, ingested vitamin C enters a pre-existing pool before absorption, which occurs only when a threshold is exceeded; in Model 2, ingested vitamin C is exchanged with a pre-existing flux before absorption. The key difference between these two models lies in the predicted profile of labelled material in plasma. Model 1 predicts that the second unlabelled dose will produce a secondary release of labelled vitamin C which will not be observed on the basis of Model 2. In all subjects Model 1 failed to predict the observed plasma concentration profiles for labelled and unlabelled vitamin C, but Model 2 fitted the experimental observations. We speculate on possible physiological explanations for this behaviour, but from the limited information available cannot unequivocally confirm the model structure by identifying the source of the supposed flux.

Factors affecting absorption of physiological doses of vitamin C in man have not been widely studied, partly because few suitable tools exist to distinguish recently absorbed vitamin C from endogenous vitamin. Stable isotope-labelled vitamin C provides such a tool. Fifteen healthy non-smoking subjects aged 26–59 years were studied. Each received 30 mg L-[1-13C]ascorbic acid orally on two occasions, 3–4 weeks apart. The ascorbate was given alone or with Fe (100 mg as ferrous fumarate) or with red grape juice, which is rich in polyphenols. Blood was collected at frequent intervals for 1 h, and then each hour for a further 3 h. Total concentration of vitamin C was measured fluorometrically and its 13C-isotope enrichment was measured by GC–MS after conversion to volatile trimethylsilyl esters. Peak plasma enrichment occurred within 25–50 min. No kinetic variables were significantly altered by the iron fumarate supplement. Grape juice attenuated vitamin C absorption, reaching significance at the 20 min time point. There were weak correlations between isotope enrichment and body weight or endogenous ascorbate concentration. The increment in total plasma ascorbate was smaller if calculated from isotope enrichment than from vitamin C concentration increase. The dilution pool was much larger than the plasma ascorbate pool. Further studies are needed to resolve these paradoxes. Stable isotope-labelled ascorbate is potentially useful for measurement of vitamin C absorption by human subjects.

The present controlled-training double-blind study (supplemented (S) group, n 7; placebo (P) group, n 10) was designed to investigate whether an antioxidant mixture (Se 150 μg, retinyl acetate mg, ascorbic acid 120 mg, α-tocopheryl succinate) would allow overloaded triathletes to avoid adaptation failure in the antioxidant system. Dietary intakes were recorded. The supplement of Se, and vitamins A and E provided 100 % of the French RDA. Four weeks of overloaded training (OT) followed 4 weeks of normal training (NT). After NT and OT, biological studies were conducted at rest and after a duathlon test (run 5 km, cycle 20 km, run 5 km). During the 4-week period of NT, blood levels of GSH levels increased in response to supplementation (P<0·05) and remained elevated during OT. Plasma glutathione peroxidase activity was significantly higher in the S group in all situations after NT and OT (P<0·01). The S group had increased erythrocyte Cu,Zn-superoxide dismutase activity in response to OT (P<0·05). Supplementation significantly reduced (P<0·05) the magnitude in duathlon-induced creatine kinase isoenzyme MB mass increase, which tended to be higher with OT (P=0·09). We conclude that the antioxidant mixture helped to preserve the antioxidant system during an OT-induced stress in subjects with initially low antioxidant intakes. Effects of supplementation during NT and/or OT are shown mostly by the alleviated muscle damage. The effects of the antioxidant mixture were observed for doses that can be provided by a diversified and well-balanced diet. The maintenance of normal nutritional status with regard to the antioxidant intake (Se, vitamins C and E) plays a key role in antioxidant adaptive effects during NT and OT.

Human ovarian carcinoma cells (MDAH 2774) were treated with sodium ascorbate (VC), menadione (VK3), or with a VC:VK3 combination for 1 h and then studied using light microscopy (LM) and scanning (SEM) and transmission electron (TEM) microscopy. Plasma membrane damage (blisters and blebs, hairy aspect) results from vitamin C (VC) treatment, while cytoskeletal damage and self-morsellation are caused by vitamin K3 (VK3) treatment. VC:VK3-treated cells exhibit exacerbated injuries characteristic of both VC and VK3 treatment as well as a significant decrease in cell diameters from 20–35 μm for control cells to 7–12 μm for VC:VK3 treatment. Moreover, after a 1-h exposure to the vitamin combination, autoschizis (43%), apoptosis (3%), and oncosis (1.9%) are observed at the percentages indicated. All cellular changes associated with autoschizis observed with SEM were confirmed by LM and TEM observations and are consistent with cell death by autoschizis: decrease in cell size, cytoplasmic self-excisions, degradation of the nucleus and nucleolus without formation of apoptotic bodies and, ultimately, karyorrhexis and karyolysis. These results also suggest that the vitamin combination may find clinical use in the treatment of ovarian cancer.

Ascorbic acid (AA), a neuromodulator in the vertebrate CNS, is released from glutamatergic neurons in exchange with glutamate uptake and, in turn, modulates the release of both glutamate and dopamine. We have reported that voltage-gated K+ currents (IK(V)) in ON-mixed rod/cone bipolar cells (Mb) were suppressed 60% by 100–200 μM AA when added to an ascorbate-free solution. However, as the in vivo [AA]o in retina is about 200 μM, we studied the effects of changes in [AA]o on IK(V) when [AA]o was varied around a baseline concentration of 200 μM. Whole-cell currents were recorded with patch-clamp methods from goldfish Mb cells in retinal slices, bathed in a solution containing 200 μM AA. We found that (1) IK(V) was enhanced (180 ± 36%, n = 9) by increases of [AA]o less than 40 μM with an average latency of 8 min. (2) However, IK(V) was suppressed without an appreciable latent period by two conditions: increases more than 40 μM [AA]o and decreases by any amount greater than 10 μM. (3) Effects of Δ[AA]o on IK(V) were blocked by a D1 dopamine receptor antagonist, SCH 23390, but not by a D2 receptor antagonist, spiperone. Increased concentrations of a D1 agonist (SKF 38390) and dopamine had similar concentration-dependent effects on IK(V) as did AA, even in the presence of 200 μM ascorbate. Ascorbate has complicated concentration-dependent effects on IK(V) of Mb cells in vitro that were mediated by D1 dopamine receptors, suggesting that dopamine and ascorbate may be involved reciprocally in modulating IK(V), with consequences on the transmission of rod signals to the inner retina.

Numerous biochemical and physiological studies have demonstrated the importance of ascorbate (ASC) as a reducing agent and antioxidant in higher plant metabolism. Of special note is the capacity of ASC to eliminate damaging activated oxygen species (AOS) including O2−· and H2O2. N2-fixing legume nodules are especially vulnerable to oxidative damage because they contain large amounts of leghaemoglobin which produces AOS through spontaneous autoxidation; thus, ASC and other components of the ascorbate–reduced glutathione (ASC–GSH) pathway are critical antioxidants in nodules. In order to establish a meaningful correlation between concentrations of ASC and capacity for N2 fixation in legume root nodules, soybean (Glycine max) plants were treated with excess ASC via exogenous irrigation or continuous intravascular infusion through needles inserted directly into plant stems. Treatment with ASC led to striking increases in nitrogenase activity (acetylene reduction), nodule leghaemoglobin content, and activity of ASC peroxidase, a key antioxidant enzyme. The concentration of lipid peroxides, which are indicators of oxidative damage and onset of senescence, was decreased in ASC-treated nodules. These results support the conclusion that ASC is critical for N2 fixation and that elevated ASC allows nodules to maintain a greater capacity to fix N2 over longer periods.

A pea (Pisum sativum cv. Puget) cultivar was grown on a medium containing different NaCl concentrations (0–160 mol m−3) in order to study the effects of salt stress on leaf water relations and on the activity of antioxidant enzymes. NaCl stress caused a rapid decline in chlorophyll content. Both leaf water (ψl) and osmotic potentials (ψs) decreased progressively with the severity of the stress (from 90–160 mol m−3 NaCl) whereas leaf turgor pressure (ψp) increased in treated plants. Pea leaves contained an iron-containing superoxide dismutase (Fe-SOD) isozyme in chloroplasts alongside a copper-zinc-containing (CuZn-SOD) form (CuZn-SOD II). The lowest NaCl concentration (70 mol m−3) had no effect on the activity of these antioxidant enzymes while higher concentrations (110–130 mol m−3) enhanced the activity of cytosolic CuZn-SOD I and chloroplastic CuZn-SOD II as well as that of mitochondrial and/or peroxisomal manganese-containing superoxide dismutase (Mn-SOD). These inductions were matched by increases in the activity of ascorbate peroxidase (APX) and monodehydroascorbate reductase (MDHAR). The increased activities coincided with decreased stomatal conductance and were unaffected by the severity of stress except in the case of CuZn-SOD II which fell to control values under the highest stress conditions (140–160 mol m−3 NaCl), when a concomitant increase in chloroplastic Fe-SOD activity was observed. Glutathione reductase (GR) and dehydroascorbate reductase (DHAR) activities were only induced under severe NaCl stress (130–160 mol m−3) and were accompanied by losses in the ascorbate and glutathione pools, lower ASC/DHA and GSH/GSSG ratios and increases in GSSG. Electron microscopy showed that the thylakoidal structure of the chloroplasts became disorganized and their starch content decreased in plants treated with 160 mol m−3 NaCl. Overall, the results suggest that salt stress is accompanied by oxidative stress, perhaps at the cell compartment level. The capacity of Puget cultivar to ensure cell turgor and to enhance the activity of enzymes involved in the defence against oxidative stress seems to be important in determining adaptation to moderate NaCl stress conditions. In plants exposed to severe NaCl stress (130–160 mol m−3) it seems that such resistance to oxidative stress is overcome, which might contribute to the deleterious effects of salt and significant growth reduction in these conditions.

The aim of this work was to examine the correspondence between apoplastic/symplastic antioxidant status and previously reported plant age-related shifts in the ozone (O3) resistance of Plantago major L. Seed-grown plants were fumigated in duplicate controlled environment chambers with charcoal/Purafil®-filtered air (CFA) or CFA plus 70 nmol mol−1 O3 for 7 h d−1 over a 42 d period. Measurements of stomatal conductance and antioxidants were made after 14, 28 and 42 d fumigation, on leaves at an equivalent stage of development (youngest fully expanded leaf, measured c. 9 d after emergence). Ozone exposure resulted in a similar decline in stomatal conductance across plant ages, indicating that increases in O3 resistance with plant age were mediated through changes in the tolerance of leaf tissue rather than enhanced pollutant exclusion. Leaf apoplastic washing fluid was found to contain ‘unspecific’ peroxidase, ascorbate peroxidase, superoxide dismutase and ascorbate, but not glutathione and the enzymes required to facilitate the regeneration of ascorbate from its oxidized forms. A weak induction in the activity of certain symplastic antioxidants was found after 14 d O3 fumigation, despite a lack of visible symptoms of injury, but shifts in symplastic antioxidant enzyme activity were not consistent with previously observed increases in resistance to O3 with plant age. By contrast, changes in ‘unspecific’ peroxidase activity and in the small pool of ascorbate in the leaf apoplast were found to accompany age-related shifts in O3 resistance. It is concluded that constituents of the leaf apoplast may constitute a potentially important front line defence against O3.

Ascorbate, often used as an antioxidant in neural studies, may also serve as a neuromodulator in the vertebrate central nervous system (CNS), in that it modulates the synaptic actions of glutamate and dopamine. Retina of fish contain a high concentration of ascorbate. The release and/or uptake of neurotransmitters are related to membrane potential, which to a large extent is determined by the activity of K+ channels. As retinal bipolar cells are subject to synaptic input from glutamatergic and dopaminergic sources, the effects of ascorbate on voltage-dependent K+ currents (IK(V)) of the mixed rod–cone ON-center bipolar cells (Mb) in goldfish retinal slices were studied using whole-cell recording techniques. IK(V) was suppressed reversibly 60% by 100–200 μM ascorbate. The effect of ascorbate was not due to changes in pH, oxidative stress, lipid peroxidation, any Ca2+-dependent or Na+-dependent action. However, the suppressive effect of ascorbate was blocked by cholera toxin and Wiptide, a protein kinase A (PKA) inhibitor. It is concluded that ascorbate, at physiological concentrations, inhibits IK(V) of bipolar cells via a GS-protein-PKA system. This effect of ascorbate should be taken into account when using ascorbate as an antioxidant in retinal studies involving dopamine.

The purpose of this study was, first to explore metabolic interactions between Cu and ascorbic acid in guinea-pigs, particularly with respect to any possible disadvantages of high ascorbatein the presence of low Cu intakes, and second, to test the hypothesis that variations in ascorbate and/or Cu status might inhence collagen cross-linking, either by inducing a change in thecross-links: hydroxyproline ratio, or by inducing a change in the pyridinoline: deoxypyridinoline cross-linls ratio. Four matched groups, each of eight male weanliig Dunkin-Hartley guinea-pigs, were maintained on purified diets containing either no added Cu, or 150 mg Cu/kg diet, and either 0·1 g or 30 g ascorbic acid/kg diet. They were then killed 8 weeks later, and the following indices were measured body and organ weights; blood haemoglobin; adrenal ascorbate concentrations; Cu concentrations in plasma, liver and femur; superoxide dismutase (EC 1.15.1.1) activity in whole blood and liver; hydroxyproline, pyridinoline and deoxypyridinoline in femur and in urine. The principal observations were: Cu intake significantly affected blood and tissue Cu concentrations and superoxide dismutase activity; and ascorbic acid intake significantlyaffected adrenal ascorbate levels and the deoxypyridinoline: pyridinoline cross-links ratio, especially in bone (femur). There was evidence of a significant interaction between ascorbateand Cu with respect to adrenal and plasma Cu concentrations, blood superoxide dismutase activityand body weights. We conclude that interactions between ascorbate and Cu at the functional level were present but modest, and that a new and potentially powerful functional index of ascorbate status may exist within the deoxypyridinoline: pyridinoliie collagen cross-link ratio.