Tolerance and safety of vitamin E: A toxicological position report

Kappus, H.

doi:10.1016/0891-5849(92)90166-e

Cited by 208 publications

(91 citation statements)

References 73 publications

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“…Large-dose vitamin E supplementation resulted in a vitamin E status in the liver and serum in HO þ E group even higher than that in the HF group and increased levels in the pancreas compared with those seen in the HF group. Since the vitamin E concentrations vary with the lipid content (33) , vitamin E levels in the liver and serum were corrected by the TAG content, but the results were the same (pancreas vitamin E levels could not be corrected by the TAG content due to the limited sample size). In the HO þ E group, the levels of glucose tolerance, serum insulin and GSIS were similar to those in the HF group (Table 3).…”

Section: Resultsmentioning

confidence: 99%

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Dietary oxidised frying oil causes oxidative damage of pancreatic islets and impairment of insulin secretion, effects associated with vitamin E deficiency

et al. 2010

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We previously reported that, in rodents, a diet with a high oxidised frying oil (OFO) content leads to glucose intolerance associated with a reduction in insulin secretion. The present study aimed at investigating the impairment of pancreatic islets caused by dietary OFO. C57BL/6J mice were divided into three groups to receive a low-fat basal diet containing 5 g/100 g of fresh soyabean oil (LF group) or a high-fat diet containing 20 g/100 g of either fresh soyabean oil (HF group) or OFO (HO group). After 8 weeks, mice in the HO group showed glucose intolerance and hypoinsulinaemia, and their islets showed impaired glucose-stimulated insulin secretion (P,0·05; HO group v. LF and HF groups). Significantly higher oxidative stress and a lower mitochondrial membrane potential were observed in the islets in the HO group compared with the LF and HF groups. Immunoblots showed that the reduction in insulin levels in HO islets was associated with activation of the c-Jun NH 2 -terminal kinase and a reduction in levels of pancreatic and duodenal homeobox factor-1. In a second study, when dietary OFO-induced tissue vitamin E depletion was prevented by large-dose vitamin E supplementation (500 IU(1·06 mmol all-rac-a-tocopherol acetate)/kg diet; HO þ E group), the OFO-mediated reduction in islet size and impairment of glucose tolerance and insulin secretion were significantly attenuated (P, 0·05; HO group v. HO þ E group). We conclude that a high level of dietary OFO ingestion impairs glucose metabolism by causing oxidative damage and compromising insulin secretion in pancreatic islets, and that these effects can be prevented by vitamin E supplementation.Key words: Oxidised frying oil: Glucose-stimulated insulin secretion: Vitamin E: Pancreatic and duodenal homeobox factor-1: c-Jun NH 2 -terminal kinase Deep-frying is a common cooking practice, and the safety of oxidised frying oil (OFO) ingested with fried food is a concern. During the deep-frying process, a series of reactions, including auto-oxidation, thermal oxidation, polymerisation, cyclisation and fission, occur in the frying oil (1) . Generally, OFO prepared using normal cooking practices as part of a nutritionally balanced diet is regarded as safe due to the induction of detoxifying cytochrome P450 enzymes and the limited absorption of toxic polymers produced during the deep-frying process (2,3) . However, animal studies have revealed that some nutritional and metabolic effects related to OFO ingestion are noteworthy.We (4 -6) and others (7,8) have shown that, in rats and mice, OFO ingestion can influence lipid metabolism through the activation of PPARa in the liver, leading to increased fatty acid catabolism. Paradoxically, impairment of glucose metabolism, i.e. glucose intolerance, is observed in OFO-fed rodents (9) . When OFO-induced effects were compared with conjugated linoleic acid-induced lipodystrophic diabetes in mice, we found that, although both are characterised by body fat loss and glucose intolerance, OFO-mediated glucose intolerance is due to ...

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Section: Resultsmentioning

confidence: 99%

“…1 mg of a-tocopherol ¼ 1·49 IU; the biological function of g-tocopherol is only 0·1 of that of a-tocopherol (33) .…”

Section: Protein Electrophoresis and Immunoblottingmentioning

confidence: 99%

Dietary oxidised frying oil causes oxidative damage of pancreatic islets and impairment of insulin secretion, effects associated with vitamin E deficiency

et al. 2010

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“…Paradoxically both studies noted a little higher rate of lung cancer and CVD among subjects receiving betacarotene. Among all the dietary AO vitamin E consisting of a family of eight members is most studied molecule wherein alpha-tocopherol has received maximum attention as it is retained in human body and has an excellent antioxidant action in stabilizing membrane structure; and that it has strong potential against oxidative stress [7,8,10,11,19,[200][201][202]. Contrary to earlier prevailing concept that supplementation with alpha-tocopherol confers protection against a large spectrum of diseases such as CVD, cancer, diabetes mellitus, Parkinsonism, Alzheimer disease preeclampsia and aging, the recent observations from large prospective, randomized placebo controlled trials have largely been negative [22].…”

Section: Inconsistencies: Antioxidant Supplements Are Boon or Banementioning

confidence: 99%

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

Singh

Chandra

Mahdi

et al. 2010

Indian J Clin Biochem

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The antioxidants are essential molecules in human system but are not miracle molecules. They are neither performance enhancers nor can prevent or cure diseases when taken in excess. Their supplemental value is debateable. In fact, many high quality clinical trials on antioxidant supplement have shown no effect or adverse outcomes ranging from morbidity to all cause mortality. Several Chochrane Meta-analysis and Markov Model techniques, which are presently best available statistical models to derive conclusive answers for comparing large number of trials, support these claims. Nevertheless none of these statistical techniques are flawless. Hence, more efforts are needed to develop perfect statistical model to analyze the pooled data and further double blind, placebo controlled interventional clinical trials, which are gold standard, should be implicitly conducted to get explicit answers. Superoxide dismutase (SOD), glutathione peroxidase and catalase are termed as primary antioxidants as these scavenge superoxide anion and hydrogen peroxide. All these three enzymes are inducible enzymes, thereby inherently meaning that body increases or decreases their activity as per requirement. Hence there is no need to attempt to manipulate their activity nor have such efforts been clinically useful. SOD administration has been tried in some conditions especially in cancer and myocardial infarction but has largely failed, probably because SOD is a large molecule and can not cross cell membrane. The dietary antioxidants, including nutrient antioxidants are chain breaking antioxidants and in tandem with enzyme antioxidants temper the reactive oxygen species (ROS) and reactive nitrogen species (RNS) within physiological limits. Since body is able to regulate its own requirements of enzyme antioxidants, the diet must provide adequate quantity of non-enzymic antioxidants to meet the normal requirements and provide protection in exigent condition. So far, there is no evidence that human tissues ever experience the torrent of reactive species and that in chronic conditions with mildly enhanced generation of reactive species, the body can meet them squarely if antioxidants defense system in tissues is biochemically optimized. We are not yet certain about optimal levels of antioxidants in tissues. Two ways have been used to assess them: first by dietary intake and second by measuring plasma levels. Lately determination of plasma/serum level of antioxidants is considered better index for diagnostic and prognostic purposes. The recommended levels for vitamin A, E and C and beta carotene are 2.2-2.8 lmol/l; 27.5-30 lmol/l; 40-50 lmol/l and 0.4-0.5 lmol/l, respectively. The requirement and recommended blood levels of other dietary antioxidants are not established. The resolved issues are (1) essential to scavenge excess of radical species (2) participants in redox homeostasis (3) selective antioxidants activity against radical species (4) there is no universal antioxidant and 5) therapeutic value in case of deficiency. The overar...

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“…Volunteers were asked to take two tablets per day of their supplements (TRF or placebo) for 56 days, preferably with lunch or dinner. This dose (400 mg per day) was chosen based on the other studies that used vitamin E supplementation (Kappus and Diplock, 1992;Meydani et al, 1997a, b).…”

Section: Tocotrienol-rich Fractionmentioning

confidence: 99%

Effects of supplementation with tocotrienol-rich fraction on immune response to tetanus toxoid immunization in normal healthy volunteers

et al. 2010

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Background/Objectives: Vitamin E is an essential fat-soluble vitamin that has been shown to induce favorable effects on animal and human immune systems. The objective of this study was to assess the effects of tocotrienol-rich fraction (TRF) supplementation on immune response following tetanus toxoid (TT) vaccine challenge in healthy female volunteers. Subjects/Methods: In this double-blinded, placebo-controlled clinical trial, participants were randomly assigned to receive either placebo (control group) or 400 mg of TRF (study group) supplementation daily. Over the 2-month period of the study, volunteers were asked to attend three clinical sessions (that is, on days 0, 28 and 56) and blood samples were obtained from the volunteers during the follow-up. On day 28, all volunteers were also vaccinated with the TT vaccine (20 Lf) intramuscularly. Results: The results from the clinical trial showed that TRF supplementation significantly increased the total vitamin E level in the plasma of the TRF-supplemented volunteers compared with the placebo group, indicating overall compliance. Volunteers supplemented with TRF showed a significantly (Po0.05) enhanced production of interferon-g and interleukin (IL)-4 by the mitogen or TT-stimulated leukocytes compared with the control group. Volunteers from the TRF group produced significantly (Po0.05) lower amounts of IL-6 compared with the placebo group. Anti-TT IgG production was also significantly (Po0.05) augmented in the TRF-supplemented group compared with the placebo group. Conclusions: We conclude that TRF has immunostimulatory effects and potential clinical benefits to enhance immune response to vaccines.

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Tolerance and safety of vitamin E: A toxicological position report

Cited by 208 publications

References 73 publications

Dietary oxidised frying oil causes oxidative damage of pancreatic islets and impairment of insulin secretion, effects associated with vitamin E deficiency

Dietary oxidised frying oil causes oxidative damage of pancreatic islets and impairment of insulin secretion, effects associated with vitamin E deficiency

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

Effects of supplementation with tocotrienol-rich fraction on immune response to tetanus toxoid immunization in normal healthy volunteers

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