Dietary antioxidants and risk of Parkinson’s disease in two population-based cohorts.

Yang F, Wolk A, Håkansson N, Pedersen NL, Wirdefeldt K

Mov Disord. 2017 Nov;32(11):1631-1636. doi: 10.1002/mds.27120. Epub 2017 Sep 7.

Abstract

BACKGROUND:

A neuroprotective effect of dietary antioxidants on Parkinson’s disease (PD) risk has been suggested, but epidemiological evidence is limited.

OBJECTIVES:

To examine the associations between intake of dietary antioxidant vitamins and total antioxidant capacity and risk of PD.

METHODS:

We prospectively assessed the relationships of dietary antioxidant vitamins C and E, ß-carotene, and total antioxidant capacity with PD risk in two population-based cohorts (38,937 women and 45,837 men).

RESULTS:

During a mean 14.9-year follow-up period, 1,329 PD cases were identified. Dietary intake of ß-carotene was associated with a lower risk of PD (hazard ratio: 0.86; 95% confidence interval: 0.78-0.95; P_trend < 0.01 for women and hazard ratio: 0.91; 95% confidence interval: 0.84-0.99; P_trend = 0.05 for men). An inverse association between dietary vitamin E and PD risk was found in women (hazard ratio: 0.87; 95% confidence interval: 0.79-0.96; P_trend = 0.02). Dietary intake of vitamin C was inversely associated with PD risk in women at borderline significance (hazard ratio: 0.91; 95% confidence interval: 0.83-1.00; P_trend = 0.04). There was no association between dietary total antioxidant capacity and PD risk in either women (hazard ratio: 0.93; 95% confidence interval: 0.84-1.02; P_trend = 0.35) or men (hazard ratio: 1.00; 95% confidence interval: 0.93-1.07; P_trend = 0.97).

CONCLUSION:

Intake of dietary vitamin E and ß-carotene was associated with a lower risk of PD.

Babura SR, Abdullah SNA, Khaza Ai H

J Nutr Sci Vitaminol (Tokyo). 2017;63(4):215-221. doi: 10.3177/jnsv.63.215.

Abstract

Tocotrienols are forms of vitamin E that are present in several important food crops. Compared to tocopherols, less research has been conducted on these compounds because of their low bioavailability and distribution in plant tissues. Both tocotrienols and tocopherols are known for their antioxidant and anticancer activities, which are beneficial for both humans and animals. Moreover, tocotrienols possess certain properties which are not found in tocopherols, such as neuroprotective and cholesterol-lowering activities. The contents of tocotrienolsin plants vary. Tocotrienols constitute more than 70% and tocopherols less than 30% of the total vitamin E content in palm oil, which is the best source of vitamin E. Accumulation of tocotrienols also occurs in non-photosynthetic tissues, such as the seeds, fruits and latex of some monocotyledonous and dicotyledonous plant species. The use of biotechnological techniques to increase the tocotrienol content in plants, their biological functions, and benefits to human health are discussed in this review.

Zadeh-Ardabili PM, Rad SK, Rad SK, Khazaài H, Sanusi J, Zadeh MH

Sci Rep. 2017 Oct 30;7(1):14365. doi: 10.1038/s41598-017-14765-3.

Abstract

Spinal cord injury (SCI) occurs following different types of crushes. External and internal outcomes of SCI are including paralysis, cavity, and cyst formation. Effects of dietary derived antioxidants, such as palm vitamin E on central nervous system (CNS) encourage researchers to focus on the potential therapeutic benefits of antioxidant supplements. In the present study, experiments were carried out to evaluate the neuro-protective effect of the palm vitamin E on locomotor function and morphological damages induced SCI. Seventy-two male rats (Sprague-Dawley) were randomly divided into four groups: sham (laminectomy); control (supplemented with the palm vitamin E at a dose of 100 mg/kg/day); untreated-SCI (partial crush, 30-33% for 20 sec); treated-SCI (partial crush, 30-33% for 20 sec supplemented with the palm vitamin E at a dose of 100 mg/kg/day). The treatment with the palm vitamin E significantly improved the hind limb locomotor function, reduced the histopathological changes and the morphological damage in the spinal cord. Also, the palm vitamin E indicated a statistically significant decrease in the oxidative damage indicators, malondialdehyde (MDA) level and glutathione peroxidase (GPx) activity in the treated-SCI compared to the untreated-SCI.

Reddy VD, Padmavathi P, Bulle S, Hebbani AV, Marthadu SB, Venugopalacharyulu NC, Maturu P, Varadacharyulu NC

Neurotoxicol Teratol. 2017 Sep;63:60-65. doi: 10.1016/j.ntt.2017.07.004. Epub 2017 Aug 1.

Abstract

Chronic and excessive alcohol consumption leads to various neurological diseases. Synaptosomes are ideal organelles to study the functional properties of the brain in alcoholism. This study focuses on the association between oxidative stress and synaptosomal membrane properties in alcohol treated rats. Sixty day old male albino rats were treated with 20% alcohol at 5g/kg body weight/ day for sixty days. Alcohol administration significantly increased the levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyls with decreased catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD) activities and reduced glutathione (GSH) content in synaptosomes. Further, alcohol administration decreased (cholesterol/phospholipids) C/P ratio in synaptosomal membranes, which was further confirmed using 1,6 diphenyl 1,3 hexatriene (DPH) as fluorescent probe. Moreover, alcohol treatment also increased membrane bound Na⁺/K⁺-ATPase, Ca²⁺-ATPase and Mg²⁺-ATPase enzyme activities. Correlation (r) analysis revealed that anisotropic (γ) values were strongly associated with lipid peroxidation (r=0.678) and Na⁺/K⁺-ATPase activity (r=0.793). The results of the present study clearly indicate that lipid peroxidation was positively correlated (r=0.621) with Na⁺/K⁺-ATPase activity and C/P ratio was negatively associated (r=-0.549) in alcohol treated animals. Similar results were found on alcohol treatment (50 and 100mM) of brain synaptosomes in vitro. But with the co-treatment of vitamin E reversed these changes. In conclusion, synaptosomal membranes properties are impaired due to increased oxidative stress, changes in lipid composition, altered fluidity and membrane bound enzyme activities. And treatment with vitamin E renders protection against ethanol-induced membrane alterations.

Dong Y, Chen X, Liu Y, Shu Y, Chen T, Xu L, Li M, Guan X

Int J Geriatr Psychiatry. 2017 Aug 23. doi: 10.1002/gps.4780. [Epub ahead of print]

Abstract

OBJECTIVE:

Whether low-serum vitamin E increases the risk of Alzheimer disease (AD) in older people remains inconclusive. This meta-analysis aims to synthesize evidence-based case-control studies to evaluate the association between serum vitamin E and the risk of AD.

METHODS:

Potentially relevant studies were selected through PubMed, Embase, Wanfang, Chongqing VIP, and China National Knowledge Infrastructure databases by using the core terms Vitamin E/alpha-tocopherol and Alzheime’s disease/senile dementia/AD in the titles, abstracts, and keywords of the articles. The association between serum vitamin E levels and AD was estimated by using the weighted mean difference (WMD) and 95% confidence interval by adopting a random effects model. Heterogeneity was assessed by using Cochran Q test and I² statistic. Forest plot was used to present the results graphically from meta-analysis. Publication bias was evaluated by using funnel plots and Egger test.

RESULTS:

We identified 17 studies that met the eligibility criteria. The studies included 2057 subjects with 904 AD patients and 1153 controls. The results indicated that AD patients had a lower concentration of serum vitamin E compared with healthy controls among older people (WMD = -6.811 μmol/L, 95% confidence interval -8.998 to -4.625; Z = -6.105, P < .001). Publication bias was not detected and sensitivity analysis performed by omitting each study, and calculating the pooled WMD again for the remaining studies indicated the results stable.

CONCLUSIONS:

Alzheimer disease is associated with a low concentration of serum vitamin E in older people. However, necessary prospective cohort studies should be conducted to determine the risk of serum vitamin E for AD in the future.

Kanchi MM, Shanmugam MK, Rane G, Sethi G, Kumar AP

Drug Discov Today. 2017 Aug 5. pii: S1359-6446(17)30137-X. doi: 10.1016/j.drudis.2017.08.001. [Epub ahead of print]

Abstract

Vitamin E family members: tocotrienols and tocopherols are widely known for their health benefits. Decades of research on tocotrienols have shown they have diverse biological activities such as antioxidant, anti-inflammatory, anticancer, neuroprotective and skin protection benefits, as well as improved cognition, bone health, longevity and reduction of cholesterol levels in plasma. Tocotrienols also modulate several intracellular molecular targets and, most importantly, have been shown to improve lipid profiles, reduce total cholesterol and reduce the volume of white matter lesions in human clinical trials. This review provides a comprehensive update on the little-known therapeutic potentials of tocotrienols, which tocopherols lack in a variety of inflammation-driven diseases.

Abubakar IB, Lim KH, Kam TS, Loh HS.

Phytomedicine. 2017 Jul 1;30:74-84. doi: 10.1016/j.phymed.2017.03.004. Epub 2017 Mar 10.

Abstract

BACKGROUND:

γ-Tocotrienol, a vitamin E isomer possesses pronounced in vitro anticancer activities. However, the in vivo potency has been limited by hardly achievable therapeutic levels owing to inefficient high-dose oral delivery which leads to subsequent metabolic degradation. Jerantinine A, an Aspidosperma alkaloid, originally isolated from Tabernaemontana corymbosa, has proved to possess interesting anticancer activities. However, jerantinine A also induces toxicity to non-cancerous cells.

PURPOSE:

We adopted a combinatorial approach with the joint application of γ-tocotrienol and jerantinine A at lower concentrations in order to minimize toxicity towards non-cancerous cells while improving the potency on brain cancer cells.

METHODS:

The antiproliferative potency of individual γ-tocotrienol and jerantinine A as well as combined in low-concentration was firstly evaluated on U87MG cancer and MRC5 normal cells. Morphological changes, DNA damage patterns, cell cycle arrests and the effects of individual and combined low-concentration compounds on microtubules were then investigated. Finally, the potential roles of caspase enzymes and apoptosis-related proteins in mediating the apoptotic mechanisms were investigated using apoptosis antibody array, ELISA and Western blotting analysis.

RESULTS:

Combinatorial study between γ-tocotrienol at a concentration range (0-24µg/ml) and fixed IC₂₀ concentration of jerantinine A (0.16µg/ml) induced a potent antiproliferative effect on U87MG cells and led to a reduction on the new half maximal inhibitory concentration of γ-tocotrienol (i.e._tIC₅₀=1.29µg/ml) as compared to that of individual γ-tocotrienol (i.e. IC₅₀=3.17µg/ml). A reduction on undesirable toxicity to MRC5 normal cells was also observed. G0/G1 cell cycle arrest was evident on U87MG cells receiving IC₅₀ of individual γ-tocotrienol and combined low-concentration compounds (1.29µg/ml γ-tocotrienol + 0.16µg/ml jerantinine A), whereas, a profound G2/M arrest was evident on cells treated with IC₅₀ of individual jerantinine A. Additionally, individual jerantinine A and combined compounds (except individual γ-tocotrienol) caused a disruption of microtubule networks triggering Fas- and p53-induced apoptosis mediated via the death receptor and mitochondrial pathways.

CONCLUSIONS:

These findings demonstrated that the combined use of lower concentrations of γ-tocotrienol and jerantinine A induced potent cytotoxic effects on U87MG cancer cells resulting in a reduction on the required individual concentrations and thereby minimizing toxicity of jerantinine A towards non-cancerous MRC5 cells as well as probably overcoming the high-dose limiting application of γ-tocotrienol. The multi-targeted mechanisms of action of the combination approach have shown a therapeutic potential against brain cancer in vitro and therefore, further in vivo investigations using a suitable animal model should be the way forward.

Epperly T, Dunay MA, Boice JL.

Am Fam Physician. 2017 Jun 15;95(12):771-778.

Abstract

Alzheimer disease comprises a syndrome of progressive cognitive and functional decline. Treatments should target cognitive and functional symptoms. Cholinesterase inhibitors, memantine, and a combination of a cholinesterase inhibitor and memantine have produced statistically significant but clinically small delays in various domains of cognitive and functional decline in select patients with Alzheimer disease. Vitamin E has been shown to delay functional decline in patients with mild to moderate Alzheimer disease, especially when taken in combination with a cholinesterase inhibitor. Structured programs of physical exercise improve physical function and reduce rates of neuropsychiatric symptoms in patients with mild to severe Alzheimer disease. Cognitive stimulation programs show benefit in maintenance of cognitive function and improved self-reported quality of life in patients with mild to moderate Alzheimer disease.

Cansev M, Turkyilmaz M, Sijben JWC, Sevinc C, Broersen LM, van Wijk N.

J Alzheimers Dis. 2017 Jun 9. doi: 10.3233/JAD-170081. [Epub ahead of print]

Abstract

Chronic consumption of a diet enriched with nutritional precursors of phospholipids, including uridine and the polyunsaturated fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), was shown previously to enhance levels of brain phospholipids and synaptic proteins in rodents. Vitamin C, vitamin E, and selenium may directly affect the breakdown or synthesis of membrane phospholipids. The present study investigated the necessity of antioxidants for the effectiveness of supplementation with uridine plus DHA and EPA (as fish oil) in rats. Rats were randomized to four treatment groups and received, for 6 weeks, one of four experimental diets, i.e., a diet low in antioxidants, a diet high in antioxidants, a diet low in antioxidants supplemented with DHA+EPA+uridine, or a diet high in antioxidants supplemented with DHA+EPA+uridine. On completion of dietary treatment, rats were sacrificed, and brain levels of phospholipids, synaptic proteins, and two enzymes involved in phospholipid synthesis (choline-phosphate cytidylyltransferase, PCYT1A, and choline/ethanolamine phosphotransferase, CEPT1) were analyzed. Levels of phospholipids, the pre- and post-synaptic proteins Synapsin-1 and PSD95, and the enzymes PCYT1A and CEPT1 were significantly enhanced by combined supplementation of DHA+EPA+uridine and antioxidants and not enhanced by supplementation of DHA+EPA+uridine with insufficient antioxidant levels. Our data suggest that dietary vitamin C, vitamin E, and selenium are essential for the phospholipid precursors’ effects on increasing levels of membrane phospholipids and synaptic proteins, the indirect indicators of synaptogenesis. Their concomitant supply may be relevant in Alzheimer’s disease patients, because the disease is characterized by synapse loss and lower plasma and brain levels of phospholipid precursors and antioxidants.

Pang X, Hou X

Mol Med Rep. 2017 May 11. doi: 10.3892/mmr.2017.6572. [Epub ahead of print]

Abstract

The purpose of the present study was to explore the combination effect of FTY720 and vitamin E on cerebral ischemia. Astrocytes were isolated from newborn Sprague‑Dawley rats and were subjected to FTY720, vitamin E, or combination of the two. The astrocyte cultures were then exposed to oxygen‑glucose deprivation (OGD) to simulate an ischemic model in vitro. Cell viability, lactate dehydrogenase (LDH) leakage and cell apoptosis were detected following 12 h of exposure to OGD. In addition, the levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, IL‑1β, total antioxidant capacity, intercellular adhesion molecule (ICAM)‑1, vascular cell adhesion molecule (VCAM)‑1, chemokine (C‑X‑C motif) ligand (CXCL)‑10, heme oxygenase (HO)‑1 and superoxide dismutase (SOD)‑1 were measured. Pre‑treatment with FTY720 or vitamin E significantly elevated the cell viability and decreased LDH release and number of apoptotic cells. Combination treatment with FTY720 and vitamin E demonstrated a synergistic protective effect on OGD‑induced cell viability, toxicity and apoptosis. Pre‑treatment with FTY720 markedly reduced the release of IL‑1β, TNF‑α, IL‑6, ICAM‑1, VCAM‑1 and CXCL‑10, and pre‑treatment with vitamin E increased the levels of antioxidant, HO‑1 and SOD‑1. However, pre‑treatment with FTY720 combined with vitamin E revealed a synergistic effect. Pre‑treatment with FTY720 combined with vitamin E exerts synergistic neuroprotective effects in the simulated cerebral ischemia in vitro.