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Study: Red Palm Oil Supplementation in Chronic Liver Disease Patients

A randomized, controlled study revealed that red palm oil (RPO, enriched with high levels of tocotrienols, tocopherols and carotenoids) supplementation decreased lipid peroxidation and endotoxemia (the presence of heat stable toxin derived from certain gram negative bacteria in the blood), production of inflammatory cytokines, and monocyte tissue factor (TF) in chronic liver disease patients.

The study, “Beneficial effect of refined red palm oil on lipid peroxidation and monocyte tissue factor in HCV-related liver disease: a randomized controlled study,” was published in Hepatobiliary & Pancreatic Diseases International. Sixty patients with mean age of 62 years old with Child A/B genotype 1 HCV-related cirrhosis with no history of alcoholic beverages consumption were recruited. The patients were randomly assigned to receive either 300 mg vitamin E (alpha-tocopherol acetate) or 15 g RPO supplementation for 8 weeks. Blood parameters such as circulating endotoxin, plasma endotoxin-inhibiting capacity, macrophage-colony stimulating factor (M-CSF), urinary isoprostane-F2α-III, and monocyte TF activity, erythrocyte malondialdehyde (MDA) were examined after the 2nd, 4th and 8th weeks. Liver ultrasound imaging was carried out to examine liver steatosis.

Tocotrienols and Whey Protein Isolates Substantially Increase Exercise Endurance Capacity in Diet -Induced Obese Male Sprague-Dawley Rats.

Betik AC, Aguila J, McConell GK, McAinch AJ, Mathai ML.

PLoS One. 2016 Apr 8;11(4):e0152562. doi: 10.1371/journal.pone.0152562.

Abstract

Obesity and impairments in metabolic health are associated with reductions in exercise capacity. Both whey protein isolates (WPIs) and vitamin E tocotrienols (TCTs) exert favorable effects on obesity-related metabolic parameters. This research sought to determine whether these supplements improved exercise capacity and increased glucose tolerance in diet-induced obese rats. As a result, both TCT and WPI groups ran >50% longer (2271 ± 185m and 2195 ± 265m respectively) than the Control group (1428 ± 139m) during the run to exhaustion test (P<0.05), TCT + WPI did not further improve exercise endurance (2068 ± 104m). WPIs increased the maximum in vitro activity of beta-hydroxyacyl-CoA in the soleus muscle (P<0.05 vs. Control) but not in the plantaris. Citrate synthase activity was not different between groups. Neither supplement had any effect on weight gain, adiposity, glucose tolerance or insulin sensitivity. In conclusion, ten weeks of both TCTs and WPIs increased exercise endurance by 50% in sedentary, diet-induced obese rats. These positive effects of TCTs and WPIs were independent of body weight, adiposity or glucose tolerance.

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Evaluation of Pharmacokinetics, and Bioavailability of Higher Doses of Tocotrienols in Healthy Fed Humans.

Qureshi AA, Khan DA, Silswal N, Saleem S, Qureshi N.

J Clin Exp Cardiolog. 2016 Apr;7(4). pii: 434.

Abstract

Tocotrienols has been known to lower serum lipid parameters below 500 mg/d, while increase lipid parameters at higher dose of 750 mg/d. δ-Tocotrienol has a novel inflammatory property of concentration-dependent inhibition and activation. Therefore, inhibition (anti-inflammatory) property of tocotrienols at low doses is useful for cardiovascular disease, whereas, activation (pro-inflammatory) property using high dose is found effective for treatments of various types of cancer. We have recently described plasma bioavailability of 125 mg/d, 250 mg/d and 500 mg/d doses of δ-tocotrienol in healthy fed subjects, which showed dose-dependent increases in area under the curve (AUC) and maximum concentration (Cmax). Hence, in the current study, higher doses of tocotrienols have used to analyze its effect on plasma pharmacokinetic parameters. The aim of this study is to evaluate the safety and bioavailability of higher doses (750 mg and 1000 mg) of annatto-based tocotrienols in healthy fed subjects. All four isomers (α-, β-, γ-, δ-) of tocols (tocotrienols and tocopherols) present in the plasmas of subjects were quantified and analyzed for various pharmacokinetic parameters. Conclusion, this study has described pharmacokinetics using higher doses of 750 mg/d and 1000 mg/d of δ-tocotrienol. These results confirmed earlier findings that Tmax was 3-4 h for all isomers of tocotrienols and tocopherols except for α-tocopherol (6 h). These higher doses of tocotrienols were found safe in humans and may be useful for treatments of various types of cancer, diabetes, and Alzheimer’s disease.

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Vitamin E Tocotrienols

By Dr Liji Thomas, MD

Natural vitamin E contains 8 isoforms, of which four are alpha, beta, gamma and delta-tocotrienols. They differ because of the presence or absence of a methyl (-CH3) group at the 2, 4’ and 8’ positions on the chromanol ring. Natural tocotrienols have this group in the R configuration at the 2 position, which is responsible for its biological activity.

Sources of tocotrienols

Tocotrienols are far less common in plants than tocopherols. However, vitamin E in monocot seeds and a few dicot seeds is mostly in the form of tocotrienols. The richest source of alpha-tocotrienol is the oil of the oil palm tree Elaeis guineensis, containing up to 800 mg/kg of this vitamin in the alpha and gamma isoforms. 70% of vitamin E in palm oil is in the form of tocotrienols, quite unlike other plant oils which contain exclusively tocopherols.

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Tocotrienol, the New Effective Cancer Killer

Do you know that a new type of vitamin E called TOCOTRIENOL can actually help kill cancer cells? Tocotrienol is a new generation of Vitamin E and the richest source of this new cancer killer is the annatto seed. You read it right: the Annatto seed.

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Vitamin E, γ-tocotrienol, Protects Against Buthionine Sulfoximine-Induced Cell Death by Scavenging Free Radicals in SH-SY5Y Neuroblastoma Cells.

Tan JK, Then SM, Mazlan M, Jamal R, Ngah WZ.

Nutr Cancer. 2016;68(3):507-17. doi: 10.1080/01635581.2016.1153671. Epub 2016 Mar 23.

Abstract

The induction of reactive oxygen species (ROS) to selectively kill cancer cells is an important feature of radiotherapy and various chemotherapies. Depletion of glutathione can induce apoptosis in cancer cells or sensitize them to anticancer treatments intended to modulate ROS levels. In contrast, antioxidants protect cancer cells from oxidative stress-induced cell death by scavenging ROS. The role of exogenous antioxidants in cancer cells under oxidative insults remains controversial and unclear. This study aimed to identify protective pathways modulated by γ-tocotrienol (γT3), an isomer of vitamin E, in human neuroblastoma SH-SY5Y cells under oxidative stress. Using buthionine sulfoximine (BSO) as an inhibitor of glutathione synthesis, we found that BSO treatment reduced the viability of SH-SY5Y cells. BSO induced cell death by increasing apoptosis, decreased the level of reduced glutathione (GSH), and increased ROS levels in SH-SY5Y cells. Addition of γT3 increased the viability of BSO-treated cells, suppressed apoptosis, and decreased the ROS level induced by BSO, while the GSH level was unaffected. These results suggest that decreasing GSH levels by BSO increased ROS levels, leading to apoptosis in SH-SY5Y cells. γT3 attenuated the BSO-induced cell death by scavenging free radicals.

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Protective effects of carnosine alone and together with alpha-tocopherol on lipopolysaccharide (LPS) plus ethanol-induced liver injury.

Kalaz EB, Aydın AF, Doğan-Ekici I, Çoban J, Doğru-Abbasoğlu S, Uysal M.

Environ Toxicol Pharmacol. 2016 Mar;42:23-9. doi: 10.1016/j.etap.2015.12.018.

Abstract

The aim of this study was to investigate the effect of carnosine (CAR) alone and together with vitamin E (Vit E) on alcoholic steatohepatitis (ASH) in rats. ASH was induced by ethanol (3 times; 5 g/kg; 12 h intervals, via gavage), followed by a single dose of lipopolysaccharide (LPS; 10 mg/kg; i.p.). CAR (250 mg/kg; i.p.) and Vit E (200 mg D-α-tocopherol/kg; via gavage) were administered 30 min before and 90 min after the LPS injection. CAR treatment lowered high serum transaminase activities together with hepatic histopathologic improvements in rats with ASH. Reactive oxygen species formation, malondialdehyde levels, myeloperoxidase activities and transforming growth factor β1 (TGF-β1) and collagen 1α1 (COL1A1) expressions were observed to decrease. These improvements were more remarkable in CAR plus Vit E-treated rats. Our results indicate that CAR may be effective in suppressing proinflammatory, prooxidant, and profibrotic factors in the liver of rats with ASH.

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Systemic administration of vitamins C and E attenuates nociception induced by chronic constriction injury of the sciatic nerve in rats.

Riffel AP, de Souza JA, Santos Mdo C, Horst A, Scheid T, Kolberg C, Belló-Klein A, Partata WA.

Brain Res Bull. 2016 Mar;121:169-77. doi: 10.1016/j.brainresbull.2016.02.004.

Abstract

Antioxidants have been tested to treat neuropathic pain, and α-Tocopherol (vitamin E–vit. E) and ascorbic acid (vitamin C–vit. C) are potent antioxidants. We assessed the effect of intraperitoneal administration of vit. C (30 mg/kg/day) and vit. E (15 mg/kg/day), given alone or in combination, on the mechanical and thermal thresholds and the sciatic functional index (SFI) in rats with chronic constriction injury (CCI) of the sciatic nerve. We also determined the lipid hydroperoxides and total antioxidant capacity (TAC) in the injured sciatic nerve. Further, we assessed the effects of oral administration of vit. C+vit. E (vit. C+E) and of a combination of vit. C+E and gabapentin (100mg/kg/day, i.p.) on the mechanical and thermal thresholds of CCI rats. The vitamins, whether administered orally or i.p., attenuated the reductions in the mechanical and thermal thresholds induced by CCI. The antinociceptive effect was greater with a combination of vit. C+E than with each vitamin given alone. The SFI was also improved in vitamin-treated CCI rats. Co-administration of vit. C+E and gabapentin induced a greater antinociceptive effect than gabapentin alone. No significant change occurred in TAC and lipid hydroperoxide levels, but TAC increased (45%) while lipid hydroperoxides decreased (38%) in the sciatic nerve from vit. C+E-treated CCI rats. Thus, treatment with a combination of vit. C+E was more effective to treat CCI-induced neuropathic pain than vitamins alone, and the antinociceptive effect was greater with co-administration of vit. C+E and gabapentin than with gabapentin alone.

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Vitamin E suppresses ex vivo osteoclastogenesis in ovariectomized rats.

Johnson SA, Feresin RG, Soung do Y, Elam ML, Arjmandi BH.

Food Funct. 2016 Mar;7(3):1628-33. doi: 10.1039/c5fo01066g.

Abstract

Postmenopausal osteoporosis may be caused, in part, by oxidative stress and inflammation. Vitamin E is a strong antioxidant which has been shown to have anti-inflammatory and bone-protective effects. The objective of this study was to investigate the effects of various doses of supplemental vitamin E on osteoclastogenesis in ovariectomized rats. Sixty 12-month-old female Sprague-Dawley rats were sham-operated (Sham) or ovariectomized (Ovx; 4 groups) and fed a diet containing basal levels of vitamin E (75 mg D-α tocopherol acetate per kg diet) for 220 days. Rats in three of the Ovx groups were given supplemental doses of vitamin E (300, 525, and 750 mg D-α tocopherol acetate per kg diet) for the last 100 days. Femoral bone marrow cells were isolated, cultured, and osteoclasts were counted and normalized to 1000 total bone marrow cells. Blood monocyte and lymphocyte counts were also determined. Osteoclast number was significantly higher in the Ovx control group and was suppressed by all three doses of vitamin E, although more effectively in the Ovx group that received 300 mg per kg diet vitamin E. Additionally, vitamin E suppressed the Ovx-induced increase in monocyte and lymphocyte production. The results of this study suggest that vitamin E supplementation suppresses osteoclastogenesis, possibly by inhibiting monocyte and lymphocyte production.

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Radioprotective Efficacy of Gamma-Tocotrienol in Nonhuman Primates.

Singh VK, Kulkarni S, Fatanmi OO, Wise SY, Newman VL, Romaine PL, Hendrickson H, Gulani J, Ghosh SP, Kumar KS, Hauer-Jensen M.

Radiat Res. 2016 Mar;185(3):285-98. doi: 10.1667/RR14127.1.

Abstract

The search for treatments to counter potentially lethal radiation-induced injury over the past several decades has led to the development of multiple classes of radiation countermeasures. However, to date only granulocyte colony-stimulating factor (G-CSF; filgrastim, Neupogen)and pegylated G-CSF (pegfilgrastim, Neulasta) have been approved by the United States Food and Drug Administration (FDA) for the treatment of hematopoietic acute radiation syndrome (ARS). Gamma-tocotrienol (GT3) has demonstrated strong radioprotective efficacy in the mouse model, indicating the need for further evaluation in a large animal model. In this study, we evaluated GT3 pharmacokinetics (PK) and efficacy at different doses of cobalt-60 gamma radiation (0.6 Gy/min) using the nonhuman primate (NHP) model. The PK results demonstrated increased area under the curve with increasing drug dose and half-life of GT3. GT3 treatment resulted in reduced group mean neutropenia by 3-5 days and thrombocytopenia by 1-5 days. At 5.8 and 6.5 Gy total-body irradiation, GT3 treatment completely prevented thrombocytopenia. The capability of GT3 to reduce severity and duration of neutropenia and thrombocytopenia was dose dependent; 75 mg/kg treatment was more effective than 37.5 mg/kg treatment after a 5.8 Gy dose. However, the higher GT3 dose (75 mg/kg) was associated with higher frequency of adverse skin effects (small abscess) at the injection site. GT3 treatment of irradiated NHPs caused no significant difference in animal survival at 60 days postirradiation, however, low mortality was observed in irradiated, vehicle-treated groups as well. The data from this pilot study further elucidate the role and pharmacokinetics of GT3 in hematopoietic recovery after irradiation in a NHP model, and demonstrate the potential of GT3 as a promising radioprotector.

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