Comparing the effects of vitamin E tocotrienol-rich fraction supplementation and α-tocopherol supplementation on gene expression in healthy older adults

OBJECTIVES This study aims to compare the differential gene expression resulting from tocotrienol-rich fraction and α-tocopherol supplementation in healthy older adults. METHODS A total of 71 eligible subjects aged 50 to 55 years from Gombak and Kuala Lumpur, Malaysia, were divided into three groups and supplemented with placebo (n=23), α-tocopherol (n=24) or tocotrienol-rich fraction (n=24). Blood samples were collected at baseline and at 3 and 6 months of supplementation for microarray analysis. RESULTS The number of genes altered by α-tocopherol was higher after 6 months (1,410) than after 3 months (273) of supplementation. α-Tocopherol altered the expression of more genes in males (952) than in females (731). Similarly, tocotrienol-rich fraction modulated the expression of more genes after 6 months (1,084) than after 3 months (596) and affected more genes in males (899) than in females (781). α-Tocopherol supplementation modulated pathways involving the response to stress and stimuli, the immune response, the response to hypoxia and bacteria, the metabolism of toxins and xenobiotics, mitosis, and synaptic transmission as well as activated the mitogen-activated protein kinase and complement pathways after 6 months. However, tocotrienol-rich fraction supplementation affected pathways such as the signal transduction, apoptosis, nuclear factor kappa B kinase, cascade extracellular signal-regulated kinase-1 and extracellular signal-regulated kinase-2, immune response, response to drug, cell adhesion, multicellular organismal development and G protein signaling pathways. CONCLUSION Supplementation with either α-tocopherol or tocotrienol-rich fraction affected the immune and drug response and the cell adhesion and signal transduction pathways but modulated other pathways differently after 6 months of supplementation, with sex-specific responses.

Radioprotective role of α-tocotrienol against oxidative damage in γ-irradiated human blood cultures / Papel radioprotectivo do α-tocotrienol contra danos oxidantes nas culturas de sangue humano γ-irradiadas

Tocotrienols are members of the natural vitamin E family which is considered one of important fat soluble vitamins. The tocotrienols react with free radicals, which are the main cause of oxidation damage to cell membranes, without formation of other free radicals in the process. All natural forms of tocotrienols have the ability to regulate peroxidation reactions and to control free radicals production within the body. This study aimed to assess the antimutagenic and antioxidant ability of y-tocotrienol at a working dose (0.04 mg/ ml) through cytogenetic (Micronucleus test) study and biochemical analysis including Caspase -3, Superoxide dismutase (SOD), Catalase (CAT) activities and Nitric Oxide (NO) concentration in y-irradiated human blood cultures. The treatment time was 72 hrs post-irradiation with gamma rays at dose of 3 Gy. Triple blood cultures for each blood sample were set up. Ionizing irradiation induces a significant increase in micronuclei (MNi) frequencies, and nucleuplasmic bridge (N bridge) accompanied by a significant rise in Caspase-3 activity and NO concentration. Furthermore, SOD and CAT activities showed significant decrease. y- tocotrienol treatment results into a decrease of MNi and N bridges numbers, enhancement of SOD and CAT activities and improvement of both NO and Caspase-3 levels, compared to irradiated cells which not treated with -tocotrienol. The present results reveal the antimutagenic and the anti-oxidant effects of y-tocotrienol against y- irradiation.

Os tocotrienóis são membros da família natural de vitamina E, que é considerada uma das vitaminas importantes solúveis em gordura. Os tocotrienóis reagem com os radicais livres, que são a principal causa do dano de oxidação das membranas celulares, sem formação de outros radicais livres no processo. Todas as formas naturais de tocotrienóis têm a capacidade de regular as reações de peroxidação e controlar a produção de radicais livres dentro do corpo. Este estudo teve como objetivo avaliar a capacidade antimutagênica e antioxidante do y-tocotrienol em uma dose de trabalho (0,04 mg/ml) através de estudo citogenético (Teste dos Micronúcleos) e análise bioquímica incluindo atividades de Caspase 3, Superóxido Dismutase (SOD), Catalase (CAT) e concentração de óxido nítrico (NO) em culturas sanguíneas humanas irradiadas com y-. O tempo de tratamento foi de 72 horas pós-irradiação com raios gama na dose de 3 Gy. Foram estabelecidas culturas de sangue triplas para cada amostra de sangue. A irradiação ionizante induz um aumento significativo nas freqüências de micronúcleos (MNi) e ponte nucleoplasmática (ponte N), acompanhada por um aumento significativo da atividade da Caspase 3 e da concentração de NO. Além disso, as atividades de SOD e CAT mostraram queda significativa. O tratamento com -tocotrienol resulta em uma diminuição do número de pontes MNi e N, aumento das atividades de SOD e CAT e melhora dos níveis de NO e Caspase 3, em comparação com células irradiadas que não foram tratadas com -tocotrienol. Os presentes resultados revelam os efeitos antimutagênicos e antioxidantes do y- tocotrienol contra a irradiação y-.

The Effectiveness of Tocotrienol Rich Fraction and Αlpha Tocoferol with Combination of Vitamin C in The Management of Systemic Inflammatory Response Syndrome (SIRS)

The pathophysiology of systemic inflammatory response syndrome (SIRS) had been described to involve various strong oxidative reactions affecting the status and progress of the patients. Antioxidant therapy had been suggested in many studies involving SIRS management. The objective of this study was to compare the role of vitamin E Tocotrienol and vitamin E Tocopherol combined with vitamin C as antioxidant therapy in the management of critically ill patients diagnosed with SIRS, admitted to the intensive care unit and high dependency wards of Universiti Kebangsaan Malaysia Medical Centre (UKMMC). It was a single blind randomized clinical trial with a total of 72 patients in which 44.4% Malays, 34.7% Chinese, 19.4% Indians and 1.4% others with 59.7% males and 40.3% females were recruited. Patients in TRI E group received Tocotrienol with Vitamin C while TOCO group received Tocopherol with Vitamin C and a control group did not receive any antioxidant. The clinical parameters (heart rate, respiratory rate, systolic blood pressure) showed improvements with significant difference at the end of study (post-intervention) as compared to admission (pre-intervention).Whereas, the sepsis (temperature, PCT, CRP and WBC) and oxidative stress (8-OHdG/Creatinine) parameters showed improvements with significant difference at the end of study (post-intervention) as compared to admission (pre-intervention). The TRI E group showed obvious improvement in clinical, sepsis and oxidative stress parameters, as compared to TOCO and control groups. This study showed that Vitamin E Tocotrienol and Vitamin E Tocopherol in combination with Vitamin C demonstrated significant improvement in the clinical and laboratory parameters during the management of SIRS. Therefore, Vitamin E in combination with Vitamin C had therapeutic benefits in the treatment of critically ill patients with SIRS.

Tocotrienol supplementation in postmenopausal osteoporosis: evidence from a laboratory study

OBJECTIVE: Accelerated bone loss that occurs in postmenopausal women has been linked to oxidative stress and increased free radicals. We propose the use of antioxidants to prevent and reverse postmenopausal osteoporosis. This study aimed to examine the effects of tocotrienol, a vitamin E analog, on bone loss due to estrogen deficiency. Our previous study showed that tocotrienol increased the trabecular bone volume and trabecular number in ovariectomized rats. In the current study, we investigated the effects of tocotrienol supplementation on various biochemical parameters in a postmenopausal osteoporosis rat model. MATERIALS AND METHODS: A total of 32 female Wistar rats were randomly divided into four groups. The baseline group was sacrificed at the start of the study, and another group was sham operated. The remaining rats were ovariectomized and either given olive oil as a vehicle or treated with tocotrienol at a dose of 60 mg/kg body weight. After four weeks of treatment, blood was withdrawn for the measurement of interleukin-1 (IL1) and interleukin-6 (IL6) (bone resorbing cytokines), serum osteocalcin (a bone formation marker) and pyridinoline (a bone resorption marker). RESULTS: Tocotrienol supplementation in ovariectomized rats significantly reduced the levels of osteocalcin, IL1 and IL6. However, it did not alter the serum pyridinoline level. CONCLUSION: Tocotrienol prevented osteoporotic bone loss by reducing the high bone turnover rate associated with estrogen deficiency. Therefore, tocotrienol has the potential to be used as an anti-osteoporotic agent in postmenopausal women. .

Effect of the tocotrienol-rich fraction on the lifespan and oxidative biomarkers in Caenorhabditis elegans under oxidative stress

OBJECTIVE: This study was performed to determine the effect of the tocotrienol-rich fraction on the lifespan and oxidative status of C. elegans under oxidative stress. METHOD: Lifespan was determined by counting the number of surviving nematodes daily under a dissecting microscope after treatment with hydrogen peroxide and the tocotrienol-rich fraction. The evaluated oxidative markers included lipofuscin, which was measured using a fluorescent microscope, and protein carbonyl and 8-hydroxy-2′-deoxyguanosine, which were measured using commercially available kits. RESULTS: Hydrogen peroxide-induced oxidative stress significantly decreased the mean lifespan of C. elegans, which was restored to that of the control by the tocotrienol-rich fraction when administered before or both before and after the hydrogen peroxide. The accumulation of the age marker lipofuscin, which increased with hydrogen peroxide exposure, was decreased with upon treatment with the tocotrienol-rich fraction (p<0.05). The level of 8-hydroxy-2′-deoxyguanosine significantly increased in the hydrogen peroxide-induced group relative to the control. Treatment with the tocotrienol-rich fraction before or after hydrogen peroxide induction also increased the level of 8-hydroxy-2′-deoxyguanosine relative to the control. However, neither hydrogen peroxide nor the tocotrienol-rich fraction treatment affected the protein carbonyl content of the nematodes. CONCLUSION: The tocotrienol-rich fraction restored the lifespan of oxidative stress-induced C. elegans and reduced the accumulation of lipofuscin but did not affect protein damage. In addition, DNA oxidation was increased. .

Evaluation of the protective effects of tocotrienol-rich fraction from palm oil on the dentate gyrus following chronic restraint stress in rats

Exposure to chronic restraint stress has been shown to cause a number of morphological changes in the hippocampal formation of rats. Tocotrienol, an isoform of vitamin E, exhibits numerous health benefits, different from those of tocopherol. Recent studies have demonstrated that tocotrienol prevents stress-induced changes in the gastric mucosa, thus indicating that it may also protect other organs such as the brain from the damaging effects of stress. Therefore, the aim of the present study was to investigate the protective effect of tocotrienol-rich fraction (TRF) extracted from palm oil on the dentate gyrus of rats following exposure to chronic restraint stress. Thirty-six male Sprague Dawley rats were divided into four groups: control, stress, tocotrienol and combination of stress and tocotrienol. Animals were stressed by restraining them for 5 hours every day for 21 consecutive days. TRF was administered via oral gavage at a dose of 200 mg/kg body weight. Our results showed that the plasma corticosterone level was significantly increased in response to stress, compared to the control. The results confirmed previous findings that chronic restraint stress suppresses cellular proliferation and reduces granule cell number in the dentate gyrus. However, TRF supplementation failed to prevent or minimize these stress-induced changes. Therefore, we conclude that TRF at the current dosage is not effective in preventing the morphological changes in the dentate gyrus induced by chronic restraint stress.

A exposição crônica ao estresse por restrição causa série de alterações morfológicas na formação do hipocampo de ratos. Tocotrienol, uma isoforma da vitamina E, apresenta inúmeros benefícios para a saúde, diferente do tocoferol. Estudos recentes demonstraram que o tocotrienol impediu alterações induzidas por estresse na mucosa gástrica, indicando, assim, a possibilidade de que ele pode, também, proteger outros órgãos, como o cérebro, dos efeitos nocivos do estresse. Dessa forma, o objetivo do presente estudo foi investigar o efeito protetor da fração rica em tocotrienol (TRF), extraída do óleo de palma, no giro denteado após exposição crônica ao estresse por restrição. Trinta e seis ratos machos Sprague Dawley foram divididos em quatro grupos: controle, estresse, tocotrienol e combinação de estresse e tocotrienol. Os animais foram estressados por restrição, 5 horas por dia, durante 21 dias consecutivos. TRF foi administrado por gavagem oral na dose de 200 mg/kg de peso corporal. Nossos resultados mostraram que o nível de corticosterona plasmática foi significativamente aumentado em resposta ao estresse em comparação ao controle. Os resultados confirmam os achados anteriores de que o estresse por restrição suprime a proliferação celular e reduz o número de células granulares do giro denteado. No entanto, a suplementação de TRF foi ineficaz para evitar ou minimizar as alterações induzidas por estresse. Assim, concluímos que TRF na dose corrente não é efetiva para prevenir as alterações morfológicas no giro denteado induzida por estresse crônico por restrição.

Identificação de δ tocotrienol e de ácidos graxos no óleo fixo de urucum (Bixa orellana Linné) / Identification of δ tocotrienols and fatty acids in fixed oil of annatto (Bixa orellana Linné)

Bixa orellana é uma planta nativa do Brasil, conhecida popularmente como urucum. O objetivo desse estudo foi extrair o óleo das sementes de B. orellana e, a partir dele, isolar e identificar o tocotrienol e quantificar seus ácidos graxos. A extração do óleo realizou-se em aparelho Soxhlet utilizando hexano como solvente extrator. O tocotrienol foi isolado por meio de métodos cromatográficos e identificado por espectrometria de ressonância magnética nuclear RMN 1H e RMN 13C. Os ácidos graxos foram quantificados por cromatografia gasosa acoplada ao espectrômetro de massa. Os resultados demonstraram a presença de δ -tocotrienol e, dentre os ácidos graxos, a ocorrência do ácido aracdônico, que até o presente momento não havia sido relatada na espécie em estudo.

Bixa orellana is a native plant of Brazil, popularly known as annatto. The purpose of this study was to isolate the oil from the seeds of B. orellana and from it, identify the antioxidant tocotrienol and quantify its fatty acids. The extraction of the oil was performed in a Soxhlet apparatus using hexane as solvent. The tocotrienol was isolated by chromatographic methods and identified by spectrometric methods NMR 1H and 13C. The fatty acids present in the oil were quantified by gas chromatography coupled with mass spectrometry. Results demonstrated the presence of δ-tocotrienol and among the fatty acids, the arachidonic acid was present, a substance which so far had not been previously reported.

Antioxidant enzyme activity and malondialdehyde levels can be modulated by Piper betle, tocotrienol rich fraction and Chlorella vulgaris in aging C57BL/6 mice

OBJECTIVE: The aim of this study was to determine the erythrocyte antioxidant enzyme activity and the superoxide dismutase, catalase, glutathione peroxidase, and plasma malondialdehyde levels in aging mice and to evaluate how these measures are modulated by potential antioxidants, including the tocotrienol-rich fraction, Piper betle, and Chlorella vulgaris. METHOD: One hundred and twenty male C57BL/6 inbred mice were divided into three age groups: young (6 months old), middle-aged (12 months old), and old (18 months old). Each age group consisted of two control groups (distilled water and olive oil) and three treatment groups: Piper betle (50 mg/kg body weight), tocotrienol-rich fraction (30 mg/kg), and Chlorella vulgaris (50 mg/kg). The duration of treatment for all three age groups was two months. Blood was withdrawn from the orbital sinus to determine the antioxidant enzyme activity and the malondialdehyde level. RESULTS: Piper betle increased the activities of catalase, glutathione peroxidase, and superoxide dismutase in the young, middle, and old age groups, respectively, when compared to control. The tocotrienol-rich fraction decreased the superoxide dismutase activity in the middle and the old age groups but had no effect on catalase or glutathione peroxidase activity for all age groups. Chlorella vulgaris had no effect on superoxide dismutase activity for all age groups but increased glutathione peroxidase and decreased catalase activity in the middle and the young age groups, respectively. Chlorella vulgaris reduced lipid peroxidation (malondialdehyde levels) in all age groups, but no significant changes were observed with the tocotrienol-rich fraction and the Piper betle treatments. CONCLUSION: We found equivocal age-related changes in erythrocyte antioxidant enzyme activity when mice were treated with Piper betle, the tocotrienol-rich fraction, and Chlorella vulgaris. However, Piper betle treatment showed increased antioxidant enzymes activity during aging.

Vitamin E: alpha-Tocopherol and the Other Forms of Vitamin E

Vitamin E has been a generic term for all tocopherol and tocotrienol derivatives. The most active form of vitamin E isoforms in vivo is regarded to be alpha-tocopherol which is the only form defined as vitamin E in the US Food and Nutrition Board, causing controversy over setting dietary reference intake (DRI) of vitamin E. However, most of the countries other than the US maintain the original concept that all isoforms are accepted as vitamin E but with different biopotency. The roles of the isoforms of vitamin E other than alpha-tocopherol have received continuous attention. Among them those of gamma-tocopherol and alpha-tocotrienol have been most studied in comparison with alpha-tocopherol, since gamma-tocopherol comprises major form of vitamin E in many plant seeds and those of the both vitamin E have been implicated in unique physiological functions. This review summarizes findings that have led a better understanding of vitamin E absorption, transport, tissue storage and various functions common and specific to vitamin E isoforms focusing alpha- and gamma-tocopherol as well as tocotrienols. It is expected to help redefining vitamin E and setting its DRI for Koreans.

Efecto de los compuestos bioactivos de algunos alimentos en la salud / Bioactive compounds on food and health-promoting properties

Los fitoquímicos y algunos componentes bioactivos despiertan especial interés en la comunidad científica, por ser sustancias con efectos benéficos en la salud, evidenciado por estudios que involucran efectos, acciones y prevención de riesgo en ciertas enfermedades. Las razones de interés de los consumidores por estas sustancias radica en obtener bienestar por medio de la dieta, por ello demandan información sobre los efectos de estas sustancias y de los alimentos funcionales. Este artículo de revisión proporciona un marco de las investigaciones que evalúan la relación entre la dieta y la salud, en especial de los componentes biológicos que aportan la connotación de funcionales a los alimentos. Aunque no se consideran nutrientes esenciales algunos de esos componentes, proporcionan una importante protección para la salud junto a una adecuada nutrición. Cada compuesto revisado en este documento, muestra la relación con la salud y posibles efectos en el tratamiento de enfermedades.

Phytochemical substances are bioactive compounds that have special interest for scientist because of the health-promoting properties that have been demonstrated in scientific studies. Some consumers are interested to eat these products to be healthier; therefore they are requiring information about of the nutritional properties in functional foods which could be placed in the product advertising label.This review focuses on researches about bioactive compounds and the relevance of functional foods for nutrition and health, bringing an overview of what is published about bioactive compounds and the relationship between diet and health. Although these compounds are not considered essential nutrients, this article discusses the biological activity of those compounds, in particular their properties and the resulting health benefits.

Vitamin E derivative alpha-tocotrienol failed to show neuroprotective effects after embolic stroke in rats

Previous studies have demonstrated that pretreatment with alpha-tocotrienol [a-TCT] can reduce ischemic damage in mice following middle cerebral artery [MCA] occlusion. It is also reported to decrease stroke dependent brain tissue damage in 12-Lox-deficient mice and spontaneously hypertensive rats. In the present study, the neuroprotective effects of a-TCT and rosiglitazone [RGZ] at 3 hr after cerebral ischemia were investigated. Stroke was induced by embolizing a preformed clot into the MCA. Rats were assigned to vehicle, a-TCT [1 or 10 mg/kg], RGZ and sham-operation. Compared to the control group, only RGZ decreased infarct volume [P<0.05], neurological deficits [P<0.05] and sensory impairments [P<0.01] but low and high doses of a-TCT did not show any significant neuroprotective effect. Our data showed that a-TCT was not neuroprotective at 3 hr after the embolic model of stroke. Further studies should be undertaken to clarify the neuroprotective effects of a-TCT after stroke

The effects of palm oil tocotrienol-rich fraction supplementation on biochemical parameters, oxidative stress and the vascular wall of streptozotocin-induced diabetic rats

OBJECTIVE: This study examined the effects of palm oil tocotrienol-rich fractions on streptozotocin-induced diabetic rats. METHODS: Animals were divided into three groups: (i) normal non-diabetic (NDM), (ii) diabetic treated (tocotrienol-rich fractions - TRF) and (iii) diabetic untreated (non-TRF). The treatment group received oral administration of tocotrienol-rich fractions (200 mg/kg body weight) daily for eight weeks. The normal non-diabetic and the diabetic untreated groups were fed standard rat feed. Blood glucose and lipid profiles, oxidative stress markers and morphological changes of the thoracic aorta were evaluated. RESULTS: Tocotrienol-rich fractions treatment reduced serum glucose and glycated hemoglobin concentrations. The tocotrienol-rich fractions group also showed significantly lower levels of plasma total cholesterol, low-density lipoprotein cholesterol, and triglyceride, as compared to the untreated group. The tocotrienol-rich fractions group had higher levels of high-density lipoprotein cholesterol, as compared to the untreated group. Superoxide dismutase activity and levels of vitamin C in plasma were increased in tocotrienol-rich fractions-treated rats. The levels of plasma and aorta malondealdehyde + 4-hydroxynonenal (MDA + 4-HNE) and oxidative DNA damage were significant following tocotrienol-rich fractions treatment. Electron microscopic examination showed that the normal morphology of the thoracic aorta was disrupted in STZ-diabetic rats. Tocotrienol-rich fractions supplementation resulted in a protective effect on the vessel wall. CONCLUSION: These results show that tocotrienol-rich fractions lowers the blood glucose level and improves dyslipidemia. Levels of oxidative stress markers were also reduced by administration of tocotrienol-rich fractions. Vessel wall integrity was maintained due to the positive effects mediated by tocotrienol-rich fractions.