Crazy for Cranberries


With the holiday season upon us I seem to have cranberries on the brain, so it should come as no surprise that one of my all-time favorite ingredients happens to be Cranberry Seed Oil. Why am I so enamored with the oil from this super fruit? When the fruit is cold pressed the resulting oil is rich in tocopherols, tocotrienols (Vitamin E) and phytosterols (plant sterols). Vitamin E is really a family of eight different isomers consisting of 4 tocopherols and 4 tocotrienols. The Vitamin E constituents found in Cranberry Seed Oils contain significant levels of alpha and gamma tocopherols and alpha and gamma tocotrienols. All of these isomers of Vitamin E provide excellent antioxidant protection and help to reinforce the barrier lipid properties of the skin.

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Effects of palm oil tocotrienol-rich fraction on biochemical and morphological alterations of liver in fenitrothion-treated rats.

Jayusman PA, Budin SB, Ghazali AR, Taib IS, Louis SR.

Pak J Pharm Sci. 2014 Nov;27(6):1873-80.


Indiscriminate application of organophosphate (OP) pesticides has led to environmental pollution and severe health problems. The aim of the present study was to evaluate the effect of palm oil tocotrienol-rich fraction (TRF) on biochemical and morphological changes of the liver in rats treated with fenitrothion (FNT), a type of OP pesticide. A total of 28 male Sprague-Dawley rats were divided into four groups; control group, TRF-supplemented group, FNT-treated group and TRF+FNT group. TRF (200 mg/kg) was supplemented 30 minutes prior to FNT (20 mg/kg) administration, both orally for 28 consecutive days. Following 28 days of treatment, plasma biochemical changes and liver morphology were evaluated. The body and absolute liver weights were significantly elevated in TRF+FNT group compared to FNT group. TRF administration significantly decreased the total protein level and restored the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in TRF + FNT group. In contrast, total bilirubin level, γ-glutamyltranferase (GGT) and cholinesterase activity in TRF + FNT group did not significantly differ from FNT group. Administration of TRF also prevented FNT-induced morphological changes of liver as observed by electron microscope. In conclusion, TRF supplementation showed potential protective effect towards biochemical and ultrastructural changes in liver induced by FNT.

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Acute Toxicity of Subcutaneously Administered Vitamin E Isomers Delta- and Gamma-Tocotrienol in Mice.

Swift SN, Pessu RL, Chakraborty K, Villa V, Lombardini E, Ghosh SP

Int J Toxicol. 2014 Oct 28.


The toxicity of parenterally administered vitamin E isomers, delta-tocotrienol (DT3) and gamma-tocotrienol (GT3), was evaluated in male and female CD2F1 mice. In an acute toxicity study, a single dose of DT3 or GT3 was administered subcutaneously in a dose range of 200 to 800 mg/kg. A mild to moderately severe dermatitis was observed clinically and microscopically in animals at the injection site at doses above 200 mg/kg. The severity of the reaction was reduced when the drug concentration was lowered. Neither drug produced detectable toxic effects in any other tissue at the doses tested. Based on histopathological analysis for both DT3 and GT3, and macroscopic observations of inflammation at the injection site, a dose of 300 mg/kg was selected as the lowest toxic dose in a 30-day toxicity study performed in male mice. At this dose, a mild skin irritation occurred at the injection site that recovered completely by the end of the experimental period. At a dose of 300 mg/kg of DT3 or GT3, no adverse effects were observed in any tissues or organs.

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Plastochromanol-8 (PC-8) is an antioxidant that, together with tocopherols and tocotrienols, belongs to the group of tocochromanols. Plastochromanol-8 has been found to occur in several plant species, including mosses, and lichens. PC-8 is found in seeds, leaves and other organs of higher plants. In leaves, PC-8 is restricted to chloroplasts. The identification of tocopherol cyclase (VTE1) as the key enzyme in the biosynthesis of PC-8 suggests that plastoglobules are the primary site of its biosynthesis. Other enzymes related with PC-8 biosynthesis in plastoglobules include: NDC1 and the ABC1-like kinase ABC1K3. The antioxidant properties of PC-8 are similar to those of other chloroplastic antioxidants in polar solvents but considerably they are enhanced in hydrophobic environments, suggesting that the unsaturated side chain performs some quenching activity. As a result of a non-enzymatic reaction, singlet oxygen can oxidize any of the 8 double bonds in the side chain of PC-8, giving at least eight hydroxy-PC-8 isomers. This review summarizes current evidence of a widespread distribution of PC-8 in photosynthetic organisms, as well as the contribution of PC-8 to the pool of lipid-soluble antioxidants in both leaves and seeds.

Synergistic inhibition of cancer cell proliferation with a combination of δ-tocotrienol and ferulic acid.

Eitsuka T, Tatewaki N, Nishida H, Kurata T, Nakagawa K, Miyazawa T

Biochem Biophys Res Commun. 2014 Oct 5


Rice bran consists of many functional compounds and thus much attention has been focused on the health benefits of its components. Here, we investigated the synergistic inhibitory effects of its components, particularly δ-tocotrienol (δ-T3) and ferulic acid (FA), against the proliferation of an array of cancer cells, including DU-145 (prostate cancer), MCF-7 (breast cancer), and PANC-1 (pancreatic cancer) cells. The combination of δ-T3 and FA markedly reduced cell proliferation relative to δ-T3 alone, and FA had no effect when used alone. Although δ-T3 induced G1 arrest by up-regulating p21 in PANC-1 cells, more cells accumulated in G1 phase with the combination of δ-T3 and FA. This synergistic effect was attributed to an increase in the cellular concentration of δ-T3 by FA. Our results suggest that the combination of δ-T3 and FA may present a new strategy for cancer prevention and therapy.

Location of α-tocopherol and α-tocotrienol to heterogeneous cell membranes and inhibition of production of peroxidized cholesterol in mouse fibroblasts.

Nakamura T, Noma A, Terao J

Springerplus. 2014 Sep 23;3:550.



α-Tocopherol (α-T) and α-tocotrienol (α-T3) are well recognized as lipophilic antioxidants. Nevertheless, there is limited knowledge on their location in heterogeneous cell membranes. We first investigated the distribution of α-T and α-T3 to the cholesterol-rich microdomains (lipid rafts and caveolae) of heterogeneous cell membranes by incubating these antioxidants with cultured mouse fibroblasts.


Levels of cellular uptake for α-T and α-T3 were adjusted to the same order, as that of the latter was much more efficient than that of the former in the cultured cells. After ultracentrifugation, α-T and α-T3 were partitioned to the microdomain fractions. When the distribution of α-T and α-T3 was further confirmed by using methyl-β-cyclodextrin (which removes cholesterol from membranes), α-T was suggested to be distributed to the microdomains (approx. 9% of the total uptake). The same treatment did not affect α-T3 content in the microdomain fractions, indicating that α-T3 is not located in these cholesterol-rich domains. However, α-T and α-T3 significantly inhibited the production of peroxidized cholesterol when cells were exposed to ultraviolet-A light.


These results suggest that α-T and α-T3 can act as membranous antioxidants against photo-irradiated cholesterol peroxidation irrespective of their distribution to cholesterol-rich microdomains.

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Tocotrienols have a nephroprotective action against lipid-induced chronic renal dysfunction in rats

Rashid Khan M, Ahsan H, Siddiqui S, Siddiqui WA

Ren Fail. 2014 Sep 18:1-8


Abstract Vitamin E is the generic term for a group of tocopherols and tocotrienols (T3). Hyperlipidemia has been known to cause progressive chronic renal dysfunction (CRD). Several investigators have reported that T3 have hypolipidemic and nephroprotective activity against free radical-related diseases. This study was conducted to determine if T3 as tocotrienol-rich fraction (TRF) from palm oil would protect against lipid-induced CRD in rats. For the induction of atherosclerosis and hyperlipidemia, Wistar male rats were fed an atherogenic diet containing 1.25% cholesterol, 0.5% cholic acid and 21% beef tallow (42.6% calories from fat). The atherogenic diet was given for 14 weeks to induce atherosclerosis. The control rats were given normal rat chow and drug control animals treated with TRF (100 mg/kg bw; orally). The first group was taken as disease control in which the animals were left untreated and given normal rat chow for six weeks, while the second group was treated with 100 mg TRF/kg bw. Atherosclerosis and renal functions were evaluated after six weeks of TRF treatment. Feeding an atherogenic diet to rats for 14 weeks resulted in dyslipidemia and impaired renal functions with decreased glomerular filtration rate. The treatment with TRF significantly reduced dyslipidemia and inhibited the development of CRD caused by atherogenic factors. These findings show that low-dose treatment of TRF may provide significant health benefits in the prevention of lipid-induced CRD. The study suggests that TRF is effective in preventing lipid-induced CRD.

Annatto Tocotrienol Helps Prevent Osteoporosis in Men

A preclinical trial using annatto tocotrienol in osteoporotic rats demonstrated that vitamin E tocotrienols are as effective as standard anti-osteoporosis therapy in men.

 Able to completely prevent erosion of the bone surface and decreased bone formation associated with testosterone deficiency, annatto tocotrienol was as effective as testosterone enanthate, one of the standard therapies used to treat osteoporosis in men.

“This study serves as a basis for the application of annatto tocotrienol in hypogonadal men as an antiosteoporotic agent,” concluded the researchers, led by pharmacologist Ima-Nirwana Soelaiman of the Universiti Kebangsaan Malaysia.

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Vitamin E (α-, β-, γ- and δ-tocopherol and -tocotrienol) is an essential factor in the human diet and regularly taken as a dietary supplement by many people, who act under the assumption that it may be good for their health and can do no harm. With the publication of meta-analyses reporting increased mortality in persons taking vitamin E supplements, the safety of the micronutrient was questioned and interactions with prescription drugs were suggested as one potentially underlying mechanism. Here, we review the evidence in the scientific literature for adverse vitamin E-drug interactions and discuss the potential of each of the eight vitamin E congeners to alter the activity of drugs. In summary, there is no evidence from animal models or randomised controlled human trials to suggest that the intake of tocopherols and tocotrienols at nutritionally relevant doses may cause adverse nutrient-drug interactions. Consumption of high-dose vitamin E supplements ( ≥  300 mg/d), however, may lead to interactions with the drugs aspirin, warfarin, tamoxifen and cyclosporine A that may alter their activities. For the majority of drugs, however, interactions with vitamin E, even at high doses, have not been observed and are thus unlikely.

Delta-tocotrienol induces apoptotic cell death via depletion of intracellular squalene in ED40515 cells.

Yamasaki M, Nishimura M, Sakakibara Y, Suiko M, Morishita K, Nishiyama K

Food Funct. 2014 Oct 22;5 (11):2842-9


Here, we examined the effect of tocotrienols (T3) on the growth of adult T-cell leukemia (ATL) cells. All three forms (β-, γ-, and δ-T3) inhibited cell proliferation in a dose-dependent manner; δ-T3 showed the strongest growth-inhibitory effect. δ-T3 increased the G1, G2/M, and subG1 populations and induced internucleosomal DNA fragmentation. δ-T3 treatment also increased the levels of cleaved caspase-3, -6, -7, -9, and poly-ADP ribose polymerase (PARP), and this was accompanied by downregulation of Bcl-2, Bcl-xL, and XIAP. Moreover, δ-T3 decreased nuclear p65 NF-κB levels, indicating downregulation of NF-κB activity. This cytotoxic effect of δ-T3 was abrogated by squalene (SQL) but not mevalonate (MVL), farnesyl diphosphate (FPP), geranylgeranyl diphosphate (GGPP), or cholesterol (CL). δ-T3 decreased intracellular SQL levels, and inhibition of de novo cholesterol synthesis did not affect the action of SQL. Furthermore, δ-T3 significantly decreased farnesyl-diphosphate farnesyltransferase 1 (FDFT1) expression. Taken together, it is evident that δ-T3, due to its ability to potently induce apoptosis via the depletion of intracellular SQL, shows the potential to be considered a therapeutic agent in patients with ATL.