A 12-week evaluation of annatto tocotrienol supplementation for postmenopausal women: safety, quality of life, body composition, physical activity, and nutrient intake

Shen CL, Wang S, Yang S, Tomison MD, Abbasi M, Hao L, Scott S, Khan MS, Romero AW, Felton CK, Mo H

BMC Complement Altern Med. 2018 Jun 28;18(1):198. doi: 10.1186/s12906-018-2263-0.



Evidence suggests that tocotrienols may benefit bone health in osteopenic women. However, their safety in this population has never been investigated. This study was to evaluate the safety of a 12-week supplementation of annato tocotrienol in postmenopausal osteopenic women, along with effects of the supplementation on quality of life, body composition, physical activity, and nutrient intake in this population.


Eighty nine postmenopausal osteopenic women were randomly assigned to 3 treatment arms: (1) Placebo (430 mg olive oil/day), (2) Low tocotrientol (Low TT) (430 mg tocotrienol/day from DeltaGold 70 containing 300 mg tocotrienol) and (3) High tocotrienol (High TT) (860 mg tocotrienol/day from DeltaGold 70 containing 600 mg tocotrienol) for 12 weeks. DeltaGold 70 is an extract from annatto seed with 70% tocotrienol consisting of 90% delta-tocotrienol and 10% gamma-tocotrienol. Safety was examined by assessing liver enzymes (aspartate aminotransferase, alanine aminotransferase), alkaline phosphatase, bilirubin, kidney function (blood urea nitrogen and creatinine), electrolytes, glucose, protein, albumin, and globulin at 0, 6, and 12 weeks. Serum tocotrienol and tocopherol concentrations were assessed and pills counted at 0, 6, and 12 weeks. Quality of life, body composition, physical activity, and dietary macro- and micro-nutrient intake were evaluated at 0 and 12 weeks. A mixed model of repeated measures ANOVA was applied for analysis.


Eighty seven subjects completed the study. Tocotrienol supplementation did not affect liver or kidney function parameters throughout the study. No adverse event due to treatments was reported by the participants. Tocotrienol supplementation for 6 weeks significantly increased serum delta-tocotrienol level and this high concentration was sustained to the end of study. There was no difference in serum delta-tocotrienol levels between the Low TT and the High TT groups. No effects of tocotrienol supplementation were observed on quality of life, body composition, physical activity, and nutrient intake.


Annatto-derived tocotrienol up to 600 mg per day for 12 weeks appeared to be safe in postmenopausal osteopenic women, particularly in terms of liver and kidney functions. Tocotrienol supplementation for 12 weeks did not affect body composition, physical activity, quality of life, or intake of macro- and micro-nutrients in these subjects.

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Vitamin E and vitamin C attenuate Di-(2-ethylhexyl) phthalate-induced blood-testis barrier disruption by p38 MAPK in immature SD rats

Shen L, Tang X, Wei Y, Long C, Tan B, Wu S, Sun M, Zhou Y, Cao X, Wei G

Reprod Toxicol. 2018 Jun 27;81:17-27. doi: 10.1016/j.reprotox.2018.06.015. [Epub ahead of print]


As an environmental endocrine disruptor, Di-(2-ethylhexyl) phthalate (DEHP) affects blood-testis barrier (BTB)-associated proteins expression, which compromises BTB integrity and causes infertility. Notably, DEHP-induced testicular toxicity is related to oxidative stress, but the specific mechanism remains unclear. Therefore, we sought to investigate this mechanism and determine whether vitamin C and vitamin E administration would attenuate the BTB impairment induced by DEHP in vivo and by Mono-(2-Ethylhexyl) Phthalate (MEHP) in vitro, respectively. HE staining and EM found that DEHP exposure led to spermatogenesis dysfunction and BTB disruption, respectively. The Western blot and immunofluorescence results showed that DEHP exposure caused BTB impairment through oxidative stress-mediated p38 mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, Vitamin E and vitamin C could alleviate the oxidative stress, block DEHP-induced spermatogenesis dysfunction and BTB disruption by inhibiting p38 MAPK signaling pathway. In summary, vitamin E and vitamin C are good candidates for the treatment of DEHP-induced male infertility.

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Cytoprotective role of vitamin E in porcine adipose-tissue-derived mesenchymal stem cells against hydrogen-peroxide-induced oxidative stress

Bhatti FUR, Kim SJ, Yi AK, Hasty KA, Cho H

Cell Tissue Res. 2018 Jun 27. doi: 10.1007/s00441-018-2857-3. [Epub ahead of print]


Survival of mesenchymal stem cells (MSCs) against oxidative stress and inflammation is vital for effective stem cell therapy. The reactive oxygen species (ROS) result in apoptosis and release of inflammatory mediators. Adipose-derived stem cells (ASCs) have shown promise for stem cell therapy owing to their anti-inflammatory and anti-oxidant activity. Previously, we showed the benefits of vitamin E against hydrogen peroxide (H2O2)-induced oxidative stress in rat bone marrow-derived MSCs. In this study, we aim to evaluate the effect of vitamin E treatment on porcine adipose-derived mesenchymal stem cells (pASCs) against H2O2-induced oxidative stress. The oxidative stress was induced by treating pASCs with 500 μM H2O2 with or without vitamin E. Viability of pASCs is enhanced after vitamin E treatment. In addition, reduced cellular toxicity, total NO level, PGE2 production and caspase-3 activity were observed after vitamin E treatment. Gene expression analysis of vitamin E-treated pASCs showed down-regulated expression for the genes associated with oxidative stress and apoptosis, viz., NOS2, Casp3, p53, BAX, MDM2, NFκB, HIF1α and VEGF-A genes. On the other hand, expression of anti-apoptotic and survival genes was up-regulated, viz., BCL2, BCL2L1 and MCL1. Furthermore, phosphorylation of Akt was attenuated following vitamin E treatment. The findings of this study may help in developing effective stem cell therapy for the diseases characterized by the oxidative stress and inflammation.

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Top 15 Vitamin E Foods & Their Benefits

From its potent antioxidant properties to its ability to protect your cells against damage, vitamin E can have a powerful effect when it comes to your health. Getting enough vitamin E foods in your diet may aid in the treatment of certain skin conditions, boost hair growth and even support healthy vision — in addition to the other vitamin E benefits these foods provide.

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Handful Of Walnuts Daily Cuts Risk Of Asthma

Gamma-tocopherol is a major form of vitamin E, which is abundant in nuts like walnuts and pecans and in the legume peanut, as well as seed oils such as corn, soybean and sesame. This type has drawn little attention compared with alpha-tocopherol, the form most commonly found in vitamin E supplements.

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11 Amazing Health Benefits of Vitamin E

A vitamin enriched diet is extremely important for your well being. Vitamins possess a number of amazing benefits that keep you strong and active. With that being said, vitamin E and its properties are considered amongst the most remarkable.

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Association between Dietary Vitamin E Intake and Esophageal Cancer Risk: An Updated Meta-Analysis

Cui L, Li L, Tian Y, Xu F, Qiao T

Send to Nutrients. 2018 Jun 21;10(7). pii: E801. doi: 10.3390/nu10070801.


Epidemiological studies have provided ambiguous evidence on the association between vitamin E and esophageal cancer risk. To resolve this controversy, we performed this meta-analysis. The literature was searched by using Excerpta Medica Database (EMBASE), PubMed, the Web of Science, and the Cochrane Library from the inception to April 2018. A random effect model was utilized to calculate the odds ratio (OR) with the 95% confidence interval (95% CI). Twelve articles reporting 14 studies involving 3013 cases and 11,384 non-cases were included. By comparing the highest category with the lowest category of dietary vitamin E intake, we found that dietary vitamin E intake was inversely related to esophageal cancer risk (OR = 0.47, 95% CI: 0.36⁻0.60). Subgroup analysis revealed that dietary vitamin E intake had a significantly negative association with both the esophageal squamous cell carcinoma risk (OR = 0.29, 95% CI: 0.18⁻0.44) and the esophageal adenocarcinoma risk (OR = 0.66, 95% CI: 0.49⁻0.88). No study significantly affected the findings in the sensitivity analysis. Publication bias was discovered, however, the OR (95% CI) remained unchanged after the trim-and-fill analysis. This meta-analysis showed that the higher dietary vitamin E intake is associated with a lower esophageal cancer risk. However, the association still needs to be upheld by more large-scaled randomized controlled trials and prospective studies.

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Incorporation of tocopherol-rich extracts from mushroom mycelia into yogurt

Bouzgarrou C, Amara K , Reis FS , Barreira JCM , Skhiri F , Chatti N , Martins A , Barros L , Ferreira ICFR

Food Funct. 2018 Jun 20;9(6):3166-3172. doi: 10.1039/c8fo00482j.


Consumers are well-informed about food additives and it is likely that they prefer natural additives over their synthetic analogues. Antioxidants represent a major class of food preservatives, among which tocopherols stand out as one of the most important examples. Interestingly, these compounds are present in relevant amounts in the mycelia of in vitro cultured mushrooms. Accordingly, the mycelia from Ganoderma lucidum, Pleurotus ostreatus and Pleurotus eryngii were used as alternative sources of tocopherols. These extracts were incorporated into different yogurt formulations, which were further compared among each other and with yogurts containing commercial α-tocopherol (E307), regarding their nutritional parameters, fatty acid profile and antioxidant activity. The proposed approach was validated as an effective functionalization strategy, particularly in the case of the G. lucidum mycelium, which showed the highest antioxidant potential, most likely as a result of its tocopherol profile. Furthermore, yogurts prepared with each mycelium extract allowed maintaining the nutritional properties observed in the “blank” yogurt formulation.

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Natural Source Vitamin E Market to Grow Due to Awareness About Healthy Lifestyle – Press Release

The easy accessibility of natural source vitamin E through an increasingly strengthening distribution network is additionally a key factor driving the market all over the world. Having successfully established a large consumer base through store-based retail channels, for example, supermarkets, health shops, hypermarkets, drugstores, mass merchandisers, and healthcare specialist retailers, the attention is currently on strengthening the e-commerce channel.

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Annatto-derived tocotrienol stimulates osteogenic activity in preosteoblastic MC3T3-E1 cells: a temporal sequential study

Wan Hasan WN, Abd Ghafar N, Chin KY, Ima-Nirwana S

Drug Des Devel Ther. 2018 Jun 13;12:1715-1726. doi: 10.2147/DDDT.S168935. eCollection 2018.



Annatto-derived tocotrienol (AnTT) has been shown to improve bone formation in animal models of osteoporosis. However, detailed studies of the effects of AnTT on preosteoblastic cells were limited. This study was conducted to investigate the osteogenic effect of AnTT on preosteoblast MC3T3-E1 cells in a time-dependent manner.


Murine MC3T3-E1 preosteoblastic cells were cultured in the different concentrations of AnTT (0.001-1 µg/mL) up to 24 days. Expression of osteoblastic differentiation markers was measured by qPCR (osterix [OSX], collagen 1 alpha 1 [COL1α1], alkaline phosphatase [ALP], and osteocalcin [OCN]) and by fluorometric assay for ALP activity. Detection of collagen and mineralized nodules was done via Direct Red staining and Alizarin Red staining, respectively.


The results showed that osteoblastic differentiation-related genes, such as OSX, COL1α1, ALP, and OCN, were significantly increased in the AnTT-treated groups compared to the vehicle group in a time-dependent manner (P<0.05). Type 1 collagen level was increased from day 3 to day 15 in the AnTT-treated groups, while ALP activity was increased from day 9 to day 21 in the AnTT-treated groups (P<0.05). Enhanced mineralization was observed in the AnTT-treated groups via increasing Alizarin Red staining from day 3 to day 21 (P<0.05).


Our results suggest that AnTT enhances the osteogenic activity by promoting the bone formation-related genes and proteins in a temporal and sequential manner.

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