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Tocotrienol Research Hub

Explore health benefits of tocotrienol through curated references and studies for various conditions.

Research References

Explore health benefits of tocotrienol through extensive research documentation.

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Tocotrienol health benefits

Index

  • Antioxidant and Anti‑Inflammatory Activities of Tocotrienol

    1. Zainal Z, Khaza’ai H, Radhakrishnan AKC, Chang SK. (2022) Therapeutic potential of palm oil vitamin E‑derived tocotrienols in inflammation and chronic diseases: Evidence from preclinical and clinical studies. Food Res Int. 156:111175. DOI:10.1016/j.foodres.2022.111175

      • Highlights clinical and animal data indicating tocotrienols improve cognitive performance and reduce neuroinflammatory markers in age‑related neurodegeneration Monash University.

    2. Malavolta, M., Pierpaoli, E., Giacconi, R., Basso, A., Cardelli, M., Piacenza, F., & Provinciali, M. (2018). Anti-inflammatory Activity of Tocotrienols in Age-related Pathologies: A SASPected Involvement of Cellular Senescence. Biological Procedures Online, 20, 22. https://doi.org/10.1186/s12575-018-0087-4

      • This study explores how tocotrienols, a form of vitamin E, may counteract age-related inflammation by modulating cellular senescence and the associated secretory phenotype (SASP), suggesting potential therapeutic roles in aging and related diseases.

    3. Ranasinghe R, Mathai M, Zulli A. (2022) Revisiting the therapeutic potential of tocotrienol. BioFactors. 48(4):813–856. https://doi.org/10.1002/biof.1873

    • A comprehensive review of tocotrienols’ nutraceutical properties—spanning anticancer, antioxidant, anti‑inflammatory, and systemic disease applications—alongside advances in targeted delivery, bioavailability enhancement, and future research directions.

  • Tocotrienol Activity in Systemic Disease - Clickable index

  1. Cancer

  2. Renal Disease

  3. Cardiovascular Disease

  4. Nervous System Disease (including dementia & Alzheimer’s)

  5. Glycemic Disease (Diabetes)

  6. Lipidomic Disease (Dyslipidemia)

  7. Skin Disease

  8. Lung Disease

  9. Eye Disease

  10. Bone Disease

Cancer

  1. Younes M, Loubnane G, Sleiman C, Rizk S. (2024) Tocotrienol isoforms: The molecular mechanisms underlying their effects in cancer therapy and their implementation in clinical trials. J Integr Med. 1–11. DOI:10.1016/j.joim.2024.01.002

    • Comprehensive review detailing how individual tocotrienol isoforms (α/β/γ/δ) target cancer hallmarks—including proliferation, apoptosis, angiogenesis, and metastasis—through modulation of signaling pathways and microRNAs. OUCI

  2. Kanchi, M. M., Shanmugam, M. K., Rane, G., Sethi, G., & Kumar, A. P. (2017). Tocotrienols: the unsaturated sidekick shifting new paradigms in vitamin E therapeutics. Drug Discovery Today, 22(12), 1765–1781. https://doi.org/10.1016/j.drudis.2017.08.001

    • This article discusses the emerging therapeutic roles of tocotrienols, emphasizing their superior antioxidant and anticancer activities compared to tocopherols.

  3. Theriault A, Chao J‑T, Wang Q, Gapor A, Adeli K. (1999) Tocotrienol: a review of its therapeutic potential. ScienceDirect

    • Comprehensive overview of tocotrienols’ antiproliferative, pro‐apoptotic, and anti‑angiogenic mechanisms in various cancer cell models ScienceDirect

  4. Tan AL, Yeh YM, Huang YT, et al. (2011) Tocotrienol as a potential anticancer agent. Carcinogenesis. 33(2):233–242. DOI:10.1093/carcin/bgq283

    • Reviews T3’s inhibition of epithelial‑to‑mesenchymal transition, VEGF‑mediated angiogenesis suppression, and induction of antitumor immunity, highlighting its promise as a chemopreventive adjuvant Oxford Academic.

  5. Shan YT, Weng JR, Shyue SK. (2011) Gamma‑tocotrienol–induced apoptosis is associated with the unfolded protein response in MCF‑7 breast cancer cells. Biochem Pharmacol. 82(8):1051–1060. DOI:10.1016/j.bcp.2011.06.005

    • Demonstrates that γ‑T3 triggers ER‑stress‑mediated apoptosis via early‑response gene induction in human breast cancer cells ScienceDirect.

  6. Mo H, Elson CE. (2004) Studies of the isoprenoid‑mediated inhibition of mevalonate synthesis applied to cancer chemotherapy and chemoprevention. Exp Biol Med (Maywood). 229(7):567–585.

    • Demonstrates γ‑tocotrienol’s synergistic inhibition of HMG‑CoA reductase and protein prenylation to suppress mammary tumor cell growth Europe PMC Sage.

Renal Disease

  1. Ranasinghe R, Mathai M, Zulli A. (2022) Revisiting the therapeutic potential of tocotrienol. BioFactors. 48(4):813–856. https://doi.org/10.1002/biof.1873

    • A comprehensive review of tocotrienols’ nutraceutical properties - spanning anticancer, antioxidant, anti‑inflammatory, and systemic disease applications, alongside advances in targeted delivery, bioavailability enhancement, and future research directions. .

  2. Tan GC, Gaby AR, et al. (2019) Tocotrienol‑rich vitamin E improves diabetic nephropathy and persists 6–9 months after washout: a phase IIa randomized controlled trial. Ther Adv Endocrinol Metab. 10:2042018819895462.

    • Phase IIa RCT in T2DM patients with DKD showing significant improvements in eGFR and serum creatinine that endured months post‑supplementation TOCOTRIENOLThe Free Library.

  3. Ravindran S, Umar S, et al. (2010) Comparative hypoglycemic and nephroprotective effects of a tocotrienol‑rich fraction from palm vs. rice bran oil in type 1 diabetic rats. Free Radic Res. 44(9):1045–1053. DOI:10.3109/10715762.2010.511783

    • In streptozotocin‑induced diabetic rats, TRF reduced hyperglycemia and oxidative‑stress‑mediated kidney damage, improving renal function parameters ScienceDirect.

  4. Shen GC, Kadir KA. (2019) Phase IIb randomized controlled trial of tocotrienol‑rich vitamin E in diabetic kidney disease. Ther Adv Endocrinol Metab. 10:2042018819895462. DOI:10.1177/2042018819895462

    • Double‑blind RCT shows 12‑week TRF supplementation significantly enhances eGFR and reduces serum creatinine in DKD patients, with benefits persisting 6–9 months post‑withdrawal NHRI -

  5. Kuhad A, Chopra K. (2009) Attenuation of diabetic nephropathy by tocotrienol: Involvement of NF‑κB signaling pathway. Life Sci. 84(9–10):296–301. DOI:10.1016/j.lfs.2008.12.014

    • In streptozotocin‑induced diabetic rats, oral δ‑tocotrienol (25–100 mg/kg) reduced albuminuria, serum creatinine, and renal TNF‑α/TGF‑β1 via NF‑κB inhibition. ScienceDirect

  6. Siddiqui S, Ahsan H, Khan MR, Siddiqui WA. (2013) Protective effects of tocotrienols against lipid‑induced nephropathy in experimental type‑2 diabetic rats by modulation in TGF‑β expression. Toxicol Appl Pharmacol. 273(2):314–324. DOI:10.1016/j.taap.2012.12.019

    • Demonstrates that tocotrienol‑rich fraction restores glomerular architecture and downregulates renal TGF‑β1 in high‑fat/streptozotocin diabetic rats. NHRI

Cardiovascular Disease

  1. Ranasinghe R, Mathai M, Zulli A. (2022) Revisiting the therapeutic potential of tocotrienol. BioFactors. 48(4):813–856. https://doi.org/10.1002/biof.1873

    • A comprehensive review of tocotrienols’ nutraceutical properties - spanning anticancer, antioxidant, anti‑inflammatory, and systemic disease applications, alongside advances in targeted delivery, bioavailability enhancement, and future research directions. .

  2. Ramanathan N, Tan E, Loh JL, et al. (2018) Tocotrienol is a cardioprotective agent against ageing‑associated cardiovascular disease and its associated morbidities. Nutr Metab (Lond). 15:6. DOI:10.1186/s12986-018-0244-4

    • Reviews preclinical and clinical data showing γ‑ and δ‑tocotrienols improve arterial compliance, inhibit HMG‑CoA reductase, and reduce mitochondrial dysfunction in ageing cardiovascular models. BioMed Central

  3. Shibata A, Tanaka K, Iwami T, et al. (2017) High‑purity tocotrienols attenuate atherosclerotic lesion formation in apoE‑KO mice. J Nutr Biochem. 39:58–66. DOI:10.1016/j.jnutbio.2016.11.006

    • δ‑ and γ‑T3 reduced plaque area and macrophage infiltration in the aorta, demonstrating potent anti‑atherogenic effects PubMed.

  4. Yeganehjoo X, Zamani N, Chitkara S, Shah AK, Mo H. (2024) The Potential Role of Tocotrienols Against Cardiovascular Diseases. In: Lipophilic Vitamins in Health and Disease. Springer. DOI:10.1007/978-3-031-55489-6_7

    • Synthesizes evidence that α‑, γ‑, and δ‑tocotrienols lower LDL‑C, inhibit atherosclerotic lesion formation, and mitigate endothelial dysfunction SpringerLink.

Nervous System Disease (Dementia & Alzheimer’s)

  1. Sen, C. K., Khanna, S., & Roy, S. (2004). Tocotrienol: the natural vitamin E to defend the nervous system? Annals of the New York Academy of Sciences, 1031, 127–142. https://doi.org/10.1196/annals.1331.013

    • This review explores the neuroprotective properties of tocotrienols, highlighting their potential in preventing neurodegenerative diseases through antioxidant and anti-inflammatory mechanisms.

  2. Ahmad Farouk Musa, Cheang Jia Min, Christina Gertrude Yap
    Role of Micronutrients in Brain Health, Nutritional Neurosciences, Springer Nature (2022).

    “Though the role of tocotrienols in traumatic brain injury … it would be a fitting tribute to qualify tocotrienol as mother nature’s gift to the brain.” https://www.researchgate.net/publication/359544603_Tocotrienols_Mother_Nature's_Gift_to_the_Brain

  3. Mangialasche, F., Kivipelto, M., Mecocci, P., Rizzuto, D., Palmer, K., Winblad, B., & Fratiglioni, L. High plasma levels of vitamin E forms and reduced Alzheimer’s disease risk in advanced age. Sage https://journals.sagepub.com/doi/abs/10.3233/JAD-2010-091450 ScienceDaily https://www.sciencedaily.com/releases/2010/07/100707102439.htm

  4. Ranasinghe R, Mathai M, Zulli A. (2022) Revisiting the therapeutic potential of tocotrienol. BioFactors. 48(4):813–856. https://doi.org/10.1002/biof.1873

    • A comprehensive review of tocotrienols’ nutraceutical properties - spanning anticancer, antioxidant, anti‑inflammatory, and systemic disease applications, alongside advances in targeted delivery, bioavailability enhancement, and future research directions. .

  5. Xia W, Mo H. (2015) Potential of tocotrienols in the prevention and therapy of Alzheimer’s disease. J Nutr Biochem. 31:1–9. DOI:10.1016/j.jnutbio.2015.10.011

    • Reviews tocotrienols’ modulation of amyloidogenesis, neuroinflammation, and prenylation pathways relevant to AD pathogenesis Frontiers.

  6. Ruth Naomi, Shafie NH, Kaniappan P, Bahari H. (2021) An interactive review on the role of tocotrienols in neurodegenerative disorders. Front Nutr. 8:754086. DOI:10.3389/fnut.2021.754086

    • Highlights tocotrienols’ neuroprotective actions—including anti‑amyloid, anti‑inflammatory, and mitochondrial support—in models of Alzheimer’s and Parkinson’s disease. Frontiers

  7. Kumar P, Singh S. (2015) Potential of tocotrienols in the prevention and therapy of Alzheimer’s disease. J Nutr Biochem. 31:1–9. DOI:10.1016/j.jnutbio.2015.10.011

    • Reviews T3’s modulation of amyloid processing, neuroinflammation reduction, and cholesterol homeostasis support relevant to AD pathogenesis ScienceDirect.

  8. Sen CK, Khanna S, Roy S. (2011) Tocotrienol protects against ischemic stroke by ameliorating oxidative stress and preserving blood–brain barrier integrity. Stroke. 42(2):355–360. DOI:10.1161/STROKEAHA.110.608547

    • α‑T3 pre‑treatment in rodent stroke models reduces infarct size and maintains BBB function via antioxidant mechanisms AHA Journals.

Glycemic Disease (Diabetes)

  1. Fazilah H, Zaiton S, et al. (2022) Delta‑tocotrienol improves glycemic control, oxidative stress, and inflammatory biomarkers in type 2 diabetes: A randomized controlled trial. Phytother Res. 36(5):2245–2254. DOI:10.1002/ptr.7113

  2. Ranasinghe R, Mathai M, Zulli A. (2022) Revisiting the therapeutic potential of tocotrienol. BioFactors. 48(4):813–856. https://doi.org/10.1002/biof.1873

    • A comprehensive review of tocotrienols’ nutraceutical properties - spanning anticancer, antioxidant, anti‑inflammatory, and systemic disease applications, alongside advances in targeted delivery, bioavailability enhancement, and future research directions. .

  3. Krawiec S. (2023 Aug 7) Meta‑analysis found that tocotrienol supplementation may support HbA1c levels in people with type 2 diabetes. Nutritional Outlook.

    • Summarizes a meta‑analysis of 10 RCTs (n=754) showing 250–400 mg/day TRF significantly lowers HbA1c, especially in early disease and higher baseline HbA1c Nutritional Outlook.

  4. Phang SCW, Ahmad B, Kadir KA, Palanisamy UDM. (2023) Effects of tocotrienol‑rich fraction supplementation in patients with type 2 diabetes: A systematic review and meta‑analysis of randomized controlled trials. Adv Nutr. 14(4):1159–1169. DOI:10.1016/j.advnut.2023.06.006

    • Meta‑analysis of 10 RCTs (n=754) showing 250–400 mg/day TRF lowers HbA1c by 0.23% (p<0.05), particularly in early disease (<10 y) and shorter interventions (<6 mo). Monash University

  5. Chiew Y, Tan SMQ, et al. (2023) Tocotrienol supplementation in metabolic syndrome: Effects on glycemic and lipid biomarkers. Nutr Metab. 20:46. DOI:10.1186/s12986-023-00745-2

    • Meta‑analysis of RCTs shows TRF significantly reduces fasting glucose and improves insulin sensitivity in metabolic syndrome subjects Tocotrienol Research.

Lipidomic Disease (Dyslipidemia)

  1. Ranasinghe R, Mathai M, Zulli A. (2022) Revisiting the therapeutic potential of tocotrienol. BioFactors. 48(4):813–856. https://doi.org/10.1002/biof.1873

    • A comprehensive review of tocotrienols’ nutraceutical properties - spanning anticancer, antioxidant, anti‑inflammatory, and systemic disease applications, alongside advances in targeted delivery, bioavailability enhancement, and future research directions. .

  2. Chin SF, Ibahim J, Makpol S, et al. (2011) Tocotrienol rich fraction supplementation improved lipid profile and oxidative status in healthy older adults: A randomized controlled study. Nutr Metab. 8:42. DOI:10.1186/1743-7075-8-42

    • 6‑month TRF (160 mg/day) in older adults increased HDL‑C and decreased protein carbonyls and AGEs, suggesting improved redox balance BioMed Central.

Skin Disease

  1. Ranasinghe R, Mathai M, Zulli A. (2022) Revisiting the therapeutic potential of tocotrienol. BioFactors. 48(4):813–856. https://doi.org/10.1002/biof.1873

    • A comprehensive review of tocotrienols’ nutraceutical properties - spanning anticancer, antioxidant, anti‑inflammatory, and systemic disease applications, alongside advances in targeted delivery, bioavailability enhancement, and future research directions. .

  2. Ghazali NI, Mohd Rais RZ, Makpol S, Chin KY, Yap WN, Goon JA. (2022 Oct 10) Effects of tocotrienol on aging skin: A systematic review. Front Pharmacol. 13:1006198. DOI:10.3389/fphar.2022.1006198

    • Reviews 18 studies demonstrating tocotrienols protect against UV‑induced oxidative damage, suppress melanogenesis, and improve collagen integrity Frontiers..

  3. Chin SF, Makpol S, et al. (2011) Tocotrienol‑rich fraction supplementation improved lipid profile and oxidative status in healthy older adults: A randomized controlled study. Nutr Metab. 8:42. DOI:10.1186/1743-7075-8-42

    • Six‑month TRF (160 mg/day) in seniors increased HDL‑C and decreased protein carbonyls, indicating improved redox balance BioMed Central.

Lung Disease

  1. Ranasinghe R, Mathai M, Zulli A. (2022) Revisiting the therapeutic potential of tocotrienol.

    • A comprehensive review of tocotrienols’ nutraceutical properties - spanning anticancer, antioxidant, anti‑inflammatory, and systemic disease applications, alongside advances in targeted delivery, bioavailability enhancement, and future research directions. NIH.

  2. Peh HY, Tan WSD, Chan TK. (2017) γ‑Tocotrienol protects against emphysema in cigarette smoke‑induced COPD. Free Radic Biol Med. 110:332–344. DOI:10.1016/j.freeradbiomed.2017.06.023

    • γ‑T3 attenuated alveolar destruction and improved lung function in a murine COPD model ScienceDirect.

  3. Ji X, Yao H, Meister M, Gardenhire DS, Mo H. (2021 May 31) Tocotrienols: Dietary Supplements for Chronic Obstructive Pulmonary Disease. Antioxidants. 10(6):883. DOI:10.3390/antiox10060883

    • Comprehensive review of δ‑ and γ‑tocotrienols’ ability to suppress NF‑κB, reduce macrophage infiltration, and improve lung function in COPD models MDPI.

Eye Disease (Diabetic Retinopathy)

  1. Ranasinghe R, Mathai M, Zulli A. (2022) Revisiting the therapeutic potential of tocotrienol.

    • A comprehensive review of tocotrienols’ nutraceutical properties - spanning anticancer, antioxidant, anti‑inflammatory, and systemic disease applications, alongside advances in targeted delivery, bioavailability enhancement, and future research directions. NIH.

  2. Chiew Y, Tan SMQ, Ahmad B, Khor SE, Kadir KA. (2021) Tocotrienol‑rich vitamin E from palm oil (Tocovid) and its effects in diabetes and diabetic retinopathy: A pilot phase II clinical trial. Asian J Ophthalmol. 17(4):375–399. DOI:10.35119/asjoo.v17i4.698

    • Eight‑week RCT in T2DM patients showing 200 mg twice daily Tocovid significantly reduces retinal hemorrhage area without adverse effects. asianjo.com

  3. Tan SMQ, Chiew Y, Ahmad B, et al. (2021) Tocotrienol‑rich vitamin E (Tocovid) attenuates retinal bleeding in diabetic retinopathy: A pilot phase II trial. Asian J Ophthalmol. 17(4):375–399. DOI:10.35119/asjoo.v17i4.698

    • Eight‑week Tocovid supplementation significantly reduced retinal hemorrhages and improved perfusion in T2DM patients with DR TOCOTRIENOL.

  4. Ibrahim S, Siam A, et al. (2022) TRF preserves retinal vascular integrity and downregulates Ang‑2 and PKC in STZ‑induced diabetic rats. Graefes Arch Clin Exp Ophthalmol. 260(9):2731–2742. DOI:10.1007/s00417-022-05965-3

    • In diabetic rats, TRF reduced VEGF, Ang‑2, and PKC expression, mitigating DR‑associated retinal lesions SpringerLink.

Bone Disease (Osteoporosis & Osteoarthritis)

  1. Ranasinghe R, Mathai M, Zulli A. (2022) Revisiting the therapeutic potential of tocotrienol. BioFactors. 48(4):813–856. https://doi.org/10.1002/biof.1873

    • A comprehensive review of tocotrienols’ nutraceutical properties - spanning anticancer, antioxidant, anti‑inflammatory, and systemic disease applications, alongside advances in targeted delivery, bioavailability enhancement, and future research directions. .

  2. Isa AM, Abd Rahman R, et al. (2017) Bone protective effects of tocotrienol: a systematic review on molecular mechanisms and preclinical studies. BMC Complement Altern Med. 17(1):265. DOI:10.1186/s12906-017-1644-2

    • Preclinical evidence that δ‑ and γ‑tocotrienols inhibit osteoclastogenesis, reduce RANKL expression, and promote osteoblast survival in osteoporosis models Science Alert.

  3. Chin KY, Ima‑Nirwana S. (2024) Updates in the skeletal and joint protective effects of tocotrienol: a mini review. Front Endocrinol. 15:1417191. DOI:10.3389/fendo.2024.1417191

    • Summarizes recent preclinical and clinical findings that δ‑ and γ‑tocotrienols inhibit osteoclastogenesis, upregulate osteoblast activity, and mitigate bone loss in osteoporosis and osteoarthritis models. Frontiers

  4. Shen CL, Mo H, Dunn DM, Watkins BA. (2021 Dec 23) Tocotrienol Supplementation Led to Higher Serum Levels of Lysophospholipids but Lower Acylcarnitines in Postmenopausal Women: A Randomized Double‑Blinded Placebo‑Controlled Clinical Trial. Front Nutr. 8:766711. DOI:10.3389/fnut.2021.766711

    • 12‑week RCT showing TT (δ‑ and γ‑isomers) supplementation favorably modulates lipid metabolites linked to bone turnover and oxidative stress in osteopenic women Frontiers.