Image of the timeline of the major research findings on palm fruit nutrients

Benefits of Palm Fruit: 35 Year Research Timeline

Published:
Dec 30, 2014
Updated:
Oct 16, 2021

Disclosure: The information on this page has not been evaluated by the Food and Drug Administration (FDA). The information on this page is for educational purposes only and should be considered preliminary and/or inconclusive and not intended for the diagnosis, treatment, cure, or prevention of any disease. The information should not be considered as a claim for any particular food or dietary supplement. Always consult a medical professional for the diagnosis and/or treatment of a disease.

Table of Contents

Intro

This article will show you the most significant research categories for red palm oil (palm fruit) based phytonutrients in relation to human health. Although hundreds of studies have been conducted, only the categories that have shown the most promise and have progressed towards human clinical research will be shown here.

In the past 30 years, scientific research has exploded for the phytonutrients in red palm oil. The major groups of phytonutrients are tocotrienols and tocopherols (tocochromanols) and carotenoids. These phytonutrients are commonly separated from each other and researched independently to more accurately characterize their unique effects. However, these phytonutrients often have an additive, or even synergistic effect, when taken together.

Note: This timeline will be kept up-to-date with the latest research findings as they are published.

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Heart & Cardiovascular

Palm Fruit Tocochromanols Increase Artery Cleansing Protein (APO-A1) in Humans

Faculty of Medicine, Malaysia
Heng EC, et al. (2013) 

This human study showed that 150 mg per day of palm fruit tocochromanols increased APO-A1 by 73% after 6 months. An increase in APO-A1 suggests that palm fruit phytonutrients can enhance lipoprotein (HDL) function and enhance the removal of plaque from blood vessel walls. [1]

Palm Fruit Tocochromanols Activate Collateral Blood Supply After Stroke Event in Dogs

Ohio State University
Sen CK., et al. (2011) 

Researchers administered palm fruit tocochromanols to dogs for 10 weeks. The dogs receiving the tocotrienols were protected from stroke. The mechanism was found to be the activation of small dormant vascular channels that fed the brain with blood while the primary artery was obstructed. This positive finding led to the development of human clinical studies. [2]

Palm Fruit Tocochromanols Promote Circulation by Enhancing Blood Vessel Flexibility 

School of Medical Sciences, Malaysia
Rasool AH, et al.(2008) 

This study supplemented volunteers with 100 mg per day of palm fruit tocochromanols. After 6 weeks the participants had a 10% improvement in pulse wave velocity (blood vessel flexibility). This study showed that palm fruit tocochromanols can improve cardiovascular health by prolonging or increasing nitric oxide activity in the blood vessel wall. [3]

Palm Fruit Tocochromanols and Carotenoids Have Synergistic Effects on Circulation Health

Dept. of Biomedical Sciences, Africa
Jacques van Rooyen, et al. (2008) 

This review article shows several mechanisms for how tocochromanols and carotenoids work together to limit LDL oxidation and optimize nitric oxide function in the blood vessel wall -- and that these phytonutrients work synergistically to provide benefits greater than the phytonutrients can provide on their own. [5]

Palm Fruit Tocochromanols Reduce Injury From Stroke In Rats

Ohio State University 
Khanna S., et al. (2005) 

This was the first study to show a positive effect of palm fruit tocochromanols in reducing stroke-induced damage to the brain in a live animal. As a result of these positive findings, researchers developed a method for analyzing stroke damage in dogs to study the effects of palm fruit tocochromanols in an animal model more closely resembling a human brain. [4]

Palm Fruit Tocochromanols Reduce LDL Oxidation in Humans

Center for Human Nutrition, Texas
D. O'Byrne, et al. (2000) 

This study found that palm fruit tocochromanols (250 mg/day for 4 weeks) help protect LDL cholesterol from free radical oxidation, thus reducing the transformation of LDL cholesterol into arterial plaque. This suggests that tocochromanols may help prevent plaque buildup by inhibiting the transformation of LDL cholesterol into plaque within the arteries. [6]

Palm Fruit Tocochromanols Show Positive Effect in Reversing Plaque Buildup in Humans

Elmhurst Medical Center
Tomeo AC, et al. (1995)

Researchers found a significant reversal of atherosclerosis (plaque) in the carotid artery of elderly subjects without any significant change in cholesterol values (~300 mg/day tocochromanols for 6-18 months). This study suggests that palm fruit tocochromanols have a positive effect on arterial health which may not be reflected by changes in cholesterol levels. [7]

Palm Fruit Tocochromanols Improve Circulation in Humans with Peripheral Vascular Disease

University of Malaya
M K Teoh, et al. (1992)

Researchers found an improvement in walking distance (+46%) in subjects suffering from peripheral artery disease (PAD) after 3 months of tocochromanols supplementation (300 mg/day). Participants were able to exercise for longer periods without pain normally associated with PAD. This study shows tocotrienols may provide circulatory benefits by improving the nitric oxide and/or inflammatory response. [8]

Palm Fruit Tocochromanols Show Inconsistent Cholesterol-Lowering Effect in Humans

University of Wisconsin & Malaya
Qureshi & Tan, et al. (1991) 

Researchers performed several small human pilot studies on palm fruit tocochromanols and found an LDL cholesterol-lowering effect (-10%) and HDL increasing effect (+7%). (4,5) However, subsequent human studies found insignificant changes in cholesterol levels, possibly related to variance in age, blood sampling methods, or inconsistent tocotrienol and tocopherol absorption. Despite the insignificant improvement in LDL/HDL levels, researchers discovered cardiovascular benefits from other mechanisms in future research. [3] [5] [6] [7] [8] [9]

Discovery of Cholesterol-Lowering Effect of Tocotrienols in Animals 

University of Wisconsin
Qureshi, et al. (1986) 

Researchers isolated and identified tocotrienols as the cholesterol-lowering fraction from cereal grains. They found that tocotrienols lower LDL cholesterol (~20%) in chickens, swine, and quail. Attention moved towards palm fruit due to its extremely rich source of tocotrienols. Palm fruit tocochromanols (i.e., tocotrienols and tocopherols) became the major focus for future research. [10]

Skin / Hair & Anti-Aging

Palm Fruit Tocochromanols Reduce Skin Inflammation from UV Exposure

Davos Life Science Pte Ltd
Wei Ney Yap (2018)

This study showed topically applied tocochromanols reduced the UV-induced inflammation by reducing cytokine production (IL-6, IL-8, and COX-2) and free radical formation by 75% compared to placebo. The topical tocochromanol cream also reduced skin redness in human volunteers when applied prior to and after UV exposure. [11]

Palm Fruit Tocochromanols Reduce Skin Scarring

Ohio State University
Sen CK., et al. (2012)

This study was intended to identify the distribution of tocochromanols in human skin after oral supplementation. Skin samples were taken from the supplemented and non-supplemented groups. Researchers noted that participants in the tocochromanols group had no scarring after the skin biopsy. Additional research is now underway to uncover the mechanism of scar prevention. [12] [13]

Palm Fruit Tocochromanols Slow the Aging of Skin by Reducing Advanced Glycosylated End Products (AGEs)

Faculty of Medicine, Malaysia
Chin SF, et al. (2011)  

This study showed 37% reductions in the cross-linking of glucose and proteins in adult humans after 6 months of palm fruit tocotrienol supplementation (208 mg/day). These findings suggest that palm fruit phytonutrients slow the aging process by reducing oxidative damage to structural proteins, thereby reducing skin wrinkling and aging. [14] [15]

Palm Fruit Tocochromanols Reduce Skin Damage from UV Exposure

Sugiyama Jogakuen University
Ymashita et al. (2008)

This study found that hairless rats supplemented with palm fruit tocochromanols for 6 weeks experienced less damage from UVB radiation, compared to a-tocopherol alone. The reduced damage was determined by skin redness and thiobarbituric acid reactive substances (TBARS). [16]

Palm Fruit Tocochromanols Increase Growth of Scalp Hairs in Humans

University of Science, Malaysia
KH Yuen, et al. (2007) 

Research with human subjects showed a 38% increase in the number of scalp hairs after 8 months of palm fruit tocochromanol supplementation (146 mg/day). The number of hairs was increased in thinning areas of the scalp in both men and women suffering from hair loss. Both human clinical trials demonstrated a significant regrowth of hair on the scalp, without side effects. [17] [18]

Palm Fruit Tocochromanols Accumulate into Skin from Dietary Intake

University of California-Berkeley
Weber, et al. (1997) 

This animal study was the first to show that palm fruit phytonutrients consumed through the diet reach the skin tissue. It was also found that the palm fruit tocotrienols had a greater preference for skin tissue than other oil-soluble phytonutrients including alpha-tocopherol, Vitamin A, and CoQ-10. The study concluded that palm fruit tocotrienols provide superior protection against sun damage to the skin. [19]

Palm Fruit Carotenoids Protect Skin from UV damage More Than Beta-Carotene Alone

Tohoku University, Japan
Someya, et al. (1994) 

This study supplemented hairless mice with palm fruit carotenoids or a single carotenoid (beta-carotene) and demonstrated enhanced UV protection from the mixed carotenoids provided by palm fruit. This study suggests that the naturally occurring mixture of alpha, beta, and gamma-carotenes stabilize each other along with an antioxidant chain offering greater protection against free radicals. [20]

Immune System & Cancer

Palm Fruit Tocochromanols Enhance the Immune Response to Vaccines

University Putra Malaysia
Mahalingam D., et al. (2011) 

In this human study, researchers showed that supplementing palm fruit tocochromanols (400 mg per day) for 2 months enhanced the immune response to a tetanus toxoid vaccination in human volunteers. This suggests that palm fruit tocotrienols can enhance the body's defense against pathological invasions. [21]

Palm Fruit Tocochromanols Show Insignificant Benefit in Women With Breast Cancer

Research Center, Malaysia
Nesaretnam, et al. (2010) 

This human study examined the effect of adding tocochromanol supplementation alongside tamoxifen therapy in women with breast cancer. Although fewer participants died in the supplemented group, the results were found to be "non-significant" due to the low number of study participants. Larger clinical trials are now under consideration. [22]

Palm Fruit Tocochromanols Inhibits Growth of Human Colon Cancer Cells 

Harbin Medical University, China
Xu WL., et al. (2009) 

This test-tube study showed inhibitory effects of palm fruit tocochromanols on colon cancer cells. The tocotrienols had the strongest activity at inducing cancer cell death by increasing the Bax / Bcl-2 ratio and activating caspase-3. [23]

Palm Fruit Tocochromanols & Carotenoids Inhibit Breast Cancer Growth Through Multiple Mechanisms

Univ. of Reading, England / Malaysia 
Shah/Nesaretnam, et al. (1997-2006)

Several test-tube studies clarified the mechanism of action of tocochromanols and carotenoids in breast cancer cells. These studies showed suppression of cancer through reduction of estrogen epoxidation, activation of cancer cell death, and other non-estrogen receptor-mediated mechanisms. These findings suggested therapeutic benefits of palm fruit phytonutrients beyond traditional anti-estrogen therapy (i.e., tamoxifen). [23] [25] [26] [27]

Palm Fruit Tocochromanols & Carotenoids increase Natural Killer Cells

The Aga Khan University
Ashfaq MK, et al. (2000) 

This in-vitro study showed that palm fruit tocochromanols and carotenoids enhanced natural killer cells, thereby enhancing the body’s ability to fight off foreign invaders. This study also demonstrated that tocotrienols increased natural killer cells 10x more effectively than regular vitamin E (alpha-tocopherol). [24]

Palm Fruit Tocochromanols Inhibit Human Breast Cancer Cells In Test-Tube 

Cancer Research Center, Ontario
Nesaretnam, et al. (1995) 

Researchers found that palm fruit tocochromanols inhibited the growth of breast cancer cells by 50% in test-tubes, while regular vitamin E (alpha-tocopherol) had no effect. These results suggest that the mixture of natural tocochromanols (i.e., tocotrienols & tocopherols) have a unique effect over alpha-tocopherol alone. [28]

Palm Fruit Carotenoids Suppress Human Cancer Cells in Test-Tube

Research Center, France
Nishino H, et al. (1989) 

Researchers found a tumor-suppressing effect in stomach, pancreatic, and skin cancer cells from mixed carotenoids obtained from palm fruit oil. This study found that the natural mixed carotenoids from palm fruit have a stronger tumor-suppressing effect than a single carotenoid (beta-carotene). [29]

Palm Fruit Oil Reduces Breast Cancer Occurrence in Rats

University of Malaya
Sundram K, et al. (1989)

Researchers administered carcinogenic DMBA to rats, then supplied the rats with diets enriched with either corn, soy, red palm oil, or refined palm oils. Diets with red palm oil had the lowest incidence of cancer. The red palm oil naturally contains the highest concentration of oil-soluble tocochromanols and carotenoids, and thus represents one of the first studies showing a potential anti-cancer effect from palm fruit phytonutrients. [30]

Brain & Nerve

Palm Fruit Tocochromanols Improves Nerve Conduction Velocity

Monash University Malaysia
Kadir, et al. (2020)

This study found that 400 mg/day of palm-based tocochromanols, provided to diabetic patients, increased nerve conduction velocities and increased nerve growth factor (NGF) after 8 weeks of supplementation. [31]

Palm Fruit Tocochromanols Reduces Signs of Neurodegeneration

Universiti Teknologi Mara, Selangor, Malaysia 
Wong JW et al. (2014)

This study found that palm-based tocochromanols (400 mg/day) given to adults with cardiovascular risk factors for 2 years prevented the expansion of white matter lesions (damaged brain tissue), which is linked to increased risk of stroke and neurodegenerative disease. [32]

Palm Fruit Tocochromanols Reach Human Brain Tissue After Oral Supplementation

Ohio State University
Sen CK., et al. (2012) 

This study established that dietary consumption of palm fruit tocochromanols (400 mg/day) reaches all vital organs in the body within 12 weeks. The study found clinically relevant concentrations of tocotrienols within the brain, suggesting that stroke benefits can be obtained in human brain tissue from oral supplementation. Phase II human clinical trials are now underway. [12]

Palm Fruit Tocochromanols Protect Against Glutamate Induced Cell Death in Rat Brain

University of California-Berkeley
Sen CK., et al. (2000) 

This test-tube study showed the superiority of palm fruit tocochromanols over the generic vitamin E (alpha-tocopherol) for neuroprotection from exposure to toxic levels of glutamate. The positive results from this study lead to the study of palm fruit tocochromanols for stroke protection in live animals. [33]

Palm Fruit Tocochromanols Show Protective Antioxidant Effect in Rat Brain

Bhabha Atomic Research Center, India
J.P. Kamat, et al. (1995) 

This early work demonstrated that palm fruit tocochromanols prevent damage to lipids and proteins in the brain at low concentrations, suggesting that dietary consumption may reach the brain in clinically relevant concentrations. [34]

Obesity & Blood Sugar

Palm Fruit Tocotrienol Reduces the Number of Fat Cells

National Taiwan University
Wu SJ., et al. (2013) 

This test-tube study showed gamma-tocotrienols caused fat cell death, further strengthening the potential anti-obesity benefit from palm fruit phytonutrients. Human clinical trials are now under consideration. [35]

Palm Fruit Phytonutrients Absorb into Fat Cells in Humans After Dietary Consumption

Ohio State University
Wan Nazaimoon WM, et al. (2012) 

A collection of human studies confirmed that consuming palm fruit phytonutrients through the diet leads to increased tocochromanols and carotenoids in fat tissue after 4-12 weeks. This provided evidence that regular dietary consumption of phytonutrients readily accumulates in human fat tissue. [12] [36]

Palm Fruit Tocochromanols Improve Blood Sugar Control in Diabetic Mice

Chinese Academy of Sciences
Fang F., et al. (2010) 

This animal study showed that palm fruit tocochromanols act as selective modulators of proliferator-activated receptors (PPARs) which increase insulin sensitivity and uptake of glucose by insulin-responsive tissues (i.e., muscle tissue). This improved glucose utilization suggests tocotrienols may help promote nutrient storage into muscle cells rather than fat cells. [37]

Palm Fruit Tocochromanols Reduce Body Fat Storage in Rats After Exposure to Stress

Universiti Kebangsaan Malaysia
Ima-Nirwana S, et al. (2004) 

Researchers administered palm fruit tocochromanols to rats and found that they stored less body fat after exposure to the stress hormone dexamethasone. Generic vitamin E (a-tocopherol) had no benefit. This study showed that tocotrienols may help reduce belly fat as a result of cortisol release from high stress. [38]

Carotenoids Inhibit Fat Cell Formation in Test-Tube

Applied Life Sciences, Japan
Kawada T, et al. (2000) 

This study showed that carotenoids suppress the growth of new fat cells by inhibiting PPAR-y2. Future research discovered that palm fruit tocochromanols encourage fat cell death, suggesting that palm fruit carotenoids and tocochromanols may have a synergistic effect against body fat. [39]

Liver & Kidney

Palm Fruit Tocochromanols Increase Kidney Filtration in Diabetic Patients

Monash University Malaysia
Kadir et al. (2019)

In this study, patients with diabetic nephropathy received 400 mg/day of palm based tocochromanols for 12 weeks and experienced a significant increase in estimate glomerular filtration rate (eGFR). This suggests that palm-based tocochromanols may improve renal function in those with impaired function. [40]

Palm Fruit Tocochromanols Reduce Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease

Research Center, Philippines
Arguillas M., et al. (2013) 

100 mg per day of palm fruit tocochromanols reduced liver stiffness in 79% of the patients after 3 months. Larger human clinical trials are now under consideration. [41]

Palm Fruit Tocochromanols Reverse Liver Damage in Patients With End-Stage Liver Disease

Ohio State University
Sen CK., et al. (2012) 

This study was intended to identify the tissue distribution of tocotrienols after oral supplementation. Prospects for liver transplants were selected for palm-based tocochromanol supplementation to examine liver tissue after transplantation. The researchers were surprised to see that after providing the palm fruit tocotrienols, 50% of the patients no longer required liver transplants. This study initiated a stage II clinical trial to test palm fruit extract for end-stage liver failure. [12]

Palm Fruit Tocochromanols Reverse Non-Alcoholic Fatty Liver Disease

Universiti Sains Malaysia
Magosso E., et al. (2010) 

This small pilot study showed reversal of non-alcoholic fatty liver disease (NAFLD) in 50% of patients after 12 months of supplementation with palm fruit tocochromanols (200 mg/day). The researchers proposed that NAFLD may be a result of a nutritional deficiency in tocotrienols. [42]

Palm Fruit Tocochromanols Reduce Liver Damage in Rats After Exposure to Carcinogen

National University of Malaysia
Ngah WZ., (1991) 

Rats fed the carcinogen 2-acetylaminofluorene had less liver damage while being supplemented with palm fruit tocochromanols. This study was one of the first records for a liver protective effect from palm fruit phytonutrients, which was followed by several studies to continue identifying the mechanisms. [43]

References

[1] HENG, E.C. et al., Supplementation with tocotrienol-rich fraction alters the plasma levels of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor from young and old individuals, Eur. J. Nutr. 52 7 (2013) 1811.

[2] RINK, C. et al., Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis, J. Cereb. Blood Flow Metab. 31 11 (2011) 2218.

[3] RASOOL, A.H.G., RAHMAN, A.R.A., YUEN, K.H., WONG, A.R., Arterial compliance and vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E, Arch. Pharm. Res. 31 9 (2008) 1212.

[4] VAN ROOYEN, J., ESTERHUYSE, A.J., ENGELBRECHT, A.-M., DU TOIT, E.F., Health benefits of a natural carotenoid rich oil: a proposed mechanism of protection against ischaemia/ reperfusion injury, Asia Pac. J. Clin. Nutr. 17 Suppl 1 (2008) 316.

[5] KHANNA, S. et al., Neuroprotective properties of the natural vitamin E alpha-tocotrienol, Stroke 36 10 (2005) 2258.

[6] O’BYRNE, D. et al., Studies of LDL oxidation following alpha-, gamma-, or delta-tocotrienyl acetate supplementation of hypercholesterolemic humans, Free Radic. Biol. Med. 29 9 (2000) 834.

[7] TOMEO, A.C., GELLER, M., WATKINS, T.R., GAPOR, A., BIERENBAUM, M.L., Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis, Lipids 30 12 (1995) 1179.

[8] TEOH, M.K., CHONG, M.K., JAMALUDIN, M., “Effects of Tocotrienol-Rich Vitamin E on Patients with Peripheral Vascular Disease”, Lipid-Soluble Antioxidants: Biochemistry and Clinical Applications, Molecular and Cell Biology Updates (ONG, A., PACKER, L., Eds), Birkhäuser Basel (1992) 606–621.

[9] HENG, K.S., HEJAR, A.R., JOHNSON STANSLAS, J., OOI, C.F., LOH, S.F., Potential of mixed tocotrienol supplementation to reduce cholesterol and cytokines level in adults with metabolic syndrome, Malaysian Journal of Nutrition 21 2 (2015) 231.

[10] QURESHI, A.A., BURGER, W.C., PETERSON, D.M., ELSON, C.E., The structure of an inhibitor of cholesterol biosynthesis isolated from barley, J. Biol. Chem. 261 23 (1986) 10544.

[11] YAP, W.N., Tocotrienol-rich fraction attenuates UV-induced inflammaging: A bench to bedside study, J. Cosmet. Dermatol. 17 3 (2018) 555.

[12] PATEL, V. et al., Oral tocotrienols are transported to human tissues and delay the progression of the model for end-stage liver disease score in patients, J. Nutr. 142 3 (2012) 513.

[13] Efficacy Of Tocotrienol a Natural Vitamin E In Biopsy Wound - Full Text View - ClinicalTrials.Gov, http://clinicaltrials.gov/ct2/show/study/NCT01579227.

[14] CHIN, S.-F. et al., Tocotrienol rich fraction supplementation improved lipid profile and oxidative status in healthy older adults: A randomized controlled study, Nutr. Metab. 8 1 (2011) 42.

[15] NOORDAM, R. et al., High serum glucose levels are associated with a higher perceived age, Age 35 1 (2013) 189.

[16] YAMADA, Y. et al., Dietary tocotrienol reduces UVB-induced skin damage and sesamin enhances tocotrienol effects in hairless mice, J. Nutr. Sci. Vitaminol. 54 2 (2008) 117.

[17] HO, D.S.S., YUEN, K.H., WONG, J.W., LIM, A.B., Palm Fruit Extract for Hair Growth: A Human Clinical Trial, US US7211274 B2, May 2007.

[18] BEOY, L.A., WOEI, W.J., HAY*, Y.K., Effects of Tocotrienol Supplementation on Hair Growth in Humans, Tropical Life Sciences Research 21 2 (2010) 91.

[19] TRABER, M.G. et al., Diet-derived and topically applied tocotrienols accumulate in skin and protect the tissue against ultraviolet light-induced oxidative stress, Asia Pac. J. Clin. Nutr. 6 1 (1997) 63.

[20] SOMEYA, K., TOTSUKA, Y., MURAKOSHI, M., KITANO, H., MIYAZAWA, T., The effect of natural carotenoid (palm fruit carotene) intake on skin lipid peroxidation in hairless mice, J. Nutr. Sci. Vitaminol. 40 4 (1994) 303.

[21] MAHALINGAM, D., RADHAKRISHNAN, A.K., AMOM, Z., IBRAHIM, N., NESARETNAM, K., Effects of supplementation with tocotrienol-rich fraction on immune response to tetanus toxoid immunization in normal healthy volunteers, Eur. J. Clin. Nutr. 65 1 (2010) 63.

[22] NESARETNAM, K., SELVADURAY, K.R., ABDUL RAZAK, G., VEERASENAN, S.D., GOMEZ, P.A., Effectiveness of tocotrienol-rich fraction combined with tamoxifen in the management of women with early breast cancer: a pilot clinical trial, Breast Cancer Res. 12 5 (2010) R81.

[23] XU, W.-L. et al., Inhibition of proliferation and induction of apoptosis by gamma-tocotrienol in human colon carcinoma HT-29 cells, Nutrition 25 5 (2009) 555.

[24] NESARETNAM, K., STEPHEN, R., DILS, R., DARBRE, P., Tocotrienols inhibit the growth of human breast cancer cells irrespective of estrogen receptor status, Lipids 33 5 (1998) 461.

[25] COMITATO, R. et al., A novel mechanism of natural vitamin E tocotrienol activity: involvement of ERbeta signal transduction, Am. J. Physiol. Endocrinol. Metab. 297 2 (2009) E427.

[26] YU, F.-L., GAPOR, A., BENDER, W., Evidence for the preventive effect of the polyunsaturated phytol side chain in tocotrienols on 17beta-estradiol epoxidation, Cancer Detect. Prev. 29 4 (2005) 383.

[27] ASHFAQ, M.K., ZUBERI, H.S., ANWAR WAQAR, M., Vitamin E and beta-carotene affect natural killer cell function, Int. J. Food Sci. Nutr. 51 Suppl (2000) S13.

[28] NESARETNAM, K., GUTHRIE, N., CHAMBERS, A.F., CARROLL, K.K., Effect of tocotrienols on the growth of a human breast cancer cell line in culture, Lipids 30 12 (1995) 1139.

[29] NISHINO, H., TAKAYASU, J., IWASHIMA, A., MURAKOSHI, M., IMANISHI, J., [Anticarcinogenesis activity of natural carotenes], C. R. Seances Soc. Biol. Fil. 183 1 (1989) 85.

[30] SUNDRAM, K., KHOR, H.T., ONG, A.S., PATHMANATHAN, R., Effect of dietary palm oils on mammary carcinogenesis in female rats induced by 7,12-dimethylbenz(a)anthracene, Cancer Res. 49 6 (1989) 1447.

[31] NG, Y.T. et al., The Effects of Tocotrienol-Rich Vitamin E (Tocovid) on Diabetic Neuropathy: A Phase II Randomized Controlled Trial, Nutrients 12 5 (2020).

[32] GOPALAN, Y. et al., Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter, Stroke 45 5 (2014) 1422.

[33] SEN, C.K., KHANNA, S., ROY, S., PACKER, L., Molecular basis of vitamin E action. Tocotrienol potently inhibits glutamate-induced pp60(c-Src) kinase activation and death of HT4 neuronal cells, J. Biol. Chem. 275 17 (2000) 13049.

[34] KAMAT, J.P., DEVASAGAYAM, T.P., Tocotrienols from palm oil as potent inhibitors of lipid peroxidation and protein oxidation in rat brain mitochondria, Neurosci. Lett. 195 3 (1995) 179.

[35] WU, S.-J., HUANG, G.-Y., NG, L.-T., γ-Tocotrienol induced cell cycle arrest and apoptosis via activating the Bax-mediated mitochondrial and AMPK signaling pathways in 3T3-L1 adipocytes, Food Chem. Toxicol. 59 (2013) 501.

[36] JOHNSON, E.J., SUTER, P.M., SAHYOUN, N., RIBAYA-MERCADO, J.D., RUSSELL, R.M., Relation between beta-carotene intake and plasma and adipose tissue concentrations of carotenoids and retinoids, Am. J. Clin. Nutr. 62 3 (1995) 598.

[37] FANG, F., KANG, Z., WONG, C., Vitamin E tocotrienols improve insulin sensitivity through activating peroxisome proliferator-activated receptors, Mol. Nutr. Food Res. 54 3 (2010) 345.

[38] IMA-NIRWANA, S., SUHANIZA, S., Effects of tocopherols and tocotrienols on body composition and bone calcium content in adrenalectomized rats replaced with dexamethasone, J. Med. Food 7 1 (2004) 45.

[39] KAWADA, T. et al., Carotenoids and retinoids as suppressors on adipocyte differentiation via nuclear receptors, Biofactors 13 1-4 (2000) 103.

[40] TAN, G.C.J. et al., 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 (2019) 2042018819895462.

[41] ARGUILLAS, M., The effect of vitamin E (mixed tocotrienol) on the liver stiffness measurement measured by transient elastography (fibroScan) among NAFLD patients, APAS Liver Week Singapore (2013).

[42] MAGOSSO, E., “Tocotrienols and Nonalcoholic Fatty Liver: a clinical experience”, presented at the The Liver Meeting, Boston, 2010.

[43] NGAH, W.Z. et al., Effect of tocotrienols on hepatocarcinogenesis induced by 2-acetylaminofluorene in rats, Am. J. Clin. Nutr. 53 4 Suppl (1991) 1076S.