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Delta-tocotrienol supplementation improves biochemical markers of hepatocellular injury and steatosis in patients with nonalcoholic fatty liver disease: A randomized, placebo-controlled trial

Muhammad Amjad Pervez, Dilshad Ahmed Khan, Atiq Ur Rehman Slehria, Aamir Ijaz

Complement Ther Med . 2020 Aug;52:102494. doi: 10.1016/j.ctim.2020.102494. Epub 2020 Jun 23.

Abstract

Objective: The aim of this study was to examine the effects of delta-tocotrienol (δ-tocotrienol) supplementation on biochemical markers of hepatocellular injury and steatosis in patients with nonalcoholic fatty liver disease (NAFLD).

Design: The study design was a two-group, randomized, double-blind, placebo-controlled trial. The patients with NAFLD were randomly assigned to receive δ-tocotrienol 300 mg twice daily or placebo for 24 weeks.

Endpoints: The primary endpoints were change from baseline in fatty liver index (FLI) and homeostasis model of insulin resistance (HOMA-IR) after 24 weeks. Secondary endpoints included change from baseline in high sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), alanine transaminase (ALT), aspartate transaminase (AST) and grading of hepatic steatosis on ultrasound. Between-group differences were tested for significance using ANCOVA. Mean differences (MD) with 95 % CIs are reported.

Results: A total of 71 patients (tocotrienol=35, placebo=36) were randomized and included in the intention to treat analysis. Compared with placebo, δ-tocotrienol significantly reduced (MD [95 % CI]) FLI (-8.52 [-10.7, -6.3]; p < 0.001); HOMA-IR (-0.37 [-0.53, -0.21]; p < 0.001), hs-CRP (-0.61[-0.81, -0.42]; p < 0.001), MDA (-0.91 [-1.20, -0.63]; p < 0.001), ALT (-8.86 [-11.5, -6.2]; p < 0.001) and AST (-6.6 [-10.0, -3.08]; p < 0.001). Hepatic steatosis was also reduced by a significantly greater extent with tocotrienol than with placebo (p =0.047). No adverse events were reported.

Conclusion: δ-tocotrienol effectively improved biochemical markers of hepatocellular injury and steatosis in patients with NAFLD. δ-tocotrienol supplementation might be considered as a therapeutic option in the management of patients with NAFLD.

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Cellular uptake and anti-inflammatory effects of palm oil-derived delta (δ)-tocotrienol in microglia

Shi Wei Tan, Daud Ahmad Bin Israf Ali, Huzwah Khaza'ai, Jia Woei Wong, Sharmili Vidyadaran

Cell Immunol . 2020 Aug 28;357:104200. doi: 10.1016/j.cellimm.2020.104200. Online ahead of print.

Abstract

Tocopherols long dominated studies on vitamin E, although interest has shifted to tocotrienols. It was previously shown that δ-tocotrienol derived from palm oil reduced nitric oxide released by BV2 microglia as early as 18 h after lipopolysaccharide stimulation. The current study measured δ-tocotrienol uptake by BV2 over a 24 h incubation period and its anti-inflammatory effects on primary microglia. Uptake of 17.5 μg/mL δ-tocotrienol by BV2 microglia began as early as 5 min and rose steeply to 21 ± 3% of the amount administered at 24 h. The amount of δ-tocotrienol retained in the lipopolysaccharide-stimulated microglia at 24 h was 14 ± 2%, with no substantial difference seen in unstimulated microglia. The same δ-tocotrienol regimen reduced nitric oxide levels by 82% at 24 h after lipopolysaccharide stimulation (p < 0.05). This was accompanied by decreased inducible nitric oxide synthase protein expression by 67 ± 5% compared to untreated controls (p < 0.05). In primary microglia, δ-tocotrienol downregulated IL-1β production, but TNF-α and IL-6 were not affected. δ-Tocotrienol also reduced prostaglandin E2 production by ~78%% and decreased transcription of COX-2 and 5-LOX, but not COX-1. This study showed the anti-inflammatory effects of δ-tocotrienol derived from palm oil and opens up interest for tocotrienol supplementation to reduce the effects of inflammatory conditions.

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Tocotrienols may complement antiplatelet drugs, reducing aspirin resistance, says new study

Recent findings from the NUTRITION human clinical trial (Natural Tocotrienol Against Ischemic Stroke Event)1 showed that supplementation with the tocotrienol EVNol Suprabio (from ExcelVite, based in Edison, NJ) may decrease aspirin resistance in patients taking blood thinning drugs. In the single-center, randomized double-blind clinical trial, 150 patients who suffered transient ischemic attacks or stroke in the previous six months were assigned to take either placebo, 400 mg of tocotrienol or 800 mg of tocotrienol in addition with aspirin or clopidogrel alone or in combination. While aspirin has been shown to reduce the relative risk of recurrent stroke by inhibiting platelet aggregation, some patients develop aspirin resistance, becoming resistant or only partially responsive to the antiplatelet effects.

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The Efficacy of Amniotic Membrane Stem Cell (AMSC) Metabolite Product and Vitamin E for Wrinkles, Spots, and Pores in Photoaging

Rahmadewi Rahmadewi, Retha Retha, Dyah Ayu Pitasari, Vidyani Adiningtyas Kusumastanto, Agatha Anindita Ayu Ardhaninggar, Irmadita Citrashanty, Maylita Sari, Menul Ayu Umborowati, Cita Rosita Sigit Prakoeswa

Dermatol Res Pract . 2020 Aug 26;2020:1584541. doi: 10.1155/2020/1584541. eCollection 2020.

Abstract

Background: It is expected that a combination of amniotic membrane stem cell metabolite product (AMSC-MP) and vitamin E after fractional CO2 laser as laser-assisted drug delivery (LADD) will provide better effects in photoaging treatment as the combination reaches the target. This promises an option for photoaging therapy in the future.

Materials and methods: Sixty women with photoaged skins were involved in this experimental study. They were then divided into two groups. The treatment group received a topical combination of AMSC-MP and vitamin E, and the control group received AMSC-MP alone after fractional CO2 laser. The treatment was repeated three times.

Result: The Janus assessment results showed a significant difference in pores in the third observation, and the average pore improvements in the treatment group were better than the control group. Wrinkle, UV spot, and polar spot did not show any significant difference.

Conclusion: A combination of the amniotic membrane stem cell metabolite product (AMSC-MP) and vitamin E after fractional CO2 laser as LADD only improves pores in photoaged skins.

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The effects of tocotrienol supplementation on lipid profile: A meta-analysis of randomized controlled trials

Shuping Zuo, Guiping Wang, QuanLe Han, Hongling Xiao, Heitor O Santos, David Avelar Rodriguez, Vahid Khani, Jianlei Tang

Complement Ther Med . 2020 Aug;52:102450. doi: 10.1016/j.ctim.2020.102450. Epub 2020 May 25.

Abstract

Background & objective: Tocotrienol supplementation has been emerged as a potent candidate for the treatment of dyslipidemia. In the present study, a systematic review and meta-analysis of randomized controlled trials was performed with the aim of examining the effects of tocotrienol supplementation on the lipid profile.

Methods: Four databases (Scopus, PubMed/Medline, Web of Science and Embase) were used to accomplish the literature search up to November 2019. Clinical trials encompassing the impact of tocotrienol supplementation on lipid profile were extracted regardless of clinical condition, with studies included involving only adults patients.

Results: A total of 15 articles with 20 arms were eligible and included in the meta-analysis to estimate the pooled effect size. Overall results showed a significant effect of tocotrienol supplementation on increasing high-density lipoprotein cholesterol (HDL-C) levels (weight mean difference (WMD): 0.146 mmol/L, I2 = 85.9%) and a non-significant influence on total cholesterol (TC) (WMD: 0.010 mmol/L, I2 = 64.5%), low-density lipoprotein cholesterol (LDL-C) (WMD: 0.095 mmol/L, I2 = 87.4%), and triglycerides (TG) (WMD: -0.112 mmol/L, I2 = 67.4%) levels. Increment in HDL-C levels was significant greater for the tocotrienol dosage ≥ 200 mg/d (WMD: 0.202 mmol/L) and ≤8 weeks (WMD: 0.278 mmol/L). Moreover, studies that investigated tocotrienol dose ≥200 mg had no heterogeneity, while showing a significant decrease in TG levels (WMD: -0.177 mmol/L).

Conclusion: The present meta-analysis demonstrated that supplementing with tocotrienols does not decrease the concentrations of LDL-C, TC and TG. However, tocotrienol supplementation was considered a candidate for increasing HDL-C levels.

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Multifunctional activity of vitamin E in animal and animal products: A review

Emrobowansan M Idamokoro, Andrew B Falowo, Chika E Oyeagu, Anthony J Afolayan

Anim Sci J . Jan-Dec 2020;91(1):e13352. doi: 10.1111/asj.13352.

Abstract

Vitamin E is an essential nontoxic fat-soluble micronutrient whose effects on livestock performance and products can be attributed to its antioxidant and nonantioxidant properties. Although it is needed in small quantity in the diet, its roles in livestock production are indispensable as it is required in boosting performance, nutritional qualities, and yield of animal and animal products. The dietary or oral supplementation of vitamin E is essential in reducing lipid oxidation in muscle, egg, and dairy products as well as lowering cholesterol concentrations and improving antioxidant status of livestock. Evidence has shown that bioavailability of vitamin E-enriched animal products could serve as an invaluable nutritional benefit to consumers; especially those in regions of limited resources where vitamin E deficiencies pose a risk that may be detrimental to some cellular activities of the body and on human health. It is therefore important to redirect research on the impact of vitamin E supplementation as antioxidant on livestock performance and animal products.

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Pyrethroid-Induced Organ Toxicity and Anti-Oxidant-Supplemented Amelioration of Toxicity and Organ Damage: The Protective Roles of Ascorbic Acid and α-Tocopherol

Mohsen S Al-Omar, Mamuna Naz, Salman A A Mohammed, Momina Mansha, Mohd N Ansari, Najeeb U Rehman, Mehnaz Kamal, Hamdoon A Mohammed, Mohammad Yusuf, Abubaker M Hamad, Naseem Akhtar, Riaz A Khan

Int J Environ Res Public Health . 2020 Aug 25;17(17):E6177. doi: 10.3390/ijerph17176177.

Abstract

The pyrethroid toxicants, fatal at high doses, are found as remnants of crop pesticides and ingredients of commercially available insecticides. The toxic effects of high-content insecticidal pyrethroid formulations are available in 0.05 g, 1.17 g, and 0.04 g pyrethroid-instilled products, namely burning coils, pyrethroid-soaked mats, and liquid formulations of pyrethroids that release pyrethroid vapor/smoke upon heating. They provided 5.46 g/kg, 21.15 g/kg, and 4.24 g/kg of toxicants to the experimental animals over a total of 3 weeks/5 h per os (p.o.) administration, producing necrosis, hyperemia, and fatty changes in the liver; fiber separation in cardiac muscles; atrophy, lymphatic infiltration, blood vessel congestion, and hyperemia in the heart tissues of the experimental animals. The glomerular tuft necrosis, cytoplasmic degeneration of renal tubular cells, necrotic tubules, congestion, and dilatation of blood vessels were observed in the kidney tissue of intoxicated animals. Air-space enlargement, interstitial inflammation, lymphocyte infiltration aggregates, connective tissue infiltration by inflammatory cells, and hyperemia were found in the lung tissues. The pyrethroid toxicants also produced nervous tissue degeneration and decreased neurons in the brain, which were observed through histopathological examinations of the brain, lungs, heart, kidneys, and liver. The protective effects of ascorbic acid (AA/vitamin C) and α-tocopherol (E307/vitamin E) at 100 mg/kg oral doses administered daily for the entire period of the toxicant exposure of three weeks to the experimental mice, aged between 3-4 months and weighing ≈30 g, ameliorated the tissue damage, as observed through the histopathological examinations. The ascorbic acid caused recovery of the liver, kidney, brain, and heart tissue damage, while α-tocopherol was effective at ameliorating the damage in the kidneys and lung tissue compared with the control groups. The high levels of tissue damage recovery suggested a prophylactic effect of the concurrent use of ascorbic acid and α-tocopherol for the subjects under the exposure of pyrethroids.

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Antioxidant Effect Of Vitamin E On Carbon Tetrachloride Induced Tubulointerstitial And Glomerular Damage In The Kidneys Of Albino Mice

Shabnum Aamir, Zia Ud Din, Zahid Sarfaraz Khan, Humaira Imtiaz, Faheem Ul Haq, Hajira Ishaq

J Ayub Med Coll Abbottabad . Jul-Sep 2020;32(3):295-298.

Abstract

Background: Chemical induced nephrotoxicity is one of the main causes of acute kidney injury. The objective of this study was to determine the antioxidant effect of vitamin E against carbon tetrachloride induced tubulointerstitial and glomerular damage in the kidney of albino mice.

Methods: The study had been conducted on albino mice. The duration of study was for five weeks. A total of 35 animals were randomly divided into five groups A, B, C, D and E .The group A served as control group, group B was administered only with carbon tetrachloride (no vitamin E) and groups C, D and E received test drug (vitamin E) in doses of 1, 10 and 50mg/kg body weight respectively along with CCl4. The animals were dissected and kidneys were excised for microscopic study for possible histo-morphological effects.

Results: It was observed that carbon tetrachloride treated experimental groups developed tubulo-interstitial and glomerular changes as compared to control group A. The results suggested that these changes were significantly reduced in vitamin E treated groups especially in dose of 50 mg/kg body weight.

Conclusions: This study reveals that tubulointerstitial and glomerular damage caused by carbon tetrachloride can be reduced by vitamin E in dose of 50 mg/kg body weight.

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Effects of pomegranate peel extract and vitamin E on the inflammatory status and endothelial function in hemodialysis patients: a randomized controlled clinical trial

Tina Jafari, Aziz A Fallah, Ali Reyhanian, Elham Sarmast

Food Funct . 2020 Aug 25. doi: 10.1039/d0fo01012j. Online ahead of print.

Abstract

Inflammation and endothelial dysfunction are major problems in hemodialysis (HD) patients. This study assessed the effects of an 8 week administration of pomegranate peel extract (PPE) and vitamin E (Vit E) alone or in combination on the biomarkers of inflammation, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and the biomarkers of endothelial function, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin, in HD patients. In a randomized, double-blind, parallel, placebo-controlled trial, 100 HD patients were randomly divided into 4 equal groups: (a) PPE + Vit E, received 2 pomegranate tablets (each tablet contained 225 mg PPE, equal to 90 mg ellagic acid) + 1 Vit E soft gel (400 IU) daily, (b) PPE, received 2 pomegranate tablets + 1 Vit E placebo soft gel daily, (c) Vit E, received 1 Vit E soft gel + 2 pomegranate placebo tablets daily, and (d) placebo, received 2 pomegranate placebo tablets + 1 Vit E placebo soft gel daily. For group allocation, a stratified block randomization procedure based on sex, age, and HD duration was used. Each intervention product and its placebo had identical shape, color, size, and packaging. Consumption of PPE + Vit E significantly reduced the serum CRP level (mean change: -7.12 ± 4.59 mg l-1, P < 0.001) compared to other groups, while reduced levels of IL-6 (mean change: -2.19 ± 2.33 pg ml-1, P < 0.001), TNF-α (mean change: -2.41 ± 3.21 pg ml-1, P = 0.008), ICAM-1 (mean change: -64.2 ± 111.0 ng ml-1, P = 0.017), and VCAM-1 (mean change: -117.7 ± 177.1 ng ml-1, P = 0.002) were observed compared to the control. There was no significant difference in the P-selectin level among the groups. Consumption of PPE or Vit E alone significantly reduced the CRP level (mean change for PPE: -3.58 ± 5.41 mg l-1, P < 0.001; mean change for Vit E: -3.25 ± 8.29 mg l-1, P = 0.002) compared to the control. As a result, consumption of PPE in combination with Vit E enhanced the inflammatory status and endothelial function in HD patients.

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Brain tocopherol levels are associated with lower activated microglia density in elderly human cortex

Francisca A de Leeuw, Julie A Schneider, Sonal Agrawal, Sue E Leurgans, Martha Clare Morris

Alzheimers Dement (N Y) . 2020 Aug 24;6(1):e12021. doi: 10.1002/trc2.12021. eCollection 2020.

Abstract

Introduction: Higher brain tocopherol levels have been associated with lower levels of Alzheimer’s disease (AD) neuropathology; however, the underlying mechanisms are unclear.

Methods: We studied the relations of α- and γ-tocopherol brain levels to microglia density in 113 deceased participants from the Memory and Aging Project. We used linear regression analyses to examine associations between tocopherol levels and microglia densities in a basic model adjusted for age, sex, education, apolipoprotein E (APOE)ε4 genotype (any ε4 allele vs. none) , and post-mortem time interval, and a second model additionally adjusted for total amyloid load and neurofibrillary tangle severity.

Results: Higher α- and γ-tocopherol levels were associated with lower total and activated microglia density in cortical but not in subcortical brain regions. The association between cortical α-tocopherol and total microglia density remained statistically significant after adjusting for AD neuropathology.

Discussion: These results suggest that the relation between tocopherols and AD might be partly explained by the alleviating effects of tocopherols on microglia activation.

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