Vitamin E (Tocotrienol)

Cognitive impairment is a hallmark of Alzheimer's disease (AD) and represents a challenge for patients and the health care system worldwide. Current pharmacological treatments of AD focus on addressing symptom management, with limited options to prevent or slow cognitive decline. Vitamin E is one of the suggested antioxidants that has a protective role against cognitive impairment (CI). We aimed to systematically review the literature and evaluate the evidence on the role of vitamin E in cognitive function. Four databases, PubMed, Scopus, Web of Science, and Cochrane Library, were searched for clinical studies published between 2012 and 2022. Study selection and data extraction followed PRISMA guidelines, and eligible studies were classified into 3 classes: vitamin E supplements, dietary vitamin E, and multivitamins containing vitamin E. A total of 43 clinical studies involving 80,488 participants were identified. Of them, one on vitamin E supplement, 18 on dietary vitamin E, and 24 on multivitamins containing vitamin E. Overall, this systematic review suggest that vitamin E, particularly when consumed as a dietary component or multivitamin supplement with other vitamins, herbs, and minerals, is associated with a protective effect against cognitive impairment, probably mediated by the synergistic effect of other components of the dietary pattern or the multivitamin supplement. However, clinical studies specifically investigating the role of tocotrienols and non-α-tocopherols isoforms, or their combinations in CI, remain limited and warrant further investigations.

Adiponectin and leptin are pivotal adipokines regulating metabolic homeostasis, with dysregulation linked to obesity, insulin resistance, and related metabolic disorders. Vitamin E, a potent antioxidant, has been proposed to modulate adipokine secretion, but existing studies report inconsistent findings. This systematic review and meta-analysis aimed to evaluate the impact of vitamin E oral supplementation on serum adiponectin and leptin levels in adults. Systematic searches were performed in major electronic databases up to August 2025 to identify eligible randomized controlled trials (RCTs). Extracted data were analyzed using STATA, and pooled effect estimates were calculated as weighted mean differences (WMDs) with 95% confidence intervals (CIs). The pooled analysis of 10 RCTs (14 effect sizes) showed that vitamin E supplementation did not significantly alter serum adiponectin (WMD: 0.67 ng/mL; 95% CI: [-0.11 - 1.44]; p = 0.093) or leptin levels (WMD: -3.60 ng/mL; 95% CI: [-7.45 - 0.25]; p = 0.067). Subgroup analyses revealed that long-term supplementation (>12 wk) significantly increased adiponectin (WMD: 1.60 ng/mL; p = 0.039), particularly in patients with nonalcoholic fatty liver disease (NAFLD) (WMD: 4.28 ng/mL; p < 0.001). Additionally, vitamin E significantly reduced leptin levels in NAFLD patients (WMD: -5.45 ng/mL; p < 0.001). This meta-analysis found no significant overall effect of vitamin E on adiponectin and leptin levels; however, long-term supplementation appears beneficial, particularly in patients with NAFLD. Heterogeneity in study design, dosage, and duration highlights the need for further well-designed RCTs to clarify the metabolic and therapeutic roles of vitamin E. Plain Language Summary: Vitamin E supplementation did not significantly change serum concentrations of adiponectin or leptin levels in adults.In subgroup analysis, long-term supplementation (>12 weeks) significantly increased serum concentrations of adiponectin (1.59 ng/mL)In patients with nonalcoholic fatty liver disease (NAFLD), vitamin E supplementation significantly increased adiponectin (4.28 ng/mL) and reduced leptin (−5.45 ng/mL) serum concentrations.

Hyperlipidemia, characterized by elevated lipid levels, is a major risk factor for cardiovascular diseases (CVD), including atherosclerosis. Tocotrienol-rich fraction (TRF), a potent form of vitamin E, has demonstrated promising lipid-lowering effects due to its antioxidant and anti-inflammatory properties. This systematic review and meta-analysis aimed to evaluate the effects of TRF on lipid profiles in hyperlipidemic experimental animal models and to comparatively assessed their suitability for preclinical research. A total of eight eligible studies published between 2002 and 2024 were included. TRF significantly reduced total cholesterol (effect size = - 4.675, p < 0.0001), LDL (- 4.847, p < 0.0001), and triglycerides (- 4.736, p < 0.0001), while significantly increasing HDL (4.001, p < 0.0001), particularly in rats and mice. Meanwhile, comparative analysis showed that New Zealand white rabbits, hamsters, and genetically modified mice exhibit lipid metabolism profiles closer to humans and respond to lower TRF doses over shorter durations. Conversely, rats, though less prone to diet-induced atherosclerosis, responded well to higher doses over longer periods. However, the predominance of rat studies, absence of standard drug comparators, and variability in dosing and duration limit translational interpretation. Future studies should utilize physiologically relevant models and adopt standardized experimental protocols to better assess TRF's therapeutic potential in CVD management. © 2025. The Author(s).

BACKGROUND AND AIM: Multiple clinical trials have been conducted to study the potential benefits of vitamin E for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Despite available evidence, vitamin E is not widely used. This study aimed to assess the effect of vitamin E on serum markers of liver inflammation, specifically serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and histology, including resolution of metabolic dysfunction-associated steatohepatitis (MASH), in adult patients with MASLD. METHODS: A systematic literature search on randomized controlled trials published in English was conducted using electronic databases. Standardized mean difference (SMD) and mean difference (MD) were used for continuous outcomes, while risk ratio (RR) was used for dichotomous outcomes, with corresponding 95% confidence interval (CI). RESULTS: A total of eight studies were included in the qualitative synthesis while seven studies were included in the meta-analysis. Vitamin E significantly reduced serum ALT and AST levels with SMD of -0.82 (95% CI, -1.13 to -0.51) and -0.68 (95% CI, -0.94 to -0.41), respectively. Vitamin E significantly reduced steatosis, lobular inflammation, and hepatocyte ballooning with a MD of -0.60 (95% CI, -0.83 to -0.37), -0.34 (95% CI, -0.53 to -0.16), -0.32 (95% CI, -0.53 to -0.12), and increased MASH resolution with a RR of 1.9 (95%CI, 1.20 to 3.02). However, vitamin E did not reduce fibrosis, with a MD of -0.23 (95% CI, -0.51 to 0.05). CONCLUSION: Vitamin E resulted in significant improvement in serum markers of liver inflammation and histology in patients with MASLD. © 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

OBJECTIVE: To compare the efficacy of tocotrienol and tocopherol in the management of patients with atherosclerotic cardiovascular diseases. METHODS: The systematic review was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines 2020, and comprised literature search from 2002 till January 5, 2023, on PubMed, Google Scholar, Cochrane Library, Google, Wiley-Inter Science Library, Medline, SpringerLink, Taylor and Francis databases. The search was conducted using key words, such as: "tocopherol", "tocotrienol", "vitamin E", "dyslipidaemia", "cardiovascular diseases" "cardioprotective", "hypercholesterolemia" and "atherosclerosis" along with Boolean operators. Human clinical studies regarding the use of tocotrienol or tocopherol or comparison of its efficacy in patients having atherosclerosis, dyslipidaemia leading to cardiovascular diseases, and studies including details of efficacy of any of the four alpha, beta, gamma, delta isomers of tocopherol or tocotrienol were included. Pertinent data from the eligible studies was retrieved and reviewed. RESULTS: Of the 516 articles identified, 26 (5%) articles met eligibility criteria. Of them 5(19%) were subjected to detailed analysis. Tocotrienol showed significant anti-oxidant efficacy at (250 mg/d) by decreasing cholesterol and serum inflammatory biomarkers i.e C-reactive protein (40%), malondialdehyde (34%), gamma-glutamyl transferase (22%) (p<0.001). Total anti-oxidant status (TAS) levels raised 22% (p<0.001) and Inflammatory cytokines i.e resistin, interleukin (IL)-1, IL-12, Interferon-gamma were decreased 15-17% (p<0.05-0.01) respectively by tocotrienol. Several microRNA (miRNA-133a, miRNA-223, miRNA-214, miRNA-155) were modulated by δ-tocotrienol. Whereas, tocopherol showed heterogeneity of results by either decreasing or increasing the risk of mortality in atherosclerotic cardiovascular diseases. CONCLUSION: Compared to tocopherol, tocotrienol was found to be safe and potential candidate for improving cardiovascular health in the management of atherosclerotic cardiovascular diseases.

CONTEXT: Vitamin E, a well-known antioxidant with numerous positive effects on human health, encompasses tocotrienol-rich fraction (TRF), a natural variant abundant in palm oil. OBJECTIVE: This systematic review analyzed findings from randomized controlled trials published until 2022 to evaluate the health impacts of palm TRF. DATA SOURCES: A literature search was performed in Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, OVID Medline, SCOPUS, and Web of Science from inception until December 2022. Thirty studies involving 2646 patients, including both healthy individuals and those with underlying conditions, were identified. RESULTS: This review shows palm TRF to be a promising natural supplement against inflammation and lipid peroxidation and that can significantly enhance overall health. Additionally, the study underscores the necessity for further research to ascertain the optimal dosage, formulation, and duration of supplementation, maximizing the potential health advantages. CONCLUSION: This systematic review provides evidence supporting the health benefits associated with palm TRF. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020204070. © The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute.

Background: Utilizing the bioactive compounds found in pigmented rice might significantly reduce the risk of breast cancer. This study aims to systematically review existing literature on the benefit of Asian pigmented rice bioactive compounds and their implication in breast cancer. Methods: Searches of the literature were conducted in two databases (Scopus and PubMed) for a systematic review. The keywords resulted in a total of 407 articles, consisting of 103 PubMed and 304 Scopus articles. 32 manuscripts were excluded because the article was over 10 years old. After excluding book chapters and non-English languages, we had 278 potential articles to be reviewed. After checking and screening the title and abstract and eliminating duplicate articles, then 66 articles were obtained. After the selection and elimination of the full-text manuscripts, finally 10 of them which met the inclusion criteria. Result: The included studies in this review were entirely based in Asia. The year of publication ranged from 2013 to 2020. Half of included studies used black rice extract, two used red jasmine rice extracts, and three used Korean rice extracts (black, red, dark purple and brown rice). All studies were conducted in vitro and three studies were compared with in vivo tests on female mice. The pigmented rice is mainly black, red, and dark purple rice, and contains a variety of peonidin-3-glucoside, cyanidin-3-glucoside, γ-oryzanol, γ-tocotrienol, proanthocyanidin, cinnamic acid, and anthocyanins that may act as pro-apoptotic, anti-proliferative, and anti-metastasis of the breast cancer cells. Conclusion: Pigmented rice is a beneficial food which possessed bioactive compounds that may have significant potential concerning a breast cancer. Copyright: © 2023 Nafisah W et al.

There are a large number of studies that have reported benefits of tocotrienol-rich fraction (TRF) in various populations with different health status. To date, no systematic reviews have examined randomized controlled trials (RCTs) on the effect of TRF supplementations specifically in patients with type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis aim to examine the changes in HbA1c (glycated hemoglobin), blood pressure, and serum Hs-CRP (C-reactive protein high sensitivity) levels at post-TRF supplementation. Online databases including PubMed, Scopus, OVID Medline, and Cochrane Central Register of Controlled Trials were searched from inception until March 2023 for RCTs supplementing TRF in patients with T2DM. A total of 10 studies were included in the meta-analysis to estimate the pooled effect size. The Cochrane Risk-of-Bias (RoB) Assessment Tool was utilized to evaluate the RoB in individual studies. The meta-analysis revealed that TRF supplementation at a dosage of 250-400 mg significantly decreased HbA1c (-0.23, 95% CI: -0.44, -0.02, P < 0.05, n = 754), particularly where the intervention duration is less than 6 mo (-0.47%, 95% CI: -0.90, -0.05, P < 0.05, n = 126) and where duration of diabetes is less than 10 y (-0.37, 95% CI: -0.68, -0.07, P < 0.05, n = 83). There was no significant reduction in systolic and diastolic blood pressure and serum Hs-CRP (P > 0.05). The present meta-analysis demonstrated that supplementing with TRF in patients with T2DM decreased HbA1c but does not decrease systolic and diastolic blood pressure and serum Hs-CRP.

BACKGROUND: Tocotrienol, a type of vitamin E, is well known for its anti-cancer and other biological activities. This systematic review aims to summarize the involvement of endoplasmic reticulum stress (ERS) and subsequent unfolded protein response (UPR) as the underlying molecular mechanisms for the anticancer properties of tocotrienol. METHOD: A comprehensive literature search was performed in March 2023 using the PubMed, Scopus, Web of Science, and EMBASE databases. In vitro, in vivo, and human studies were considered. RESULT: A total of 840 articles were retrieved during the initial search, and 11 articles that fit the selection criteria were included for qualitative analysis. The current mechanistic findings are based solely on in vitro studies. Tocotrienol induces cancer cell growth arrest, autophagy, and cell death primarily through apoptosis but also through paraptosis-like cell death. Tocotrienol-rich fractions, including α-, γ- and δ-tocotrienols, induce ERS, as evidenced by upregulation of UPR markers and/or ERS-related apoptosis markers. Early endoplasmic reticulum calcium ion release, increased ceramide level, proteasomal inhibition, and upregulation of microRNA-190b were suggested to be essential in modulating tocotrienol-mediated ERS/UPR transduction. Nevertheless, the upstream molecular mechanism of tocotrienol-induced ERS is largely unknown. CONCLUSION: ERS and UPR are essential in modulating tocotrienol-mediated anti-cancer effects. Further investigation is needed to elucidate the upstream molecular mechanism of tocotrienol-mediated ERS.

OBJECTIVE: To evaluate and compare the pharmacokinetic parameters, especially bioavailability, of annatto-based tocotrienol with palm tocotrienol-rich fraction in healthy human volunteers for better therapeutic outcome. METHODS: The systematic review was conducted between April and August 2021 in accordance with the Preferred Reporting Items for Systematic Review and Meta Analysis guidelines, and comprised search on PubMed, Google Scholar, Pakmedinet and Google search engines for open-label or double-blind randomised controlled trials involving healthy human volunteers published till January 2021. Key words used included annatto-based tocotrienol, palm tocotrienol-rich fraction, absorption and bioavailability. Boolean operators were also used, like tocotrienol AND bioavailability, annatto tocotrienol AND pharmacokinetics. RESULTS: Of the 230 articles identified, 50(21.7%) articles met the eligibility criteria. Of them, 7(14%) were selected for data extraction and detailed analysis. Pharmacokinetic parameters of annatto-based tocotrienol were better than palm-derived tocotrienol. Oral administration of all the isomers of annatto-based tocotrienols resulted in dose-dependent increase in area under curve and plasma levels. Amongst all the isomers of annatto-based and palm-derived tocotrienol, delta isomer of annatto-based tocotrienol had the highest bioavailability with area under curve 7450±89 ng/ml, time to reach peak plasma levels 4 hours, maximum plasma concentration 1591±43 ng/nl and elimination half-life 2. 68 ±0.29 hrs. Pharmacokinetic parameters of delta isomer of annatto-based tocotrienol was greater than palm tocotrienol-rich fraction. CONCLUSIONS: Bioavailability of annatto-based tocotrienol was better than that of palm-derived tocotrienol-rich fraction. Delta isomer of annatto-based tocotrienol had the highest bioavailability amongst all isomers of tocotrienol.

Background: This study investigates the effects of a tocotrienol-enriched drink on oxidative damage and genomic stability in older adults over a 6-month period. Methods: A total of 67 participants (27 males and 40 females, mean age 60.45 ± 5.75 years) were enrolled in this double-blinded, two-arm, parallel randomized controlled trial. Baseline, mid-point, and end-point assessments were conducted to monitor various health parameters. Significant Group × Time interaction effects were observed for several key outcomes. Results: Group A demonstrated significantly better improvements in QOL-Psychological (p = 0.014, Partial Eta Squared = 0.153), suggesting a beneficial impact of tocotrienol supplementation on mental well-being. Additionally, Group A showed more favorable trends in TNF-α (p = 0.04), T-SOD (p = 0.04), catalase (p = 0.02), and telomerase (p = 0.02), suggesting potential antioxidant and genomic stability improvements over time. Conclusions: In a nutshell, tocotrienol supplementation may exert beneficial effects on psychological well-being, oxidative stress modulation, and genomic stability in aging populations.

PURPOSE: Tocotrienol-rich fraction (TRF), an antioxidant, can treat rheumatoid arthritis (RA) which is an autoimmune inflammatory illness that causes severe joint pain. Preclinical studies on rats reveal that TRF reduces RA. The clinical study on RA patients has not been extensively investigated. A six month, randomized, double-blind, placebo-controlled trial was conducted to evaluate the efficacy of Tocotrienol-Rich Fraction supplementation in reducing disease activity in patients with moderate-to-severe RA as measured by the Disease Activity Score-28 (DAS 28). METHODS: TRF supplementation was investigated in RA patients with an MDA-CRP score of 28 joints (DAS 28). In this RCT, 50 active RA patients were randomly assigned to receive 400 mg of TRF (TocovidTM) or placebo (palm olein) daily (1:1). Both groups had the same dose of conventional disease-modifying anti-rheumatic drugs (cDMARDS) throughout the intervention. Questionnaires, pain intensity measurements, and laboratory analysis were done at baseline and trial conclusion. Patients' data were collected after one, three, six months of supplementation and three months post-intervention. DAS28 joints, CRP, ESR, SJC, TJC, and total health scale (VAS) were measured. RESULTS: Daily supplementation with 400 mg of TRF for six months significantly improved clinical outcomes in patients with moderate-to-severe RA. TRF supplementation effectively reduced joint stiffness, edema, and discomfort, while also significantly lowering the DAS 28. Furthermore, TRF supplementation alleviated knee pain, improved physical function, and was well-tolerated with no reported side effects. CONCLUSION: This RCT shows that daily supplementation of 400 mg of TRF for six months lowers RA disease activity by reducing stiffness, edema, and joint discomfort. © 2025. Springer-Verlag GmbH Germany, part of Springer Nature.

Background: Tocotrienol has garnered significant attention due to its potent antioxidant and anti-inflammatory effects in ameliorating cardiovascular-related comorbidities. The present study aimed to elucidate the effects of tocotrienol-enriched oat supplementation on individuals with metabolic syndrome (MetS). Method: This was a randomized, double-blind, placebo-controlled human clinical trial. Patients with MetS were randomized to the tocotrienol-enriched oat (TO), oat (O) or control (C) groups. Both TO and O groups were supplemented twice daily for 12 weeks, while group C did not receive any intervention. Changes in the metabolic profile of individuals were considered as the primary endpoint. The secondary endpoints included the morphological assessment of nutritional and anthropometric parameters and health-related quality of life. Other measurements included compliance and tolerability to the study regime. Results: The rate of MetS remission in the TO and O groups was approximately twice than that in the control group (37.0% vs. 18.5%). After 12 weeks, the TO group showed significant improvements in the fasting blood glucose (-4.5%), blood pressure (systolic: -4.2%; diastolic: -5.3%), high density lipoprotein-cholesterol (HDL-C) (+34.1%), and triglyceride (-7.1%) (p < 0.05) levels. Group TO demonstrated an increase in muscle mass (+0.301 kg, p < 0.05) and reduced body fat (-0.775%, p < 0.05). Both the TO and O groups showed improvements in the overall HR-QoL, and the visual analogue scale (VAS) score. Conclusion: Twelve weeks of tocotrienol-enriched oat supplementation improved surrogate endpoints associated with MetS. This complementary dietary management approach may be more effective at alleviating MetS symptoms than the pharmacological approach alone and could be a safe dietary strategy for secondary prevention.

BACKGROUND: Vitamin E from palm oil, known as the tocotrienol-rich fraction (TRF), has been shown to have immune-enhancing activity. To date, only one dose of TRF (400 mg daily) has been tested in a clinical trial. The proposed study will evaluate the immune-enhancing activity effects of lower doses (200, 100 and 50 mg) in a clinical trial using an influenza vaccine as the immunological challenge. METHODS: A single-centre, randomised, parallel, double-blinded, placebo-controlled clinical trial with balance allocation involving five arms will be conducted. The healthy volunteers recruited will be randomly assigned to one of the arms, and they will be asked to take the respective supplements (400 mg, 200 mg, 100 mg, 50 mg of TRF or placebo) daily with their dinner. The volunteers will receive the influenza vaccine after four weeks. They will be asked to return to the study site four weeks later. A blood sample will be taken for the study at baseline, four and eight weeks. Primary outcome measures will be antibody levels to influenza, blood leucocyte profile and cytokine production. Secondary outcomes will be correlating plasma vitamin E levels with immune responses, plasma proteins and gene expression patterns. The findings from this study will be published in relevant peer-reviewed journals and presented at relevant national and international scientific meetings. CONCLUSIONS: The recent world events have created the awareness of having a healthy and functional immune system. Nutrition plays an important role in helping the immune system to function optimally. This study will show the effects of lower doses of TRF in boosting the immune response of healthy individuals and also elucidate the mechanisms through which TRF exerts its immune-enhancing effects. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) [ ACTRN12622000844741] dated 15 June 2022. PROTOCOL VERSION: 2. Copyright: © 2024 Radhakrishnan AK et al.

BACKGROUND: Childhood obesity is a growing concern, and non-alcoholic fatty liver disease (NAFLD) is a significant consequence. Currently, there are no approved drugs to treat NAFLD in children. However, a recent study explored the potential of vitamin E enriched with tocotrienol (TRF) as a powerful antioxidant for NAFLD. The aims of the present study were to investigate the effectiveness and safety of TRF in managing children with obesity and NAFLD. METHODS: A total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored. RESULTS: APO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045). CONCLUSION: The study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the futu

PURPOSE: Triplet chemotherapy might be more effective than doublet chemotherapy in metastatic colorectal cancer (mCRC), but it may also be marked by increased toxicity. To investigate whether δ-tocotrienol, a vitamin E analogue, with possible neuroprotective and anti-inflammatory effects, reduces the toxicity of triplet chemotherapy, we conducted a randomized, double-blind, placebo-controlled trial in mCRC patients receiving first-line 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI). MATERIAL AND METHODS: Seventy patients with mCRC were randomly assigned (1:1) to receive FOLFOXIRI plus either δ-tocotrienol or placebo at the Department of Oncology, Vejle Hospital, Denmark. Eligibility criteria were adenocarcinoma in the colon or rectum, age 18-75 years and ECOG performance status 0-1. FOLFOXIRI was given in eight cycles followed by four cycles of 5-fluorouracil. δ-tocotrienol 300 mg or placebo × 3 daily was added during chemotherapy and for a maximum of two years. The primary endpoint was time to hospitalization or death during treatment with chemotherapy. RESULTS: Median time to first hospitalization or death was 3.7 months in the placebo group (95% CI 1.93-not reached (NR)), and was NR in the δ-tocotrienol group (95% CI 1.87-NR) with a hazard ratio of 0.70 (95% CI 0.36-1.36). Grade 3-4 toxicities were uncommon in both groups, except for neutropenia, which occurred in 19 patients (58%) in the placebo group and 17 patients (50%) in the δ-tocotrienol group. There were no grade 3 or 4 peripheral sensory neuropathy. In the placebo group, 24 patients (71%) had oxaliplatin dose reductions compared to 17 patients (47%) in the δ-tocotrienol group (p = 0.047). CONCLUSION: The addition of δ-tocotrienol to FOLFOXIRI did not statistically significant prolong the time to first hospitalization or death compared to FOLFOXIRI plus placebo. Toxicity was manageable and not statistically different. There was a statistically significant difference in dose reductions of oxaliplatin pointing to a possible neuroprotective effect of δ-tocotrienol.

Neoadjuvant treatment of breast cancer is applied to an increasing extent, but treatment response varies and side effects pose a challenge. The vitamin E isoform delta-tocotrienol might enhance the efficacy of chemotherapy and reduce the risk of side effects. The aim of this study was to investigate the clinical effect of delta-tocotrienol combined with standard neoadjuvant treatment and the possible association between detectable circulating tumor DNA (ctDNA) during and after neoadjuvant treatment with pathological treatment response. This open-label, randomized phase II trial included 80 women with newly diagnosed, histologically verified breast cancer randomized to standard neoadjuvant treatment alone or in combination with delta-tocotrienol. There was no difference in the response rate or frequency of serious adverse events between the two arms. We developed a multiplex digital droplet polymerase chain reaction (ddPCR) assay for the detection of ctDNA in breast cancer patients that targets a combination of two methylations specific for breast tissue (LMX1B and ZNF296) and one cancer specific methylation (HOXA9). The sensitivity of the assay increased when the cancer specific marker was combined with the ones specific to breast tissue (p < 0.001). The results did not show any association between ctDNA status and pathological treatment response, neither at midterm nor before surgery. © 2023. The Author(s).

OBJECTIVE: To determine the effect of δ-tocotrienol and resveratrol mixture (TRM) supplementation in comparison to placebo for 24 weeks, on the relative expression of miRNAs (miRNA-130b-5p, miRNA-221-5p, miR-15b-5p, miRNA-122-5p, and miRNA-376b-5p) in patients with Metabolic syndrome (MetS). DESIGN: This randomized placebo-controlled trial was conducted at the tertiary care institute of the NUMS, Rawalpindi, Pakistan. A total of 82 adult MetS patients were enrolled and randomly grouped into the TRM group (n = 41) and the Placebo group (n = 41). Patients in the TRM group were given 400 mg capsules (δ-tocotrienol 250 mg; Resveratrol 150 mg) and placebo received (cellulose 400 mg capsule) twice daily for 24 weeks. RESULTS: The TRM supplementation revealed a significant (p < 0.001) upregulation of 3.05-fold in miRNA-130b-5p and 2.45-fold in miRNA-221-5p while miRNA-122-5p was downregulated by 2.22-fold as compared to placebo. No significant difference was observed in miRNA-15b-5p and miRNA-376b-5p. Moreover, TRM group participants with reverted MetS had significantly (p < 0.05) upregulated miRNA-130b-5p, miRNA-221-5p, and downregulated miRNA-122-5p relative to non-reverted patients with MetS. CONCLUSION: Daily TRM supplementation may improve metabolic syndrome by upregulated miR-130b-5p, which is involved in central obesity and inflammation, as well as miR-221-5p, which is involved in insulin resistance. Additionally, TRM downregulate of miRNA 122, which improved dyslipidemia.

MicroRNAs (miRNAs) play a key role in the regulation of genes for normal metabolism in the liver. Dysregulation of miRNAs is involved in the development and progression of non-alcoholic fatty liver disease (NAFLD). We aimed to explore changes in circulating miRNA expression in response to delta-tocotrienol (δT3) and alpha-tocopherol (αTF) supplementation and correlate them with relevant biochemical markers in patients with NAFLD. In total, 100 patients with NAFLD were randomized to either receive δT3 (n = 50) 300 mg or αTF (n = 50) 268 mg twice/day for 48 weeks. Plasma expression of miRNA-122, -21, -103a-2, -421, -375 and -34a were determined at baseline, 24 and 48 weeks of intervention using RT-qPCR. Both δT3 and αTF significantly downregulated expression of miRNA-122, -21, -103a-2, -421, -375 and -34a. Moreover, δT3 was more effective than αTF in reducing expression of miRNA-375 and -34a. A significant correlation was observed between miRNA expression and biochemical markers of hepatic steatosis, insulin resistance (IR), oxidative stress (OS), inflammation and apoptosis. δT3 and αTF exert hepato-protective effects by downregulating miRNAs involved in hepatic steatosis, IR, OS, inflammation and apoptosis in patients with NAFLD. Furthermore, δT3 has more pronounced effects than αTF in reducing miR-375 and miR-34a, which are linked to regulation of inflammation and apoptosis.

Background: Metabolic syndrome (MetS) is a cluster of central obesity, hypertension, hyperglycemia, and dyslipidemia. It is a global health issue with an increased risk of cardiovascular disease. Recently, a few natural products have been reported with promising anti-inflammatory and antioxidative effects. We aimed to evaluate the impact of δ-tocotrienol and resveratrol mixture (TRM) supplementation on cardiometabolic risk factors and biomarkers in patients with MetS. Methods: A randomized controlled trial was conducted at the hospitals of National University of Medical Sciences Rawalpindi, Pakistan. A total of 82 patients with MetS aged 18-60 years were enrolled based on International Diabetes Federation-2005 diagnostic criteria and randomly grouped into TRM (n = 41) and placebo (n = 41). Patients in the TRM group were given a 400 mg capsule (δ-tocotrienol 250 mg; resveratrol 150 mg), and a placebo (cellulose 400 mg) twice daily for 24 weeks. The biochemical tests were analyzed on ADVIA 1800 Chemistry® analyzer and inflammatory biomarkers by ELISA methods. Results: In the TRM group, a significant reduction in waist circumference, blood pressure, mean (95% confidence interval) of fasting plasma glucose -0.15 mmol/L (-0.22 to -0.08), serum triglyceride -0.32 mmol/L (-0.47 to -0.17), and increment in high-density lipoprotein cholesterol were observed as compared with placebo. TRM supplementation also improved biomarkers: high-sensitive C-reactive protein -0.61 mg/L (-0.89 to -0.33), interleukin-6-1.99 pg/mL (-2.50 to -1.48), tumor necrosis factor-α -2.19 pg/mL (-2.55 to -1.83), malondialdehyde -0.48 μmol/L (-0.65 to -0.30), and total antioxidant capacity 1.71 U/mL (1.29 to 2.13). Conclusion: TRM supplementations improved cardiometabolic risk factors and biomarkers of inflammation and oxidative stress without any significant side effects in the patients with MetS. Clinical Trials Registry: The clinical trial was registered in Sri Lanka Clinical Trials Registry (https://slctr.lk/trials/slctr-2019-021).

Gamma-tocotrienol (GT3) is one of the constituents of vitamin E that demonstrated significant radioprotective efficacy in murine and nonhuman primate (NHP) models. Considering the antioxidant activity of GT3 and its role in terminating lipid peroxidation, we hypothesize that mechanism of radioprotective effect of GT3 may involve the inhibition of irradiation-induced ferroptosis-a form of regulated cell death characterized by excessive, iron-dependent, peroxidation of lipids in cellular membranes. To test this hypothesis, the metabolomic and proteomic data from serum samples of GT3- or vehicle-treated NHPs exposed to 12 Gy (partial- or total-body) radiation was analyzed with focus on lipid peroxidation markers and proteins involved in iron metabolism. Four secondary lipid peroxidation products were identified including 4-oxo-2-nonenal (4-ONE), 4-hydroperoxy-2-nonenal (4-HPNE), 3,4-epoxynonanal (3,4-ENA), and trans-4,5-epoxy-(2E)-decenal (4,5-EDE). In vehicle-treated animals, their concentrations increased significantly as soon as 4 h after irradiation and then gradually declined. GT3 treatment mitigated this radiation-induced increase. In addition to lipid peroxidation products, similar patterns of change were observed for several polyunsaturated, monounsaturated, and saturated fatty acids as well as amino acids such as lysine and its derivatives. Taken together, these metabolomic changes suggest that irradiation induces cellular membrane damage through enhanced lipid peroxidation, while GT3 exerts a protective effect against this process. In addition, GT3 increased serum levels of haptoglobin and hemopexin-two plasma scavenger proteins that play complementary protective roles in iron and heme homeostasis. Although the present study does not conclusively demonstrate that GT3 mediates radioprotection via inhibition of ferroptosis, the data suggest that GT3 limits membrane damage and reduces susceptibility to ferroptosis by enhancing iron and heme scavenging. Further investigation into the interaction between GT3 and key components of ferroptosis following exposure to ionizing radiation is therefore warranted.

BACKGROUND/AIM: Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, have been reported to exert anti-cancer effects. Recently, sterol regulatory element-binding protein 2 (SREBP2) has been shown to be involved in statin resistance in cancer cells. Inhibiting SREBP2 enhances the anti-cancer effects of statins in several cancer cell lines. Three-dimensional (3D) cultured cells are known to exhibit different drug sensitivities compared to two-dimensional (2D) cultured cells. In this study, we evaluated the cytotoxicity induced by combined treatment with atorvastatin and SREBP2 inhibitors in 2D and 3D cultured colorectal cancer (CRC) cells. MATERIALS AND METHODS: 25-Hydroxycholesterol and δ-tocotrienol were used as SREBP2 inhibitors. The viability of 2D and 3D cultured cells was measured using the MTT assay and the CellTiter-Glo® 3D Cell Viability Assay. Gene expression levels were analyzed by qRT-PCR. Protein levels were determined by western blotting. RESULTS: 3D cultured cells exhibited lower statin sensitivity compared to 2D cultured cells. The expression levels of SREBP2 and its target genes differed between 2D and 3D cultured cells. In 2D cultured cells, SREBP2 inhibitors blocked atorvastatin-induced SREBP2 activation and enhanced the cytotoxicity of atorvastatin. However, in 3D cultured cells, SREBP2 inhibitors failed to enhance atorvastatin-induced cytotoxicity, although they successfully suppressed atorvastatin-induced SREBP2 activation. CONCLUSION: The efficacy of a combined statin and SREBP2 inhibitors strategy differs substantially between 2D and 3D cultured CRC cells. 3D cultured cells may possess an SREBP2-independent mechanism of statin resistance that differs from that of 2D cultured cells.

BACKGROUND/AIM: Bortezomib, a proteasome inhibitor, exhibits limited efficacy against colorectal cancer (CRC); therefore, strategies to enhance bortezomib sensitivity in CRC are required. Previous studies have reported that 6-O-carboxypropyl-α-tocotrienol (T3E) enhances bortezomib sensitivity in several cancer cells. In this study, we investigated the anticancer effect of combined treatment with T3E and bortezomib in CRC cells. MATERIALS AND METHODS: Cells were treated with T3E and bortezomib in combination, and cell viability, apoptosis, proteasome activity, and endoplasmic reticulum stress induction were evaluated. In addition, we assessed the effects of T3E on the activation of nuclear factor erythroid 2-related factor 1 (NRF1) and nuclear factor erythroid 2-related factor 3 (NRF3), which are involved in bortezomib resistance. RESULTS: The combined treatment with T3E and bortezomib induced more potent cytotoxicity against CRC cells than either treatment alone. Furthermore, T3E enhanced bortezomib-induced proteasome inhibition and endoplasmic reticulum stress. Notably, the combined treatment with T3E and bortezomib did not induce cytotoxicity in non-cancerous cells. We also observed that T3E did not suppress NRF1 and NRF3, which are resistance factors to bortezomib. Rather, T3E sustained the activation of NRF1 induced by bortezomib. CONCLUSION: T3E enhanced the anticancer effects of bortezomib without suppressing NRF1 and NRF3. T3E may be a promising compound for expanding the therapeutic use of bortezomib in CRC.

Microalgae such as Chlorella vulgaris are gaining attention as sustainable and nutritionally valuable feed ingredients, with the potential to partially replace soybean meal in broiler diets. However, dietary inclusion of 20% C. vulgaris has been attempted, but negatively affected growth performance due to limited digestibility. This study examined the effects of including 20% Chlorella vulgaris (C. vulgaris) in broiler diets, either alone, extruded, or combined with 0.3% pancreatin supplementation, on blood parameters, plasma biochemistry, and liver composition. From day 7 to 35 of age, four dietary treatments were applied: a standard control diet (CTR), a diet with 20% C. vulgaris (CV), a diet with 20% C. vulgaris supplemented with 0.3% pancreatin (CVEN), and a diet containing 20% extruded C. vulgaris (CVEX). Findings showed that C. vulgaris dietary incorporation, regardless of treatment, led to a significant reduction in growth performance and an increase in specific plasma lipid parameters (p < 0.05) when compared with the CTR diet. However, in CVEN animals, such adverse effects were mitigated, resulting in improvements in final body weight and average body weight gain. Dietary inclusion of C. vulgaris modulated hepatic composition without affecting total hepatic lipid content. Chlorella-based diets lowered PUFA/SFA and n-6/n-3 ratios and increased specific fatty acids, particularly C16:0 and 20:5n-3. Hepatic cholesterol and antioxidant-related compounds, including β-carotene, chlorophyll a-like pigments, α-tocopherol, and, in untreated C. vulgaris, γ-tocopherol and γ-tocotrienol, were increased, and multivariate analysis clearly separated CTR diet-fed birds from Chlorella-fed groups. Multivariate analysis identified treatment-related patterns in both blood and liver samples. PCA of plasma parameters clearly separated all dietary groups. Conversely, hepatic PCA distinguished control from C. vulgaris treatments, which clustered together regardless of processing or enzyme supplementation, indicating consistent liver responses to microalgae dietary inclusion. Overall, these findings indicate that a 20% inclusion level of C. vulgaris requires digestibility-enhanc

Neuroinflammation is a chronic inflammatory response that contributes to synaptic dysfunction and neuronal damage, it is a common feature among various neurodegenerative diseases such as Alzheimer's Disease (AD), Parkinson's Disease (PD) and Huntington's Disease (HD). Tocotrienol-rich fraction (TRF) is a form of vitamin E that is known for its anti-inflammatory, antioxidant and neuroprotective properties. Yet, it has not been adequately investigated in both cellular and animal neuroinflammation models. In this study, the potential therapeutic effects of TRF were investigated in-vitro using BV2 microglial cells and also in-vivo in a pilot study using Sprague Dawley rats. TRF at 5 and 10 µg/mL were found to reduce nitric oxide (NO) and reactive oxygen species (ROS) levels. Furthermore, in-vivo treatment with TRF significantly increases the recognition index implying improvement in cognition ability. Gene expression analysis showed downregulation of RelA, TNF-α and IL-6 while NFE2L2 and BDNF were upregulated. These findings suggests that TRF may help mitigates neuroinflammation and oxidative stress, indicating its potential as a candidature for further investigation in neurodegenerative diseases associated with chronic neuroinflammation. © 2026. The Author(s).

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic small vessel disease, causing recurrent stroke and progressive cognitive decline, with no disease-modifying treatment available. Tocotrienols, members of the vitamin E family, have demonstrated neuroprotective effects in preclinical studies. We evaluated the efficacy and safety of a tocotrienol-rich vitamin E complex (HOV12020) in patients with CADASIL. METHODS: In this randomised, double-blind, placebo-controlled trial, 51 patients (median age (range): 58 years (43-73 y), male (n = 24, 47%)) with genetically confirmed CADASIL were assigned (1:1) to receive HOV12020 or placebo for 24 months. The primary endpoint was treatment failure, defined as any stroke occurrence, disability progression, or cognitive decline, and was analysed within a Bayesian framework to estimate the probability of treatment benefit. The secondary endpoints included the time to the first failure event, changes in clinical and cognitive scores, and safety. Exploratory MRI endpoints were analysed using quantile regression with Wilcoxon rank-sum sensitivity tests. EudraCT 2019-002867-23; ClinicalTrials.govNCT04658823. FINDINGS: Patients were enrolled in the trial between 15/01/2021 and 11/02/2022. Treatment failure occurred in 68.0% of patients in the HOV12020 group and 61.5% in the placebo group, both exceeding the 40% placebo event rate that was initially expected. Bayesian analysis indicated a low posterior probability of benefit, meeting the predefined futility criteria. No significant differences were observed in the secondary endpoints or exploratory MRI measurements. HOV12020 was well tolerated, with an excellent safety profile and no excess of adverse events. INTERPRETATION: HOV12020 did not reduce clinical progression in CADASIL over 24 months. Bayesian analysis confirmed futility, suggesting that tocotrienol-rich vitamin E is unlikely to confer benefits in the advanced stages of the disease. This rigorously designed trial illustrated the potential of Bayesian randomised studies in a rare, slowly progressive cerebral small vessel disease as CAD

Lentil seeds are packed with essential nutrients and health-promoting phytochemicals, yet the dual effect of biopriming and germination on their chemical and functional properties is not fully resolved. Thus, the current study investigates the impact of bacterial biopriming (B. pomilus and E. hormaechei) followed by germination on reshaping the chemical and biological attributes of lentil seeds using UPLC-MS metabolomics and chemometrics approaches. Sixty-nine metabolites spanning amino acids, phenolic acids, flavonoids, proanthocyanidins, gibberellins, and fatty acids were annotated. OPLS-DA analysis exhibited an obvious separation pattern among the samples reflecting their chemical heterogeneity, where the compounds mainly gallocatechin, phloretin, α-tocotrienol, and eicosapentanoic acid were significantly augmented in sprouted (unprimed) samples, while the sprouted samples bioprimed with B. pomilus witnessed a striking accumulation of carboxyvanillic acid, resveratrol, isorhamnetin, gibberellic acid, and gibberellin A4. Further, E. hormaechei biopriming significantly fortified rosmarinic acid, syringic acid, quercetin, apigenin, and linolenic acid. Functionally, bioprimed sprouts displayed superior α-amylase and α-glucosidase inhibition and enhanced glucose uptake relative to raw and unprimed germinated seeds, aligning with higher levels of sinapic acid, apigenin, isorhamnetin, and linolenic acid. These findings position microbe-assisted germination as a sustainable strategy to fortify the functional attributes of lentil seeds for nutraceutical applications. © 2026. The Author(s).

Objectives: Cerebrovascular function declines with normal ageing, and the antioxidant and anti-inflammatory properties of Vitamin E may maintain or improve this. The aim of this systematic review is to evaluate the effect of vitamin E on cerebrovascular function in both pre-clinical and clinical populations.Methods: Six databases (PubMed, MEDLINE, Web of Science, Scopus, ScienceDirect, and CINAHL) were searched in 2024 using keywords such as 'vitamin E', tocopherol, tocotrienol, 'cerebrovascular function', and related medical subject heading terms.Results: Of the 335 records returned, no clinical studies were identified. Ten pre-clinical studies met the inclusion criteria and were included for analysis. Due to heterogeneity in study designs and outcomes, a meta-analysis was not performed. Across animal models of cerebral ischaemia and haemorrhagic hypoperfusion, vitamin E supplementation improved cerebral blood flow, reduced intracranial pressure, and enhanced cerebrovascular responsiveness, thus reflecting improved cerebrovascular function. Furthermore, studies examining platelet aggregation reported delayed thrombus formation, likely mediated by reduced oxidative stress and improved endothelial function and nitric oxide bioavailability. However, with heterogeneous outcomes from pre-clinical studies and a lack of clinical studies, the translatability of data to the effect of chronic consumption on cerebrovascular function in humans is limited.Discussion: Pre-clinical data suggest that the antioxidant capacity of vitamin E and its regulatory effect on platelet aggregation may improve cerebrovascular function. However, the absence of clinical data limits translation to human populations. Future well-designed studies in older adults are warranted to determine whether vitamin E supplementation can preserve or improve cerebrovascular function throughout the ageing process.

INTRODUCTION: Breast cancer is a highly prevalent malignancy in women, necessitating the discovery of novel therapeutic approaches. Researchers have focused on various medicinal plants for their therapeutic benefits, including anti-carcinogenic properties. These plants are abundant in nature, generally safe, cost-effective, and exhibit lower toxicity compared to currently available synthetic cancer treatments. MATERIALS AND METHODS: This study employed a bioinformatic approach to identify potential biomarkers and signaling pathways. Analysis of Gene Expression Omnibus (GEO) dataset GSE21946 (Gamma tocotrienol-treated MCF-7 cells) revealed 250 differentially expressed genes (DEGs), including 175 upregulated and 75 downregulated genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses identified significant functional pathways and candidate genes. Protein- protein interaction (PPI) network analysis further revealed four key gene candidates: EGR1, JUN, SREBF1, and TGIF1. RESULTS: This study also evaluated the identification of potent bioactive compounds through computational screening of 10 phytochemicals with established anticancer properties to inform the development of effective breast cancer therapies. Using the SwissADME and admetSAR online servers, these phytochemicals were assessed for pharmacokinetic properties and pharmacophore features. DISCUSSION: Docking studies were conducted with the four hub gene targets. The results indicated that Quercetin (-6.1 to -7.7 Kcal/mol) and Kaempferol (-6.0 to -7.3 Kcal/mol) exhibited the highest negative binding affinities and strongest H-bond interactions with all four targeted proteins when compared to FDA-approved standard drugs Alpelisib, Capivasertib, Elacestrant, and Silibinin. CONCLUSION: These findings may facilitate the development of traditional medicinebased therapeutic strategies and provide insights for potential lead optimization in breast cancer drug discovery.

Osteocytes function as central regulators of skeletal health by acting as mechanosensors that control bone remodelling mediated by osteoblasts and osteoclasts. Disrupted osteocyte function, often driven by oxidative stress and linked to ageing and osteoporosis, contributes to pathological bone remodelling. Tocotrienols (TTs), a family of vitamin E, are intensively investigated for their bone-protective effects, with mechanisms that involve reducing intracellular reactive oxygen species, enhancing antioxidant defences, and modulating signalling pathways of bone remodelling. Preliminary studies suggest that TTs exert protective and anabolic effects by influencing osteocytes, including shielding them from oxidative damage. In vivo models using ovariectomised or metabolic syndrome rats demonstrated that TT supplementation modulated key osteocyte-secreted factors, including sclerostin, dentin matrix protein 1, Dickkopf-related protein 1, fibroblast growth factor 23, and receptor activator of nuclear factor κB ligand. However, the current evidence is limited by the use of models that may not fully represent degenerative osteoporosis, restricted dose-dependent studies, and the challenge of real-time in vivo monitoring. This perspective summarises the reported effects of TTs on osteocytes' function and emphasises the critical need for future research to employ more representative animal models, advanced imaging techniques, and complex 3D co-culture or bone explant systems to accurately define the mechanism of action of TTs and their resulting functional outcomes on overall bone quality.

BACKGROUND: In recent years, androgenetic alopecia (AGA) has emerged as a significant public health concern due to its high prevalence and progressive nature. In addition to progressive scalp thinning and hair loss, patients often experience psychological distress and diminished quality of life. While standard treatments such as finasteride and minoxidil are effective, their side effects and adherence issues limit long-term use, making the exploration of safe and accessible intervention strategies essential. Dietary supplements, claimed to promote hair growth by inhibiting androgen pathways and improving the follicular microenvironment, have become an attractive adjunct for both clinicians and patients due to their low cost and ease of use. However, existing studies have limitations, including the diversity of supplements, small sample sizes, and the lack of direct comparisons among different supplements, making it unclear how they compare in terms of efficacy and safety. This study aims to use a network meta-analysis (NMA) to compare the effectiveness and safety of various dietary supplements based on outcomes such as hair density and terminal hair density, providing evidence-based support for clinical decision-making. METHODS: A systematic search was conducted in English-language databases such as PubMed, Cochrane Library, Embase, and Web of Science for randomized controlled trials (RCTs) investigating the use of dietary supplements for treating AGA. Stata 16.0 software was used for network meta-analysis, and Revman 5.4 software was utilized for evaluating study quality and bias risk; additionally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was applied to rate the certainty (quali

Among the distressing side effects of cancer treatments, hair loss is one of the most disturbing for the quality of life and adherence to therapy in breast cancer patients. Many patients take nutritional supplements to prevent hair loss or enhance regrowth. Based on their mechanism and timing of use, nutritional supplements could be divided into safe, cautious, debated, and contraindicated categories. Non-contraindicated supplements generally include safe supplements like vitamin D, which is not known to interfere with cancer treatments. Those that are contraindicated include phytoestrogens and compounds affecting estrogen pathways because of the risk of stimulating tumor growth in cancers sensitive to estrogen. Antioxidants like tocotrienols and resveratrol are given judiciously because of potential interference with cancer therapies dependent on reactive oxygen species. Supplements debated, including nicotinamide, folate, and iron, pose a risk by promoting cellular proliferation or altering the tumor microenvironment. Biotin is nontox

BACKGROUND: Hair loss/thinning is a common side effect of tamoxifen in estrogen receptor (ER) positive breast cancer therapy. Some nutraceuticals known to promote hair growth are avoided during breast cancer therapy for fear of phytoestrogenic activity. However, not all botanical ingredients have similarities to estrogens, and in fact, no information exists as to the true interaction of these ingredients with tamoxifen. Therefore, this study sought to ascertain the effect of nutraceuticals (+/- estrogen/tamoxifen), on proliferation of breast cancer cells and the relative expression of ERα/β. METHODS: Kelp, Astaxanthin, Saw Palmetto, Tocotrienols, Maca, Horsetail, Resveratrol, Curcumin and Ashwagandha were assessed on proliferation of MCF7, T47D and BT483 breast cancer cell lines +/- 17β-estradiol and tamoxifen. Each extract was analysed by high performance liquid chromatography (HPLC) prior to use. Cellular ERα and ERβ expression was assessed by qRT-PCR and western blot. Changes in the cellular localisation of ERα:ERβ and their ratio following incubation with the nutraceuticals was confirmed by immunocytochemistry. RESULTS: Estradiol stimulated DNA synthesis in three different breast cancer cell lines: MCF7, T47D and BT483, which was inhibited by tamoxifen; this was mirrored by a specific ERa agonist in T47D and BT483 cells. Overall, nutraceuticals did not interfere with tamoxifen inhibition of estrogen; some even induced further inhibition when combined with tamoxifen. The ERα:ERβ ratio was higher at mRNA and protein level in all cell lines. However, incubation with nutraceuticals induced a shift to higher ERβ expression and a localization of

Comment in JAMA Dermatol. 2023 Aug 1;159(8):892-893. doi: 10.1001/jamadermatol.2023.1779. JAMA Dermatol. 2023 Aug 1;159(8):893. doi: 10.1001/jamadermatol.2023.1762. JAMA Dermatol. 2023 Aug 1;159(8):891-892. doi: 10.1001/jamadermatol.2023.1776. IMPORTANCE: Despite the widespread use of nutritional supplements and dietary interventions for treating hair loss, the safety and effectiveness of available products remain unclear. OBJECTIVE: To evaluate and compile the findings of all dietary and nutritional interventions for treatment of hair loss among individuals without a known baseline nutritional deficiency. EVIDENCE REVIEW: The MEDLINE, Embase, and CINAHL databases were searched from inception through October 20, 2021, to identify articles written in English with original findings from investigations of dietary and nutritional interventions in individuals with alopecia or hair loss without a known baseline nutritional deficiency. Quality was assessed with Oxford Centre for Evidence Based Medicine criteria. Outcomes of interest were disease course, both objectively and subjectively measured. Data were evaluated from January 3 to 11, 2022. FINDINGS: The database searches yielded 6347 citations to which 11 articles from reference lists were added. Of this total, 30 articles were included: 17 randomized clinical trials (RCTs), 11 clinical studies (non-RCT), and 2 case series studies. No diet-based interventional studies met inclusion criteria. Studies of nutritional interventions with the highest-quality evidence showed the potential benefit

Unlike the epidermis, which regenerates continually, hair follicles anchored in the subcutis periodically regenerate by spontaneous repetitive cycles of growth (anagen), degeneration (catagen), and rest (telogen). The loss of hair follicles in response to injuries or pathologies such as alopecia endangers certain inherent functions of the skin. Thus, it is of interest to understand mechanisms underlying follicular regeneration in adults. In this work, a phytochemical rich in the natural vitamin E tocotrienol (TRF) served as a productive tool to unveil a novel epidermal pathway of hair follicular regeneration. Topical

The potential hair growth-promoting activity of rice bran supercritical CO2 extract (RB-SCE) and major components of RB-SCE, linoleic acid, policosanol, γ-oryzanol, and γ-tocotrienol, were evaluated with the histological morphology and mRNA expression levels of cell growth factors using real-time reverse transcriptase-polymerase chain reaction (PCR) in C57BL/6 mice. RB-SCE showed hair growth-promoting potential to a similar extent as 3% minoxidil, showing that the hair follicles were induced to be in the anagen stage. The numbers of the hair follicles were significantly increased. In addition, mRNA expression levels of vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and keratinocyte growth factor (KGF) were also significantly increased and that of transforming growth factor-β (TGF-β) decreased in RB-SCE-treated groups. Among the major components of RB-SCE, linoleic acid and γ-oryzanol induced the formation of hair follicles according to examination of histological morphology and mRNA expression levels of cell growth factors. In conclusion, our results demonstrate that RB-SCE, particularly linoleic acid and γ-oryzanol, promotes hair growth and suggests RB-SCE can be applied as hair loss treatment.

Studies have shown an association between oxidative stress and alopecia. Patients with alopecia generally exhibit lower levels of antioxidants in their scalp area as well as a higher lipid peroxidation index. Tocotrienols belong to the vitamin E family and are known to be potent antioxidants. Hence, a study was conducted to investigate the effect of tocotrienol supplementation on hair growth in volunteers suffering from hair loss. Twenty one volunteers were randomly assigned to orally receive 100 mg of mixed tocotrienols daily while 17 volunteers were assigned to receive placebo capsule orally. The volunteers were monitored for the number of hairs in a pre-determined scalp area as well as the weight of 20 strands of 1 cm length hair clippings at 0 (before supplementation), 4 and 8 months. The number of hairs of the volunteers in the tocotrienol supplementation group increased significantly as compared to the placebo group, with the former recording a 34.5% increase at the end of the 8-month supplementation as compared to a 0.1% decrease for the latter. Nevertheless, the cumulative weight of 20 strands of hair clippings did not differ much from the baseline for both supplementation groups at the end of the study period. In conclusion, this trial demonstrated that supplementation with tocotrienol capsules increases hair number in volunteers suffering from hair loss as compared to the placebo group. This observed effect was most likely to be due to the antioxidant activity of tocotrienols that helped to reduce lipid peroxidation and oxidative stress in the scalp, which are reported to be associated with alopecia. Publisher: Kajian telah menunjukkan bahawa terdapat perhubungan di antara oksidatif stres dengan keguguran rambut. Pesakit yang mengalami keguguran rambut secara amnya mempamerkan paras a