Serum Metabolomic Response to Low- And High-Dose Vitamin E Supplementation in Two Randomized Controlled Trials

Jiaqi Huang, Howard N Hodis, Stephanie J Weinstein, Wendy J Mack, Joshua N Sampson, Alison M Mondul, Demetrius Albanes

Cancer Epidemiol Biomarkers Prev . 2020 Apr 20. doi: 10.1158/1055-9965.EPI-20-0187.

Abstract

Background: Vitamin E is an essential micronutrient and critical human antioxidant previously tested for cancer preventative effects with conflicting clinical trial results that have yet to be explained biologically.

Methods: We examined baseline and on-trial serum samples for 154 men randomly assigned to receive 400 IU vitamin E (as alpha-tocopheryl acetate; ATA) or placebo daily in the Vitamin E Atherosclerosis Prevention Study (VEAPS), and for 100 men administered 50 IU ATA or placebo daily in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC). Over 970 metabolites were identified using ultrahigh-performance LC/MS-MS. Linear regression models estimated the change in serum metabolites of men supplemented with vitamin E versus those receiving placebo in VEAPS as compared with ATBC.

Results: Serum alpha-carboxyethyl hydrochroman (CEHC) sulfate, alpha-tocopherol, and beta/gamma-tocopherol were significantly altered by ATA supplementation in both trials (all P values ≤5.1 × 10^-5, the Bonferroni multiple comparisons corrected statistical threshold). Serum C₂₂ lactone sulfate was significantly decreased in response to the high-dose vitamin E in VEAPS (β = -0.70, P = 8.1 × 10^-6), but not altered by the low dose in ATBC (β = -0.17, P = 0.4). In addition, changes in androgenic steroid metabolites were strongly correlated with the vitamin E supplement-associated change in C₂₂ lactone sulfate only in the VEAPS trial.

Conclusions: We found evidence of a dose-dependent vitamin E supplementation effect on a novel C₂₂ lactone sulfate compound that was correlated with several androgenic steroids.

Impact: Our data add information on a differential hormonal response based on vitamin E dose that could have direct relevance to opposing prostate cancer incidence results from previous large controlled trials.

Eric John Visser, Peter D Drummond, Julia L A Lee-Visser

Pain Pract . 2020 Apr 19. doi: 10.1111/papr.12902.

Abstract

Objective: To investigate the preventive effects of a combined antioxidant drug (N-acetylcysteine, vitamin E, and vitamin C [NEC]) on migraine outcomes. Migraine is characterized by increased oxidative stress and neurogenic inflammation in the brain; therefore, antioxidants may have a migraine preventive effect.

Design: Randomized, double-blind, sham-controlled pilot study.

Setting: Australian community.

Subjects: Adults reporting 2 to 8 migraines per month for at least a year.

Methods: After a 1-month baseline period, 35 subjects completed 3 months of treatment with NEC (n = 19) or sham (n = 16) capsules. The primary outcome was the difference in mean number of headaches per month between baseline and final month of the trial for NEC and sham groups; secondary outcomes are listed below.

Results: For NEC there was a significant decrease in mean number of headaches by 3.0 per month (P = 0.004) compared with 1.4 for sham (P = 0.073); there was no significant difference in these changes between the 2 groups (P = 0.052). Average monthly headache (P = 0.041) and migraine frequency (P = 0.018) were significantly less for NEC vs. sham. In NEC subjects, there was a significant decrease in average monthly migraine days (-3.1), moderate/severe headache days (-3.2), migraine duration, headache pain scores, and acute headache medication use.

Conclusions: This is the first randomized controlled trial to find that combined antioxidant therapy with NEC reduces headaches and migraines in adult migraineurs. Given the limitations of this pilot study, an adequately powered randomized controlled trial is planned to further investigate antioxidant prophylaxis in migraine.

Dazhe James Cao, Kim Aldy, Stephanie Hsu, Molly McGetrick, Guido Verbeck, Imesha De Silva, Sing-Yi Feng

J Med Toxicol . 2020 Apr 16. doi: 10.1007/s13181-020-00772-w.

Abstract

Electronic cigarettes (e-cigarettes) are battery-operated devices to insufflate nicotine or other psychoactive e-liquid aerosols. Despite initial claims of e-cigarettes as a nicotine-cessation device, aggressive marketing of e-cigarettes has led to an explosion in adolescents’ and young adults’ use over the last few years. Coupled with a lack of adequate investigation and regulation of e-cigarettes, the USA is facing an outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) starting in mid-2019. While little long-term health hazard data are available, the components and constituents of e-cigarettes may adversely impact health. Propylene glycol and glycerin are humectants (water-retaining excipients) that generate pulmonary irritants and carcinogenic carbonyl compounds (e.g., formaldehyde, acetaldehyde, and acrolein) when heated in e-cigarettes. Metals contained in heating coils and cartridge casings may leach metals such as aluminum, chromium, iron, lead, manganese, nickel, and tin. Flavoring agents are considered safe for ingestion but lack safety data for inhalational exposures. Diacetyl, a common buttery flavoring agent, has known pulmonary toxicity with inhalational exposures leading to bronchiolitis obliterans. In 2019, clusters of lung injury associated with e-cigarette use were identified in Wisconsin and Illinois. Patients with EVALI present with a constellation of respiratory, gastrointestinal, and constitutional symptoms. Radiographically, patients have bilateral ground glass opacifications. As of February 18, 2020, the Centers for Disease Control has identified 2807 hospitalized patients diagnosed with either “confirmed” or “probable” EVALI in the US. Currently, vitamin E acetate (VEA) used as a diluent in tetrahydrocannabinol vape cartridges is implicated in EVALI. VEA cuts tetrahydrocannabinol oil without changing the appearance or viscosity. When inhaled, pulmonary tissue lacks the mechanism to metabolize and absorb VEA, which may lead to its accumulation. While most EVALI patients were hospitalized, treatment remains largely supportive, and use of corticosteroids has been associated with clinical improvement. The outbreak of EVALI highlights the need for regulation of e-cigarette devices and e-liquids. Clinicians need to be aware of the health hazards of e-cigarettes and be vigilant in asking about vaping.

Takano M, Higa S, Furuichi Y, Naka R, Yumoto R

Drug Metab Pharmacokinet. 2020 Apr;35(2):214-219. doi: 10.1016/j.dmpk.2019.12.001. Epub 2019 Dec 20

Abstract

Effect of long-term treatment with cigarette smoke extract (CSE) on the function and expression of P-glycoprotein (P-gp) in lung alveolar epithelial cells was examined using A549/P-gp cell line expressing P-gp. CSE treatment suppressed P-gp activity in a concentration- and treatment time-dependent manner. The suppression of P-gp activity by CSE was irreversible for at least 96 h after removal of CSE. In addition, CSE treatment suppressed the expression of P-gp mRNA and protein. In order to understand the mechanisms underlying P-gp suppression by CSE, the role of reactive oxygen species (ROS) was examined. CSE treatment increased intracellular ROS level, and suppressed catalase activity. α-Tocopherol suppressed ROS production by CSE, and ameliorated the suppression of P-gp activity by CSE, suggesting that ROS is involved in CSE-induced suppression of P-gp. The role of intracellular signaling pathways such as the nuclear factor κB and mitogen-activated protein kinase pathways was also examined. Among these pathways, the involvement of extracellular signal-regulated kinase (ERK) pathway was suggested. Taken together, long-term CSE treatment may suppress P-gp via modulation of ROS level and ERK pathway in alveolar epithelial cells.

Ong TS, Chu CC1 Tan CP, Nyam KL

J Oleo Sci. 2020;69(4):297-306. doi: 10.5650/jos.ess19250.

Abstract

Plant seed oil is often incorporated into the cream emulsions to provide multifunctional effects on the skin. In the current study, pumpkin seed oil (PSO) was used to develop a stable oil-in-water emulsion. The study aimed to optimise PSO cream formulation and determine the synergistic effect of the PSO with vitamin E oil added. The physical properties, antioxidant activities and storage stability of the formulations were analysed. Besides, the synergistic effect of the best formulation was analysed based on α-tocopherol content using ultra-high performance liquid chromatography (UHPLC). The storage stability test was assessed upon storing at 25 ± 2°C and 40 ± 2°C for 12 weeks. The best formulation (20% PSO, vitamin E oil and beeswax) selected showed physically and microbiologically stable. The incorporation of vitamin E oil into the formulation produced with PSO was found to be compatible, as it showed a synergistic effect in the amount of α-tocopherol content (combination index (CI) = 0.98). Thus, PSO had shown its potency to be incorporated into the topical products with a promising potential in delivering additional properties that can nourish the skin.

Lee KA, Park JC, Park YK

Nutr Res Pract. 2020 Apr;14(2):143-151. doi: 10.4162/nrp.2020.14.2.143. Epub 2019 Dec 13.

Abstract

BACKGROUND/OBJECTIVES:

The nutrition of the elderly depends on various factors. Oral health, especially oral dryness, can be an important risk factor. In this study, we attempted to determine whether dry mouth is associated with compromised nutrient intakes.

SUBJECTS/METHODS:

A total of 120 participants aged 65-86 yrs (mean age: 69 ± 1 y) were included in this study. Demographic and health-related characteristics, living status, meals, number of medications, medical conditions, chewing ability, and quality of life, the Oral Health Impact Profile (the OHIP-14) were assessed. We performed one day 24-hr recall assessment for nutrient analyses. The differences of the means between the dry-mouth and non-dry-mouth groups were analyzed. Elderly subjects with xerostomia-induced dry mouth were classified as those who reported at least one dryness symptom on a questionnaire.

RESULTS:

A significant difference in population distribution was observed among the elderly who took medications for hypertension, diabetes and osteoporosis and was significantly higher in the dry-mouth group (70.2%) than in the non-dry-mouth group (44.4%) (P = 0.005). Compared with the non-dry-mouth group (50.8%), a significantly higher proportion (73.7%) of participants in the dry-mouth group took multiple medicines (≥ 4 medications) (P = 0.019). The intakes of vegetable fat, vitamin E, folate and water in the dry-mouth group were lower than in the non-dry-mouth group. The intakes of fluoride and ω-3 fatty acids were significantly lower in the dry-mouth group than in the non-dry-mouth group.

CONCLUSION:

The participants in the dry-mouth group exhibited low nutrient and water intakes. It is recommended that the elderly with dry mouth should drink sufficient water and receive targeted and specific nutritional guidance to prevent malnutrition.

Nehdi IA, Sbihi HM, Tan CP, Al-Resayes SI, Rashid U, Al-Misned FA, El-Serehy HA

J Oleo Sci. 2020 Apr 13. doi: 10.5650/jos.ess19298. [Epub ahead of print]

Abstract

Allium ampeloprasum L., commonly known as wild leek, is an edible vegetable that has been cultivated for centuries. However, no detailed studies have been undertaken to valorize A. ampeloprasum seed oil. This study aims to evaluate the physicochemical properties, chemical composition, and antioxidant activity of A. ampeloprasum seed oil. The seed oil content was found to be 18.20%. Gas chromatography-mass spectrometry (GC-MS) showed that linoleic acid (71.65%) was the dominant acid, followed by oleic acid (14.11%) and palmitic acid (7.11%). A. ampeloprasum seed oil exhibited an oxidative stability of 5.22 h. Moreover, γ- and δ-tocotrienols were the major tocols present (79.56 and 52.08 mg/100 g oil, respectively). The total flavonoid content (16.64 µg CE /g oil) and total phenolic content (62.96 µg GAE /g oil) of the seed oil were also determined. The antioxidant capacity of the oil, as evaluated using the ABTS assay (136.30 µM TEAC/g oil), was found to be significant. These findings indicate that A. ampeloprasum seeds can be regarded as a new source of edible oil having health benefits and nutritional properties.

X M Ding, Y D Mu, K Y Zhang, J P Wang, S P Bai, Q F Zeng, H W Peng

Asian-Australas J Anim Sci . 2020 Apr 12. doi: 10.5713/ajas.19.0934.

Abstract

Objective: The objective of this study was to determine whether a dietary vitamin E (VE) supplement could alleviate any detrimental effects of aged corn on lipid metabolism and antioxidant status in laying hens.

Methods: The experiment consisted of a 2 × 3 factorial design with two corn types (normal corn and aged corn (stored for 4 yr) and three concentrations of VE (0, 20 and 100 IU/kg). A total of 216 Lohmann laying hens (50 wk of age) were randomly allocated into six treatment diets for 12 wk. Each treatment had 6 replicates of 6 hens per replicate.

Results: The results show that aged corn significantly decreased the content of low-density lipoprotein cholesterol (LDL-C) (P< 0.05), and reduced chemokine-like receptor 1 (CMKLR1) mRNA expression (P< 0.05) in the liver compared to controls. Diet with VE did not alter the content of crude fat and cholesterol (P> 0.05), or acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL), fatty acid synthase (FAS) or CMKLR1 mRNA expression (P> 0.05) in the liver among treatment groups. Aged corn significantly increased the content of malondialdehyde (MDA) (P< 0.05) and decreased superoxide dismutase (SOD) activity (P< 0.05) in the liver. VE increased the content of MDA (P< 0.05) but decreased glutathione peroxidase (GSH-PX) activity in serum (P< 0.01) and in the ovaries (P< 0.05). Adding VE at 20 and 100 IU/kg significantly increased GSH-PX activity (P< 0.05) in liver and in serum (P< 0.01), 100 IU/kg VE significantly increased SOD activity (P< 0.05) in serum. Aged corn had no significant effects on GSH-PX mRNA or SOD mRNA expression (P< 0.01) in the liver and ovaries. Addition of 100 IU/kg VE could significantly increase SOD mRNA expression (P< 0.01) in the liver and ovary.

Conclusion: Aged corn affected lipid metabolism and decreased the antioxidant function of laying hens. Dietary VE supplementation was unable to counteract the negative effects of aged corn on lipid metabolism. However, addition of 100 IU/kg VE prevented aged corn-induced lipid peroxidation in the organs of laying hens.

Azimzadeh M, Jelodar G

J Anim Physiol Anim Nutr (Berl). 2020 Apr 12. doi: 10.1111/jpn.13360. [Epub ahead of print]

Abstract

Advances in telecommunication and their broad usage in the community have become a great concern from the health aspect. The object of the present study was to examine the effects of exposure to 900 MHz RFW on brain Iron (Fe), Copper (Cu), Zinc (Zn) and Manganese (Mn) concentration, and the protective role of pre-treatment of vitamin E on mentioned elements homoeostasis. Twenty adult male Sprague-Dawley rats (200 ± 20 g) randomly were divided into four groups. Control group (without any exposure, received distilled water), treatment control group (orally received 250 mg/kg BW/d vitamin E), treatment group (received 250 mg/kg BW/d vitamin E and exposed to 900 MHz RFW) and sham-exposed group (exposed to 900 MHz RFW). Animals (with freely moving in the cage) were exposed to RFW for 30 consecutive days (4 hr/day). The levels of the above mentioned elements in the brain tissue were determined on the last day using atomic absorption spectrophotometry. Exposure to 900 MHz RFW induced a significant increase in the Fe, Cu, Mn levels and Cu/Zn ratio accompanied by a significant decrease in Zn level in the sham-exposed group compare to control group. Vitamin E pre-treatment improved the level of Fe, Cu, Mn and Cu/Zn ratio, except in the Zn concentration. Exposure to 900 MHz RFW caused disrupted trace elements homoeostasis in the brain tissue and administration of vitamin E as an antioxidant and neuroprotective agent improved the situation.

Yi-Ming Chen, Huashuai Li, Yen-Shuo Chiu, Chi-Chang Huang, Wen-Chyuan Chen

Evid Based Complement Alternat Med . 2020 Apr 11;2020:8312647. doi: 10.1155/2020/8312647. eCollection 2020

Abstract

It has been reported that abundant nitric oxide content in endothelial cells can increase exercise performance. The purpose of this study was to evaluate the potential beneficial effects of a combined extract comprising L-arginine, L-glutamine, vitamin C, vitamin E, folic acid, and green tea extract (LVFG) on nitric oxide content to decrease exercise fatigue. Male ICR (Institute of Cancer Research) mice were randomly divided into 4 groups and orally administered LVFG for 4 weeks. The 4-week LVFG supplementation significantly increased serum nitric oxide content in the LVFG-1X and LVFG-2X groups. Antifatigue activity and exercise performance were evaluated using forelimb grip strength, exhaustive swimming test, and levels of serum lactate, ammonia, glucose, and creatine kinase (CK) after an acute swimming exercise. LVFG supplementation dose-dependently improved exercise performance and nitric oxide content, and it dose-dependently decreased serum ammonia and CK activity after exhaustive swimming test. LVFG’s antifatigue properties appear to manifest by preserving energy storage (as blood glucose) and increasing nitric oxide content. Taken together, our results show that LVFG could have the potential for alleviating physical fatigue due to its pharmacological effect of increasing serum nitric oxide content.