Reduction in Migraine and Headache Frequency and Intensity With Combined Antioxidant Prophylaxis (N-acetylcysteine, Vitamin E, and Vitamin C): A Randomized Sham-Controlled Pilot Study

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

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


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.

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Review of Health Consequences of Electronic Cigarettes and the Outbreak of Electronic Cigarette, or Vaping, Product Use-Associated Lung Injury

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.


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.

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Influence of omega-3 fatty acid and vitamin co-supplementation on metabolic status in gestational diabetes: A meta-analysis of randomized controlled studies

Li F, Pei L, Huang G, Ye H

Eur J Obstet Gynecol Reprod Biol. 2020 Apr;247:191-197. doi: 10.1016/j.ejogrb.2020.02.024. Epub 2020 Feb 26.



Omega-3 fatty acid and vitamin E or D co-supplementation may be an important approach to improve metabolic status in gestational diabetes, but the results are conflicting. This systematic review and meta-analysis was conducted to evaluate the effect of omega-3 fatty acid and vitamin co-supplementation on metabolic status in gestational diabetes.


PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials (RCTs) assessing the influence of omega-3 fatty acid and vitamin co-supplementation compared with placebo on metabolic status in gestational diabetes were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies.


Four RCTs were included in the meta-analysis. Compared with control interventions for gestational diabetes, omega-3 fatty acid and vitamin E or D co-supplementation was associated with significantly reduced fasting plasma glucose [mean difference (MD) -10.47, 95 % confidence interval (CI) -15.33 to -5.61, p < 0.0001], homeostasis model of assessment-insulin resistance (MD -1.6, 95 % CI=-2.44 to -0.77, p = 0.0002), malondialdehyde (MD -1.00, 95 % CI -1.05 to -0.95, p < 0.00001) and triglycerides (MD 26.22, 95 % CI -38.94 to -13.51, p < 0.0001), as well as increased antioxidant capacity (MD 173.51, 95 % CI 164.72-182.30, p < 0.00001), but showed no obvious effect on nitric oxide (MD 5.95, 95 % CI -7.48 to 19.37, p = 0.39) or total cholesterol (MD 1.63, 95 % CI -13.46 to 16.72, p = 0.83).


Omega-3 fatty acid and vitamin co-supplementation may have a favourable effect on metabolic status in gestational diabetes.

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Role of Magnetic Resonance Imaging in the Monitoring of Patients with Nonalcoholic Fatty Liver Disease: Comparison with Ultrasonography, Lipid Profile, and Body Mass Index

Makhija N, Vikram NK, Kaur G, Sharma R, Srivastava DN, Madhusudhan KS

J Clin Exp Hepatol. 2020 Mar-Apr;10(2):139-149. doi: 10.1016/j.jceh.2019.09.002. Epub 2019 Sep 20.



The aim of this study was to study the role of magnetic resonance imaging (MRI) in monitoring hepatic fat content in cases of nonalcoholic fatty liver disease (NAFLD).


41 adults (mean age: 39 years, 22 males; 19 females) with NAFLD were included after obtaining approval from the institutional ethics committee. The baseline clinical (weight, body mass index [BMI]) and biochemical parameters, fatty liver grade on ultrasonography (USG), and hepatic fat signal fraction (FSF) using dual-echo chemical shift imaging and proton density fat fraction on magnetic resonance spectroscopy (MRS-PDFF) were assessed, before and after intervention (dietary and lifestyle changes and oral vitamin E for six months). They were categorized into Group A (good compliance to intervention) and Group B (poor compliance), and the clinical and imaging parameters were compared between them.


After intervention, Group A (n = 30) showed significant reduction in BMI (28.35 ± 3.25 to 27.14 ± 3.24 kg/m2P < 0.001), hepatic FSF (19.30 ± 9.09% to 11.18 ± 7.61%; P < 0.05), and MRS-PDFF (18.79 ± 8.53% to 10.64 ± 6.66%). In Group B (n = 11), there was significant increase in BMI (28.85 ± 2.41 to 29.31 ± 2.57 kg/m2P < 0.001), hepatic FSF (18.96 ± 9.79% to 21.48 ± 11.80%; P < 0.05), and reduction in high-density lipoproteins (P < 0.05). Although there was good correlation between USG and MRS in quantifying liver fat (r = 0.84-0.87; P < 0.001), USG was unable to detect <5.3% change in hepatic fat. There was poor correlation between lipid profile and MRS-PDFF. Change in body weight significantly correlated with change in hepatic fat content (r = 0.76; P < 0.001).


MRI is useful in accurately quantifying and in monitoring hepatic fat content and is better than clinical and biochemical parameters and USG.

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Suppression of P-glycoprotein by cigarette smoke extract in human lung-derived A549/P-gp cells

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


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.

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Preparation and Evaluation Pumpkin Seed Oil-based Vitamin E Cream Formulations for Topical Application

Ong TS, Chu CC1 Tan CP, Nyam KL

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


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.

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Tuning mPEG-PLA/vitamin E-TPGS-based Mixed Micelles for Combined Celecoxib/Honokiol Therapy for Breast Cancer

Jiahui Sun, Jing Li, Qi Liu, Min Jiang, Mengjia Yang, Siwen Zhan, Tong Qiu, Kaiyong He, Xueqiong Zhang

Eur J Pharm Sci . 2020 Apr 15;146:105277. doi: 10.1016/j.ejps.2020.105277. Epub 2020 Feb 24.


This study aimed to develop, evaluate, and optimize the mPEG-PLA/vitamin E-TPGS mixed micelle drug delivery system to encapsulate celecoxib (CXB) and honokiol (HNK) for intravenous treatment of breast cancer. To this end, we formulated CXB-loaded mPEG-PLA/vitamin E-TPGS (PV-CXB) and HNK-loaded mPEG-PLA/vitamin E-TPGS (PV-HNK) mixed micelles and analyzed their characteristics. The 4T1 cell line was used for cytotoxicity determination and cellular uptake experiments, and for establishing a 4T1-bearing mouse model for histopathology, immunofluorescence, terminal deoxynucleotidyl transferase-mediated nick end labeling, and Western blot analysis. The synergistic effects of PV-CXB and PV-HNK combination therapy were investigated in vitro and in vivo using the coefficient of drug interaction values. The mean size of PV-CXB and PV-HNK prepared with optimal formulation was approximately 50 nm, with a spherical shape. PV-CXB and PV-HNK combination therapy exhibited cytotoxicity in 4T1 cells in vitro. However, the toxicity of PV-CXB and PV-HNK combination therapy was not apparent in normal tissues (heart, liver, spleen, lung, and kidney) in vivo and reduced the expression of collagen fibers in tumor tissues. Moreover, the combination therapy reduced the expression of tumor growth biomarkers (Foxp3, CD4, Gr-1, CD11b, CD31, Ki67, FoxM1, and VEGF). In addition, the tumor cell apoptosis rate reached 45.71 ± 0.62%. The combined treatment with PV-CXB and PV-HNK showed synergistic effect both in vitro and in vivo. Thus, the PV-CXB and PV-HNK drug delivery system could be used as a potential combination therapy for breast cancer .

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Nutrient intakes and medication use in elderly individuals with and without dry mouths

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.



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.


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.


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.


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.

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Chemical Composition, Oxidative Stability, and Antioxidant Activity of Allium ampeloprasum L. (Wild Leek) Seed Oil

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]


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.

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Vitamin E Improves Antioxidant Status but Not Lipid Metabolism in Laying Hens Fed a Aged Corn-Containing Diet

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.


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.

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