Targeted Nutritional Intervention for Patients With Mild Cognitive Impairment: The Cognitive impAiRmEnt Study (CARES) Trial 1

Rebecca Power, John M Nolan, Alfonso Prado-Cabrero, Robert Coen, Warren Roche, Tommy Power, Alan N Howard, Ríona Mulcahy

J Pers Med . 2020 May 25;10(2):E43. doi: 10.3390/jpm10020043.

Abstract

Omega-3 fatty acids (ω-3FAs), carotenoids, and vitamin E are important constituents of a healthy diet. While they are present in brain tissue, studies have shown that these key nutrients are depleted in individuals with mild cognitive impairment (MCI) in comparison to cognitively healthy individuals. Therefore, it is likely that these individuals will benefit from targeted nutritional intervention, given that poor nutrition is one of the many modifiable risk factors for MCI. Evidence to date suggests that these nutritional compounds can work independently to optimize the neurocognitive environment, primarily due to their antioxidant and anti-inflammatory properties. To date, however, no interventional studies have examined the potential synergistic effects of a combination of ω-3FAs, carotenoids and vitamin E on the cognitive function of patients with MCI. Individuals with clinically confirmed MCI consumed an ω-3FA plus carotenoid plus vitamin E formulation or placebo for 12 months. Cognitive performance was determined from tasks that assessed global cognition and episodic memory. Ω-3FAs, carotenoids, and vitamin E were measured in blood. Carotenoid concentrations were also measured in tissue (skin and retina). Individuals consuming the active intervention (n = 6; median [IQR] age 73.5 [69.5-80.5] years; 50% female) exhibited statistically significant improvements (p < 0.05, for all) in tissue carotenoid concentrations, and carotenoid and ω-3FA concentrations in blood. Trends in improvements in episodic memory and global cognition were also observed in this group. In contrast, the placebo group (n = 7; median [IQR] 72 (69.5-75.5) years; 89% female) remained unchanged or worsened for all measurements (p > 0.05). Despite a small sample size, this exploratory study is the first of its kind to identify trends in improved cognitive performance in individuals with MCI following supplementation with ω-3FAs, carotenoids, and vitamin E.

Wang L, Chen Q, Zhuang S, Wen Y, Cheng W, Zeng Z, Jiang T, Tang C

J Ethnopharmacol. 2020 May 23;254:112670. doi: 10.1016/j.jep.2020.112670. Epub 2020 Mar 3.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Anoectochilus roxburghii (A. roxburghii) is a popular folk medicine in many Asian countries, which has been used traditionally for treatment of some diseases such as diabetes, tumors, hyperlipemia, and hepatitis. The ethanol extract from A. roxburghii was recently shown to exert better ability to scavenge free radicals in vitro and possess antioxidant on natural aging mice in vivo.

AIM OF THE STUDY:

This study is to characterize the chemical composition, and investigate the protective effect of the A. roxburghii flavonoids extract (ARF) against hydrogen peroxide (H₂O₂)-induced oxidative stress in LO2 cells in vitro and D-galactose (D-gal)-induced aging mice model in vivo, and explore the underlying mechanisms.

MATERIALS AND METHODS:

The chemical components of the flavonoids extract fromA. roxburghii were detected by ultraperformance lipid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). H₂O₂ was used to establish an oxidative stress model in LO2 cells. Cytotoxic and protective effects of ARF on the LO2 cells were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Moreover, the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) in cell supernatants were measured by commercial reagent kits. Kun-Ming mice were induced to aging with D-gal (400 mg/kg, BW) by subcutaneous injection for 58 days. From the 28th day to the 58th day of D-gal treatment, ARF (122.5, 245 and 490 mg/kg, BW) and vitamin E (100 mg/kg, BW) were orally administrated to aging mice once a day for consecutive 30 days. After 25 days of the treatment with ARF, learning and memory were assessed using Morris Water Maze (MWM). At the end of the test period, the animals were euthanized by cervical dislocation, and the levels of SOD, GSH-PX, and MDA in serum, liver homogenates and brain homogenates were measured. The levels of monoamine oxidase (MAO) and acetylcholinesterase (AchE) were determined in brain homogenates. Skin and liver histopathological morphology were observed by H&E staining. Furthermore, antioxidant-related gene expression levels in the liver were carried out by quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS:

Nine flavonoids were identified in the extracts of A. roxburghii. In vitro assay, a high concentration of ARF (>612.5 μg/ml) reduced the survival rate and had toxic effects on LO2 cells. In addition, ARF (245 μg/ml, 490 μg/ml) and Vitamin C (200 μg/ml) markedly inhibited generations of MDA and increased activities of SOD, GSH-PX in H₂O₂-induced LO2 cells supernatants. In vivo assay, ARF (122.5 mg/kg, 245 mg/kg and 490 mg/kg) and Vitamin E (100 mg/kg) not only ameliorated learning and memory ability but also improved skin and liver pathological alterations. Strikingly, ARF significantly decreased MDA and MAO levels, markedly enhanced antioxidant enzyme (SOD and GSH-PX) activities. Further, compared to the D-gal group, ARF could obviously up-regulate glutathione peroxidase-1 (GPx-1) and glutathione peroxidase-4 (GPx-4) mRNA levels.

CONCLUSIONS:

These findings suggested that ARF protects LO2 cells against H₂O₂-induced oxidative stress and exerts the potent anti-aging effects in D-gal aging mice model, which may be related to the inhibition of oxidative stress. Flavonoid compounds may contribute to the anti-oxidative capability and modulating aging.

Jacquelyn Medina, Vikas Gupta

In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan. 2020 May 21.

Excerpt

Vitamin E or tocopherol is a fat-soluble vitamin functioning as an antioxidant, protecting the cell membrane. As with all vitamins, the body does not form vitamin E. It solely forms from photosynthetic processes of plants, and therefore must be consumed from outside sources in small quantities. It is found abundantly in olive and sunflower oils, as well as nuts, soybeans, avocados, wheat, and green leafy vegetables.

Nathan K Cobb, Jigna N Solanki

Respir Care . 2020 May;65(5):713-718. doi: 10.4187/respcare.07733.

Abstract

“E-cigarettes” are a class of consumer devices designed to deliver drugs, primarily nicotine or marijuana oils, to the lung by vaporization. Regulation of the devices in the United States is relatively minimal, and research on both epidemiology and potential toxicity has focused on nicotine devices. In 2019, an outbreak of an acute respiratory illness in the United States was traced back to the contamination of e-cigarette fluids with vitamin E acetate, which had been used to disguise the dilution of marijuana oils. The outbreak, termed “e-cigarette or vaping associated lung injury” by the U.S. Centers for Disease Control, was characterized by pulmonary infiltrates and hypoxia, which usually required hospitalization and, often, admission to ICUs. The syndrome sickened >2,600 people, mostly young men, and killed >50 people before it began to abate 6 months later. No current regulations exist to prevent a similar event with the same or different chemical contaminants. Absent such regulation, respiratory practitioners should be prepared to evaluate, identify, and treat future cases of acute lung toxicity from e-cigarettes.

Agnieszka Piątek-Guziewicz, Agnieszka Dąbek, Magdalena Przybylska-Feluś, Paweł Zagrodzki, Tomasz Mach, Małgorzata Zwolińska-Wcisło

Pol Arch Intern Med . 2020 May 19. doi: 10.20452/pamw.15369. Online ahead of print.

Abstract

The pathogenesis of celiac disease (CD) is complex and has not been fully elucidated. It has been postulated that oxidative stress, because of an increase in the concentration of reactive oxygen species and antioxidant capacity reduction, is one of the processes possibly involved in gliadin toxicity. Oxidative imbalance induced by gliadin peptides in enterocytes leads to the activation of the transcription of proinflammatory cytokines and enzymes, such as inducible nitric oxide synthase (iNOS), which in turn causes an increased production of nitric oxide (NO) metabolites favoring oxidative stress. Based on the our previous study, we hypothesized that persistent nitrosative stress despite gluten-free diet (GFD) may be responsible for persistent histopathologic changes and that GFD is only partially able to improve oxidative imbalance. Hence, serum NO levels seem to be useful as a marker of treatment efficacy, and alterations in these levels could indicate CD activity. It is possible that oral antioxidant supplementation may decrease the toxic effects of peptides. In the current study, we aimed to evaluate the effect of treatment with oral vitamin E on oxidative imbalance in adult patients with CD on GFD. For that purpose, we assessed the fasting plasma levels of nitrate as a marker of endogenous NO production and oxidative stress. Moreover, we monitored the individual components of antioxidant capacity. To the best of our knowledge, this is the first study evaluating the effects of oral vitamin E supplementation on oxidative imbalance in patients with CD.

Poudel A, Gachumi G, Badea I, Bashi ZD, El-Aneed A

J Pharm Biomed Anal. 2020 May 10;183:113104. doi: 10.1016/j.jpba.2020.113104. Epub 2020 Jan 9.

Abstract

A novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously quantify phytosterols (brassicasterol, campesterol, stigmasterol and β-sitosterol) and tocopherols (alpha, beta, gamma and delta) entrapped in the lipid bilayer of a liposomal formulation. Apart from liposomes (a pharmaceutical product), the developed method was able to quantify target analytes in agricultural products, thus showing wide applications. Atmospheric pressure chemical ionization (APCI) was employed due to the enhanced ionization of phytosterols and tocopherols in comparison to electrospray ionization. Unlike published work, the chromatographic conditions were modified to simplify the analytical approach. For the first time, a simple isocratic elution (acetonitrile:methanol 99:1 v/v) was utilized for the separation of four phytosterols and four tocopherols in a single run. A substantially better baseline separation of phytosterols were obtained in comparison to reported methods by using poroshell C18 column. The method has a total run time of 7 min, which is the shortest run time among all reported quantitative methods for the simultaneous determination of four phytosterols and four tocopherols. Calibration curves for all phytosterols were linear in the range of 0.05-10 μg/mL. In the case of tocopherols, alpha tocopherol showed linear response in the range of 0.25-10 μg/mL. However, gamma and delta tocopherols exhibited quadratic relationship in the same concentration range (0.25-10 μg/mL). Validation parameters met the International Conference on Harmonization (ICH) guidelines in terms of selectivity, accuracy, precision, repeatability, sensitivity, matrix effects, dilution integrity and stability. The method was, for the first time, successfully applied for the quantifying phytosterols and tocopherols entrapped inside liposomes. An interesting chromatographic phenomenon was observed during sample analysis. Alpha tocopherol (entrapped in the liposomal lipid bilayer) was found to elute at two retention times, 2.53 min and 3.60 min. Such dual separation was not observed in calibration standards and quality controls. It was concluded that the chiral recognition ability of liposomes made up of phosphatidylcholine separated the enantiomers of alpha tocopherol, giving rise to two peaks at two different retention time. To sum, the reported novel LC-MS/MS method addresses three major analytical shortcomings, namely i)longer run time, ii)complex gradient elution and iii)poor baseline separation of phytosterols and tocopherols.

Tahereh Moadeli, Fleur Ponton, Phillip W Taylor

J Insect Physiol . 2020 May 15;104058. doi: 10.1016/j.jinsphys.2020.104058. Online ahead of print.

Abstract

Tephritid fruit flies are commonly reared on artificial larval diets for laboratory studies and for sterile insect technique pest management programs. While significant effort has been invested in developing artificial larval diets, surprisingly little is known about the specific nutritional requirements of tephritid flies. Recently developed gel larval diets have provided new opportunities for nutritional studie s in Queensland fruit fly, Bactrocera tryoni (‘Q-fly’). Wheat germ oil (WGO) is the main source of fatty acids and vitamin E in this diet, and is key for production of high-quality adults. To identify the importance of nutritional components of WGO for Q-fly productivity and quality, linoleic, linolenic, oleic and palmitic fatty acids as well as α-tocopherol (vitamin E) were included in the diet individually and in combination. Diets that included all of the tested fatty acids or just unsaturated fatty acids performed as well as diets containing WGO in most quality control parameters except fecundity, and addition of vitamin E reduced the pupal productivity. Considering individual fatty acids, larval diets containing only linolenic acid produced adults with higher percentage of fliers than did larval diets containing only palmitic acid or oleic acid. Compared with diets containing WGO, nutritional requirements for egg production in Q-fly were not entirely met by either grouped fatty acids or individual polyunsaturated, monounsaturated or saturated fatty acids, however, diets containing linoleic acid alone produced more eggs than any other fatty acid. The present study is a significant advance in understanding of the role of fatty acids as a component of WGO in larval diet in meeting the needs of developing Q-fly for somatic performance, but highlight also that other, untested, components of WGO appear to be important for reproduction.

Farias JS, Santos KM, Lima NKS, Cabral EV, Aires RS, Veras AC, Paixão AD, Vieira LD

Arch Biochem Biophys. 2020 May 15;684:108306. doi: 10.1016/j.abb.2020.108306. Epub 2020 Feb 17.

Abstract

Maternal endotoxemia has been shown to increase renal collagen deposition in the offspring. Renal fibrosis is a hallmark of progressive chronic kidney disease. It was investigated whether maternal reactive oxygen species (ROS) leads to renal fibrosis or exacerbates unilateral ureteral obstruction (UUO)-induced renal fibrosis in the offspring of dams treated with lipopolysaccharide (LPS). Furthermore, it was studied the role of matrix metalloproteinases (MMPs) in these changes. Adults Wistar rats were obtained from dams submitted to LPS administration through the third part of gestation. To evaluate the role of maternal ROS, part of the dams received α-tocopherol simultaneously with LPS. Part of the offspring in each group was submitted to UUO at adulthood when sub-groups were treated with NADPH oxidase inhibitor, apocynin. Maternal LPS administration increased proteinuria, systolic arterial pressure and renal collagen deposition in adult offspring. LPS offspring rats also presented higher MMP-2 activity in parallel to a decreased renal cortical TIMP-2 content. These changes were correlated to increased amounts of TGF-β1 and NOX2. Maternal α-tocopherol treatment prevented collagen deposition and reduced arterial pressure in adult offspring. α-Tocopherol also inhibited maternal endotoxemia-induced changes in TGF-β1/NOX2/MMP-2 signaling. UUO led to increased collagen deposition in the contralateral kidneys of LPS offspring, which was correlated to increased NADPH oxidase activity and prevented by NADPH oxidase inhibition. In summary, maternal endotoxemia led to alterations in the TGF-β1/NOX2/MMP-2 signaling pathway in renal tissue concomitant with collagen deposition, therefore contributing to hypertension in adult offspring.

Ziyang Xu, Zhan Ye, Youdong Li, Jinwei Li, Yuanfa Liu

J Oleo Sci . 2020 May 14. doi: 10.5650/jos.ess19307. Online ahead of print.

Abstract

For the controversy still existed about the oxidation stability of the high oleic oils compared with palm oil (PO), this study was aimed to explore the possible reason causing the controversies. Total polar compounds (TPC) was used to evaluate the oxidation stability of oils. Results showed there exist two kinds of lineal changes about the content of total polar compounds (TPC) in each oil, which were closely linked with the fatty acid composition and the tocochromanols content. The possible influence of the initial quality of oils also should be considered. The TPC of high oleic peanut oil (HOPO), high oleic sunflower oil (HOSO), high oleic rapeseed oil (HORO) and PO increased slowly at the initial period mainly owing to the antioxidation of tocochromanols, then sharply after 24, 48, 36 and 72 h respectively, when tocochromanols in each oil almost reduced below the detection limit. After that, the major factor would be fatty acids, particularly PUFA. It showed that the major tocochromanols in different oils (e.g. α, γ-tocotrienols in PO, α, γ-tocopherols in HORO and HOPO, and α-tocopherols in HOSO), could impose the main effects of inhibiting the TPC generation in the initial thermal treatment. The TPC in HORO significantly increased after 84 hours of heat process, which might be caused by the higher content of the polyunsaturated fatty acids (PUFA) (i.e. C18:2 and C18:3). However, the content of the saturated fatty acid (SFA) did not show statistically significant change during the thermal treatment.

Paul E Harper, Andres T Cavazos, Jacob J Kinnun, Horia I Petrache, Stephen R Wassall

Langmuir . 2020 May 12;36(18):4908-4916. doi: 10.1021/acs.langmuir.0c00176. Epub 2020 Apr 30.

Abstract

Vitamin E (α-tocopherol) and a range of other biological compounds have long been known to promote the H_II (inverted hexagonal) phase in lipids. Now, it has been well established that purely hydrophobic lipids such as dodecane promote the H_II phase by relieving extensive packing stress. They do so by residing deep within the hydrocarbon core. However, we argue from X-ray diffraction data obtained with 1-palmitoyl-2-oleoylphosphatidylcholine (POPE) and 1,2-dioleoylphosphatidylcholine (DOPE) that α-tocopherol promotes the H_II phase by a different mechanism. The OH group on the chromanol moiety of α-tocopherol anchors it near the aqueous interface. This restriction combined with the relatively short length of α-tocopherol (as compared to DOPE and POPE) means that α-tocopherol promotes the H_II phase by relieving compressive packing stress. This observation offers new insight into the nature of packing stress and lipid biophysics. With the deeper understanding of packing stress offered by our results, we also explore the role that molecular structure plays in the primary function of vitamin E, which is to prevent the oxidation of polyunsaturated membrane lipids.