Duality of Tocopherol Isoforms and Novel Associations with Vitamins Involved in One-Carbon Metabolism: Results from an Elderly Sample of the LifeLines Cohort Study

Sotomayor CG, Minović I, Eggersdorfer ML, Riphagen IJ, de Borst MH, Dekker LH, Nolte IM, Frank J, van Zon SKR, Reijneveld SA, van der Molen JC, Vos MJ, Kootstra-Ros JE, Rodrigo R, Kema IP, Navis GJ, Bakker SJL

Nutrients. 2020 Feb 23;12(2). pii: E580. doi: 10.3390/nu12020580.

Abstract

Whether the affinity of serum vitamin E with total lipids hampers the appropriate assessment of its association with age-related risk factors has not been investigated in epidemiological studies. We aimed to compare linear regression-derived coefficients of the association of non-indexed and total lipids-indexed vitamin E isoforms with clinical and laboratory characteristics pertaining to the lipid, metabolic syndrome, and one-carbon metabolism biological domains. We studied 1429 elderly subjects (non-vitamin supplement users, 60-75 years old, with low and high socioeconomic status) from the population-based LifeLines Cohort and Biobank Study. We found that the associations of tocopherol isoforms with lipids were inverted in total lipids-indexed analyses, which may be indicative of overcorrection. Irrespective of the methods of standardization, we consistently found positive associations of α-tocopherol with vitamins of the one-carbon metabolism pathway and inverse associations with characteristics related to glucose metabolism. The associations of γ-tocopherol were often opposite to those of α-tocopherol. These data suggest that tocopherol isoforms and one-carbon metabolism are related, with beneficial and adverse associations for α-tocopherol and γ-tocopherol, respectively. Whether tocopherol isoforms, or their interplay, truly affect the one-carbon metabolism pathway remains to be further studied.

Kutbi HA, Hammouda SA

Diabetol Metab Syndr. 2020 Feb 18;12:17. doi: 10.1186/s13098-020-00525-3. eCollection 2020.

Abstract

BACKGROUND:

Existing evidence suggest that low concentrations of vitamin A and E may have a contribution to the development of diabetes complications; however, data regarding the status of vitamin A and E among individuals with prediabetes are lacking. This study aimed to examine the association of plasma concentrations of vitamin A and E with the glycemic control status among first trimester pregnant Saudi women.

METHODS:

In this cross-sectional study, 1102 first trimester pregnant Saudi women were recruited from antenatal clinics. Sociodemographic and anthropometric information were collected, and laboratory analyses of blood glycated hemoglobin (A1C) and plasma vitamins A and E were performed. Subjects were classified as normoglycemic, prediabetic, or undiagnosed diabetic. Multinomial regression models adjusted for age estimated the adjusted odds ratios (aORs) and [95% confidence intervals (CIs)].

RESULTS:

Among the sample, 78.8% (n = 868) had normal glycemic control, while 19.1% (n = 211) had prediabetes and 2.1% (n = 23) had undiagnosed diabetes. Plasma concentrations of vitamin A and E of prediabetic participants were at a level midway between that of normoglycemic and diabetic participants (p < 0.01). Compared to subjects with normoglycemic status, those with higher concentrations of vitamin A and E had lower odds of being prediabetic (aOR = 0.27 [0.21-0.35] and aOR = 0.95 [0.94-0.96], respectively) or diabetic (aOR = 0.18 [0.13-0.24] and aOR = 0.93 [0.92-0.94], respectively).

CONCLUSIONS:

Our findings indicate a possible contribution of vitamins A and E to the progression of prediabetes to diabetes. Future longitudinal studies are needed to elucidate the association between the antioxidant status and dysglycemia. Clinicians should monitor the glycemic and the antioxidant status closely and provide dietary guidance where needed.

Weber D, Kochlik B, Demuth I, Steinhagen-Thiessen E, Grune T, Norman K

Redox Biol. 2020 Feb 13;32:101461. doi: 10.1016/j.redox.2020.101461. [Epub ahead of print]

Abstract

Regular consumption of fruits and vegetables, which is related to high plasma levels of lipid-soluble micronutrients such as carotenoids and tocopherols, is linked to lower incidences of various age-related diseases. Differences in lipid-soluble micronutrient blood concentrations seem to be associated with age. Our retrospective analysis included men and women aged 22-37 and 60-85 years from the Berlin Aging Study II. Participants with simultaneously available plasma samples and dietary data were included (n = 1973). Differences between young and old groups were found for plasma lycopene, α-carotene, α-tocopherol, β-cryptoxanthin (only in women), and γ-tocopherol (only in men). β-Carotene, retinol and lutein/zeaxanthin did not differ between young and old participants regardless of the sex. We found significant associations for lycopene, α-carotene (both inverse), α-tocopherol, γ-tocopherol, and β-carotene (all positive) with age. Adjusting for BMI, smoking status, season, cholesterol and dietary intake confirmed these associations, except for β-carotene. These micronutrients are important antioxidants and associated with lower incidence of age-related diseases, therefore it is important to understand the underlying mechanisms in order to implement dietary strategies for the prevention of age-related diseases. To explain the lower lycopene and α-carotene concentration in older subjects, bioavailability studies in older participants are necessary.

Wong SK, Kamisah Y, Mohamed N, Muhammad N, Masbah N, Fahami NAM, Mohamed IN, Shuid AN, Saad QM, Abdullah A, Mohamad NV, Ibrahim NI, Pang KL, Chow YY, Thong BKS, Subramaniam S, Chan CY, Ima-Nirwana S, Chin AK

Nutrients. 2020 Jan 19;12(1). pii: E259. doi: 10.3390/nu12010259.

Abstract

Tocotrienol (T3) is a subfamily of vitamin E known for its wide array of medicinal properties. This review aimed to summarize the health benefits of T3, particularly in prevention or treatment of non-communicable diseases (NCDs), including cardiovascular, musculoskeletal, metabolic, gastric, and skin disorders, as well as cancers. Studies showed that T3 could prevent various NCDs, by suppressing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the mevalonate pathway, inflammatory response, oxidative stress, and alternating hormones. The efficacy of T3 in preventing/treating these NCDs is similar or greater compared to tocopherol (TF). TF may lower the efficacy of T3 because the efficacy of the combination of TF and T3 was lower than T3 alone in some studies. Data investigating the effects of T3 on osteoporosis, arthritis, and peptic ulcers in human are limited. The positive outcomes of T3 treatment obtained from the preclinical studies warrant further validation from clinical trials.

Fujiwara Y

J Nutr Sci Vitaminol (Tokyo). 2019;65(Supplement):S34-S37. doi: 10.3177/jnsv.65.S34.

Abstract

The dietary fat intake of Japanese is thought to be more appropriate than in Western countries; however there is a range of differences of individuals in the amounts of fat intake and n-6/n-3 ratio. Therefore, it is important what kind of vegetable oils are used for cooking in order to consider the total balance of fat intake. Rice bran oil (RBO) is expected to reduce plasma cholesterol and be useful for prevention of cardiovascular disease because it contains several effective ingredients. RBO is rich in linoleic and oleic acid. RBO contains γ-oryzanol, which is well known to reduce plasma cholesterol levels. Furthermore, it contains tocotrienols, which are analogs of vitamin E, reported to have unique bioactivity different from that of α-tocopherol. The biological function of these components and their potential to prevent Japanese lifestyle-related diseases are discussed.

Fukui K.

J Nutr Sci Vitaminol (Tokyo). 2019;65(Supplement):S185-S187. doi: 10.3177/jnsv.65.S185.

Abstract

Vitamin E is a natural lipophilic vitamin, and the most famous function of vitamin E is an antioxidant activity. Because we have α-tocopherol transfer protein, many vitamin E-related reports are about α-tocopherol. Recently, other vitamin E isoforms, tocotrienols are focusing. Because tocotrienols have unique biological functions such as induction of apoptosis, neuroprotective and anti-obesity effects. Tocotrienols contain in annatto, palm, whole wheat and rice bran. Rice is a typical food in the East Asian countries and Japan. Recently, intake of whole rice is a popular in young women of Japan. Previously, we demonstrated that treatment with tocotrienols on the neuronal cells shows a strong antioxidant effect compared to the tocopherols. In this review, I introduce about neuroprotective and anti-obesity effects of tocotrienols. I would like to show daily intake of whole rice is very good for our health in this review.

Wong SK, Chin KY, Ima-Nirwana S

Int J Environ Res Public Health. 2019 Sep 9;16(18). pii: E3313. doi: 10.3390/ijerph16183313.

Abstract

A positive association between metabolic syndrome (MetS) and osteoporosis has been demonstrated in previous animal studies. The mechanisms of MetS in orchestrating the bone remodelling process have traditionally focused on the interactions between mature osteoblasts and osteoclasts, while the role of osteocytes is unexplored. Our earlier studies demonstrated the bone-promoting effects of tocotrienol using a rat model of osteoporosis induced by MetS. This study aimed to investigate the expression of osteocyte-derived peptides in the bone of rats with MetS-induced osteoporosis treated with tocotrienol. Age-matched male Wistar rats (12-week-old; n = 42) were divided into seven experimental groups. Two groups served as the baseline and normal group, respectively. The other five groups were fed with a high-carbohydrate high-fat (HCHF) diet to induce MetS. The five groups of HCHF animals were treated with tocopherol-stripped corn oil (vehicle), annatto tocotrienol (60 and 100 mg/kg), and palm tocotrienol (60 and 100 mg/kg) starting from week 8. At the end of the study, the rats were sacrificed and their right tibias were harvested. Protein was extracted from the metaphyseal region of the proximal right tibia and levels of bone peptides, including osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), were measured. The vehicle-treated animals displayed higher levels of sRANKL, SOST, DKK-1, FGF-23, and PTH as compared to the normal animals. Oral supplementation of annatto and palm tocotrienol (60 and 100 mg/kg) reduced the levels of sRANKL and FGF-23 in the HCHF animals. Only 100 mg/kg annatto and palm tocotrienol lowered SOST and DKK-1 levels in the HCHF animals. In conclusion, tocotrienol exerts potential skeletal-promoting benefit by modulating the levels of osteocytes-derived bone-related peptides.

Asbaghi O, Choghakhori R, Abbasnezhad A

Diabetes Metab Syndr. 2019 Jul - Aug;13(4):2525-2531. doi: 10.1016/j.dsx.2019.07.001. Epub 2019 Jul 9.

Abstract

BACKGROUND:

Results of the studies assessed the effect of omega-3 and vitamin E co-supplementation on lipid profile in patients with metabolic syndrome (MS) are contradictory. Therefore, we carried out a systematic review and meta-analysis of randomized controlled trials (RCTs), to assess the effect of omega-3 and vitamin E co-supplementation on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in patients with MS.

METHODS:

A systematic search was performed to find the related articles, up to April, 2019. There was no language and time limitation. Meta-analyses were carried out using both the random and fixed effects model where appropriate, and I2 index was used to evaluate the heterogeneity.

RESULTS:

Search yielded 1236 publications. Five RCTs with 254 patients were eligible. Results of the meta-analysis indicated that omega-3 and vitamin E co-supplementation significantly reduced the serum concentrations of TG and LDL, whereas, it had no significant effect on the serum levels of TC and HDL in overweight patients with MS.

CONCLUSION:

Present systematic review and meta-analysis revealed that omega-3 and vitamin E co-supplementation have beneficial effects on lipid profile of overweight patients with MS. It significantly reduced the serum levels of TG and LDL in such patients.

Cabral EV, Vieira LD, Sant'Helena BRM, Ribeiro VS, Farias JS, Aires RS, Paz ST, Muzi-Filho H, Paixão AD, Vieyra A

Clin Exp Pharmacol Physiol. 2019 Aug 14. doi: 10.1111/1440-1681.13161. [Epub ahead of print]

Abstract

Maternal salt overload programs cardiovascular and renal alterations in the offspring. However, beneficial and harmful effects of high dose vitamin E supplementation have been described in humans and animals. We investigated the hypothesis as to whether cardiac and renal alterations can be programmed by gestational salt overload, and can become further modified during lactation and after weaning. Male Wistar rats were used, being the offspring of mothers that drank either tap water or 0.3 M NaCl for 20 days before and during pregnancy. α-Tocopherol (0.35 g/kg) was administered to mothers daily during lactation or to their offspring for 3 weeks post-weaning. Systolic blood pressure (tcSBP) was measured in juvenile rats aged 210 days. The response of mean arterial pressure (MAP) and heart rate (HR) to intravenous infusion of angiotensin II (Ang II) was also examined. Left ventricle plasma membrane (PMCA) and sarcoplasmic reticulum Ca²⁺-ATPase (SERCA) activities, and certain parameters of renal function, were measured. Maternal saline programmed for increased body mass and kidney mass/body mass ratio, increased tcSBP, increased mean arterial pressure and heart rate with anomalous response to infused Ang II. In the heart, saline increased PMCA and α-Tocopherol per se increased PMCA/SERCA. In the kidney, the most remarkable result was the silent saline programming of Cr_Cl , which was sensitized for a sharp decrease after α-Tocopherol. In conclusion, the combination of maternal saline overload and high α-Tocopherol immediately after birth leads to simultaneous cardiovascular and renal alterations in the young offspring, like those encountered in type V cardiorenal syndrome.

Choi Y, Lee S, Kim S, Lee J, Ha J, Oh H, Lee Y, Kim Y, Yoon Y

Int J Food Sci Nutr. 2019 Jul 12:1-5. doi: 10.1080/09637486.2019.1639637. [Epub ahead of print]

Abstract

This study evaluated if vitamin E consumption affects gut microbiota. Mice were grouped into control, low vitamin E (LV), and high vitamin E (HV). LV and HV were fed DL-α-tocopherol at 0.06 mg/20 g and 0.18 mg/20 g of body weight per day, respectively, for 34 days. Body weight of mice was measured before and after vitamin E treatment. Animals were sacrificed, liver, spleen, small intestine and large intestine collected, and weight and length were measured. Composition of gut microbiota was determined by microbiome analysis. Spleen weight index of LV was the highest. However, liver weight indices and intestinal lengths were not different. Body weights of LV group were higher than those of control. Ratio of Firmicutes to Bacteroidetes was different in LV compared to control and HV. These results indicate that low-level consumption of vitamin E increases spleen and body weight, and changes gut microbiota.