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.

Abstract

INTRODUCTION:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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

Sadikan MZ, Nasir NAA, Agarwal R, Ismail NM

Biomolecules. 2020 Apr 5;10(4). pii: E556. doi: 10.3390/biom10040556.

Abstract

: Oxidative stress plays an important role in retinal neurodegeneration and angiogenesis associated with diabetes. In this study, we investigated the effect of the tocotrienol-rich fraction (TRF), a potent antioxidant, against diabetes-induced changes in retinal layer thickness (RLT), retinal cell count (RCC), retinal cell apoptosis, and retinal expression of vascular endothelial growth factor (VEGF) in rats. Additionally, the efficacy of TRF after administration by two different routes was compared. The diabetes was induced in Sprague-Dawley rats by intraperitoneal injection of streptozotocin. Subsequently, diabetic rats received either oral or topical treatment with vehicle or TRF. Additionally, a group of non-diabetic rats was included with either oral or topical treatment with a vehicle. After 12 weeks of the treatment period, rats were euthanized, and retinas were collected for measurement of RLT, RCC, retinal cell apoptosis, and VEGF expression. RLT and RCC in the ganglion cell layer were reduced in all diabetic groups compared to control groups (p < 0.01). However, at the end of the experimental period, oral TRF-treated rats showed a significantly greater RLT compared to topical TRF-treated rats. A similar observation was made for retinal cell apoptosis and VEGF expression. In conclusion, oral TRF supplementation protects against retinal degenerative changes and an increase in VEGF expression in rats with streptozotocin-induced diabetic retinopathy. Similar effects were not observed after topical administration of TRF.

Huang X, Guo Y, Li P, Ma X, Dong S, Hu H, Li Y, Yuan L.

J Nutr Health Aging. 2020;24(3):290-299. doi: 10.1007/s12603-020-1328-1.

Abstract

OBJECTIVES:

Malnutrition of vitamin A (retinol) and vitamin E (α-tocopherol, α-TOH) was observed in type 2 diabetes mellitus (T2DM) or dementia patients. However, how these vitamins affect cognitive function of subjects with T2DM was seldom reported. The objective of this study was to determine the association of circulating retinol and α-TOH with cognition in aging subjects with T2DM.

METHODS:

A total of 448 T2DM subjects and 448 age, gender and education matched control subjects (aged 55-75 years) were included in the study. Demographic characters of the participants were collected. Food frequency questionnaire (FFQ) method was used to collect dietary intake information. To assess the status of cognition, the MoCA test was used. Circulating retinol and α-TOH levels were compared between T2DM and non-T2DM subjects. Correlation of circulating retinol and α-TOH levels with cognitive function was analyzed in T2DM subjects. The effect of serum retinol and α-TOH levels on the risk of MCI in T2DM patients was explored.

RESULTS:

We found that T2DM-MCI subjects demonstrate lower serum retinol level than T2DM-nonMCI subjects (P < 0.01). Serum retinol level was positively correlated to cognitive function in T2DM subject (P < 0.05). T2DM subjects with higher circulating retinol level demonstrate higher cognitive scores in visual and executive, attention, language, memory and delayed recall domains (P < 0.05).

CONCLUSION:

Diminished circulating retinol predicts an increased risk of MCI in T2DM patients. Our findings provide suggestions that optimal retinol nutritional status might benefit cognition and decrease the risk of MCI in aging subjects with T2DM.

Livny A, Schnaider Beeri M, Heymann A, Moshier E, Berman Y, Mamistalov M, Shahar DR, Tsarfaty G, Leroith D, Preiss R, Soleimani L, Silverman JM, Bendlin BB, Levy A, Ravona-Springer R

J Alzheimers Dis. 2020 Feb 12. doi: 10.3233/JAD-191294. [Epub ahead of print]

Abstract

BACKGROUNDS:

The efficacy of vitamin E in prevention of diabetes-related complications differs by Haptoglobin (Hp) genotype.

OBJECTIVE:

To examine the role of Hp genotype in the relationship of vitamin E intake with brain volume in cognitively normal elderly patients with type 2 diabetes.

METHODS:

Brain volumes for the superior, middle, and inferior frontal gyri and for the middle temporal gyrus were generated from structural T1 MRI in 181 study participants (Hp 1-1: n = 24, Hp 2-1: n = 77, Hp 2-2: n = 80). Daily vitamin E intake was assessed using the Food Frequency Questionnaire. Analyses of covariance, controlling for demographic and cardiovascular variables was used to evaluate whether the association of daily vitamin E intake with brain volume was modified by Hp genotype.

RESULTS:

Average age was 70.8 (SD = 4.2) with 40% females, and mean Mini-Mental State Examination score of 28.17 (SD = 1.90). A significant interaction was found between vitamin E intake and Hp genotype in inferior frontal gyrus’ volume; p = 0.0108. For every 1 microgram increase in vitamin E intake, the volume of the inferior frontal gyrus decreased by 0.955% for Hp 1-1 (p = 0.0348), increased by 0.429% for Hp 2-1 (p = 0.0457), and by 0.077% for Hp 2-2 (p = 0.6318). There were no significant interactions between vitamin E intake and Hp genotype for the middle (p = 0.6011) and superior (p = 0.2025) frontal gyri or for the middle temporal gyrus (p = 0.503).

CONCLUSIONS:

The effect of dietary vitamin E on the brain may differ by Hp genotype. Studies examining the impact of vitamin E on brain-related outcomes should consider Hp genotype.

Kayhan Kuştepe E, Bahar L, Zayman E, Sucu N, Gül S, Gül M

Biotech Histochem. 2020 Feb 4:1-12. doi: 10.1080/10520295.2019.1695942. [Epub ahead of print]

Abstract

We investigated the effects of α-lipoic acid (AL) and α-tocopherol (AT) on renal histopathology in a streptozotocin (STZ) induced diabetic rat model. Adult male rats were divided into six groups: group 1, saline only; group 2, AL only; group 3, AT only; group 4, STZ only; group 5, STZ + AL; group 6 STZ + AT. Experimental diabetes was induced by STZ. AL and AT were administered for 15 days. Kidney sections were examined using a light microscope after hematoxylin and eosin (H & E), periodic acid-Schiff (PAS) and caspase-3 staining. Histological damage to glomeruli, tubule epithelial cells and basement membrane was observed in group 4. Administration of AT and AL reduced renal injury in the diabetic rats. Group 5 exhibited a greater curative effect on diabetic rats than group 6. AT and AL may be useful for preventing diabetic renal damage.

Tan GCJ, Tan SMQ, Phang SCW, Ng YT, Ng EY, Ahmad B, Palamisamy UDM, Kadir KA

Ther Adv Endocrinol Metab. 2019 Dec 25;10:2042018819895462. doi: 10.1177/2042018819895462. eCollection 2019.

Abstract

Chronic hyperglycemia in type 2 diabetes mellitus increases oxidative stress and inflammation which contributes to long-term diabetic kidney disease. Tocotrienol-rich vitamin E, as Tocovid, has been shown to reduce oxidative stress and inflammation to ameliorate diabetes in rat models and human subjects. In this prospective, multicenter, double-blinded, placebo-controlled clinical trial, 54 patients (duration = 18.4 years, HbA1c = 8.8%) with diabetic nephropathy were randomized to receive Tocovid 200 mg or placebo for 12 weeks. Fasting blood samples were taken to measure HbA1c, serum creatinine, estimate glomerular filtration rate (eGFR), urine albumin:creatinine ratio, malondialdehyde, tumor necrosis factor receptor-1, vascular cell adhesion molecule-1 (VCAM-1), and thromboxane-B2. Patients were reassessed 6-9 months post-washout. After 12 weeks of supplementation, Tocovid significantly decreased serum creatinine levels (mean difference: -3.3 ± 12.6 versus 5.4 ± 14.2, p = 0.027) and significantly increase eGFR (mean difference: 1.5 ± 7.6 versus -2.9 ± 8.0, p = 0.045) compared with placebo. There were no significant changes in HbA1c, blood pressure, and other parameters. Subgroup analysis revealed that in patients with low serum vitamin E concentrations at baseline, Tocovid reduced serum creatinine, eGFR, and VCAM-1 significantly. After 6-9 months of washout, persistent difference in serum creatinine remained between groups (mean difference: 0.82 ± 8.33 versus 11.26 ± 15.47, p = 0.031), but not eGFR. Tocovid at 400 mg/day significantly improved renal function in 12 weeks of supplementation, as assessed by serum creatinine and eGFR, which remained significant 6-9 months post-washout.

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.

Di Vincenzo A, Tana C, El Hadi H, Pagano C, Vettor R, Rossato M

nt J Mol Sci. 2019 Oct 15;20(20). pii: E5101. doi: 10.3390/ijms20205101.

Abstract

Diabetes mellitus is a metabolic disorder characterized by the development of vascular complications associated with high morbidity and mortality and the consequent relevant costs for the public health systems. Diabetic kidney disease is one of these complications that represent the main cause of end-stage renal disease in Western countries. Hyperglycemia, inflammation, and oxidative stress contribute to its physiopathology, and several investigations have been performed to evaluate the role of antioxidant supplementation as a complementary approach for the prevention and control of diabetes and associated disturbances. Vitamin E compounds, including different types of tocopherols and tocotrienols, have been considered as a treatment to tackle major cardiovascular outcomes in diabetic subjects, but often with conflicting or even negative results. However, their effects on diabetic nephropathy are even less clear, despite several intervention studies that showed the improvement of renal parameters after supplementation in patients with diabetic kidney disease. Then we performed a review of the literature about the role of vitamin E supplementation on diabetic nephropathy, also describing the underlying antioxidant, anti-inflammatory, and metabolic mechanisms to evaluate the possible use of tocopherols and tocotrienols in clinical practice.

Soleymani H, Ghorbani M, Allahverdi A, Shojaeilangari S, Naderi-Manesh H

J Mol Graph Model. 2019 Sep;91:194-203. doi: 10.1016/j.jmgm.2019.06.006. Epub 2019 Jun 14.

Abstract

Lack of perfect insulin signaling can lead to the insulin resistance, which is the hallmark of diabetes mellitus. Activation of insulin and its binding to the receptor for signaling process initiates via B-chain C-terminal hinge conformational change through an open structure to “wide-open” conformation. Observational studies and basic scientific evidence suggest that vitamin D and E directly and/or indirectly prevent diabetes through improving glucose secretion and tolerance, activating calcium dependent endopeptidases and thus improving insulin exocytosis, antioxidant effect and reducing insulin resistance. On the contrary, clinical trials have yielded inconsistent results about the efficacy of vitamin D supplementations for the control of glucose hemostasis. In this work, best binding modes of vitamin D₃ and E on insulin obtained from AutoDock Vina were selected for Molecular Dynamic, MD, study. The binding energy obtained from Molecular Mechanics- Poisson Boltzman Surface Area, MM-PBSA method, revealed that Vitamins D₃ and E have good affinity to bind to the insulin and vitamin Ehas higher binding energy (-46 kj/mol) by engaging more residues in binding site. Distance and angle calculation results illustrated that vitamin E changes the B-chain conformation and it causes the formation of wide-open/active form of insulin. Vitamin E increases the Val^B12-Tyr^B26 distance to ∼15 Å and changes the hinge angle to ∼65°. Consequently, essential hydrophobic residues for binding to insulin receptor exposed to surface in the presence of vitamin E. However, our data illustrated that vitamin D₃ cannot change B-chain conformation. Thus our MD simulations propose a model for insulin activation through vitamin E interaction for therapeutic approaches.