High-dose dietary supplementation of vitamin A induces brain-derived neurotrophic factor and nerve growth factor production in mice with simultaneous deficiency of vitamin A and zinc

Abstract

Marginal vitamin A and zinc (Zn) deficiency often co-exist in many populations. Vitamin A plays a trophic role in brain and is important for its development. We investigated effects of dietary supplementation of vitamin A on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) production in mice depleted for vitamin A and Zn. After 3 months' feeding with a low vitamin A and Zn (LVA-LZ) diet, mice were divided into two groups and replenished with either normal or high vitamin A with low Zn diet for an additional 2 months. Levels of BDNF and NGF were measured from extracts of hippocampus, cortex and cerebellum at the end of the third and fifth months. The LVA-LZ group tended to show decreased amounts of the BDNF and NGF, while animals supplemented with high vitamin A along with Zn deficiency had high BDNF and NGF concentrations. From these results, we conclude that vitamin A may increase BDNF and NGF levels.     

High-dose dietary supplementation of vitamin A induces brain-derived neurotrophic factor and nerve growth factor production in mice with simultaneous deficiency of vitamin A and zinc

Marginal vitamin A and zinc (Zn) deficiency often co-exist in many populations. Vitamin A plays a trophic role in brain and is important for its development. We investigated effects of dietary supplementation of vitamin A on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) production in mice depleted for vitamin A and Zn. After 3 months' feeding with a low vitamin A and Zn (LVA-LZ) diet, mice were divided into two groups and replenished with either normal or high vitamin A with low Zn diet for an additional 2 months. Levels of BDNF and NGF were measured from extracts of hippocampus, cortex and cerebellum at the end of the third and fifth months. The LVA-LZ group tended to show decreased amounts of the BDNF and NGF, while animals supplemented with high vitamin A along with Zn deficiency had high BDNF and NGF concentrations. From these results, we conclude that vitamin A may increase BDNF and NGF levels.     

Zinc monotherapy increases serum brain-derived neurotrophic factor (BDNF) levels and decreases depressive symptoms in overweight or obese subjects: A double-blind,randomized, placebo-controlled trial

Abstract

Objective

Previous studies have shown a positive effect of zinc as an adjunctive therapy on reducing depressive symptoms. However, to our knowledge, no study has examined the effect of zinc monotherapy on mood. The aim of the present study was to determine the effects of zinc monotherapy on depressive symptoms and serum brain-derived neurotrophic factor (BDNF) levels in overweight or obese subjects.

Methods

Fifty overweight or obese subjects were randomly assigned into two groups and received either 30 mg zinc or placebo daily for 12 weeks. At baseline and post-intervention, depression severity was assessed using Beck depression inventory II (BDI II), and serum BDNF and zinc levels were determined by enzyme-linked immunosorbent assay and atomic absorption spectrophotometry, respectively.

Results

The trial was completed with 46 subjects. After a 12-week supplementation, serum zinc and BDNF levels increased significantly in the zinc-supplemented group compared with the placebo group. BDI scores declined in both the groups at the end of the study, but reduction in the zinc-supplemented group was significantly higher than the placebo group. More analysis revealed that following supplementation, BDI scores decreased in subgroup of subjects with depressive symptoms (BDI ≥ 10) (n = 30), but did not change in the subgroup of non-depressed subjects (BDI < 10) (n = 16). Moreover, a significant inverse correlation was observed between serum BDNF levels and depression severity in all participants. Interestingly, a significant positive correlation was found between serum BDNF and zinc levels at baseline.

Conclusion

Zinc monotherapy improves mood in overweight or obese subjects most likely through increasing BDNF levels.     

Vitamin A and Zinc Supplementation of Preschool Children

Objective: To determine whether supplementation of vitamin A and/or zinc (Zn) improved serum levels of these nutrients and/or height and weight gains in preschool children, 22 to 66 months, living in Belize, Central America.

Methods: Subjects received either Zn, vitamin A, Zn and vitamin A or a placebo, (70 mg Zn and/or 3030 RE vitamin A, once per week) for 6 months in a 2×2 factorial design. Forty-three children, from a population of 104 prescreened, completed the study; they were selected, prior to treatment, for low/marginal serum concentrations of these micronutrients.

Results: Serum Zn levels were greater (16%, p<0.001) for those who received Zn. In contrast, after vitamin A treatment there were no differences in serum vitamin A among groups. Although increases in height (+4.4 cm, p<0.001) and weight (+0.79 kg, p<0.001), compared with baseline values, were numerically greatest for children who received both supplements, only the vitamin A supplementation effect was significant, resulting in increased height (+1.4 cm, p<0.002) and greater weight gain (+0.15 kg, p<0.03) compared to those receiving no vitamin A. Vitamin A supplementation alone significantly increased (p<0.001) hemoglobin concentration.

Conclusion: The results suggest that the preschool children in this study, prescreened for low/marginal serum concentrations from a larger population prior to treatment, were enduring inadequate vitamin A and, to a lesser degree, Zn nutriture. Height and weight gain were significantly increased in the subjects who received a single weekly supplement 3030 RE of vitamin A.     

The relationship between dietary quality,serum brain-derived neurotrophic factor (BDNF) level,and the Val66met polymorphism in predicting depression

Background: Brain-derived neurotrophic factor (BDNF), a neurotrophic factor implicated in the pathogenesis of depression, may be influenced by dietary quality. Both dietary quality and serum BDNF have been researched independently in regard to their effect on depression; however, there is limited research investigating the relationship between the two factors and how they interact in depression. Additionally, a single-nucleotide polymorphism (SNP) (Val66Met) in the BDNF gene, which has been implicated in BDNF levels and depression, may contribute to the complex relationship between depression, dietary quality, and BDNF level.

Methods: One hundred and eighty-seven participants with major depressive disorder and 55 non-depressed healthy controls were recruited for this case–control analysis. The relationship between dietary quality and depression was assessed via a novel dietary quality score (the Australian Dietary Quality Score). Serum BDNF levels were measured and the Val66Met SNP was genotyped.

Results: Healthy controls had a significantly higher diet quality than depressed participants (t?=?2.435, P?=?0.016). A logistic regression model investigating age, sex, serum BDNF levels, dietary quality and depression, as well as any interactions, found that lower dietary quality, and surprisingly, higher BDNF levels, were associated with increased depression risk, P?=?0.037 and P?<?0.001, respectively. Neither seasonality (at the time of recruitment) nor the Val66Met polymorphism was associated with BDNF levels in this sample. Furthermore, there was no evidence of interaction between the Val66Met polymorphism, BDNF levels, dietary quality, and depression.

Conclusion: Higher dietary quality was associated with both decreased depression incidence and severity in this cross-sectional analysis. The Val66Met polymorphism did not appear to predict BDNF levels, depression incidence, or modify the relationship between dietary quality and BDNF. Further studies utilizing a larger sample size are needed to confirm this finding.     

Effects of olive polyphenols administration on nerve growth factor and brain-derived neurotrophic factor in the mouse brain

ObjectivePolyphenols are chemicals derived from plants known to possess antioxidant and anti-inflammatory properties. High intake of fruit and vegetables is believed to be beneficial to human health. Various studies have suggested that dietary polyphenols may protect against cancer and cardiometabolic and neurodegenerative diseases. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are neurotrophins that play key roles in brain cell development, growth, and survival. The aim of this study was to investigate whether or not administration of olive (Olea europaea L.) polyphenols could have an effect on NGF and BDNF content and the expression of their receptors, TrkA and TrkB, respectively, in the mouse brain.MethodsNGF and BDNF were measured by enzyme-linked immunosorbent assay. TrkA and TrkB were measured by Western blotting.ResultsWe found NGF and BDNF elevation in the hippocampus and olfactory bulbs and a decrease in the frontal cortex and striatum. These data were associated with potentiated expression of TrkA and TrkB in the hippocampus and olfactory bulbs but no differences between groups in the striatum and frontal cortex. Polyphenols did not affect some behavioral mouse parameters associated with stressing situations.ConclusionsAltogether, this study shows that olive polyphenols in the mouse may increase the levels of NGF and BDNF in crucial areas of the limbic system and olfactory bulbs, which play a key role in learning and memory processes and in the proliferation and migration of endogenous progenitor cells present in the rodent brain.     

Effect of eye NGF administration on two animal models of retinal ganglion cells degeneration

The aim of this study was to investigate the effect of nerve growth factor (NGF) administration on retinal ganglion cells (RGCs) in experimentally induced glaucoma (GL) and diabetic retinopathy (DR). GL was induced in adult rats by injection of hypertonic saline into the episcleral vein of the eye and diabetes (DT) was induced by administration of streptozoticin. Control and experimental rats were treated daily with either ocular application of NGF or vehicle solution. We found that both animal models present a progressive degeneration of RGCs and changing NGF and VEGF levels in the retina and optic nerve. We then proved that NGF eye drop administration exerts a protective effect on these models of retinal degeneration. In brief, our findings indicate that NGF can play a protective role against RGC degeneration occurring in GL and DR and suggest that ocular NGF administration might be an effective pharmacological approach.     

Zinc supplementation alters thyroid hormone metabolism in disabled patients with zinc deficiency.

We examined zinc (Zn) status in relation to thyroid function in disabled persons, because the association between Zn deficiency and thyroid function remains controversial.

After measuring serum free 3,5,3′-triiodothyronine (T3) and free thyroxine (T4) in 134 persons, TSH-releasing hormone (TRH) injection test and estimation of Zn status were conducted in persons with low free T3.

Thirteen had low levels of serum free T3 and normal T4. Patients with elevated levels of serum 3,3′,5′-triiodothyronine (rT3) showed an enhanced reaction of serum thyrotropin (TSH) after TRH injection. Nine of 13 patients had mild to moderate Zn deficiency evaluated by body Zn clearance and increased urinary Zn excretion. After oral supplementation of Zn sulphate (4-10 mg/kg body weight) for 12 months, levels of serum free T3 and T3 normalized, serum rT3 decreased, and the TRH-induced TSH reaction normalized. Serum selenium concentration (Type 1 T4 deionidase contains selenium in the rat) was unchanged by Zn supplementation.

Zn may play a role in thyroid hormone metabolism in low T3 patients and may in part contribute to conversion of T4 to T3 in humans.     

Effects of Zinc and Selenium Supplementation on Thyroid Function in Overweight and Obese Hypothyroid Female Patients: A Randomized Double-Blind Controlled Trial

Objective: Zinc (Zn) and selenium (Se) are essential trace elements involved in thyroid hormone metabolism. This study was conducted to investigate the effects of Zn and Se supplementation on thyroid function of overweight or obese female hypothyroid patients in a double-blind, randomized controlled trial.

Methods: Sixty-eight female hypothyroid patients were randomly allocated to one of the 4 supplementation groups receiving Zn + Se (ZS; 30 mg Zn as zinc-gluconate and 200 μg Se as high-selenium yeast), Zn + placebo (ZP), Se + placebo (SP), or placebo + placebo (PP) for 12 weeks. Serum Zn, Se, free and total triiodothyronine (FT3 and FT4), free and total thyroxine (FT4 and TT4), thyroid-stimulating hormone (TSH), and anthropometric parameters were measured. Dietary intake was recorded using 24-hour food recall. Physical activity questionnaire was completed.

Results: No significant alterations were found in serum Zn or Se concentrations. Mean serum FT3 increased significantly in the ZS and ZP groups (p < 0.05) but this effect was significant in the ZP group compared to those in SP or PP groups (p < 0.05). Mean serum FT4 increased and TSH decreased significantly (p < 0.05) in the ZS group. TT3 and TT4 decreased significantly in the SP group (p < 0.05). Mean FT3:FT4 ratio was augmented significantly in the ZP group (p < 0.05). No significant treatment effects were found for TT3, FT4, TT4, or TSH between groups.

Conclusion: This study showed some evidence of an effect of Zn alone or in combination with Se on thyroid function of overweight or obese female hypothyroid patients.     

Effect of vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms: A randomized,double blind,placebo-controlled trial

Objectives: Previous studies have shown that serum levels of vitamin D were lower in attention deficit hyperactivity disorder (ADHD) children compared to healthy controls. The aim of the study was to determine the effect of vitamin D supplementation as adjunctive therapy to methylphenidate on symptoms of children with ADHD.

Methods: Sixty-two children aged 5–12 years with a diagnosis of ADHD based on DSM-IV criteria were randomly assigned into two groups to receive either 2000IU vitamin D or placebo in addition to methylphenidate for 8 weeks. Symptoms severity was assessed by Conner's Parent Rating Scale-Revised[S] (CPRS), ADHD rating scale-IV (ADHD-RS), and Weekly Parent Ratings of Evening and Morning Behavior (WPREMB) at weeks 0, 4, and 8. Serum levels of 25(OH)D were measured at baseline and after 8 weeks. Anthropometric variables, dietary intake, physical activity, sun exposure, and side effects were assessed.

Results: Fifty-four participants completed the trial. After 8 weeks of supplementation, serum levels of 25(OH)D significantly increased in the vitamin D group. ADHD symptoms decreased significantly in both groups (P?P?=?0.013, 0.016, respectively), but no differences were found in symptoms by CPRS and ADHD-RS scales.

Discussion: Vitamin D supplementation as adjunctive therapy to methylphenidate improved ADHD evening symptoms. Future research is needed to clarify vitamin D effects as monotherapy in ADHD and its mechanism.

The trial was registered in www.irct.ir is (IRCT201404222394N10).     

Potential Antioxidant Effects of Zinc and Chromium Supplementation in People with Type 2 Diabetes Mellitus

Objective: To determine the effects of combined zinc (Zn) and chromium (Cr) supplementation on oxidative stress and glucose homeostasis of people with type 2 diabetes.

Design: Tunisian adult subjects with HbA1C >7.5% were supplemented for 6 months with 30 mg/d of Zn as Zn gluconate or 400 μg/d of Cr as Cr pidolate or combined Zn/Cr supplementation or placebo. The effects of supplementation on plasma zinc (Zn), copper (Cu), selenium (Se), urinary Zn, Cr, plasma thiobarbituric acid reactive substances (TBARS), Cu-Zn superoxide dismutase (SOD) and Se glutathione peroxidase (GPx) in red blood cells, blood lipids and lipoproteins, HbA1C and fasting glucose were measured at the beginning of the study and after six months.

Results: At the beginning of the study, more than 30% of the subjects may have been Zn deficient with plasma Zn values less than 10.7 μmol/L, whereas levels of plasma Cu, Se and antioxidant RBC enzyme activities were in the normal ranges. Following supplementation, there were significant decreases of plasma TBARS in the Cr (13.6%), Zn (13.6%) and Zn/Cr (18.2%) groups with no significant changes in the placebo group. The value for the TBARS of the control healthy Tunisian subjects was 2.08 ± 0.04 μmol/L and that of the Tunisian subjects with diabetes was 3.32 ± 0.05 μmol/L. This difference of 1.24 μmol/L between the control group and the subjects with diabetes was reduced from 36% to 50% in the three supplemented groups. Supplementation did not modify significantly HbA1C nor glucose homeostasis. No adverse effects of Zn supplementation were observed on Cu status, HDL cholesterol nor interactions in Zn or Cr.

Conclusions: These data suggest the potential beneficial antioxidant effects of the individual and combined supplementation of Zn and Cr in people with type 2 DM. These results are particularly important in light of the deleterious consequences of oxidative stress in people with diabetes.     

BDNF levels in adipose tissue and hypothalamus were reduced in mice with MSG-induced obesity

Objectives: To observe the expression of brain-derived neurotrophic factor (BDNF) in hypothalamic and adipose tissue in mice with monosodium glutamate (MSG)-induced obesity.

Methods: The effects of hypothalamic lesions, specifically arcuate nucleus (ARC) lesions, induced by MSG injection were studied in male ICR mice at the neonatal stage. The following parameters were compared: body weight, body length, Lee's index, food intake, body temperature, fat weight, and levels of total cholesterol (CHOL), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and blood glucose (GLU). The BDNF expression levels in hypothalamic and adipose tissue were measured using western blotting.

Results: Compared with the control group, the model group body had significantly higher weight, Lee's index, food intake, fat weight, CHOL, TG, LDL, HDL, and GLU levels. BDNF expression levels in hypothalamic and adipose tissue were markedly down-regulated in the model group.

Discussion: BDNF may be closely associated with MSG-induced hypothalamic obesity.     

The Effect of Vitamin A Supplementation on Thyroid Function in Premenopausal Women

Objective: Vitamin A and its retinoid derivates play an important role in regulation of normal growth and development. Vitamin A has been shown to regulate thyroid hormone metabolism and inhibit thyroid-stimulating hormone (TSH) secretion via down regulation of TSH-β gene expression; however, the effect of vitamin A on thyroid function in obese individuals who are at higher risk of subclinical hypothyroidism is still unclear. In the present study we investigate the impact of vitamin A supplementation on thyroid function in obese women.

Method: A 4-month randomized, double blind controlled trial was conducted among 84 healthy women aged 17–50 years old: 56 were obese (body mass index [BMI] 30–35 kg/m²) and 28 were nonobese (BMI 18.5–24.9 kg/m²). Obese women were randomly allocated to receive either vitamin A (25,000 IU/d retinyl palmitate) or placebo. Nonobese women received vitamin A. At baseline and 4 months after intervention, serum concentrations of TSH, total thyroxine (T4), total triiodothyronine (T3), retinol-binding protein (RBP), and transthyretin (TTR) were measured.

Results: Baseline concentrations of thyroid hormones, RBP and TTR were not significantly different between groups. Vitamin A caused a significant reduction in serum TSH concentrations in obese (p = 0.004) and nonobese (p = 0.001) groups. Serum T3 concentrations also increased in both obese and nonobese vitamin A–treated groups (p < 0.001). Serum T4 decreased in all 3 groups after treatment. The results showed a significant reduction in serum RBP in the obese group after vitamin A supplementation (p = 0.007), but no significant change was seen in serum TTR.

Conclusions: Serum TSH concentrations in vitamin A–treated subjects were significantly reduced; therefore, vitamin A supplementation might reduce the risk of subclinical hypothyroidism in premenopausal women.     

Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder

Objective: High prevalence of vitamin D deficiency was previously reported in children with Autism Spectrum Disorder (ASD), but little is known about the efficacy of vitamin D3 treatment in ASD, although data from pilot studies seem promising. We hypothesized that serum vitamin D levels are reduced in ASD and correlate with the severity of disease. Also, we hypothesized that vitamin D3 treatment may be beneficial for a considerable portion of children with ASD.

Methods: In total, 215 children with ASD and 285 healthy control children were recruited in our study. Thirty seven of 215 ASD children received vitamin D3 treatment. The Autism Behaviour Checklist (ABC) and the Childhood Autism Rating Scale (CARS) were used to assess autism symptoms. High-performance liquid chromatography was used to assess the serum 25-hydroxyvitamin D [25(OH) D] level. Evaluations of ABC, CARS, and serum 25(OH) D levels were performed before and after 3 months of treatment.

Results: Serum levels of 25(OH) D were significantly lower in ASD children than typically developing children. Levels of serum 25(OH) D were negatively correlated with ABC total scores and language subscale scores. After vitamin D3 supplementation, symptom scores were significantly reduced on the CARS and ABC. In addition, the data also suggest that treatment effects were more pronounced in younger children with ASD.

Conclusion: Vitamin D deficiency might contribute to the aetiology of ASD. Supplementation of vitamin D3, which is a safe and cost-effective form of treatment, may significantly improve the outcome of some children with ASD, especially younger children (identifier ChiCTR-CCC-13004498).

Clinical Trial Registration: The trial ‘Association of Polymorphisms of Vitamin D Metabolism-Related Genes With Autism and the Treatment of Autism with Vitamin D’ has been registered at www.chictr.org/cn/proj/show.aspx? proj=6135 (identifier ChiCTR-CCC-13004498).     

Blueberry supplementation attenuates microglia activation and increases neuroplasticity in mice consuming a high-fat diet

Objectives: Consuming a high-fat diet (HFD) may result in behavioral deficits similar to those observed in aging animals. Blueberries may prevent and even reverse age-related alterations in neurochemistry and behavior. It was previously demonstrated that middle-aged mice fed HFD had impaired memory; however, supplementation of HFD with blueberry reduced these memory deficits. As a follow-up to that study, the brain tissue from HFD-fed mice with and without blueberry supplementation was assessed to determine the neuroprotective mechanism(s) by which blueberry allayed cognitive dysfunction associated with HFD.

Methods: Mice were fed HFDs (60% calories from fat) or low-fat diets (LFD) with and without 4% blueberry (freeze-dried, U.S. Highbush Blueberry Council). Microglia activation was assessed ex vivo and in vitro. The hippocampus was assessed for brain-derived neurotrophic factor (BDNF) and neurogenesis by measuring doublecortin (DCX).

Results: There was significantly less microglia ionized calcium binding adaptor molecule 1 staining and fewer microglia in the brains of mice fed HFD?+?blueberry compared to mice fed LFD and HFD. BV-2 microglial cells treated with serum collected from the mice fed the diets supplemented with blueberry produced less nitric oxide compared to cells treated with serum from mice fed HFD. BDNF levels were higher and the number of DCX-positive cells was greater in the hippocampus of mice fed HFD?+?blueberry compared to mice fed HFD.

Discussion: This study demonstrated that supplementation of a HFD with blueberry reduced indices of microglia activation and increased neuroplasticity, and these changes may underlie the protection against memory deficits in HFD-fed mice supplemented with blueberry.     

Study of the Determinants of Vitamin D Status in Pediatric Patients With Osteogenesis Imperfecta

Objective: Vitamin D is essential to the development and maintenance of the skeleton, especially for children with bone disorders such as osteogenesis imperfecta (OI). We evaluated serum 25-hydroxyvitamin D (25-OHD) levels to assess the relationship between determinants of vitamin D status in pediatric patients with OI.

Methods: This cross-sectional study evaluated sex, age, weight, height, body mass index, OI type, sunscreen use, season of assessment, sun exposure, vitamin D and calcium supplementation, bisphosphonate treatment, bone mineral density (BMD), milk and soda consumption, mobility, and time of sedentary activity. Levels of serum 25-OHD, calcium, parathyroid hormone (PTH), phosphorus, and alkaline phosphatase (ALP) were analyzed. Serum levels of 25-OHD were classified according to sufficient (>30 ng/ml or 75 nmol/L), insufficient (20–30 ng/ml or 50–75 nmol/L), moderately deficient (20–10 ng/ml or 50–25 nmol/L), and severely deficient (<10 ng/ml or 25 nmol/L).

Results: Fifty-two patients were included and 46 (88.4%) were classified as having insufficient or deficient 25-OHD. An inverse correlation between serum 25-OHD and time of sedentary activity (r = ?0.597, p < 0.001) and a positive correlation with height (r = 0.521, p = 0.046) and whole body BMD (r = 0.586, p = 0.022) were observed. A significant difference between the number of glasses of milk consumed (p = 0.010) was observed.

Conclusion: To optimize bone health, patients with OI need to be educated regarding habits that can improve serum 25-OHD levels, such as a reduction in periods of inactivity, the importance of sun exposure, and increasing consumption of milk and fortified dairy products.     

The Effects of Coenzyme Q10 Supplementation on Glucose Metabolism,Lipid Profiles,Inflammation, and Oxidative Stress in Patients With Diabetic Nephropathy: A Randomized,Double-Blind,Placebo-Controlled Trial

Objective: Data on the effects of coenzyme Q10 (CoQ10) supplementation on glucose metabolism, lipid profiles, inflammation, and oxidative stress in subjects with diabetic nephropathy (DN) are scarce. This research was done to determine the effects of CoQ10 supplementation on metabolic status in subjects with DN.

Methods: This randomized double-blind placebo-controlled clinical trial was done in 50 subjects with DN. Participants were randomly assigned into two groups to intake either 100 mg/day CoQ10 supplements (n = 25) or placebo (n = 25) for 12 weeks. Fasting blood samples were obtained at first and after 12-week intervention to quantify metabolic profiles.

Results: After 12 weeks of treatment, compared with the placebo, CoQ10 supplementation resulted in significant decreases in serum insulin levels (?3.4 ± 6.8 vs +0.8 ± 6.4 µIU/mL, p = 0.02), homeostasis model of assessment-estimated insulin resistance (?1.0 ± 2.0 vs +0.2 ± 1.8, p = 0.03), homeostasis model of assessment-estimated B cell function (?12.3 ± 26.3 vs +3.5 ± 23.1, p = 0.02) and HbA1c (?1.1 ± 1.0 vs ?0.1 ± 0.2%, p < 0.001), and a significant improvement in quantitative insulin sensitivity check index (+0.009 ± 0.01 vs ?0.006 ± 0.01, p = 0.01). In addition, CoQ10 supplementation significantly decreased plasma malondialdehyde (MDA) (?0.6 ± 0.5 vs +0.5 ± 1.0 µmol/L, p < 0.001) and advanced glycation end products levels (AGEs) (?316.4 ± 380.9 vs +318.6 ± 732.0 AU, p < 0.001) compared with the placebo. Supplementation with CoQ10had no significant impacts on fasting plasma glucose (FPG), lipid profiles, and matrix metalloproteinase-2 (MMP-2) compared with the placebo.

Conclusions: Taken together, our study demonstrated that CoQ10 supplementation for 12 weeks among DN patients had favorable effects on glucose metabolism, MDA, and AGEs levels, but unchanged FPG, lipid profiles, and MMP-2 concentrations.     

Diet and gene interaction.

Objective: To investigate the effect of chromium picolinate (CP) supplementation on body composition, resting metabolic rate (RMR), selected biochemical parameters and iron and zinc status in moderately obese women participating in a 12-week exercise program.

Methods: Forty-four women, 27 to 51 years of age, were randomly assigned to two groups based on their body mass index. Subjects received either 400 μg/day of chromium as a CP supplement or a placebo in double-blind fashion and participated in a supervised weight-training and walking program two days per week for 12 weeks. Body composition and RMR were measured at baseline, 6 and 12 weeks. Selected biochemical parameters and iron and zinc status were measured at baseline and 12 weeks.

Results: Body composition and RMR were not significantly changed by CP supplementation. No significant differences in fasting plasma glucose, serum insulin, plasma glucagon, serum C-peptide and serum lipid concentrations or in iron and zinc indices were found between the two groups over time. Serum total cholesterol concentration significantly decreased (p = 0.0016) over time for all subjects combined, probably as a result of the exercise training. Exercise training significantly reduced total iron binding capacity (TIBC) by 3% for all subjects combined (p = 0.0011).

Conclusions: Twelve weeks of 400 μg/day of chromium as a CP supplement did not significantly affect body composition, RMR, plasma glucose, serum insulin, plasma glucagon, serum C-peptide and serum lipid concentrations or iron and zinc indices in moderately obese women placed on an exercise program. The changes in serum total cholesterol levels and TIBC were a result of the exercise program.     

Investigation of brain-derived neurotrophic factor (BDNF) gene expression in hypothalamus of obese rats: Modulation by omega-3 fatty acids

Purpose: The aim of this study was investigating the effect of omega-3 fatty acids (ω-3 FAs) on brain-derived neurotrophic factor (BDNF) gene expression, using in vivo and in vitro models, to unravel the potential mechanisms of polyunsaturated fatty acids use in obesity.

Materials and methods: Twenty-nine Sprague-Dawley rats were divided into three groups; lean controls fed normal chow diet for 14 weeks, obese controls fed 60% of their diet as saturated fats for 14 weeks, and ω-3 FAs-treated rats fed 60% saturated fat diet for 14 weeks with concomitant oral administration of 400?mg/kg/day ω-3 FAs, mainly docosahexaenoic acid and EPA, from week 12 to week 14. For the in vitro experiment, hypothalamic cells from six obese rats were cultured in the presence of different concentrations of ω-3 FAs to determine its direct effect on BDNF expression.

Results: In vivo results showed that obesity has negative effect on BDNF gene expression in rat hypothalamus that was reversed by administration of ω-3 FAs. Obese rats showed hypercholesterolemia, hypertriglyceridemia, normoinsulinemia, hyperglycemia and hyperleptinemia. Treatment with ω-3 FAs showed significant decrease in serum total cholesterol and TAG. Also serum glucose level and HOMA index were decreased significantly. In vitro results demonstrated the increase in BDNF expression by ω-3 FAs in a dose-dependent manner.

Conclusions: Obesity causes down-regulation of BDNF gene expression that can be reversed by ω-3 FAs treatment, making them an interesting treatment approach for obesity and metabolic disease.     

Protein microparticulation: the principle and the process.

Objective: To evaluate the usefulness of the body zinc clearance test in the diagnosis of marginal zinc deficiency and to estimate the efficacy of oral zinc supplementation on growth in short children.

Methods: Zinc status was evaluated in 30 (19 boys and 11 girls) Japanese children with short stature using the body zinc clearance test. Changes in growth after oral zinc supplementation (ZnSO₄ · 7H₂O; 5 mg/kg/day in two divided doses) were studied.

Results: Basal serum zinc concentrations were 75.0±12.7 μg/dl and zinc clearance values were 19.1±5.8 ml/kg/hour in the 30 subjects. The correlation coefficient between serum zinc concentrations and zinc clearance values was as small as ?0.36. There were nine cases whose body zinc clearance values were high and serum zinc concentrations were low, indicating definite zinc deficiency. There were nine cases whose body zinc clearance values were high, despite normal serum zinc concentrations, indicating marginal zinc deficiency. The mean height velocity for males was 5.3 cm/year before zinc supplementation and 7.8 cm/year after the therapy; and the mean SD score for height for age improved from ?1.85 to ?1.53. The mean height velocity for females was 5.1 cm/year before zinc supplementation and 5.9 cm/year after the therapy, and the mean SD score for height for age changed from ?2.02 to ?2.03.

Conclusion: The body zinc clearance test was much more useful than serum zinc concentrations in diagnosing marginal zinc deficiency. Oral zinc supplementation improved the height velocity in short males, but not in short females.