3 . 2014
Physiology and biochemistry nutrition

Effects of vitamins deficiency on the cytochrome Р450 inducibility in rats


The purpose of the study was to determine multi-vitamin deficiency effects on the inducibility of main isoforms of cytochrome P450 in the rat liver. The study was carried out on 4 groups of Wistar rats. Rats of the 1 st and 3 rd group received semi-synthetic diets containing adequate (100% of recommended vitamin level) level of vitamins, the 2 nd and 4 th – the semi-synthetic diet containing vitamins in the amount of 20% from adequate level. The duration of the experiment was 4 weeks. During the last week indole-3-carbinol (I-3-C) in dose of 20 mg/kg body weight was added to the diet of the 3 rd and 4 th group of rats. Vitamin E content in liver and blood serum declined by 59 and 34%, respectively in rats which were fed vitamin-deficient diet (2 nd group); vitamin A level decreased by 5 times in the liver, but was not changed in blood serum. Multi-vitamin deficiency in the diet led to the increase in the liver ethoxyresorufin O-dealkylase (EROD) activity of CYP1A1, methoxyresorufin O-dealkylase (MROD) activity of CYP1A2 and testosterone 6β-hydroxylase (6β-TG) activity of CYP3A by 11, 80 and 53%, respectively, and gene expression of CYP1A1, CYP1A2, CYP3A and AhR by 8,5; 1,6; 2,4 and 3,6 fold. In rats fed diet with adequate levels of vitamins (3 rd group) I-3-C increased activity of EROD and MROD by 4,4 and 5,5 fold, and the expression of CYP1A1, CYP1A2 and AhR genes by 148; 3 and 3,5 fold compared to the parameters of the 1st group (without I-3-C). Multi-vitamin deficiency increased I-3-C-related induction of EROD activity and expression of CYP1A1 and CYP1A2 genes, but decreased I-3-C-related induction of the MROD activity. Thus, 5-fold reducing of vitamin content in rat diet lead to significant changes in activity and inducibility of cytochrome P450 of CYP1A and 3A family, which play a key role in the detoxification and metabolism of drugs.

State of the energy-supply system of the liver mitochondria under the conditions of alimentary deficiency of protein

The NADH-dehydrogenase and succinate dehydrogenase activity of the rats’ liver mitochondria under the conditions of alimentary deprivation of protein has been studied. Research was carried out on 65 white non-linear rats divided according to the diet protein content into three groups: 1 – rats fed a hypoprotein diet (7% of protein, 10% of fat и 83% of carbphydrates; n=26); 2 – rats fed a protein-free diet (n=26); 3 – rats fed a complete semi-synthetic ration (14% of protein, 10% of fat и 76% of carbphydrates; n=13). The NADH-dehydrogenase activity was estimated by spectrophotometric method, succinate dehydrogenase activity – by the intensity of reduction of the potassium ferricyanide. It has been estimated that the decrease of NADH-dehydrogenase activity of mitochondria occurred on the 14 th day of feeding rats with protein-free diet, and four-week feeding of rats under these conditions lead to the decrease of enzyme activity by 5,5 fold compared with the control group (0,506±0,040 nmol NADH/min/mg of protein) and by 3,0 fold compared with the previous stage of the experiment. At the same time a hypoprotein diet caused 2-fold decrease of NADH-dehydrogenase activity of liver mitochondria only on the 28 th day. It has been shown that the succinate dehydrogenase activity didn’t change significantly after two-week maintenance of rats on a protein-free diet as compared with control, while the four-week maintenance on both hypoprotein and protein-free diet lead to the decrease of the succinate dehydrogenase activity. Specifically, under the conditions of the hypoprotein diet succinate dehydrogenase activity of liver mitochondria decreased twofold and under the conditions of the protein free diet – threefold. Probably, the disorders at the level of Complex I of respiratory chain underlie the realization of the changes in the system of energy biotransformation in mitochondria under the conditions of alimentary protein deficiency.

Effects of nighttime snacking in students on their physiological parameters


The purpose of the research was a comparative assessment of the level of diet nutrients, characteristics of higher nervous activity, specificity of chronobiological changes of the sleep-wake cycle, the daily dynamics of cortisol level and total antioxidant activity in saliva in students with the presence of night eating compared with students who do not eat at night.The participants were 72 university students aged 17–22 years (59 females and 13 males), a self-administered diet diary for a week was used to acquire dietary pattern and nutrient content. All participants were divided into two groups: group 1 – students with food consumption from 06.00 am to 10.00 pm without night meals (n=34), and group 2 – students, whose food consumption include all day period and night snaking from 10.00 pm to 06.00 am (n=38).High nervous activity parameters were detected according to the Eysenck questionnaire, Spielberg and Taylor anxiety tests, the test «Stress», the threefactor eating questionnaire; chronobiological state was evaluated according to sleep quality, sleep hygiene, daily sleepiness, chronotype. Levels of cortisol and total antioxidant activity were estimated in saliva twice a day: in the morning and in the evening. In both groups, the majority of students (97%) have reduced consumption of vitamins and minerals such as biotin, vitamin D, choline, iodine, cobalt, manganese, sulfur, fluorine and zinc. Deficit of carbohydrates was found in 93% of respondents. The number of students with calcium deficiency was increased in the group 2 compared to the group 1 and reached 27,8% vs 3% (p<0,05), niacin insufficiency was revealed in 41,7% vs 18,2% (p<0,05) and proteins insufficiency frequency reached 30,6% vs 0% (p<0,05).The students from the group 2 had a significantly lower (p<0,05) intake of vitamins A, B 6 and C. In the group 2 it was detected the time shift of food consumption acrophase (15,1 h vs. 13,8 h; p<0,05), decrease of persons with morning chronotype (5,55% vs 24,24%; p<0,05), increase of anxiety and daily sleepiness (26 vs 20; p<0,01, and 10 vs 6; p<0,03 respectively); decrease of sleep quality (13 vs 15; p<0,01), increase of evening saliva cortisol level [9,41 (6,96; 13,11) vs 6,51 (5,61; 9,88) ng/ml; p<0,005) and decrease of saliva total antioxidant activity in the morning [13,00 (9,82; 14,98) vs 16,41 (15,21; 17,51) mg/l; p<0,001] and in the evening [11,11 (7,85; 12,89)vs 14,32 (13,27; 15,29) mg/l; p<0,001].

Antioxidative and membranotropic activities of rosmarinic acid


The metabolic damages and inflammatory diseases are closely connected with high increase of the contents of the reactive oxygen species (ROS) and lipid peroxidation products in organism. In connection with this natural antioxidants are actively used for efficient fight with oxidative stress. In current work we have estimated an antioxidative potential of rosmarinic acid (RA), which is broadly wide-spread amongst plants and possesses the useful spectrum of biological activities. It has been shown that RA noticeably exceeded known antioxidants in test on antioxidant activities in Hb–H2O2 –luminol and 2,2’-azo bis (2-methylpropionamidine) dihydrochloride–luminol systems, as well as on inhibition of linoleic acid peroxidation. On antioxidant activities the investigated substances can be arranged in the following order: RA > dihydroquercetin > trolox > ascorbic acid. RA molecules are localized mainly in the lipid bilayer of polar groups, but have no significant effect on its structural and functional properties: RA does not cause significant changes in permeability of planar bilayer membranes in a dose range of 0,5 to 10 μg/ml. Spontaneous incorporating of 1 mol% of RA into the lipid bilayer is sufficient for the complete prevention of lipid peroxidation. Thus, the antioxidant activity of RA is based on its ability to inhibit the initiation stage of free radical reactions of lipid peroxidation, largely caused by the formation of ROS. In this regard RA, as a powerful and effective inhibitor of ROS and lipid peroxidation, has great potential for wide use not only in medicine but also in the food industry to preserve the quality of perishable food products.

The system of quality control and food safety

Regulation of food supplements In the European Union and its member States. Part I


The article discusses aspects of the regional (the European Union) and national (European countries) regulation of food supplements. The definition of the supplement category is given. The contemporary issues of nutrition in developed countries are discussed, and the essential role of food supplements in the diet is emphasized. In particular, the use of vitamins, minerals, botanicals and their chemical constituents in food supplements as well as the issue of setting maximum daily limits are discussed. The positive lists of vitamins, minerals and their chemical modifications are presented. The paper also outlines aspects of supplement safety, requirements for their labelling and pre-market notification procedure.


Gradation in the level of vitamin consumption: possible risk of excessive consumption


The ratio between the levels of consumption of certain vitamins and minerals recommended daily allowance for labelling purposes < maximum supplement levels < tolerable upper intake level (UL) < safe level (limit) of consumption ≤ therapeutic dose] has been characterized. Vitamin A and beta-carotene maximum supplement levels coincides with UL, and recommended daily allowance for these micronutrients coincides with the maximal level of consumption through dietary supplements and/or multivitamins. Except for vitamin A and betacarotene recommended daily allowance for other vitamins adopted in Russia are considerably lower than the upper safe level of consumption. For vitamin A and beta-carotene there is a potential risk for excess consumption. According to the literature data (meta-analysis) prolonged intake of high doses of antioxidant vitamins (above the RDA) both alone and in combination with two other vitamins or vitamin C [>800 μg (R.E.) of vitamin A, >9,6 mg of beta-carotene, >15 mg (T.E.) of vitamin E] do not possess preventive effects and may be harmful with unwanted consequences to health, especially in well-nourished populations, persons having risk of lung cancer (smokers, workers exposed to asbestos), in certain conditions (in the atmosphere with high oxygen content, hyperoxia, oxygen therapy). Proposed mechanisms of such action may be due to the manifestation of prooxidant action when taken in high doses, shifting balance with other important natural antioxidants, their displacement (substitution), interference with the natural defense mechanisms. Athletes are the population group that requires attention as used antioxidant vitamins A, C, E, both individually and in combination in extremely high doses. In summary, it should be noted that intake of physiological doses which are equivalent to the needs of the human organism, as well as diet inclusion of fortified foods not only pose no threat to health, but will bring undoubted benefits, filling the existing lack of vitamins in the ration.

Hygiene of nutrition

Toxicological assessment of nanostructured silica. I. Integral indices, adducts of dna, tissue thiols and apoptosis in liver


The purpose of this study is evaluation of some parameters of toxicity of nanostructured SiO2 when orally administered to rats for 3 months. We used commercial SiO2 preparation, obtained by gas-phase hydrolysis of tetrachlorosilane with a size of the primary nanoparticles close to 5–30 nm, which was characterized as NM by several independent methods. SiO2 in the form of sonicated aqueous dispersion was administered to male rats with initial weight of 80±4 g for the first 30 days by intragastric gavage and then for 62 days with consumed diets in daily dose of 0,1; 1,0; 10 and 100 mg/kg body weight. The control animals received vehicle – deionized water. Weight gain, relative mass of internal organs, intestinal permeability to protein macromolecules (determination of ovalbumin level in blood serum by solid-phase bivalent immunoassay), urinary excretion of oxidative degradation product of DNA 8-oxo-2-deoxyguanosine (8-oxo-G) (by reversed phase HPLC), the level of thiol compounds in liver (spectrophotometrically), liver cell apoptosis (flow cytometer), fixing efficiency of passive avoidance (CRPA) have been measured. It has been shown that three-month administration of nanostructured SiO2 in all doses resulted in animal body weight decrease by 10–15%; a significant increase in adrenal weight was noticed under doses of 1 and 10 mg/kg and urinary 8-oxo-G excretion was significantly reduced at the dose 10 mg/kg. At the maximum dose of NM, 100 mg/kg, after 2 months of administration the number of animals decreased that entered the dark compartment of the experimental setup at initial testing of CRPA. The rest of the studied indices did not experience any significant changes depending on the dose of NM. It is concluded that no toxic effect were expressed in indices studied under the influence of nanostructured SiO2 in rats at daily doses up to 100 mg per kg body weight for 3 months.

Micronutrients in human nutrition

Hygienic aspects of iodic deficiency in the children’s population of the Saratov region

The analysis of clusters of iodine-scarce states formation among the children’s population of the Saratov Region is submitted. The hygienic assessment of iodine content in raw food materials and foodstuffs grown up and made on the territory of the Saratov Region is given. It has been revealed that various food groups were characterized by a low iodine content, which was (mcg/100 g) in the bread – 4,5±1,0; 3,6±0,8 in wheat grain; 2,7±0,6 in buckwheat; 2,5±1,1 in beans; 1,95±0,9 in peas. The actual iodine content in local vegetables and fruits was 1,3–1,6 fold below than the standard chemical composition according to the national tables, in river fish – twice. The quality analysis of the iodated salt sold in the trading network has been carried out. It has been found out that the use of the iodated salt with low iodine content has decreased the additional direct population risk from 12,34% in 2000 to 0,48% in 2010. For the last few years the use of the iodated salt tends to increase in the Saratov Region.In 2011 the iodated salt was used by 37,2% of urban population and 29,0% of villagers. In 2011 88,6% of school students were provided with the iodated salt in educational institutions of the area. It has been shown that the formation of mass iodine-scarce states among the population in the Saratov Region has lasted for a long time. The screening researches of urine excretion in the organized groups of surveyed children revealed an average level of iodine deficiency.In 2011 the iodine deficiency of moderate degree was registered in 18 areas of the Saratov Region, in 6 – of easy degree, whereas the moderately severe deficiency areas were not registered.

Effectiveness of the use of iodized milk protein to improve girls’ sufficiency with iodine

The work presents the results of the research capabilities of the use of iodized milk protein as a component of food supplement and enriched food product for the correction of iodine sufficiency in girls. Milk iodinated protein was produced by the enzyme-effective iodization of amino acid residues of cow’s milk whey proteins. The study involved 30 girls, whose average age was 19,9±1,4 years. Participants of observation were divided into three groups, for 10 people each. The first group received daily serving of meat cutlets (50g), enriched with dairy iodinated protein. Iodine content in the finished minced was 100 mcg. The second group received iodinated milk protein in the form od food supplement with iodine content of 100 mcg. The third group was a control one. The duration of observations was 30 days. To assess the effectiveness of measures the concentration of iodine in urine, blood levels of thyroid-stimulating hormone and free thyroxine have been determined, changes in cognitive processes (memory and attention) with the use of psychological tests have been evaluated. Studies have shown the effectiveness of using of iodized milk protein for the correction of iodine deficiency in girls. The use of iodized protein, as part of the enriched product and in the form of food supplement increased urinary iodine level and had a positive influence on the state of the hypophysial-thyroid system. In addition, the use of iodized milk protein helped to improve the cognitive functions of the students, which can be considered as an additional positive effect of correction of iodine deficiency.
Diet treatment

Assessment of efficiency of dietotherapy with addition of a vitamin-mineral complex in patients with diabetes mellitus type 2


The influence of diet inclusion of vitamin and mineral complex (VMC), potassium and magnesium in the form of asparaginate on micronutrient status, body composition and biochemical parameters in patients with diabetes mellitus type 2 (DM2) has been investigated. 120 female patients with DM2 and obesity of I–III degree (mean age – 58±6 years) have been included in the study. The patients were divided into two groups: main group (n=60) and control group (n=60). For 3 weeks patients of both groups received a low-calorie diet (1600 kcal/day). Patients of the main group received VMC, providing an additional intake of vitamins C and E (100–120% RDA), beta-carotene (40% RDA), nicotinamide (38% RDA), pantothenic acid and biotin (60% RDA), vitamins B 12 , B 2 and folic acid (75–83% RDA), vitamins B 1 and B 6 (160–300% RDA), zinc (100% RDA) and chromium (400% RDA), and also received magnesium (17,7% RDA) and potassium (9,4% RDA) in the form of asparaginate. Body composition, biochemical parameters and micronutrient status (blood serum level of vitamins C, D, B 6 , B 12 , folate, potassium, calcium, magnesium, zinc, phosphorus) were evaluated in all patients before and after the 3-week course of diet therapy. After the low-calorie diet therapy average body weight reduction was 4,2±0,2 kg in the main group, and 4,4±0,1 kg in the control group, without statistically significant differences between groups. Statistically significant decrease of total cholesterol, triglycerides, and glucose concentration in blood serum was registered in both groups. It should be noted that in the control group glycemia decreased on 1,2±0,1 mmol/l, while the main group showed a decrease on 1,8±0,1 (p<0,05) to normal values (5,4±0,1 mmol/l). Initial assessment of vitamin and mineral status revealed that most patients were optimal supplied with vitamins and minerals. After the dietotherapy significant increase of vitamin C, 25-hydroxyvitamin D, vitamin В 6 , folate, vitamin В 12 , potassium, magnesium, calcium, zinc and phosphorus concentration in blood serum was observed in patients receiving VMC. While in the control group statistically significant decrease of vitamin C, magnesium, zinc and phosphorus concentration in blood serum after the treatment was revealed. The obtained data shows the necessity of addition of the vitamin-mineral complex to the diet of patients with DM2 and obesity.


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Viktor A. Tutelyan
Full Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Scientific Director of the Federal Research Centre of Nutrition, Biotechnology and Food Safety (Moscow, Russia)

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