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Complex Assessment of the Blood Oxidative Metabolism in Qualified Athletes

The study confirmed a previously stated hypothesis that suggested a heterogeneity in the shifts of oxidative metabolism within professional athletes compared to the 'normal' population. This suggests that different approaches will be necessary to correct oxidative shifts within professional athletes.

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Blood Trace Elements under Personalized Metabolic Correction: The Preliminary Data

The study showed a positive effect when taking the vitamin-mineral complex on the metabolism of trace elements, in particular iron, copper, selenium and zinc.

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Iron metabolism under selective individualized correction

Based on a number of biochemical indicators, including total blood iron level, serum concentration of the trace element and ferritin levels; the randomised controlled one-centre study confirmed that the method used had a positive impact on the personalised correction of iron metabolism.

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Analysis of some components of blood proteome in "Healthy population"

The screening study established that a significant part of the megapolis population classified as practically healthy persons, have deviations from the physiological interval for a number of proteome components.

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Study of Microelement Status in "Healthy" Population of Megapolis

The study revealed large proportions of people with low plasma concentrations of zinc, magnesium and other vital elements, with 42% of the subjects having an excess of lithium.

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Lipid metabolism in blood

The volunteers who received the vitamin-mineral complex have shown significant restructuring of lipid metabolism, manifested in a decrease in total cholesterol level.

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Before / after – our clients' results

This study on the effects of the individual bioniq formula has proved that it caused a healthy metabolic status and a balanced amount of micronutrients in our clients.

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Complex Assessment of the Blood Oxidative Metabolism in Qualified Athletes

Abstract

The purpose of this research was to study the structure of the shifts in the blood oxidative metabolism in professional athletes. Materials and Methods: The study included 262 highly qualified athletes aged between 19 and 29 years. The control group consisted of healthy untrained volunteers of similar age. In blood plasma, we estimated the levels of 8-isoprostane, ox-LDL, alpha- and beta-carotene, alpha- and gamma-tocopherols, and tissue-specific antioxidants (lycopine, luteine and zeaxantine) and the activity of SOD and GP.

Results: Thus, in qualified athletes, characteristic changes in the state of oxidative metabolism, concerning the components of the pro- and antioxidant systems, were determined; however, the inhomogeneity of these metabolic transformations attracts attention. The revealed regularity allows confirming the previously stated hypothesis about the heterogeneity of shifts in oxidative metabolism in professional athletes, which suggests different approaches to their correction. (International Journal of Biomedicine. 2018;8(3):235-239.) 

Key Words: oxidative stress • professional athletes • blood oxidative metabolism • antioxidants

Abbreviations

GPx, glutathione peroxidase; GR, glutathione reductase; LPO, lipid peroxidation; OS, oxidative stress; ox-LDL, oxidized lowdensity lipoprotein; SOD, superoxide dismutase.


Introduction

In the conditions of disadaptation, including professional sports, there are significant shifts in oxidative metabolism, typically characterized by an intensification of LPO against a background of decreasing antioxidant reserves in organs and tissues.(1-5) The pronounced manifestation of this trend, which is an independent pathogenetic mechanism known as OS, is considered as an independent syndrome.(3-8) Some researchers also give a 3-degree gradation of the severity of this syndrome,(9-12) implying a differentiated approach to the evaluation of the pathological state being studied and, consequently, its management. In view of this circumstance, the possibility and necessity of diagnostics and pathogenetic correction of OS is assumed.(6,10,13-15) In relation to diagnostics, technologies and methods for estimating the shifts in oxidative metabolism have been proposed and are being developed. They are based on the determination of laboratory markers of varying degrees of specificity in biological substrates, the study of spontaneous biochemiluminescence of body fluids and tissues, and the use of modern instrumental techniques (instrumental techniques such as electron paramagnetic resonance and fluorescent probes. and others).(4,9,16,17) It should be noted that the determination of qualitative and quantitative criteria for the diagnosis of the state of pro- and antioxidant systems is necessary not only for the purpose of detecting OS,(2,6,13,16) but also for monitoring the adaptive capabilities of individual systems and the organism as a whole, including in sports medicine, adaptation, and environmental physiology.(13,18,19)

The second aspect of the problem, pathogenetic correction of OS, is related to the development of measures to correct the disturbances in oxidative metabolism.(10,14,15,20,21) This correction can be performed in two ways: by normalizing metabolism in general and/or by administering into the body natural and synthetic compounds that have antioxidant activity. In this case, the first path is nonspecific, since almost any pharmacological agents can be considered as compounds having indirect antioxidant activity and, therefore, as contributing to the optimization of one or more metabolic components.(6,15,20-22)

Taking into account the peculiarities of metabolic processes in professional athletes, who are forced to adapt to intensive regular physical training and to psychoemotional stress during competitive activity,(4,7,11,20,23) determining oxidative metabolism shifts and their severity in professional athletes seems very interesting. At the same time, in the special literature, there is not enough information about the nature of such disturbances, but there are single studies that assume the presence of OS in qualified athletes.(3,8,11,16,21,24)

The purpose of this research was to study the structure of the shifts in the blood oxidative metabolism in professional athletes.

Materials and Methods 

The study included 262 highly qualified athletes— representatives of cyclic sports (ski races, rowing, cycling, athletics, and orienteering) with a sport title from Candidate for Master of Sport of Russia to Master of Sport of the International Class (Group 1) aged between 19 and 29 years. The control group (Group 2) consisted of healthy untrained volunteers of similar age (n=35). 

The present study was approved by the local Ethics Committee of Federal Medical Biophysical Center named after A.I. Burnazyan (Record No.18 dated 10.12.2015). Written informed consent was obtained from each patient. 

The serum level of 8-isoprostane was determined by ELISA using an 8-isoprostane ELISA kit (“USBiological”, USA). Quantitative determination of ox-LDL was carried out by ELISA in a microplate format using the automatic immunoassay analyzer “Evolis” (Bio-Rad, Germany-USA) with Biomedica Gruppe reagents. The SOD activity was estimated by inhibiting the auto-oxidation of epinephrine in carbonate buffer at pH10.0 after the addition of blood hemolysate samples in proportions 1:50, according to the method of M. Sun and S. Zigman (1978). GPx activity was analyzed by measuring the oxidation of reduced glutathione in the presence of t-butylhydroperoxide (Moin 1986), and GR activity by its ability to catalyze NADPH-dependent reduction of oxidized glutathione (Karpischenko AI, 2002). Alpha- and beta-carotene and alpha- and gamma-tocopherol were determined according to the technique of Moisenok et al. (2009). The level of tissue-specific blood antioxidants (lycopene, lutein and zeaxanthin) was determined by chromatographic mass spectrometry, according to A.V. Grigoriev (2005) and N.L. Batsukova & E.R. Yaremko (2015).

Statistical analysis was performed using the Statistica 6.1 software package (StatSoft Inc, USA). The mean (M), standard error of the mean (SEM), and standard deviation (SD) were calculated. The Shapiro-Wilk test was used in testing for normality. Multiple comparisons were performed with a one-way ANOVA. A probability value of P<0.05 was considered statistically significant.

Results and Discussion

In qualified athletes, the levels of most parameters of the studied metabolic component were significantly different from those in untrained individuals. Thus, in Group 1, the plasma level of 8-isoprostane (Figure 1) was 1.25 times higher than in Group 2 (P<0.05). Taking into account that the plasma concentration of 8-isoprostane is considered as an integral laboratory marker of OS,(25) the observed tendency indicates excessive stimulation of free radical oxidation processes induced by intensive physical training.

Fig. 1. The plasma level of 8-isoprostane in professional athletes and healthy untrained volunteers (*- P<0.05).


At the same time, the level of ox-LDL in Group 1 was 16% lower than in Group 2 (P<0.05, Figure 2), which is apparently related to the predominant effect of the studied factor, not on LPO, but on oxidative damage of other biomacromolecules, in particular, on the oxidative modification of proteins. 

Fig. 2. The plasma level of ox-LDL in professional athletes and healthy untrained volunteers (*- P<0.05).

This is indirectly evidenced by the character of the shift in SOD activity observed in highly trained athletes (Figure 3). Thus, in Group 1, a moderate inhibition of the catalytic properties of this enzyme was found in comparison with Group 2. Changes in the level of this parameter, on the one hand, indicate the active participation of the enzyme in the utilization of the free radicals formed (by removing the superoxide radical anion from the biological fluid), and, on the other hand, can reflect the partial oxidative modification of SOD as a large protein molecule.

Fig. 3. The catayitic activity of SOD in professional athletes and healthy untrained volunteers.

The pronounced activation of free radical processes in qualified athletes is also evidenced by the dynamics of plasma concentrations of non-tissue-specific, non-enzymatic antioxidants. In particular, the level of alpha and gammatocopherol in Group 1 was significantly lower than in Group 2 (Figure 4). At the same time, this trend is most significant for gamma-tocopherol, the concentration of which in Group 1 was 1.68 times lower than in Group 2, whereas the level of alphatocopherol decreased only 1.23 times (P<0.05 in both cases).

Fig. 4. The plasma level of alpha-tocopherol and gammatocopherol in professional athletes and healthy untrained volunteers (*- P<0.05).


It should be emphasized that not only does the absolute decrease in the levels of both tocopherols take place, but, taking into account the lipophilic nature of the latter, there is also a decrease in the “plasma vitamin E level/plasma cholesterol level” ratio, which decreased in Group 1 by 1.25 times compared to Group 2 (P<0.05).

Similar, but less pronounced, changes were recorded for another group of non-enzymatic antioxidants—carotenes (Figure 5). In professional athletes, the plasma level of alpha-carotene decreased more significantly than the plasma concentration of beta-carotene (by 1.3 and 1.1 times, respectively, P<0.05 in both cases). This further confirms the deficit of the antioxidant potential, which is formed under the influence of regular, intense physical activity and indicates the development of OS in these conditions.


Fig. 5. The plasma level of alpha-carotene and betacarotene in professional athletes and healthy untrained volunteers (*- P<0.05).

This tendency fully applies to tissue-specific antioxidants also (Figure 6). In particular, the plasma levels of zeaxanthin, lycopene and lutein were significantly reduced in Group 1 compared to Group 2 (up to 1.9 times, P<0.05).

Fig. 6. The plasma level of lycopene, zeaxanthin and lutein in professional athletes and healthy untrained volunteers (*- P<0.05).


Thus, in qualified athletes, characteristic changes in the state of oxidative metabolism, concerning the components of the pro- and antioxidant systems, were determined. At the same time, the heterogeneity of the nature of the loads used, as well as the presence of individual features of free radical processes, allow one to assume the heterogeneity of their changes under conditions of regular intensive physical training. For a more detailed study of such trends, we used the method of assessing the state of oxidative metabolism, based on a joint examination of the values of parameters characterizing the activity and reserves of pro- and antioxidant systems (Figure 7). 

Attention is drawn to the fact that in almost all cases of pairwise comparisons, structural diagrams allow us to distinguish 2 subgroups of athletes, which indicates the expediency of creating two variants of metabolic support oriented to the type of metabolism modification (Figure 7).

Fig. 7. Two-dimensional comparative analysis of indicators of the state of pro- and antioxidant blood systems in professional athletes and healthy untrained volunteers.

It is interesting that paired comparisons performed between the indices characterizing separately the state of pro- and antioxidant systems, as well as between 2 parameters of one of the listed components of oxidative metabolism, also demonstrate the dichotomous heterogeneity of Group 1. Thus, the representation of Group 1 in the coordinates “GP activity - SOD activity” allows us to identify 2 subgroups in this group (Figure 8).

Fig. 8. Distribution of the results of examination of professional athletes in the coordinate system "GPx activity-SOD activity."

Thus, the conducted complex study made it possible to demonstrate the presence of shifts in the blood oxidative metabolism induced by occupations in professional sports. At the same time, the obtained data confirm the formation of OS in qualified athletes; however, the inhomogeneity of these metabolic transformations attracts attention. The revealed regularity allows confirming the previously stated hypothesis about the heterogeneity of shifts in oxidative metabolism in professional athletes, which suggests different approaches to their correction. Further research in this area can be aimed at developing the OS management, taking into account the type of reactions of the blood oxidative metabolism in conditions of regular and intense physical activity

Competing interests

The authors declare that they have no competing interests.

References

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2. Statsenko EA. [Characteristics of lipid peroxidation and markers of endogenous intoxication in monitoring physical loads during rower training]. Vopr Kurortol Fizioter Lech Fiz Kult. 2011;(3):41–5. [Article in Russian]

3. Aguiló A, Tauler P, Fuentespina E, Tur JA, Córdova A, Pons A. Antioxidant response to oxidative stress induced by exhaustive exercise. Physiol Behav. 2005;84(1):1-7.

4. Margonis K, Fatouros IG, Jamurtas AZ, Nikolaidis MG, Douroudos I, Chatzinikolaou A, et al. Oxidative stress biomarkers responses to physical overtraining: implications for diagnosis. Free Radic Biol Med. 2007;43(6):901-10.

5. Vider J, Lehtmaa J, Kullisaar T, Vihalemm T, Zilmer K, Kairane C, Landõr A, Karu T, Zilmer M. Acute immune response in respect to exercise-induced oxidative stress. Pathophysiology. 2001;7(4):263-270.

6. Kalinkin LA, Statsenko EA, Ponomareva AG, Morozov VN, Kutnyakhova LV, Krivoshchapov MV, et al. [Oxidative stress in physical training: methods of diagnosis and correction of antioxidant status]. Bulletin of Sport Science. 2014;2:31- 35. [Article in Russian]

7. Dreissigacker U, Wendt M, Wittke T, Tsikas D, Maassen N. Positive correlation between plasma nitrite and performance during high-intensive exercise but not oxidative stress in healthy men. Nitric Oxide. 2010 Sep 15;23(2):128-35. doi: 10.1016/j.niox.2010.05.003.

8. Steinberg J, Gainnier M, Michel F, Faucher M, Arnaud C, Jammes Y. The post-exercise oxidative stress is depressed by acetylsalicylic acid. Respir Physiol Neurobiol. 2002 Apr;130(2):189-99.

9. Peretyagin SP, Martusevich AK, Vanin AF. [Molecularcellular mechanisms of transformation of homeostasis of biosystems with reactive oxygen species and nitrogen]. Medical Almanac. 2013; 3: 80-81. [Article in Russian]

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12. Veskoukis AS, Nikolaidis MG, Kyparos A, Kouretas D. Blood reflects tissue oxidative stress depending on biomarker and tissue studied. Free Radic Biol Med. 2009;47(10):1371-4. doi: 10.1016/j.freeradbiomed.2009.07.014.

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14. Cholewa J, Poprzęcki S, Zajac A, Waskiewicz Z. The influence of vitamin C on blood oxidative stress parameters in basketball players in response to maximal exercise. Science & Sports. 2008;23(3-4):176–182.influence of vitamin C on blood oxidative stress parameters in basketball players in response to maximal exercise. Science & Sports. 2008;23(3-4):176–182.

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Analysis of some components of blood proteome in "Healthy population"

Abstract

The aim of the study was to study some components of blood proteome in healthy megapolis population. Methods: The study included 2025 people examined in the framework of preventive medical examination and referred to its results to 1–2 groups of health (the category of healthy people) and did not have at the time of examination of chronic and acute diseases. The age of the examined persons was in the range of 20–50 years (median — 34.8 years). Total protein level, plasma concentrations of C-reactive protein, ferritin and homocysteine were selected as markers of blood proteome. Results: Our screening study allowed establishing that a significant part of the population of the megapolis, classified as practically healthy persons, has deviations from the physiological interval for a number of proteome components. This is most evident in shifts in plasma concentrations of C-reactive protein and ferritin. So, in more than half of the individuals levels of C-reactive protein was outside the normal range. The distribution structure for ferritin shows the opposite trend. 

Keywords — blood proteome, C-reactive protein, ferritin, homocysteine

Intoduction

Currently, proteomics, being one of the most widely known synthetic biological disciplines, is considered as a fundamental basis for the development of personalized laboratory diagnostics [1, 7]. In whole, proteome is a set of all protein components of a biological sample [3]. It is shown that proteomic methods can study the protein structure of both biological fluids and various tissues of the body [3, 5]. This allows us to distinguish biomarkers of a number of pathological conditions and diseases, carrying out their molecular diagnosis, including — at an early stage of their formation [5, 8, 9]. The most commonly analyzed biological sample for proteomic analysis is serum or plasma [6–10]. In most cases, proteomic analysis involves a mass spectrometric study of biological substrates [7, 12, 15], but it is also possible to selectively evaluate individual components of the proteome by biochemical analysis of the concentration of metabolites [2, 3, 8, 11]. This is especially important for cohort studies that are performed as part of screening testing of a large population [2, 5, 9]. In recent decades, the emphasis of medicine has gradually shifted from diseases treating to preventive medicine [12–14, 17]. This is due to the high frequency of prenosological conditions that require timely correction. In turn, such a statement of the problem is determined by the need for a detailed study of the prevalence of metabolic disorders, including shifts in proteome components in the population classified as healthy individuals [5, 11, 12, 17]. In this regard, the aim of the study was to study some components of blood proteome in healthy megapolis population.


Methods

The study included 2025 people examined in the framework of preventive medical examination and referred to its results to 1–2 groups of health (the category of healthy people) and did not have at the time of examination of chronic and acute diseases. The age of the examined persons was in the range of 20–50 years (median — 34.8 years). All people included in the study, after obtaining informed consent, were subjected to extensive laboratory testing. Total protein level, plasma concentrations of C-reactive protein, ferritin and homocysteine were selected as markers of blood proteome. All these parameters were determined by standard laboratory methods. All patients were tested in the morning. The gradation of the level of indicators was made according to the existing standard (reference) laboratory intervals. Additionally we used a quartile approach, highlighting the reduced and increased level of the parameter and four quartiles. The normal distribution of the trait values corresponding to the Gauss distribution was taken as the population norm. The structure of distribution of values of the parameter, essentially different from the last, was considered deviating. The data were processed in the software package Statistica 6.1.


Results

The quartile analysis of the formed group of people allowed to establish that the structure of the distribution of the values of the selected proteome components differs significantly from the standard Gauss distribution (Fig. 1–4). Thus, the level of total protein is found at low values in 14.93% of the examined individuals (Fig. 1). In addition, attention is drawn to the fact that this parameter is recorded at the lower limit of the norm corresponding to 1 quartile in 33.79% of people. Interesting data were obtained with respect to the level of C-reactive protein in blood plasma (Fig. 2). It was revealed that among the examined people, referred to the results of preventive examination to the category of practically healthy persons, in 54.81% of cases there was an increased level of the indicator. In addition, in 14.97% of the examined people the concentration of C-reactive protein was fixed at the upper limit of the norm corresponding to the 4th quartile. The most significant deviation from the standard distribution structure was revealed for the main iron – transport blood protein-ferritin (Fig. 3). It was found that the reduced level of this indicator was typical for 26.87% of the surveyed group of people, and in 47.65% of cases it was at the lower limit of the norm (1 quartile). According to the homocysteine concentration, the formed group corresponded to the Gauss distribution to the greatest extent, however, a certain shift was observed for this parameter as well (Fig. 4). Thus, 11.68% of the surveyed persons had a reduced value of the indicator, and it was at the lower limit of the norm in 31.31% of cases. On the contrary, an increased level of homocysteine was recorded in 5.79% of people.


Fig. 1. Quartile structure of total level of blood protein in healthy people

Fig. 2. Quartile structure of C-reactive protein level in the blood of healthy people

Fig. 3. Quartile structure of ferritin level in the blood of healthy people

Fig. 4. Quartile structure of homocysteine level in the blood of healthy people

Discussion

Laboratory biomarkers are known to be the basis of personalized medicine [1, 3, 5, 8, 12, 14]. These include components of the proteome such as C-reactive protein, ferritin and homocysteine. C-reactive protein, which belongs to the category of acute phase proteins, is one of the markers of inflammatory reaction [4, 5]. In addition, its level is considered as a predictor of various chronic diseases, including cardiovascular disease and degenerative diseases of the musculoskeletal system [16, 17]. In our study it was found that more than 54% of the population of the megapolis, belonging to the category of healthy persons, has an increased level of the indicator. This indicates the need for their in-depth study for diagnosis and early correction of prenosological conditions. Also, the study showed that a significant part of the population of a large city (about 27%) has deviations of ferritin concentration from the physiological level, and about half of the people demonstrate the trend to reduce the level of this metabolite. Such data confirm the literature data on the heterogeneity of the population according to this criterion [11], and there is evidence that both the increase and decrease in the level of this parameter is associated with an increase in the risk of cardiovascular disease [8, 11]. Similar shifts are shown by us for the concentration of homocysteine in the blood plasma of residents of the megapolis. In total, about 43% of the surveyed people had a reduced value of the parameter or located at the lower limit of the norm. It is also considered as a negative criterion, which is a potential marker of prenosological disorders, including neurological disorders (in particular, Alzheimer's disease [10], sleep disorders [2]) and even sexual dysfunction [13]. Thus, an extensive study has demonstrated the presence of significant shifts in the plasma concentration of a number of proteome components, which requires further in-depth analysis for personalized correction.


Conclusion

Our screening study allowed to establish that a significant part of the population of the megapolis, classified as practically healthy persons, has deviations from the physiological interval for a number of proteome components. This is most evident in shifts in plasma concentrations of C-reactive protein and ferritin. So, more than half of the individuals having levels of C-reactive protein outside the normal range. The distribution structure for ferritin shows the opposite trend.


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  13. Yang H.F., Kao T.W., Lin Y.Y. et al. Does Serum Homocysteine Explain the Connection Between Sexual Frequency and Cardiovascular Risk? // J Sex Med. – 2017. – Vol. 14, N 7. – P. 910–917
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  15. Zhang Y., Wang C.C., Niu R. Screening on serumbiomarkers in idiopathic pulmonary fibrosis patientsby proteomics technology // Zhonghua Liu Xing BingXue Za Zhi. – 2018. – Vol. 39, N 8. – P. 1117–1120
  16. Su J., Cui L., Yang W. et el. Baseline high-sensitivity C-reactive protein predicts the risk of incidentankylosing spondylitis: Results of a community-basedprospective study // PLoS One. – 2019. – Vol. 14, N2. – e0211946.
  17. Hsu P.F., Pan W.H., Yip B.S. C-Reactive ProteinPredicts Incidence of Dementia in an Elderly AsianCommunity Cohort // J Am Med Dir Assoc. – 2017.– Vol. 18, N 3. – P. 277.e7-277.e11.

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Blood Trace Elements under Personalized Metabolic Correction: The Preliminary Data

Abstract

The purpose of the work was to estimate the dynamics of blood trace elements under the use of personalized vitamin and mineral complex. Methods. The study aimed to the estimation of the effect of a personalized vitamin and mineral complex on the blood parameters of practically healthy people (n=252), first of all - on microelement homeostasis. Each of the surveyed individuals was taken twice to determine the concentration of trace elements (before the course and immediately after its completion). The duration of the course was fixed and was 30 days with a daily single admission. The composition of the vitamin and mineral complex was selected individually based on the results of initial testing for those components that were present in deficient or pre-deficient concentrations in a particular patient. Determination of the level of trace elements in peripheral blood was performed by atomic absorption spectrometry on the apparatus "Shimadzu AA7000" (Japan). Results. The study allowed to demonstrate the presence of a deficit or pre-deficit state in the blood content of trace elements in the considered group of practically healthy people. The analysis of the effectiveness of the course individualized vitamin and mineral complex, has allowed to establish its beneficial effect on the metabolism of some trace elements. In this preliminary study we observed this tendency on the example of particularly iron, copper, selenium and zinc. 

Key words: metabolic correction; blood; iron; cupper; selenium; zinc

Introduction

Even at a session of the medical and biological Department of the USSR Academy of Medical Sciences in 1975, it was discussed the allocation of a special group of compounds that can have a pronounced physiological effect in minimal quantities. They were combined under the name of biologically active substances [19, 24, 25]. At the same time, even a brief acquaintance with the chemical structure of food products suggests that they contain most of the groups of biologically active substances discussed at the mentioned session (alkaloids, hormones and hormone like compounds, vitamins, trace elements, biogenic amines, neurotransmitters, substances with pharmacological activity, etc.) [3-6, 9, 11, 15, 23].

However, the biological, physiological and regulatory activity of these substances is still not sufficiently taken into account by pharmacologists and doctors of various specialties. Moreover, many of the biologically active substances are present in food in equal and sometimes higher doses than the doses used in Russian Pharmacopoeia [23, 25]. On the other hand, many of them serve as the closest precursors of potent compounds that, when isolated from food, are the object of purely pharmacological research [2, 11, 19, 21, 23]. It is in this context, i.e. from the point of view of biologically significant impact of various food components on the course of metabolic processes in both healthy and diseased organisms, it is necessary to consider the role of the main micronutrients, taking into account a number of new information about the mechanisms of their therapeutic and preventive action [3, 4, 7-9].

It is well-known that in a healthy condition, trace elements constituting the living body are regulated and maintained their balance of each other and their range of physiological optimum concentration in order to maintain the normal vital functions [8, 9, 15]. Essential trace elements are in humans the chromium (Cr), cobalt (Co), copper (Cu), fluorine (F), iodine (I), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), zinc (Zn), and questionably the boron (B) and vanadium (V) [1, 8-10]. When the optimum conditions of their balance and their homeostasis, however, are broken down by deficiency or excess of certain trace element, an excess accumulation or deficiency of specified element is induced and it follows that peculiar disease is caused according to function of each specified element [10, 14-18]. Hence, one of the important tasks of micronutrientology is to substantiate, create and prevent the use of entire ensembles of functionally interconnected micronutrients of different nature and structure [4, 7, 13, 20, 21].

One of the least studied aspects of the potential therapeutic effect of biologically active substances and micronutrients is the analysis of their influence on the microelement status of the body. In this regard, The purpose of the work was to estimate the dynamics of blood trace elements under the use of personalized vitamin and mineral complex.

Materials and methods

The study aimed to the estimation of the effect of a personalized vitamin and mineral complex on the blood parameters of practically healthy people (n=252), first of all - on microelement homeostasis. Our study consists of two stages. On first stage we tested the plasma level of 23 trace elements. The average value and its standard deviation were calculated for each parameter. At the next stage, using the current standards of indicators for this certified laboratory, we divided the area of values into 6 ranges: below the norm, 1-4 quartiles of the norm, above the norm. Data was represented as a percentage for each of the selected ranges.

All data about blood trace elements were used for second stage of our study. In this stage we formed personal vitamin and mineral complex for all patients. The composition of this complex was selected individually based on the results of initial testing for those components that were present in deficient or pre-deficient concentrations in a particular patient.

Each of the surveyed individuals was taken twice to determine the concentration of trace elements (before the course and immediately after its completion). The duration of the course was fixed and was 30 days with a daily single admission. All patients were tested in the morning. The level of trace elements in peripheral blood was determined by atomic adsorption spectrometry using the Shimadzu AA7000 device (Japan).

Statistical processing was performed using the standard statistics method. Statistical analysis of the data was performed with Statistica 6.0 program. Data were expressed as means ± SE, the Student’s t-test was used for detection of statistical difference.

Study was approved with local bioethics committee. All persons in including in this study signed standard informed consent sheet.

Results

First stage of our study allowed to state the initial level of blood trace elements in healthy people. We fixed that significant part of our group of “healthy subjects” values has deviated from population reference intervals. For visualization of prevalence of these deviations in trace elements homeostasis we used quartile method. The quartile analysis of the microelement status of the population of the megalopolis made it possible to establish that the structure of their distribution differs significantly from the a priori assumed Gaussian distribution for a large number of indicators. 

In addition, it is shown that a number of trace elements also have a deficit state. Thus, more than half of the surveyed individuals (55.3%) show a reduced concentration of copper, and another 14% of people on this indicator belong to the 1 quartile, showing a predeficit state (Fig. 1). This element, being a component of a number of enzymes, belongs to the category of biogenic, and also determines the need to correct its level.

A similar but significantly smoother structure was registered for the plasma level of zinc (Fig. 1). However, according to this parameter, a significant part of the population (7.7%) has hypozincemia, which can be considered as a pre-pathology

The study of the profile of other microelements in the blood of patients allowed us to establish that in many parameters there was a pre-deficit or deficit state. This especially included for concentrations of iron, copper, selenium, and zinc.

Taking into account the fact that these compounds are essential for the functioning of the body, they were included, if necessary, in the composition of the applied vitamin and mineral complex. That is why on second stage of our study we tested the efficiency of complex individual metabolic correction. Effect of this metabolic support was estimated after the month of daily administration of the complex. It was found that the course intake of the latter provides an increase in the concentration of iron in a month of daily use by 40.6%. The plasma copper level was elevated at 8.0% (p<0.05). We also observed positive dynamics for other trace elements. For example, plasma level of selenium was increased at 59.2% after personalized correction. The concentration of zinc was fixed in 119.5% to initial value (Fig. 2-3). It should be emphasized that all these shifts were statistically significant (p<0.05 for all parameters). These trends were fully comparable to the data obtained based on an assessment of the average individual deltas of patient parameter levels. It is important to underlined that most pronounced shifts were verified for persons with preliminary deficiency of these elements.

Fig. 1. Plasma level of cupper and zink in healthy people (in %)

Fig. 2. The influence of personalized vitamin and mineral complex on plasma level of iron and cupper («*» - statistical value of differences to initial state p<0,05)

Fig. 3. The influence of personalized vitamin and mineral complex on plasma level of selenium and zinc («*» - statistical value of differences to initial state p<0,05)

Conclusion

In whole, the study allowed us to demonstrate the presence of a deficit or pre-deficit state in the blood content of trace elements in the considered group of practically healthy people. The analysis of the effectiveness of the course individualized vitamin and mineral complex, has allowed to establish its beneficial effect on the metabolism of some trace elements. In this preliminary study we observed this tendency on the example of particularly iron, copper, selenium and zinc.

References

  1. Abdel-Gawad M, Elsobky E, Shalaby MM et al (2016) Quantitative Evaluation of Heavy Metals and Trace Elements in the Urinary Bladder: Comparison Between Cancerous, Adjacent Non-cancerous and Normal Cadaveric Tissue. Biol Trace Elem Res. 174(2):280- 286.
  2. Aguiló A at al. (2005) Antioxidant response to oxidative stress induced by exhaustive exercise. Physiology & Behavior 84:1–7.
  3. Arakawa Y (2016) Trace elements maintaining the vital functions. Nihon Rinsho. 74(7):1058-65.
  4. Benderli Cihan Y, Oztürk Yıldırım S. (2011) A discriminant analysis of trace elements in scalp hair of healthy controls and stage-IIIB non-small cell lung cancer (NSCLC) patients. Biol Trace Elem Res. 144(1-3):272-94. doi: 10.1007/s12011-011-9086-x.
  5. Dreißigacker U at al. (2010) Positive correlation between plasma nitrite and performance during high intensive exercise but not oxidative stress in healthy men. Nitric Oxide Biol. Chem. 23:128- 135.
  6. Esterbauer H., Gebicki J., Puhl H., Jurgens G. (1992) The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radical Biol. Med. 13:341-390.
  7. Hansen AF, Simić A, Åsvold BO et al (2017) Trace elements in early phase type 2 diabetes mellitus-A population-based study. The HUNT study in Norway. J Trace Elem Med Biol. 40:46-53. doi: 10.1016/j.jtemb.2016.12.008.
  8. Iyengar GV (1987) Reference values for the concentrations of As, Cd, Co, Cr, Cu, Fe, I, Hg, Mn, Mo, Ni, Pb, Se, and Zn in selected human tissues and body fluids. Biol Trace Elem Res. 12(1):263-95. doi: 10.1007/BF02796686.
  9. Iyengar V, Woittiez J (1988) Trace elements in human clinical specimens: evaluation of literature data to identify reference values. Clin Chem. 34(3):474-81.
  10. Janka Z (2019) Tracing trace elements in mental functions. Ideggyogy Sz. 72(11-12):367-379. doi: 10.18071/isz.72.0367.
  11. Kazimirko VK, Maltsev VI, Butylin VYu, Gorobets NI (2004) Free radical oxidation and antioxidant therapy. Kiev, Morion.
  12. López-Jornet P, Juan H, Alvaro PF (2014) Mineral and trace element analysis of saliva from patients with BMS: a crosssectional prospective controlled clinical study. J Oral Pathol Med. 43(2):111-6. doi: 10.1111/jop.12105.
  13. Marín-Martínez L, Molino-Pagán D, López-Jornet P (2019) Trace elements in saliva and plasma of patients with type 2 diabetes: Association to metabolic control and complications. Diabetes Res Clin Pract. 157:107871. doi: 10.1016/j.diabres.2019.107871.
  14. Nawi AM, Chin SF, Azhar Shah S, Jamal R (2019) Tissue and serum trace elements concentration among colorectal patients: a systematic review of case-control studies. Iran J Public Health. 48(4):632-643.
  15. Nordberg M, Nordberg GF (2016) Trace element researchhistorical and future aspects. J Trace Elem Med Biol. 38:46-52. doi: 10.1016/j.jtemb.2016.04.006.
  16. Pasha Q, Malik SA, Shah MH (2008) Statistical analysis of trace metals in the plasma of cancer patients versus controls. J Hazard Mater. 153(3):1215-21.
  17. Siddiqui K, Bawazeer N, Joy SS (2014) Variation in macro and trace elements in progression of type 2 diabetes. Scientific World Journal 2014:461591. doi: 10.1155/2014/461591.
  18. Sohrabi M, Gholami A, Azar MH. et al (2018) Trace element and heavy metal levels in colorectal cancer: comparison between cancerous and non-cancerous tissues. Biol Trace Elem Res. 183(1):1-8. doi: 10.1007/s12011-017-1099-7.
  19. Stacenko EA (2007) Comparison of vitamine and mineral complexes for pharmacological support of antioxidant status of junior sportsman. Medical journal (4):109–111.
  20. Wach S, Weigelt K, Michalke B et al (2018) Diagnostic potential of major and trace elements in the serum of bladder cancer patients. J Trace Elem Med Biol. 46:150-155. doi: 10.1016/j.jtemb.2017.12.010.
  21. Xu B, Zhang Y, Chen Y et al (2020) Simultaneous multielement analysis by ICP-MS with simple whole blood sample dilution and its application to uremic patients undergoing long-term hemodialysis. Scand J Clin Lab Invest.20:1-9. doi: 10.1080/00365513.2020.1729401.
  22. Yaman M, Kaya G, Simsek M (2007) Comparison of trace element concentrations in cancerous and noncancerous human endometrial and ovary tissues. Int J Gynecol Cancer. 17(1):220-8.
  23. Zaitsev VG, Ostrovsky OV, Zakrevsky VI (2003) Interaction between chemical composition and action target as basis of classification of direct antioxidants. Experimental and clinical pharmacology 66(4):66-70.
  24. Zborovskaya IA, Bannikova MV (1995) Antioxidant system of organism, its role in metabolism. Clinical aspects. Gerald of Russian Academy of Medical Sciences (6):53-60.
  25. Zenkov NK, Lankin VZ, Menschikova EB (2001) Oxidative stress. Biochemicaland pathophysiological aspects. Moscow, Science.

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Before / after – our clients' results

Your health starts with science!

The participants were tested initially, and then after 2 and 4 months of taking their personalized bioniq formula.

MICRONUTRIENTS

The study showed that the main deficiency found was a lack of vitamin D.

Vitamin D / 50-100 ng/mL

Vitamin D is crucial for the metabolism of phosphorus and calcium, bone strength, and the functioning of the immune system (it stimulates the differentiation of the cells and is involved in T cell activation). Vitamin D deficiency can lead to a loss of bone density, which can contribute to osteoporosis and fractures (broken bones). It most commonly occurs in people when they have inadequate sunlight exposure, an insufficient diet, some medications or due to diseases that may affect the absorption and metabolism of this vitamin.


In the bioniq LIFE formula, its dosage is selected individually based on the results of the primary test. Since vitamin D is fat-soluble and is stored in lipids and organic compounds, it is released slowly, providing optimal blood concentration. After 2 months of taking the formula, bioniq LIFE clients showed a significant increase in their vitamin D levels in the blood.

Another common problem found mostly in women – is iron deficiency.

Regular intake of the bioniq LIFE formula contributes to an increased concentration of both iron (by the second check-up) and the protein depositing it - ferritin (by the third check-up) in the blood.

Serum Iron / 15-25 µmol/L

Serum iron is a medical laboratory test that measures the amount of circulating iron that is bound to transferrin and serum ferritin.

Ferritin /10-150 µg/L

Low level of the ferritin can be caused by haemorrhage, the poor absorption of iron, or an insufficient amount of certain foods in a diet. In the long term, the lack of ferritin can lead to an iron deficiency - or in other words, anaemia.

Levels of other trace elements, such as copper and zinc, have already reached the desired reference parameters by the second check-up, while levels of potassium, selenium and cadmium normalised only by the third check-up.

HEAVY METALS

While it is clear what to do with a microelement deficiency, what if there is a microelement excess?

A common problem especially found in people living in large cities, is the increased concentration of heavy metals.

*in our earlier studies a large number of those living in cities had hyperlithiemia.

Lead / 125-140 µg/L

Lead is a cumulative toxicant that affects multiple body systems and is particularly harmful to young children who have higher levels of absorption than adults. It is stored in the teeth and bones, where it accumulates over time. Lead in the body is distributed to the brain, liver, kidney and bones and it's elevated levels result in the failing of those systems. In the case of lead poisoning, symptoms include stomach pain, vomiting and convulsions.

Cobalt / 0-1 µg/L

Elevated levels of cobalt is a rare phenomenon found mostly in those consuming large amounts of vitamin В12, involved directly in the production of cobalt, or have endoprosthesis. It can cause severe damage to the skin and heart, enlargement of the thyroid and increased blood pressure.

Mercury / 0-5 µg/L

Mercury is a toxic heavy metal which is widely dispersed in nature. Most human exposure results from fish consumption or dental amalgam. Among the symptoms of poisoning are a burning sensation in the mouth and respiratory difficulties. In the case of long term poisoning, mercury disrupts the lungs, kidneys and nervous system.

Lithium / 1-35 µg/L

Lithium poisoning can occur when a person takes too much mood-stabilizing medication that contains lithium. It can also develop when the body does not excrete lithium properly. An overdose can cause symptoms that range from mild to severe, which includes muscle twitching, tremors and thirst.

A regular intake of the bioniq LIFE formula has helped remove any excess amounts of heavy metals from the body. The study showed a steady decrease by the second check-up.

HEALTH RISK FACTORS

In the study, we also measured levels of liver-released homocysteine and C-reactive protein, where an increased concentration can lead to endothelial dysfunctions, atherosclerosis and other cardiovascular diseases that could otherwise be easily prevented.

Homocysteine / 8-12 µmol/L

Homocysteine is an amino acid produced by the body by chemically altering adenosine. Its levels in the blood may be elevated for many reasons including genetic causes. Homocystinuria symptoms include developmental delays, osteoporosis, atherosclerosis, cardiovascular and Alzheimer's diseases. Effectively, Vitamins B6 and B12 can lower blood homocysteine levels.

C-reactive protein / 1-5 mg/L

C-reactive protein is an "acute phase protein," an early indicator of infectious or inflammatory conditions in blood vessels and is associated with the risk of development of atherosclerosis and cardiovascular diseases. Acetylsalicylic acid and statins can reduce elevated CRP levels in the blood.

Positive changes include a detected decrease in uric acid concentration, and cholesterol levels.

Results

This study on the effects of the individual bioniq LIFE formula has proved that it caused a healthy metabolic status and a balanced amount of micronutrients in our clients.

We are really pleased by the positive results of our bioniq customers!

Text: Lab34
Photos: Pexels.com

Iron metabolism under selective individualized correction

Abstract

The aim of the study was to study the effect of individually formed vitamin and mineral complex is containing iron on the metabolism of this trace element. Methods: we examined healthy persons (n=314), is randomizing into 2 groups. The main group (n=116) received a vitamin and mineral complex with the necessary amount of iron (the dose was calculated based on the results of the initial laboratory examination of the patient) during 30 days, and the comparison group (n=198) got a similar complex without iron-containing component. Prior to administration of the complex and immediately upon completion of the full course, the total iron concentration in the blood, serum iron level and ferritin content in the blood were determined. Results: the randomized controlled one-center study confirmed the positive effect of the course of personalized correction of iron metabolism on a number of its biochemical indicators (total iron level in the blood, serum concentration of this trace element and the amount of ferritin).

Keywords — iron, blood level, personalized correction.

Introduction

Iron deficiency is one of the most common problems of the population of large cities [1, 2, 5]. Numerous epidemiological studies indicate, on the one hand,a sufficiently high frequency of iron deficiency anemiaand associated pathological conditions [1–3] and, onthe other hand, indicate a significant proportion ofpersons with subclinical manifestations of metabolicdisorders of this trace element [6]. Thus, according tothe results of our previous studies, up to 27% of theadult population of the metropolis have either fullfledged or subclinical (at the level of the lower quartile)serum iron deficiency [4]. These facts clearly indicatethe feasibility of targeted detection and personalizedcorrection of iron deficiency. In this regard, the aim ofthe work was to study the effect of individually formedvitamin and mineral complex is containing iron on themetabolism of this trace element.

Methods

The study was designed as an open prospective, randomized controlled trial. It included 314 people belonging to the category of practically healthy people. The inclusion criteria were the age from 20 to 50 years, the absence of acute or chronic in the acute stage of pathology, as well as the presence of subclinical or clinical serum iron deficiency. All participants in the study signed informed consent prior to the initial survey. Further, the examined persons were randomized into 2 groups: the main group (n=116), representatives of which received a vitamin and mineral complex containing the necessary amount of iron (the dose was calculated based on the results of the initial laboratory examination of the patient), and the comparison group (n=198), which received a similar complex, the only difference of which was the absence of an iron-containing component. The duration of reception of the complex was 30 days. Prior to administration of the complex and immediately upon completion of the full course, the total iron concentration in the blood (in µg/l), serum iron level (in µmol/l) and ferritin content in the blood (in µg/l) were determined. All these parameters were evaluated by standard methods. The data were processed in the software package Statistica 6.1.

Fig. 1. Total blood level of the iron before and after the administration ofvitamin and mineral complex

Fig. 2. Blood serum level of the iron before and after the administration ofvitamin and mineral complex

Fig. 3. Blood level of the ferritin before and after the administration ofvitamin and mineral complex

Results

It was found that the majority of the studied parameters in the second control point of observation did not change relative to the first one (Fig. 1–3). Thus, the total concentration of iron in the blood and its serum level remained at the initial values (Fig. 1 and 2), while the amount of the main iron-transport protein of the blood — ferritin — even showed a downward trend (-2.6%; p<0.1). On the contrary, the personalized correction of the metabolism of the microelement under consideration contributed to the increase of all the studied parameters (Fig. 1–3). In particular, there was an increase in the total concentration of iron in the blood by 13.4% compared with the baseline (p<0.05), exceeding the value characteristic of the comparison group by 10.0% (p<0.05). A similar dynamics was recorded for serum iron level (an increase of 16.8% relative to baseline values and 8.3% — to the comparison group (p<0.05 for both cases))

The changes in ferritin levels were significant too (Fig. 3). It was found that the concentration of this iron transport protein in the representatives of the main group increased by 5.1% compared to the first control point and by 7.7% - relative to the comparison group (p<0.05 for both cases)

Conclusion

Thus, the randomized controlled one-center study confirmed the positive effect of the course of personalized correction of iron metabolism on a number of its biochemical indicators (total iron level in the blood, serum concentration of this trace element and the amount of ferritin).

References

  1. Cohen-Solal A., Leclercq C., Deray G. et al. Iron deficiency: an emerging therapeutic target in heart failure // Heart. – 2014. – Vol. 100, №18. – P. 1414–1420.
  2. Cusick S.E., Mei Z., Freedman D.S. et al. Unexplained decline in the prevalence of anemia among US children and women between 1988–1994 and 1999–2002 // Am J Clin Nutr. – 2008. – Vol. 88, №6. – P. 1611–1617.
  3. Klip I.T., Comin-Colet J., Voors A.A. et al. Iron deficiency in chronic heart failure: an international pooled analysis // Am Heart J. – 2013. – Vol. 165, №4. – P. 575–582.e3.
  4. Martusevich A.K., Karuzin K.A. Cohort study of microelement status in “healthy” population of Russian megapolis // Biomedicine (Taiwan). – 2019. – Vol. 9, Iss. 3. – e142.
  5. Parikh A., Natarajan S., Lipsitz S.R., Katz S.D. Iron deficiency in community-dwelling US adults with self-reported heart failure in the National Health and Nutrition Examination Survey III: prevalence and associations with anemia and inflammation // Circ Heart Fail. – 2011. – Vol. 4, №5. – P. 599–606.
  6. Sirbu O., Sorodoc V., Jaba I.M. et al. The influence of cardiovascular medications on iron metabolism in patients with heart failure // Med

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Study of Microelement Status in "Healthy" Population of Megapolis

Cohort study of microelement status in “healthy” population of megapolis

Abstract

The aim of the study was at the cohort assessment of microelement status in large city residents classified as “apparently healthy people”. The population study included 2,025 randomly selected middle-aged (2045 years) persons without chronic diseases or acute infectious pathologies. The set of subjects was standardized by age and gender. A blood sample was taken once from each person to determine concentrations of microelements. The level of peripheral blood microelements were determined by atomic absorption spectrometry using «Shimadzu AA7000» device (Japan). The study of a large population of city residents demonstrated inhomogeneity in their microelement status. Deficit conditions were found for a number of values, including concentrations of potassium, sodium, nickel, stibium, chromium and cadmium. At the same time, there are large proportions of persons with low plasma concentrations of copper and even lower plasma concentrations of zinc and magnesium. On the contrary, 42% of the persons show high concentrations of lithium. Such disturbances of microelement homeostasis (pre-pathological condition) make it necessary to perform targeted correction for the purpose of preventing the development of pathological conditions associated with microelement deficiencies.

Key words: Trace elements / Blood / Population / Megapolis

1. Introduction

Great public attention is currently focused on the problem of vitamin deficiency [1–4]. The latter is attributable, in particular, to nutritional habits, the environment and lifestyle in the world’s major cities [3, 5]. This situation can be corrected partially by prescribing various vitamins, promoting healthy lifestyle, including dietary principles [6–10]. The relevance of the problem is also confirmed by that the World Health Association has declared the current decade to be the Decade of Action on Nutrition (20112012) [11].

Fig. 1 Blood concentrations of potassium and sodium in apparently healthy large city residents. (quartile structure)

Fig. 2 Blood concentrations of calcium and magnesium in apparently healthy large city residents. (quartile structure)

Fig. 3 Plasma concentration of copper in large city residents. (quartile structure)

Fig. 4 Plasma Concentration of Cadmium in Large City Residents. (quartile structure)

Fig. 5 Blood concentrations of some microelements in apparently healthy large city residents. (quartile structure)

Fig. 6 Plasma concentration of lithium in large city residents. (quartile structure)

Table 1. Level of some microelements in “healthy” population of megapolis. (n = 2,025)

The other equally important but often neglected aspect of the general problem is the deficit of microelements, the role of which is significantly less known. At the same time, according to M. Houston (2008, 2010), both vitamin deficiency and microelement homeostasis disorders must be corrected concurrently [12, 13]. In order to solve the problem properly, full information on its status is required. However, there is only isolated data in world literature which relates primarily to evaluations of certain microelement concentrations in body fluids and tissues in particular diseases [1, 13]. In this case, they are generally pathogenetically associated with the related disease [1, 10, 14, 15]. Moreover, mineral homeostasis for a wide range of elements remains largely unstudied in residents of major cities who identify themselves as “apparently healthy people” [12, 13, 16–18]. On the other hand, people in this category are traditionally exposed only to superficial examination, mostly relating to the monitoring of vitamin and mineral homeostasis. From the perspective of preventive medicine, it is advisable for this segment of the population to detect and timely correct prenosological disorders for the purpose of their timely individual correction and, thus, preventing the development and progression of microelementosis [12, 14, 19, 20].

In this regard, the work is aimed at the cohort assessment of microelement status in large city residents classified as “apparently healthy people”.

2. Methods

The population study was conducted with 2,025 randomly selected persons. We included in this study middle-aged (20-45 years) peoples. Exclusion criterias was an absence of chronic diseases or acute infectious pathologies. The set of subjects was standardized by age and gender. All the patients signed the informed consent for inclusion in this study.

A blood sample was taken once from each person to determine concentrations of microelements. All subjects were tested during the morning hours. The level of peripheral blood microelements were determined by atomic absorption spectrometry using «Shimadzu AA7000» device (Japan).

The study was approved by a local Ethics Committee of the Privolzhsky Federal Medical Research Center (N°31; 14/12/2015).

Statistical analysis was performed by means of variation statistics. Mean and standard deviations were calculated for each parameter. At the next stage, as per the valid standard values of the certified laboratory, the region of values was divided into 6 ranges: below normal, quartiles 1 to 4 (Q1 = 0-25% of reference interval; Q2 = 26-50%; Q3 = 51-75%; Q4 = 76-100%), above normal. The data was expressed as a percentage for each of the selected ranges.

3. Results and discussion

It is interesting to note that the average plasma concentrations of all studied microelements, except for lithium, did not deviate markedly from the physiological standard (Table 1). At the same time, the quartile analysis of the microelement status in the large city population established that the distribution patterns differ significantly from the a priori expected Gaussian distribution by a large number of parameters.

It is important to emphasize that this tendency fully applies not only to microelements but also to the elements classified as principal biogenic ones. So, the distribution pattern of the tested persons by potassium concentration showed that more than a third of the patients (33.7%) were at the lower limit of normal (quartile 1), which indicates latent hypokaliemia (Fig. 1A).

A similar situation is observed for the blood concentration of sodium, although its shift is smoother as compared to the distribution pattern for blood potassium (Fig. 1B). Nevertheless, hyponatremia and the level close to it (quartile 1) are recorded in 32.5% of the tested apparently healthy adult citizens.

As for other rare earth metals (calcium and magnesium), lower values were also registered in most cases (Fig. 2), and greater percentages of persons were in a deficiency state (5.6% and 7%, respectively). Furthermore, the values were lower in about a third of the tested persons (29.2% for calcium and 30.8% for magnesium). Taking into account wide-ranging biological functions of these elements, their deficit can be considered as a pre-pathological condition which requires targeted individual correction.

Our studies established that there are also deficiencies of a number of microelements. Thus, over a half of the tested persons (55.3%) show decreased concentration of copper, and 14% of subjects fall into quartile 1 for this value, showing the pre-deficit condition (Fig. 3). Being a component of a wide range of enzymes, this element belongs to the category of biogenic elements, which makes it necessary to correct its concentration as well.

An even more pronounced disturbance of microelement homeostasis was registered for cadmium concentration (Fig. 4). For this element, all tested large city residents showed a deficit (3.6%) or quartile 1-2 (68.5% and 27.9%, respectively), not exceeding the median reference interval.

A less pronounced downshift disturbance of the distribution pattern was also observed for other microelements, such as nickel, stibium and chromium (Fig. 5). The most pronounced shift among them was registered for chromium concentration, with chromium deficiency and decreased value (quartile 1) found in 31.2% of the persons tested (Fig. 5C). In opposite, we fixed that a significant part of tested population (about 50%) has high concentration of nickel and stibium in blood plasma (3 and 4 quartile or above normal value).

This may indirectly indicate man-made pollution in a large megapolis. This trend is more pronounced in the plasma level of nickel, in which a larger proportion of healthy people had a value above normal.

It is interesting that there is a reverse tendency for some microelements showing increased values. In particular, over 42% of the large city population is characterized by high lithium concentrations, and another 21.2% of the tested persons show a tendency towards an increase in the concentration of this element (Fig. 6A). A similar but much more smoothed pattern was registered for plasma zinc concentration, although for this parameter, a significant proportion of the population (7.7%) has hypozincemia, which can be considered as a pre-pathological condition.

4. Conclusion

The study of a large population of city residents demonstrated inhomogeneity in their microelement status. Deficit conditions were found for a number of values, including concentrations of potassium, sodium, nickel, stibium, chromium and cadmium. At the same time, there are large proportions of persons with low plasma concentrations of copper and even lower plasma concentrations of zinc and magnesium. On the contrary, 42% of the persons show high concentrations of lithium. Such disturbances of microelement homeostasis (pre-pathological condition) make it necessary to perform targeted correction for the purpose of preventing the development of pathological conditions associated with microelement deficiencies. In this regard, our further research will be focused on evaluating the effectiveness of personalized correction of micronutrient deficiencies in various metabolic parameters.

Conflicts of interest statement

The authors wish to disclose no conflicts of interest.

References

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Metabolic correction

Blood Trace Elements under Personalized Metabolic Correction: The Preliminary Data

Abstract

The purpose of the work was to estimate the dynamics of blood trace elements under the use of personalized vitamin and mineral complex. Methods. The study aimed to the estimation of the effect of a personalized vitamin and mineral complex on the blood parameters of practically healthy people (n=252), first of all - on microelement homeostasis. Each of the surveyed individuals was taken twice to determine the concentration of trace elements (before the course and immediately after its completion). The duration of the course was fixed and was 30 days with a daily single admission. The composition of the vitamin and mineral complex was selected individually based on the results of initial testing for those components that were present in deficient or pre-deficient concentrations in a particular patient. Determination of the level of trace elements in peripheral blood was performed by atomic absorption spectrometry on the apparatus "Shimadzu AA7000" (Japan). Results. The study allowed to demonstrate the presence of a deficit or pre-deficit state in the blood content of trace elements in the considered group of practically healthy people. The analysis of the effectiveness of the course individualized vitamin and mineral complex, has allowed to establish its beneficial effect on the metabolism of some trace elements. In this preliminary study we observed this tendency on the example of particularly iron, copper, selenium and zinc. 

Key words: metabolic correction; blood; iron; cupper; selenium; zinc

Introduction

Even at a session of the medical and biological Department of the USSR Academy of Medical Sciences in 1975, it was discussed the allocation of a special group of compounds that can have a pronounced physiological effect in minimal quantities. They were combined under the name of biologically active substances [19, 24, 25]. At the same time, even a brief acquaintance with the chemical structure of food products suggests that they contain most of the groups of biologically active substances discussed at the mentioned session (alkaloids, hormones and hormone like compounds, vitamins, trace elements, biogenic amines, neurotransmitters, substances with pharmacological activity, etc.) [3-6, 9, 11, 15, 23].

However, the biological, physiological and regulatory activity of these substances is still not sufficiently taken into account by pharmacologists and doctors of various specialties. Moreover, many of the biologically active substances are present in food in equal and sometimes higher doses than the doses used in Russian Pharmacopoeia [23, 25]. On the other hand, many of them serve as the closest precursors of potent compounds that, when isolated from food, are the object of purely pharmacological research [2, 11, 19, 21, 23]. It is in this context, i.e. from the point of view of biologically significant impact of various food components on the course of metabolic processes in both healthy and diseased organisms, it is necessary to consider the role of the main micronutrients, taking into account a number of new information about the mechanisms of their therapeutic and preventive action [3, 4, 7-9].

It is well-known that in a healthy condition, trace elements constituting the living body are regulated and maintained their balance of each other and their range of physiological optimum concentration in order to maintain the normal vital functions [8, 9, 15]. Essential trace elements are in humans the chromium (Cr), cobalt (Co), copper (Cu), fluorine (F), iodine (I), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), zinc (Zn), and questionably the boron (B) and vanadium (V) [1, 8-10]. When the optimum conditions of their balance and their homeostasis, however, are broken down by deficiency or excess of certain trace element, an excess accumulation or deficiency of specified element is induced and it follows that peculiar disease is caused according to function of each specified element [10, 14-18]. Hence, one of the important tasks of micronutrientology is to substantiate, create and prevent the use of entire ensembles of functionally interconnected micronutrients of different nature and structure [4, 7, 13, 20, 21].

One of the least studied aspects of the potential therapeutic effect of biologically active substances and micronutrients is the analysis of their influence on the microelement status of the body. In this regard, The purpose of the work was to estimate the dynamics of blood trace elements under the use of personalized vitamin and mineral complex.

Materials and methods

The study aimed to the estimation of the effect of a personalized vitamin and mineral complex on the blood parameters of practically healthy people (n=252), first of all - on microelement homeostasis. Our study consists of two stages. On first stage we tested the plasma level of 23 trace elements. The average value and its standard deviation were calculated for each parameter. At the next stage, using the current standards of indicators for this certified laboratory, we divided the area of values into 6 ranges: below the norm, 1-4 quartiles of the norm, above the norm. Data was represented as a percentage for each of the selected ranges.

All data about blood trace elements were used for second stage of our study. In this stage we formed personal vitamin and mineral complex for all patients. The composition of this complex was selected individually based on the results of initial testing for those components that were present in deficient or pre-deficient concentrations in a particular patient.

Each of the surveyed individuals was taken twice to determine the concentration of trace elements (before the course and immediately after its completion). The duration of the course was fixed and was 30 days with a daily single admission. All patients were tested in the morning. The level of trace elements in peripheral blood was determined by atomic adsorption spectrometry using the Shimadzu AA7000 device (Japan).

Statistical processing was performed using the standard statistics method. Statistical analysis of the data was performed with Statistica 6.0 program. Data were expressed as means ± SE, the Student’s t-test was used for detection of statistical difference.

Study was approved with local bioethics committee. All persons in including in this study signed standard informed consent sheet.

Results

First stage of our study allowed to state the initial level of blood trace elements in healthy people. We fixed that significant part of our group of “healthy subjects” values has deviated from population reference intervals. For visualization of prevalence of these deviations in trace elements homeostasis we used quartile method. The quartile analysis of the microelement status of the population of the megalopolis made it possible to establish that the structure of their distribution differs significantly from the a priori assumed Gaussian distribution for a large number of indicators. 

In addition, it is shown that a number of trace elements also have a deficit state. Thus, more than half of the surveyed individuals (55.3%) show a reduced concentration of copper, and another 14% of people on this indicator belong to the 1 quartile, showing a predeficit state (Fig. 1). This element, being a component of a number of enzymes, belongs to the category of biogenic, and also determines the need to correct its level.

A similar but significantly smoother structure was registered for the plasma level of zinc (Fig. 1). However, according to this parameter, a significant part of the population (7.7%) has hypozincemia, which can be considered as a pre-pathology

The study of the profile of other microelements in the blood of patients allowed us to establish that in many parameters there was a pre-deficit or deficit state. This especially included for concentrations of iron, copper, selenium, and zinc.

Taking into account the fact that these compounds are essential for the functioning of the body, they were included, if necessary, in the composition of the applied vitamin and mineral complex. That is why on second stage of our study we tested the efficiency of complex individual metabolic correction. Effect of this metabolic support was estimated after the month of daily administration of the complex. It was found that the course intake of the latter provides an increase in the concentration of iron in a month of daily use by 40.6%. The plasma copper level was elevated at 8.0% (p<0.05). We also observed positive dynamics for other trace elements. For example, plasma level of selenium was increased at 59.2% after personalized correction. The concentration of zinc was fixed in 119.5% to initial value (Fig. 2-3). It should be emphasized that all these shifts were statistically significant (p<0.05 for all parameters). These trends were fully comparable to the data obtained based on an assessment of the average individual deltas of patient parameter levels. It is important to underlined that most pronounced shifts were verified for persons with preliminary deficiency of these elements.

Fig. 1. Plasma level of cupper and zink in healthy people (in %)

Fig. 2. The influence of personalized vitamin and mineral complex on plasma level of iron and cupper («*» - statistical value of differences to initial state p<0,05)

Fig. 3. The influence of personalized vitamin and mineral complex on plasma level of selenium and zinc («*» - statistical value of differences to initial state p<0,05)

Conclusion

In whole, the study allowed us to demonstrate the presence of a deficit or pre-deficit state in the blood content of trace elements in the considered group of practically healthy people. The analysis of the effectiveness of the course individualized vitamin and mineral complex, has allowed to establish its beneficial effect on the metabolism of some trace elements. In this preliminary study we observed this tendency on the example of particularly iron, copper, selenium and zinc.

References

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Lipid metabolism in blood

Abstract

Introduction: The purpose of the study was to evaluate the effectiveness of personalized correction of violations of fat metabolism when using an individually prescribed vitamin and mineral complex.

Methods: The study included 313 volunteers who belong to the category of "practically healthy people" and do not have a severe chronic pathology. All participants in the study were randomly assigned to the main group (n = 197) and the comparison group (n = 116). At the first stage, the state of blood lipid metabolism was evaluated in the representatives of both formed groups, and the laboratory examination complex included: determination of the total cholesterol concentration, the concentration of low- and high-density cholesterol, and the level of triglycerides. Patients of the main group were additionally monitored for the level of blood trace elements and a wide range of biochemical parameters. Taking into account the results of the latter, the composition of the vitamin and mineral complex was individually selected for them. The duration of its daily intake for all members of the main group was 60 days. Patients in the comparison group received a placebo for a similar time period.

Result & Conclusion: The study of the effectiveness of the personalized vitamin and mineral complex allowed us to demonstrate the positive effect of daily intake (for 2 months) on the parameters of blood lipid metabolism. It was manifested in a decrease in the total concentration of cholesterol, which was mainly provided by a decrease in the level of cholesterol contained in low-density.

Introduction

There is an extremely high prevalence of significant lipid metabolism disorders in the modern population1, 2, 3, 4, which later serve as one of the main reasons for the formation and progression of cardiovascular and cerebrovascular pathology, obesity, metabolic syndrome, and other ailments. Chronic shifts in fat metabolism indicators are currently considered to be predictor of an unfavorable course and other pathogenetic disorders unrelated to dyslipidemia (e.g. diabetes mellitus, hypo- and hyperthyroidism, etc.) 1, 5, 6, 7, 8.

Epidemiological studies carried out with the involvement of various groups of people, including those belonging to the category of "practically healthy persons", have allowed us to establish certain findings. Notably, in a significant proportion of the examined individuals, the main laboratory markers of the state of lipid metabolism (e.g. total cholesterol, low-density lipoprotein cholesterol, and triglyceride concentration) are either at elevated levels or approaching them, remaining in the border quartile of the norm (Q4)4, 5, 8, 9. This indicates a high latent risk of effective participation of dyslipidemia in the development of the above diseases, primarily with respect to the cardiovascular profile1, 6, 10, 11.

Based on this, it is extremely important to choose the most effective and physiological ways to correct the observed disorders of fat metabolism1, 3, 8, 11, 12. Traditionally, the first recommendation for such a group of patients is to change the nature of nutrition13, 14, 15, but without pharmacological support, this measure does not always allow for the full leveling of the considered shifts in metabolic processes, especially if there are significant deviations of laboratory parameters from the age reference range8, 10, 13, 16. In this situation, targeted and individualized pharmacological support is necessary12, 15. At the same time, the potential specificity of metabolic shifts, taking into account the individual characteristics of the body, determines the feasibility of using a personalized approach for correction; however, there are currently no effective means to ensure that15, 16, 17, 18.

To solve this problem, we have been creating and testing a system of individual metabolic correction for a number of years, based on preliminary extended monitoring of the metabolic and microelement status of the body, followed by the formation of the composition of the vitamin and mineral complex and step-by-step monitoring of its effectiveness19, 20. The expediency of this complex for restoring the body's mineral homeostasis has been shown21, but its effect on lipid metabolism has not been previously considered.

In this regard, the purpose of the study was to evaluate the effectiveness of personalized correction of changes in fat metabolism when using an individually prescribed vitamin and mineral complex.

Material — Methods

Patients

The study included 313 volunteers (19-54 years old) who belong to the category of "practically healthy people" and do not have any severe chronic pathology. All participants in the study were randomly assigned to the main group (n = 197) and the treatment group (n = 116). The full design of our survey is illustrated in Figure 1. The distribution of estimated persons by gender is also shown in Figure 1.

Figure 1 . Design scheme for our study (as CONSORT 2010 Flow Diagram).

Inclusion criteria were:

  • Age from 18 to 60 years;
  • Absence of chronic and acute pathology;
  • Informed consent to participate in the study.

Exclusion criteria were:

  • Age under 18 years and over 60 years;
  • Presence of chronic and acute pathology;
  • Declination to participate in the study;
  • Allergy to some components of the complex.

Laboratory examination protocol

At the first stage, the state of blood lipid metabolism was evaluated for the subjects of both groups. The laboratory examination complex included the following: determination of the total cholesterol concentration, the level of low-density and high-density lipoprotein cholesterol (Ch-LPLD and Ch-LPHD, respectively), and triglycerides. All parameters were determined using standard methods. Parameters of lipid metabolism were monitored before and immediately after the end of the full course of treatment (for the treatment group), with the comparison group as a control.

At the second stage, we calculated individual deltas (between second control point [after full course of complex/placebo intake] and first point [baseline — before treatment course]) for each tested parameter. The group deltas of the parameters were calculated as the sum of the deltas of each patient in this group.

Scheme of appointment of individual vitamin and mineral complex

Patients of the treatment group were additionally monitored for the level of 23 blood trace elements (Na, K, Ca, Mg, Fe, Cu, Zn, Se, Cd, Pb, Al, Cr, Li, B, Co, Si, Mn, Mo, As, Ni, Hg, Sb, and Ti) and a wide range of biochemical parameters representing Fe metabolism, hepatic and intoxication makers, main hormones, and carbohydrate metabolism. Based on the results of this multiparametric laboratory examination, we formed the composition of a personal vitamin and mineral complex. The composition of the complex was supposed to replace the components of those metabolites for which the level was detected below or at the lower limit of the norm19, 20. This method allowed us to select personalized components of the complex.

The duration of the daily intake of the complex for all members of the treatment group was 60 days. Patients in the comparison group received a placebo for a similar time period.

Statistics

The results were processed using the Statistica 6.0 program22. All the data were processed with standard algorithms of descriptive statistics and were presented as Mean±SD. The dynamics of indicators were studied in two ways: by calculating the average values for the group and by using "individual deltas" (differences in indicators) separately for each subject.

Results

It is known that the total cholesterol level is an integral indicator that characterizes the state of lipid metabolism. Analysis of the dynamics of this parameter allows us to establish that there were shifts in the concentration of total cholesterol in the second control point, but the severity of each was not the same (Figure 2). For example, in the treatment group who received a vitamin-mineral complex during the month, these changes were statistically significant (5.26 vs. 5.03 mmol/l; p < 0.05 in relation to the first control point). On the contrary, the comparison group showed a decrease in the parameter level only at the trend level (5.26 vs. 5.07 mmol/l; p < 0.1 relative to the initial level).

Figure 2 . Plasma level of total cholestrol in dymamics of the use of vitamine and mineral complex (treatment group) vs . placebo (astericks indicates the presence of statistically valued differences to baseline level, p < 0.05).

In this regard, an illustrative estimate of the average individual deltas was made in addition to the standard statistical approach. On its basis, it was found that in the treatment group the average value of individual deltas was -0.33 mmol/l (p < 0.05), and in the comparison group, the value was only -0.12 mmol/l (p > 0.1).

Similar dynamics were observed for low-density lipoprotein cholesterol (Figure 3). According to this parameter, a statistically significant decrease was found in the treatment group (3.28 vs. 3.10; p < 0.05 relative to the first control point), and there were no significant changes in the placebo subjects (3.28 vs. 3.22; p > 0.1). This indicates a positive transformation of the state of lipid metabolism since the reduction of total cholesterol is directly provided by reducing the most atherogenic fraction of cholesterol contained in low-density lipoproteins. We can assume that similar dynamics can be observed for very low-density lipoproteins and chylomicrons, but these indicators were not considered in this study. In contrast, there were no statistically significant shifts in cholesterol included in the fraction of high-density lipoprotein (1.48 vs. 1.44 and 1.48 vs. 1.43 for treatment and comparison groups, respectively).

Figure 3 . Plasma level of cholesterol in lipoproteins of high and low density (Ch-LPHD and Ch-LPLD, respectively) in dynamics of the use of vitamin and mineral complex (treatment group) vs . placebo (comparison group) (asterisks indicates the presence of statistically valued differences to baseline level, p < 0.05).

The above trends were implemented to assess the individual deltas of the parameters, as shown in Figure 4. In particular, for low-density lipoprotein cholesterol in the treatment group, this criterion was equal to -0.26 mmol/l (p < 0.05), while in the treatment group it was -0.06 mmol/l (p > 0.1). All of the above indicates the presence of positive changes in the concentration of cholesterol contained in low-density lipoproteins. It should be noted that in terms of low-density lipoprotein cholesterol and triglycerides, there were no significant variations in both the treatment group and the comparison group.

Figure 4 . Plasma level of triglycerides in dynamics of the use of vitamin and mineral complex (treatment group) vs . placebo (comparison group) (asterisks indicates the presence of statistically valued differences to baseline level, p < 0.05).

Such dynamics indicates that the volunteers who received the vitamin-mineral complex have a moderate but significant restructuring of lipid metabolism, which consists in reducing the atherogenic fraction of cholesterol. These indicators characterize the integral shifts in metabolism that are formed as a result of the indirect effect of the studied complex (lipid components were not included in the composition of the applied complex)19.

Discussion

Given the high prevalence of cardiovascular pathology and metabolic disorders, timely and complete correction of lipid metabolism shifts play a significant role in the primary and secondary prevention of cardiovascular incidents, which are important even for a cohort of people belonging to conditionally "practically healthy" individuals1, 6, 11, 17. At the same time, it is important to emphasize that standard means of pharmacological correction3, 7, 10, 23, i.e. the first line of which is carried, in particular statins5, 8, 24, are usually prescribed in the presence of pronounced violations of lipid metabolism. However, for moderate shifts or borderline indicators, the corrections are limited to dietary recommendations14, 15, 16, 24, 23. It is the disclosure of the optimization possibilities of the latter case that concerns our study. We demonstrated that the individualized administration of the vitamin-mineral complex according to the developed algorithm (after a preliminary extended laboratory examination of the patient19, 20) helped to reduce both the total concentration of cholesterol and its pro-atherogenic fraction contained in low-density lipoproteins. It should be noted that this effect is indirect since the complex does not include components that directly affect fat metabolism. Therefore, the revealed positive effect of the studied vitamin and mineral complex is due to non-specific normalization of metabolism, in general.

The remaining integral parameters of lipid metabolism, including the concentration of triglycerides and high-density lipoproteins, were initially within the limits of the physiological norm, and not approaching the boundary values. In our opinion, this causes the absence of significant changes in their concentration at the end of the course of taking the complex.

The main limitations of our study were the limited location of the study and the need to conduct the research on a larger sample size, with the study repeated at least twice.

Conclusion

The study of the effectiveness of the personalized vitamin and mineral complex allowed us to demonstrate the positive effect of its daily intake (for 2 months) on the parameters of blood lipid metabolism. The vitamin-mineral complex treatment course led to a decrease in the total concentration of cholesterol, which mainly resulted from the decrease in the level of cholesterol contained in low-density lipoproteins.

Abbreviations

Ch-LPHD: cholesterol in lipoproteins of high density

Ch-LPLD: cholesterol in lipoproteins of low density

Q4: fourth quartile

Acknowledgments

Not applicable.

Author’s contributions

A.K.M. and K.A.K. contributed to the conceptualization and design of the study, the acquisition, analysis and interpretation of data. They were drafting the article and revising the article critically for important intellectual content. All authors read and approved the final manuscript.

Funding

This article had no financial support of this faculty.

Availability of data and materials

Data and materials used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

This study was conducted in accordance with the amended Declaration of Helsinki. The study was approved by Local Ethic Committee of Burnazyan’s Medical Biophysical Center, and all participants provided written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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