Platelet mitochondrial function and endogenous coenzyme Q10 levels are reduced in patients after COVID-19.

BACKGROUND: After an acute treatment for coronavirus disease (COVID-19), some symptoms may persist for several weeks, for example: fatigue, headaches, muscle and joint pain, cough, loss of taste and smell, sleep and memory disturbances, depression. Many viruses manipulate mitochondrial function, but the exact mechanisms of SARS-CoV-2 virus effect remain unclear. We tested the hypothesis that SARS-CoV-2 virus may affect mitochondrial energy production and endogenous biosynthesis of coenzyme Q10 (CoQ10). METHODS: Ten patients after COVID-19 and 15 healthy individuals were included in the study. Platelets isolated from peripheral blood were used as an accessible source of mitochondria. High-resolution respirometry for the evaluation of platelets mitochondrial function, and HPLC method for CoQ10 determination were used. Oxidative stress was evaluated by TBARS concentration in plasma. RESULTS: Platelet mitochondrial respiratory chain function, oxidative phosphorylation and endogenous CoQ10 level were reduced in the patients after COVID-19. CONCLUSION: We assume that a reduced concentration of endogenous CoQ10 may partially block electron transfer in the respiratory chain resulting in a reduced adenosine triphosphate (ATP) production in the patients after COVID-19. Targeted mitochondrial therapy with CoQ10 supplementation and spa rehabilitation may improve mitochondrial health and accelerate the recovery of the patients after COVID-19. Platelet mitochondrial function and CoQ10 content may be useful mitochondrial health biomarkers after SARS-CoV-2 infection (Tab. 3, Fig. 3, Ref. 46).

Treatment with coenzyme Q10, omega-3-polyunsaturated fatty acids and their combination improved bioenergetics and levels of coenzyme Q9 and Q10 in skeletal muscle mitochondria in experimental model of arthritis.

Rheumatoid arthritis (RA) and its animal model adjuvant arthritis (AA) are inflammatory diseases characterized by chronic inflammation, systemic oxidative stress and disturbed mitochondrial bioenergetics of skeletal muscle. The present study aimed to evaluate the effects of coenzyme Q10 - CoQ10 (100 mg/kg b.w.), omega-3-polyunsaturated fatty acids - omega-3-PUFA (400 mg/kg b.w.) and their combined treatment in AA on impaired skeletal muscle mitochondrial bioenergetics, inflammation and changes in levels CoQ9 and CoQ10 in plasma. Markers of inflammation (C-reactive protein, monocyte-chemotactic protein-1), antioxidant capacity of plasma, respiratory chain parameters of skeletal muscle mitochondria and concentrations of CoQ9 and CoQ10 in plasma and in muscle tissue were estimated. Treatment of the arthritic rats with CoQ10, omega-3-PUFA alone and in combination partially reduced markers of inflammation and increased antioxidant capacity of plasma, significantly increased concentrations of coenzyme Q in mitochondria and improved mitochondrial function in the skeletal muscle. Combined treatment has similar effect on the mitochondrial function as monotherapies; however, it has affected inflammation and antioxidant status more intensively than monotherapies. Long-term supplementary administration of coenzyme Q10 and omega-3-PUFA and especially their combination is able to restore the impaired mitochondrial bioenergetics and antioxidant status in AA.

Is mitochondrial bioenergetics and coenzyme Q10 the target of a virus causing COVID-19?

COVID-19 ‒ a coronavirus disease, affected almost all countries in the world. It is a new virus disease, nobody has prior immunity to it, human population is prone to infections. In March 11 2020, WHO declared the pandemic status. The main symptoms include: fever, dry cough and fatigue. Virus proteins need mitochondrial energy for their own survival and replication. Upon viral infections, mitochondrial dynamics and metabolism can be modulated, which can influence the energy production in the host cells. Coenzyme Q10 is an integral component of mitochondrial respiratory chain and the key component of mitochondrial ATP production. The exact pathobiochemical mechanism of the disease is unknown. Modulated mitochondrial dynamics and metabolism with lower CoQ10 levels in viral infections leads us to the hypothesis that one of the main pathobiochemical effects of SARS-Cov-2 virus could be mitochondrial bioenergetics dysfunction with CoQ10 deficit leading to the reduction of its endogenous biosynthesis. The mechanism might be virus induced oxidative stress causing a mutation of one or more of the nine COQ genes, resulting in primary CoQ10 deficiency. New perspective for patients with COVID-19 may be supportive targeting therapy with coenzyme Q10 to increase the energy production, immunity and decrease oxidative stress (Fig. 1, Ref. 51). Keywords: COVID-19, virus, mitochondrial bioenergetics, coenzyme Q10, oxidative stress.

The importance of coenzyme Q10 and its ratio to cholesterol in the progress of chronic kidney diseases linked to non- -communicable diseases.

OBJECTIVES: The mortality of patients with chronic kidney diseases (CKD) increases with the decrease in glomerular filtration rate (eGFR). In the progress of CKD that is closely linked to non-communicable diseases (NCDs), the role of coenzyme Q10 (CoQ10) is not fully evaluated. We aimed to evaluate the importance of CoQ10, CoQ10/cholesterol ratio, and oxidative stress in the progress of CKD. PATIENTS AND METHODS: The control group was constituted of 19 healthy subjects who volunteered to enrol in the study, CKD group consisted of 58 patients with CKD, of whom 54 had CKD combined with hypertension, 22 had CKD combined with hypertension and diabetes type 2 , and 18 had CKD combined with hypertension and statin therapy. We observed age, BMI, creatinine, uric acid, eGFR, hemoglobin, CRP, glucose, lipids fraction, and liver enzymes. Coenzyme Q10-TOTAL (ubiquinol+ubiquinone) in platelets and plasma were determined using HPLC method with UV detection. Indexed of CoQ10/lipid fractions were evaluated. Oxidative stress was determined as thiobarbituric acid­reactive substances (TBARS). RESULTS: With increased stages of CKD, eGFR and CoQ10 as well as its ratio to lipids were significantly reduced while TBARS increased. CONCLUSION: We assume that lower endogenous CoQ10 level may be one of the reasons of kidney dysfunction. CoQ10/lipids ratio and increase in oxidative stress can predict the progression of CKD in patients with arterial hypertension, diabetes mellitus and dyslipidemia (Tab. 2, Fig. 4, Ref. 49).

Platelet mitochondrial bioenergetic analysis in patients with nephropathies and non-communicable diseases: a new method.

OBJECTIVES: To test the hypothesis if mitochondrial bioenergetic function analyzed in circulating platelets may represent peripheral signature of mitochondrial dysfunction in nephropathy associated to non-communicable human diseases such as cardiovascular diseases, diabetes and with statins treatment. METHODS: High-resolution respirometry was used for analysis of mitochondrial bioenergetics in human platelets isolated from peripheral blood. This method is less-invasively compared to skeletal muscle biopsy. Patients with nephropathies and in combination with non-communicable diseases were included in the study. RESULTS: This pilot study showed platelet mitochondrial bioenergy dysfunction in patients with nephropathies and non-communicable diseases. Positive effect of treatment with 10 mg atorvastatin on platelet mitochondrial respiratory chain Complex I-linked respiration and ATP production in patients with nephropathies, diabetes and 80 mg atorvastatin in patient with nephropathy and dialysis was found. Positive effect of 80 mg fluvastatin treatment, and negative effect of thrombocytopenia and renal transplantation on platelet mitochondrial bioenergy was determined. CONCLUSION: High-resolution respirometry allowed detection of small changes in platelet mitochondrial function. This method could be used as a sensitive bioenergetic test of mitochondrial function for diagnosis and monitoring the therapy in patients with nephropathy (Tab. 1, Fig. 3, Ref. 39).

Effects of complete water fasting and regeneration diet on kidney function, oxidative stress and antioxidants.

OBJECTIVE: The aim of the study was to observe the influence of 11-days complete water fasting (WF) and regeneration diet (RD) on renal function, body weight, blood pressure and oxidative stress. BACKGROUND: Therapeutic WF is considered a healing method. METHODS: Ten volunteers drank only water for 11 days, followed by RD for the next 11 days. Data on body weight, blood pressure, kidney functions, antioxidants, lipid peroxidation, cholesterols, triacylglycerols and selected biochemical parameters were obtained. RESULTS: WF increased uric acid and creatinine and decreased glomerular filtration rate. After RD, the parameters were comparable to baseline values. Urea was not affected. Lipid peroxidation (TBARS) decreased and maintained stable after RD. Fasting decreased α-tocopherol and increased γ-tocopherol, no significant changes were found after RD. Coenzyme Q10 decreased after RD. HDL-cholesterol decreased in WF. Total- and LDL-cholesterol decreased after RD. Other biochemical parameters were within the range of reference values. CONCLUSIONS: The effect of the complete fasting on kidney function was manifested by hyperuricemia. Renal function was slightly decreased, however maintained within the reference values. After RD, it returned to baseline values. The positive effect of the complete water fasting was in the reduction of oxidative stress, body weight and blood pressure (Tab. 3, Ref. 25).

Importance of the assessment of coenzyme Q10, alpha-tocopherol and oxidative stress for the diagnosis and therapy of infertility in men.

UNLABELLED: Male infertility is one of the most stressful factors of couples, being present in about 40% cases. It is usually caused by a low number of sperm (oligozoospermia) or poor sperm motility (asthenozoospermia). The sperm motility is used as an indicator of semen quality and male infertility. To the impairment of male reproduction health can contribute genetic, nutritional and environmental factors, smoking and drugs. It is well documented that excessive reactive oxygen species (ROS) production decreases sperm motility, impairs sperm function, damages the morphology of spermatozoa (1, 2). To the decreased sperm motility contribute also disturbances of sperm mitochondrial function and energy production, low levels of coenzyme Q10 and carnitine, as well as sperm mitochondrial deoxyribonucleic acid (DNA) defects. The origin of sperm dysfunction, however, is not well understood. BACKGROUND: Oxidative stress has been established as a major factor in the pathogenesis of male infertility. Low level of coenzyme Q10 contributes to the decreased sperm motility, which plays a vital role in sperm mitochondrial energy production and neutralization of reactive oxygen species (ROS).The aim of the present study was to find out, if an assessment of coenzyme Q10-TOTAL (CoQ10-TOTAL), α-tocopherol, γ-tocopherol and oxidative stress could contribute to the diagnosis of infertility in men. SUBJECTS AND METHODS: Two groups of infertile men, according to sperm motility (a+b and b+c) were included in the study. CoQ10-TOTAL, α-tocopherol, γ-tocopherol in plasma and seminal fluid, and parameter of oxidative stress (thiobarbituric acid reactive substances - TBARS) in plasma were determined. RESULTS: Higher sperm density and decreased sperm pathology were found in group a+b vs b+c (class a and b - fast and weak forward motility, class c - nonprogressive motility). Concentrations of CoQ10-TOTAL and α-tocopherol were significantly increased in seminal fluid of groups a+b vs b+c, opposite results were estimated in plasma. Concentrations of γ-tocopherol in plasma and seminal fluid of both groups were similar. Plasmatic TBARS concentrations were increased in both groups of infertile men. CONCLUSION: We suppose that incorporation of oxidative stress assessment, CoQ10-TOTAL and α-tocopherol concentrations in seminal fluid and plasma into routine andrology can play an important role for the diagnosis and targeted therapy of male infertility (Tab. 1, Ref. 16).

Ratio of lipid parameters to coenzyme Q10 could be used as biomarker of the development of early complications of obesity in children.

BACKGROUND: Chronic obesity is associated with reduced levels of antioxidants, increased free oxygen radicals, and oxidative stress. Child obesity may lead to the development of complications, such as changes in metabolism, metabolic syndrome, neurological, cardiological, respiratory, renal, gastrointestinal, endocrinological, and musculoskeletal conditions. The aim of the present study is to establish whether there is a correlation between basal CoQ10 plasma concentration and the ratio of lipid parameters to CoQ10 in obese children. METHODS: The study included 101 obese children and 20 non-obese children, aged 10-18 years. Antioxidants - CoQ10-OX, α-tocopherol, ß-carotene - in plasma were measured by HPLC method with UV detector, and plasma malondialdehyde spectrophotometrically. RESULTS: High correlation was found between plasma concentration of CoQ10 and the ratio of total Chol/CoQ10-OX as well as between CoQ10-OX and the ratio of HDL Chol/CoQ10 in plasma of obese children. The lowest correlation was between plasma concentration of CoQ10-OX and the ratio of LDL Chol/CoQ10 , as well as between CoQ10-OX and the ratio of TAG/CoQ10 in obese children. CONCLUSION: An increase of the ratios of lipid parameters to CoQ10 is associated with child obesity and could be used as biomarkers of early complications in the development of obesity in children (Tab. 3, Fig. 5, Ref. 22).

Effects of atorvastatin on heart mitochondrial function and coenzyme Q content in the experiment.

We focused on determination of whether atorvastatin: 1) reduces CoQ content, 2) impairs mitochondrial function and 3) induces dose-dependent changes. Although the high dose of atorvastatin exerted a beneficial effect on the lipid peroxidation in plasma, coenzyme Q content was reduced and heart mitochondrial function was impaired. Physicians should be aware when prescribing statins mainly in higher doses to the patients with co-existing proved or supposed CoQ10 deficiency resulting from age-related decline, and metabolic or mitochondrial diseases (Ref. 3).

Complementary therapy in diabetic patients with chronic complications: a pilot study.

BACKGROUND: Oxidative stress and dysregulation of antioxidant function play a pivotal role in the diabetic complications. METHODS: Fifty-nine patients with diabetes were randomly assigned into three groups. 1) PL group (n = 19): Polarized light (PL) was applied to neuropathic ulcers of diabetic foot twice daily for ten minutes in pulse regimen during three months. 2) QALA group (n = 20): Antioxidants (60 mg hydrosoluble CoQ10, 100 mg alpha-lipoic acid (ALA) and 200 mg vitamin E) were used in two daily doses for three months. 3) QALAPL group (n = 20): Patients used antioxidants along with PL applications. To test for differences in means, paired Student's t-test (before and after three months) was used. RESULTS: Three months application of PL significantly increased plasma concentrations of coenzyme Q10, alpha-tocopherol, tau-tocopherol and beta-carotene, and decreased lactate dehydrogenase (LDH) activity. Supplementation with antioxidants decreased plasma lipid peroxides, increased concentration of CoQ10 and improved echocardiographic parameters. Simultaneous application of PL and antioxidants significantly stimulated plasma CoQ10 and alpha-tocopherol concentrations, decreased LDH activity and contributed to improvement in heart left ventricular function in diabetics. CONCLUSION: Thus the data show that supportive therapy with PL along with the antioxidants hydrosoluble CoQ10, alpha-lipoic acid and vitamin E is an effective way of controlling the complications of type 2 diabetes (Tab. 7, Fig. 2, Ref. 44).

Simvastatin decreased coenzyme Q in the left ventricle and skeletal muscle but not in the brain and liver in L-NAME-induced hypertension.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (statins) have been proven to reduce effectively cholesterol level and morbidity and mortality in patients with coronary heart disease and/or dyslipoproteinemia. Statins inhibit synthesis of mevalonate, a precursor of both cholesterol and coenzyme Q (CoQ). Inhibited biosynthesis of CoQ may be involved in some undesirable actions of statins. We investigated the effect of simvastatin on tissue CoQ concentrations in the rat model of NO-deficient hypertension induced by chronic L-NAME administration. Male Wistar rats were treated daily for 6 weeks with L-NAME (40 mg/kg) or with simvastatin (10 mg/kg), another group received simultaneously L-NAME and simvastatin in the same doses. Coenzyme Q(9) and Q(10) concentrations were analyzed by high performance liquid chromatography. L-NAME and simvastatin alone had no effect on CoQ concentrations. However, simultaneous application of L-NAME and simvastatin significantly decreased concentrations of both CoQ homologues in the left ventricle and slightly decreased CoQ(9) concentration in the skeletal muscle. No effect was observed on CoQ level in the liver and brain. We conclude that the administration of simvastatin under the condition of NO-deficiency reduced the level of CoQ in the heart and skeletal muscle what may participate in adverse effect of statins under certain clinical conditions.

Functional remodeling of heart mitochondria in acute diabetes: interrelationships between damage, endogenous protection and adaptation.

Rats with streptozotocin-diabetes develop mechanisms of endogenous protection (MEP) that participate actively in functional remodeling of cardiac sarcolemma. Remodeling of sarcolemma is a sign of damage but it also protects the cells of the diabetic heart (DH) against additional energy disbalance due to excessive Ca(2+) entry. Since yet, cardiac mitochondria (MIT) were investigated predominantly from the aspect of damage only. Aims of the present study were: i) to distinguish between acute diabetes-induced changes in function of rat heart MIT which clearly belong to damage from those that reflect the MEP and participate in functional remodeling of the MIT; ii) elucidate the significance of MEP-induced changes in heart MIT for cardiac energetics. Acute diabetes (8 days) was induced in adult male Wistar rats by streptozotocin (STZ, 65 mg.kg(-1) i.p., single dose). On the day 8 after STZ administration, the diabetic animals exhibited 300-330 % increase in blood glucose, triacylglycerols and cholesterol as well as 89.6 % increase in glycohemoglobin (all p < 0.01). The blood level of insulin dropped by 53 % (p < 0.02). State 3 and state 4 oxygen consumptions of DH MIT were decreased against the controls, leading to drop of the respiratory control index (17.9 and 7.3 %) and oxidative phosphorylation rate (OPR, 27.5 and 24.6 %; all p < 0.003-0.02). These effects of damage yielding in strained energy balance of the acute DH were partially alleviated by MEP. The latter involved temporary preservation of the ADP : O ratio, with participation of elevated MIT Mg(2+)-ATPase activity as well as increased formation of MIT substrate and energy transition pores (both p < 0.05). Hence, the energy disbalance of the acute DH was finally manifested in 13 % loss in its AMP content only (p < 0.05). Results indicate that MIT in STZ-DH are functionally remodeled. Defective O2 consumption by MIT renders molecular changes suggestive of a mild hypoxic state but an increase in Mg(2+)-ATPase activity and facilitated energy delivery from MIT to the cytoplasm indicate the presence of MEP acting in the MIT and alleviating the effect of decreased oxidative energy production in the acute DH.

L-arginine fails to protect against myocardial remodelling in L-NAME-induced hypertension.

BACKGROUND: We investigated whether the substrate for nitric oxide synthesis L-arginine is able to modify hypertension and left ventricular hypertrophy development induced by chronic blockade of nitric oxide synthase activity by NG-nitro-L-arginine-methyl ester (L-NAME). MATERIAL AND METHODS: Four groups of rats were investigated: control, L-arginine 1.5 g kg-1, L-NAME 40 mg kg-1, and L-NAME +L-arginine in corresponding doses. Systolic blood pressure was measured by non-invasive tail-cuff plethysmography each week. After 4 weeks, the animals were sacrificed and hydroxyproline and coenzyme Q9 and Q10 concentrations in the left ventricle, and nitric oxide synthase activity in the left ventricle, kidney and brain were investigated. RESULTS: In the L-NAME group, nitric oxide synthase activity was decreased in the left ventricle, kidney and brain, and hypertension, left ventricular hypertrophy and fibrosis developed. Heart remodelling was associated with the decrease of coenzyme Q9 and Q10 concentrations in the left ventricle. Simultaneous treatment with L-NAME and L-arginine prevented nitric oxide synthase activity diminution in the left ventricle but not in the kidney and brain, and completely failed to prevent hypertension, left ventricular hypertrophy and fibrosis. Nevertheless, l-arginine prevented the diminution of coenzyme Q9 and Q10 concentrations in the left ventricle. CONCLUSIONS: We conclude that L-arginine failed to prevent hypertension, left ventricular hypertrophy and fibrosis development despite restoration of nitric oxide synthase activity in the left ventricle. However, L-arginine prevented the diminution of coenzyme Q levels in the left ventricle.

Regeneration of coenzyme Q9 redox state and inhibition of oxidative stress by Rooibos tea (Aspalathus linearis) administration in carbon tetrachloride liver damage.

The effect of rooibos tea (Aspalathus linearis) on liver antioxidant status and oxidative stress was investigated in rat model of carbon tetrachloride-induced liver damage. Synthetic antioxidant N-acetyl-L-cysteine (NAC) was used for comparison. Administration of carbon tetrachloride (CCl4) for 10 weeks decreased liver concentrations of reduced and oxidized forms of coenzyme Q9 (CoQ9H2 and CoQ9), reduced -tocopherol content and simultaneously increased the formation of malondialdehyde (MDA) as indicator of lipid peroxidation. Rooibos tea and NAC administered to CCl4-damaged rats restored liver concentrations of CoQ9H2 and alpha-tocopherol and inhibited the formation of MDA, all to the values comparable with healthy animals. Rooibos tea did not counteract the decrease in CoQ9, whereas NAC was able to do it. Improved regeneration of coenzyme Q9 redox state and inhibition of oxidative stress in CCl4-damaged livers may explain the beneficial effect of antioxidant therapy. Therefore, the consumption of rooibos tea as a rich source of natural antioxidants could be recommended as a market available, safe and effective hepatoprotector in patients with liver diseases.

Decreased levels of coenzyme Q(10) in patients with bronchial asthma.

BACKGROUND: The contribution of free oxygen radicals in the pathogenesis of bronchial asthma is generally accepted. The modulation of antioxidative defence by supplementation with antioxidants represents additive therapy in complex management of disease. The aim of the study was to assess the levels of coenzyme Q10, alpha-tocopherol, and beta-carotene both in plasma and whole blood, and malondialdehyde (MDA) and eosinophil cationic protein (ECP) in plasma of asthmatics (As). METHODS: Fifty-six As (15 males and 41 females) aged from 19 to 72 years (mean age 46 years) suffering from allergic asthma were enrolled into the study. The control group comprised 25 healthy volunteers (16 males, 9 females) aged 25-50 years. RESULTS: The concentrations of CoQ10 decreased significantly both in plasma and whole blood, compared with healthy volunteers (0.34 +/- 0.15 micromol/l vs. 0.52 +/- 0.15 micromol/l, 0.33 +/- 0.14 micromol/l vs. 0.50 +/- 0.13 micromol/l, P < 0.001, P< 0.001, respectively). The levels of alpha-tocopherol were decreased both in plasma and whole blood in comparison with controls [24.10 micromol/l (19.8; 30.5), vs. 33.20 micromol/l (28.25; 38.05), 17.22 +/- 6.45 micromol/l vs. 21.58 +/- 7.92 micromol/l, P= 0.006, P = 0.01, respectively]. The levels of MDA were elevated over the reference range in both groups (reference range < 4.5 micromol/l). No changes were seen in beta-carotene concentrations. Positive correlation was found between whole blood CoQ10 and alpha-tocopherol concentrations. CONCLUSION: Results of the study suggest a possible contribution of suboptimal concentrations of CoQ10 on antioxidative dysbalance in As and provide a rationale for its supplementation.

Levels of coenzyme Q10 in asthmatics.

BACKGROUND: The contribution of free oxygen radicals in the pathogenesis of bronchial asthma is generally accepted. The modulation of antioxidative defence by supplementation with antioxidants represents additive approach in complex management of the disease. The aim of the study was to assess the levels of coenzyme Q10, alpha-tocopherol, beta-carotene and malondialdehyde (end-stage parameter of lipid peroxidation) in asthmatics (As). METHODS: Fifty six As (15 males and 41 females) aged from 19 to 72 yrs (mean age 46 yrs) were enrolled into the study. The control group comprised of 25 healthy volunteers (16 males, 9 females) aged 25-50 years. RESULTS: Concentrations of CoQ10 and alpha-tocopherol, decresed significantly both in plasma and whole blood, compared with healthy volunteers (p < 0.009, p < 0.004; p < 0.035, p < 0.001, respectively). The level of MDA was elevated, but not statisticaly significantly. No changes were seen in beta-carotene levels. Positive correlation was found between concentrations of CoQ10 and alpha-tocopherol. CONCLUSION: Our results suggest possible contribution of suboptimal concentrations of CoQ10 on antioxidative dysbalance in As and provide rationale for its supplementation with clinical evaluation. (Tab. 2, Fig. 1, Ref. 39.).

[Effect of coenzyme Q10 in patients with kidney diseases]. / Ucinok koenzýmu Q10 u pacientov s ochoreniami obliciek.

BACKGROUND: Coenzyme Q10 belongs to important antioxidants and it has a key role in the synthesis of adenosinetriphosphate. Its beneficial effect was proved in several diseases, e.g. in mitochondrial encephalopathy, mitochondrial myopathy, mitochondrial cardiomyopathy. MATERIAL AND METHODS: All 15 patients of the studied group (5 with tubulopathy and 10 with chronic tubulointersticial nephritis) received antioxidative therapy for three months (E vitamin, C vitamin, riboflavin) and for the last two months coenzyme Q10 was added. Renal functions, spectrum of lipids, parameters of lipid peroxidation (malondialdehyde), levels of alpha-tocopherol, beta-carotene, coenzyme Q10. RESULTS: Before the substitutive antioxidative treatment, coenzyme Q10 levels reached in blood 0.11 +/- 0.03 mumol/l and 0.15 +/- 0.04 mumol/l in plasma. These values were well below the reference range (rr) is 0.4 +/- 1.0 mumol/l). After the substitution coenzyme Q10 levels significantly increased (p < 0.001) to the values of 1.66 +/- 0.16 mumol/l in blood and to 1.78 +/- 0.27 mumol/l in plasma. Plasma levels of beta-carotene increased from the markedly subnormal values 0.25 +/- 0.07 mumol/l (rr > 0.8 mumol/l) to 0.56 +/- 0.02 mumol/l (no statistical difference). Plasma levels of alpha-tocopherol remained within the reference range 32.15 +/- 4.73 mumol/l (rr 15-30 mumol/l) and they increased up to the plasma level of 44.83 +/- 5.82 mumol/l during the period of testing. Malondialdehyde levels did not significantly change within the testing period. No changes in renal functions and parameters of lipid metabolism were described. Patients well tolerated the treatment and no adverse effects were seen during the period of observation. CONCLUSIONS: Our results ascertained that levels of antioxidant CoQ10 were lower in patients with nephropathy who underwent conservative treatment with peroral substation. Such deficit can be amended by CoQ10 administration, which could be therefore taken as complementary treatment of nephrology.

Can nutrition influence circadian rhythm and heart rate variability?

Recent studies indicate that there is an interaction between biorhythms, the biological clock and triggers, which may be important in the pathogenesis of altered heart rate variability (HRV) and blood pressure variability (BPV). Circadian rhythms are under the influence of, and physiological variables are mediated by the activation of the adrenals, sympathetic/parasympathetic, hypothalamic and pituitary activity. Emotional stress, physical exertion, sleep deprivation and large fatty meals are major triggers of myocardial ischemia, angina, infarction, sudden cardiac death (SCD) and stroke. These events have been reported to exhibit a circadian variation with increased frequency in the second quarter of the day, which has also been observed in our studies on Indians. Recent studies indicate that altered HRV and BPV are also important in the pathogenesis and progression of heart failure, atheroma and thrombosis. Mediation via beta-blockers, oestrogens, n-3 fatty acids, vitamin E and coenzyme Q10 and fasting appears to have a beneficial influence whereas progestins, nifedipine, stress and exercise may have an adverse effect on HRV and BPV. We have reported that plasma levels of vitamin E and C are lower in the second quarter of the day than at other times, indicating their role in the pathogenesis of variability and cardiac events. Prospective studies also indicate that HRV and BPV are important and independent risk factors for cardiovascular events. However, no study has yet been conducted in patients with abnormal HRV and BPV in a randomized, placebo-controlled intervention trial to find out whether improvement in variability can cause a significant reduction in cardiovascular events. There is a need to study the role of n-3 fatty acids, coenzyme Q10, the effect of regular physical training, medication and ACE inhibitors in patients with abnormal HRV and BPV to demonstrate that improving variability can modulate cardiovascular events.