CYP7A1, NPC1L1, ABCB1, and CD36 Polymorphisms Associated with Coenzyme Q10 Availability Affect the Subjective Quality of Life Score (SF-36) after Long-Term CoQ10 Supplementation in Women

The single nucleotide polymorphisms (SNPs) rs3808607, rs2072183, rs2032582, and rs1761667 are associated with coenzyme Q₁₀ (CoQ₁₀) bioavailability in women after long-term CoQ₁₀ supplementation. However, the beneficial aspects of the association between these SNPs and CoQ₁₀ supplementation remain unknown. We investigated their relationship using the subjective quality of life score SF-36 by reanalyzing previous data from 92 study participants who were receiving ubiquinol (a reduced form of CoQ₁₀) supplementation for 1 year. Two-way repeated-measures analysis of variance revealed a significant interaction between rs1761667 and the SF-36 scores of role physical (p = 0.016) and mental health (p = 0.017) in women. Subgrouping of participants based on the above four SNPs revealed significant interactions between these SNPs and the SF-36 scores of general health (p = 0.045), role emotional (p = 0.008), and mental health (p = 0.019) and increased serum CoQ₁₀ levels (p = 0.008), suggesting that the benefits of CoQ₁₀ supplementation, especially in terms of psychological parameters, are genotype-dependent in women. However, significant interactions were not observed in men. Therefore, inclusion of SNP subgrouping information in clinical trials of CoQ₁₀ supplementation may provide conclusive evidence supporting other beneficial health effects exerted by the association between these SNPs and CoQ₁₀ on women.     

Effects of selenium supplementation on cardiovascular disease incidence and mortality: secondary analyses in a randomized clinical trial

Despite the documented antioxidant and chemopreventive properties of selenium, studies of selenium intake and supplementation and cardiovascular disease have yielded inconsistent findings. The authors examined the effect of selenium supplementation (200 microg daily) on cardiovascular disease incidence and mortality through the entire blinded phase of the Nutritional Prevention of Cancer Trial (1983-1996) among participants who were free of cardiovascular disease at baseline (randomized to selenium: n = 504; randomized to placebo: n = 500). Selenium supplementation was not significantly associated with any of the cardiovascular disease endpoints during 7.6 years of follow-up (all cardiovascular disease: hazard ratio (HR) = 1.03, 95% confidence interval (CI): 0.78, 1.37; myocardial infarction: HR = 0.94, 95% CI: 0.61, 1.44; stroke: HR = 1.02, 95% CI: 0.63, 1.65; all cardiovascular disease mortality: HR = 1.22, 95% CI: 0.76, 1.95). The lack of significant association with cardiovascular disease endpoints was also confirmed when analyses were further stratified by tertiles of baseline plasma selenium concentrations. These findings indicate no overall effect of selenium supplementation on the primary prevention of cardiovascular disease in this population.     

Clinical and biochemical effects of coenzyme Q10, vitamin E,and selenium supplementation to psoriasis patients

ObjectiveThe aim of the present study was to evaluate clinical effects of supplementation with antioxidants to patients with severe erythrodermic (EP) and arthropathic (PsA) forms of psoriasis.MethodsFifty-eight patients were hospitalized, treated by conventional protocols, and randomly assigned to four groups. Groups EP1 and PsA1 were supplemented with coenzyme Q₁₀ (ubiquinone acetate, 50 mg/d), vitamin E (natural α-tocopherol, 50 mg/d), and selenium (aspartate salt, 48 μg/d) dissolved in soy lecithin for 30–35 d. Groups EP2 and PsA2 (placebo) received soy lecithin. Clinical conditions were assessed by severity parameters. Markers of oxidative stress included superoxide production, copper/zinc-superoxide dismutase, and catalase activities in the circulating granulocytes, in the affected epidermis, and plasma levels of nitrites/nitrates.ResultsAt baseline patients had an increased superoxide release from granulocytes (10.0 ± 0.5, 2.9 ± 0.2, and 1.5 ± 0.1 nmol/L per 10⁶ cells/h for EP, PsA, and donors, respectively), increased copper/zinc-superoxide dismutase and catalase activities in granulocytes in EP patients and decreased in PsA patients, decreased activity of copper/zinc-superoxide dismutase (0.3 ± 0.0, 1.8 ± 0.1, and 2.2 ± 0.2 U/mg protein for EP, PsA, and donors, respectively), and altered activity of catalase in psoriatic epidermis. Plasma levels of nitrites/nitrates were greater than normal in psoriatic patients. Supplementation resulted in significant improvement of clinical conditions, which corresponded to the faster versus placebo normalization of the oxidative stress markers.ConclusionSupplementation with antioxidants coenzyme Q₁₀, vitamin E, and selenium could be feasible for the management of patients with severe forms of psoriasis.     

Folic acid and vitamin B12 supplementation lowers plasma homocysteine but has no effect on serum bone turnover markers in elderly women: a randomized,double-blind,placebo-controlled trial

An elevated homocysteine level is a newly recognized risk factor for osteoporosis. Older individuals may have elevated homocysteine levels due to inadequate folate intake and/or lower absorption of vitamin B₁₂. The aim of this study was to determine whether there is an impact of folic acid and vitamin B₁₂ supplementation on homocysteine levels and, subsequently, on bone turnover markers in older women with mildly to moderately elevated homocysteine levels. It is hypothesized that supplementation with folic acid and vitamin B₁₂ will improve homocysteine levels and, in turn, positively modify bone turnover markers in this population. This randomized, double-blind, placebo-controlled trial included 31 women (65 to 93 years) with homocysteine levels greater than 10 μmol/L. Participants were randomly assigned to receive either a daily folic acid (800 μg) and vitamin B₁₂ (1000 μg) (n = 17) or a matching placebo (n = 14) for 4 months. The results showed significantly lower homocysteine concentrations in the vitamin group compared to the placebo group (10.6 vs 18.5 μmol/L, P = .007). No significant difference in serum alkaline phosphatase or C-terminal cross-linking telopeptide of type I collagen was found between the vitamin and placebo groups before or after supplementation. The use of folic acid and vitamin B₁₂ as a dietary supplement to improve homocysteine levels could be beneficial for older women, but additional research must be conducted in a larger population and for a longer period to determine if there is an impact of supplementation on bone turnover markers or other indicators of bone health.     

Effects of coenzyme Q10 supplementation on inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, and homocysteine) in patients with coronary artery disease

ObjectiveThe purpose of this study was to investigate the effects of coenzyme Q10 supplementation on inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], and homocysteine) in patients with coronary artery disease (CAD).MethodsPatients with CAD (n = 51) were randomly assigned to a placebo group (n = 14) or one of two coenzyme Q10-supplemented groups (60 mg/d, Q10-60 group, n = 19; 150 mg/d, Q10-150 group, n = 18). The intervention was administered for 12 wk. Plasma coenzyme Q10 concentration, inflammatory markers (hs-CRP, IL-6, and homocysteine), malondialdehyde, and superoxide dismutase activities were measured.ResultsForty subjects with CAD completed the intervention study. The plasma coenzyme Q10 concentration increased significantly in the Q10-60 and Q10-150 groups (P < 0.01). After 12 wk of intervention, the inflammatory marker IL-6 (P = 0.03) was decreased significantly in the Q10-150 group. Subjects in the Q10-150 group had significantly lower malondialdehyde levels and those in the Q10-60 (P = 0.05) and Q10-150 (P = 0.06) groups had greater superoxide dismutase activities. Plasma coenzyme Q10 was inversely correlated with hs-CRP (r = ?0.20, P = 0.07) and IL-6 (r = ?0.25, P = 0.03) at baseline. After supplementation, plasma coenzyme Q10 was significantly correlated with malondialdehyde (r = ?0.35, P < 0.01) and superoxide dismutase activities (r = 0.52, P < 0.01). However, there was no correlation between coenzyme Q10 and homocysteine.ConclusionCoenzyme Q10 supplementation at a dosage of 150 mg appears to decrease the inflammatory marker IL-6 in patients with CAD.     

Effect of onion peel extract supplementation on the lipid profile and antioxidative status of healthy young women: a randomized,placebo-controlled,double-blind,crossover trial

The consumption of fruits and vegetables that have high polyphenol content has been previously associated with a reduced risk for cardiovascular disease. We investigated the effects of onion peel extract on plasma total antioxidant capacity, lipid peroxidation, and leukocyte DNA damage. This study was a randomized, double-blind, placebo-controlled, crossover trial. Healthy female subjects received either onion peel extract or placebo (dextrin) for two weeks, underwent a 1-week washout period, and then received the other treatment for an additional two weeks. After two weeks of onion peel extract supplementation, the total cholesterol level, low-density lipoprotein cholesterol level, and atherogenic index significantly decreased (P < 0.05). No changes were observed in activities of erythrocyte antioxidant enzymes or levels of lipid peroxidation markers following onion peel extract supplementation. Additionally, no significant difference was found in plasma antioxidant vitamin (retinol, tocopherols, carotenoids, and coenzyme Q10) levels or ex vivo H₂O₂-provoked oxidative DNA damage after onion peel extract supplementation. The present interventional study provides evidence of the health benefits of onion peel extract and demonstrates its effects in modulating lipid profiles in healthy young Korean women.     

Coenzyme Q10 supplementation reduces oxidative stress and increases antioxidant enzyme activity in patients with coronary artery disease

ObjectiveThe purpose of this study was to investigate the effect of coenzyme Q10 supplementation on oxidative stress and antioxidant enzyme activity in patients with coronary artery disease (CAD).MethodsThis was an intervention study. Patients who were identified by cardiac catheterization as having at least 50% stenosis of one major coronary artery or receiving percutaneous transluminal coronary angioplasty (n = 51) were randomly assigned to the placebo group (n = 14) or one of the two coenzyme Q10-supplemented groups (60 mg/d, n = 19 [Q10-60 group]; 150 mg/d, n = 18 [Q10-150 group]). Intervention was administered for 12 wk. Patients’ blood samples were analyzed every 4 wk for plasma coenzyme Q10 concentrations, malondialdehyde (MDA), and antioxidant enzyme (catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase) activity.ResultsForty-three subjects with CAD completed intervention study. Plasma coenzyme Q10 concentration increased significantly after coenzyme the Q10-150 intervention (P < 0.01). The MDA levels were significantly lower than baseline in the Q10-150 group at week 4 (P = 0.03). The Q10-150 group had significantly lower MDA levels than the placebo group at week 8 (P = 0.03). With respect to antioxidant enzyme activity, subjects in the Q10-150 group had significantly higher CAT (P = 0.03) and SOD (P = 0.03) activity than the placebo group at week 12. The plasma coenzyme Q10 concentration was significantly correlated with MDA levels (r = ?0.35, P = 0.02) and CAT (r = 0.43, P = 0.01) and SOD activity (r = 0.39, P = 0.01). The ratio of plasma coenzyme Q10 to total cholesterol was significantly correlated with SOD activity (r = 0.39, P = 0.02). The ratio of plasma coenzyme Q10 to low-density lipoprotein was significantly correlated with CAT (r = 0.35, P = 0.04) and SOD (r = 0.45, P = 0.01) activity. However, there was no relation between coenzyme Q10 concentration and glutathione peroxidase activity.ConclusionCoenzyme Q10 supplements at a dose of 150 mg can decrease oxidative stress and increase antioxidant enzyme activity in patients with CAD. A higher dose of coenzyme Q10 supplements (>150 mg/d) might promote rapid and sustainable antioxidation in patients with CAD.     

Coenzyme Q10 supplementation ameliorates inflammatory signaling and oxidative stress associated with strenuous exercise

Background

Exhausting exercise induces muscle damage associated with high production of free radicals and pro-inflammatory mediators.

Aim

The objective of this study was to determine for the first time and simultaneously whether oral coenzyme Q₁₀ (CoQ₁₀) supplementation can prevent over-expression of inflammatory mediators and oxidative stress associated with strenuous exercise.

Methods

The participants were classified in two groups: CoQ₁₀ group (CG) and placebo group (PG). The physical test consisted in a constant run (50?km) that combined several degrees of high effort (mountain run and ultra-endurance), in permanent climbing.

Results

Exercise was associated with an increase in TNF-α, IL-6, 8-hydroxy-2′-deoxyguanosine (8-OHdG), and isoprostane levels, revealing the degree of inflammation and oxidative stress induced. Oral supplementation of CoQ₁₀ during exercise was efficient reducing oxidative stress (decreased membrane hydroperoxides, 8-OHdG and isoprostanes generation, increased catalase, and total antioxidant status), which would lead to the maintenance of the cell integrity. Data obtained also indicate that CoQ₁₀ prevents over-expression of TNF-α after exercise, together with an increase in sTNF-RII that limits the pro-inflammatory actions of TNF. Moreover, CoQ₁₀ supplementation reduced creatinine production.

Conclusions

CoQ₁₀ supplementation before strenuous exercise decreases the oxidative stress and modulates the inflammatory signaling, reducing the subsequent muscle damage.     

Influence of early trace element and vitamin E supplements on antioxidant status after major trauma: a controlled trial

Negative selenium and zinc balances occur after major trauma, potentially compromising antioxidant defenses. The aim of this study was to determine if micronutrient supplementation could modulate the blood antioxidant status. 32 patients admitted to surgical ITU with major trauma were randomized to receive either selenium alone, selenium plus copper, zinc and tocopherol, or placebo for 5 days after injury. Blood samples were collected on days 0, 1, 2, 5, 10 and 20 and analyzed for plasma selenium, copper, zinc, tocopherol, glutathione peroxidase and total antioxidant capacity (TAC), and for erythrocyte antioxidant enzymes. Plasma selenium and tocopherol concentrations were low on admission, but increased significantly (p = 0.001) with supplementation, whereas there was an early significant fall in TAC (p < 0.002) in the selenium supplemented groups. Plasma glutathione peroxidase activity increased significantly between days 2 and 5 with supplementation (p = 0.02), but erythrocyte enzyme activity was unaffected. The unexpected early fall in plasma TAC with supplementation may reflect mobilization of antioxidant defenses.     

Growth Hormone (GH) Treatment in Non-GH Deficient Chronic Disease

Objective: This trial evaluated the effect of antioxidant supplementation on the urinary excretion of 11-dehydro TXB₂/2,3 dinor 6 keto PGF_1α ratio, a marker of the pathogenesis of thrombosis and arteriosclerosis.

Methods: This study was a randomised, double-blind, placebo-controlled trial involving 186 presumably healthy volunteers. One hundred received a multi-antioxidant supplementation and 86 a placebo for two years. Blood zinc, selenium, beta-carotene, vitamin C and E and urinary excretion of 11-dehydro TXB₂ and 2,3 dinor 6 keto PGF_1α were measured.

Results: Baseline subject characteristics did not differ between the two groups. Blood zinc, selenium, and beta-carotene concentrations significantly increased between baseline and two years in the multi-antioxidant supplementation group supporting subject compliance (p < 0.05). At two years, the median urinary 11-dehydro TXB₂/2,3 dinor 6 keto PGF_1α ratio was significantly lower in the multi-antioxidant supplementation group (3.4 versus 2.78, p = 0.015). Serum selenium concentration was the only antioxidant studied that was significantly related to the urinary 11-dehydro TXB₂/2,3 dinor 6 keto PGF_1α ratio.

Conclusions: These results support the hypothesis that a low-dose multi-antioxidant supplementation may contributes to a reduction in platelet activation which is beneficial for cardiovascular function.     

Coenzymes Q9and Q10: Contents in Foods and Dietary Intake

Coenzyme Q₉and Q₁₀contents in 35 food items were determined and coenzyme Q intake of Finns was estimated. The analytical method employed direct solvent extraction or saponification before extraction and quantification using high-pressure liquid chromatography (HPLC) equipped with diode array detection. Intakes of coenzymes Q₉and Q₁₀were estimated using the determined values and food consumption data from a national dietary survey. Contents of coenzymes Q₁₀and Q₉in foods varied from 157.9 μg/g to below the detection limit and from 8.5 μg/g to below the detection limit, respectively. Average intakes of coenzyme Q₁₀were 5.4 mg/day (men) and 3.8 mg/day (women) while daily intakes of coenzyme Q₉were 0.6 mg (men) and 0.4 mg (women). Coenzyme Q₁₀was primarily obtained from meat, poultry, fish and rapeseed oil. Cereals were the major source of coenzyme Q₉.     

Coenzyme Q(10), vitamin E, selenium, and methionine in the treatment of chronic recurrent viral mucocutaneous infections

ObjectiveHost defense and latency determinants in viral recurrent dermatologic infections are not entirely understood, as conventional protocols are inadequate to achieve fast healing and relapse prevention. Endogenously produced oxygen/nitrogen reactive species (ROS/RNS) are essential for antiviral immune defense, while their excess may aggravate skin inflammation. Here, we sought a nutritional approach capable of controlling ROS/RNS balance to accelerate recovery and inhibit recurrences of two mucocutaneous chronic DNA-virus infections.MethodsTwo controlled clinical trials evaluated the feasibility of ROS/RNS-modulating nutriceutical dosages of coenzyme Q₁₀, RRR-α-tocopherol, selenium aspartate, and L-methionine associated with established therapies. Clinical trial 1 evaluated 68 patients with relapsing human papillomavirus skin warts treated with cryotherapy followed by 180 d of nutriceutical/placebo administration. Clinical trial 2 compared the combination of acyclovir followed by 90 d of nutriceutical administration versus acyclovir alone in patients with recurrences of herpes simplex genitalis (n = 60) or herpes zoster (n = 29). Viral DNA levels were assessed by polymer chain reaction, biomarkers of antiviral defense (peroxynitrite and IFNα/γ) and antioxidant capacity (lipophilic antioxidants and glutathione) were assayed by biochemical/enzyme-linked immunosorbent assay techniques in blood fractions.ResultsIn both trials, the nutriceutical induced significantly faster healing (P < 0.01-0.05) with reduced incidence of relapses (P < 0.05) as compared to control groups, which was confirmed by decreased viral load and increased antiviral cytokine and peroxynitrite plasma levels. Plasma antioxidant capacity was higher (P < 0.01) in the experimental versus control groups.ConclusionsResults document positive clinical outcomes of the selected nutriceutical associated with conventional protocols in the management of relapsing mucocutaneous human papillomavirus and herpes infections.     

Coenzyme Q10 supplementation ameliorates inflammatory markers in patients with multiple sclerosis: a double blind,placebo, controlled randomized clinical trial

Abstract

Objectives

Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease of central nervous system and recent studies show that inflammatory processes are highly associated with neurodegeneration in the brain. The purpose of this study was to investigate the effect of coenzyme Q10 supplementation on inflammatory and anti-inflammatory markers in patients with MS.

Methods

This randomized, double-blind, placebo-controlled clinical study was performed among 48 patients with relapsing–remitting MS. Subjects were randomly assigned to a placebo group (n = 24) or coenzyme Q10 (CoQ10)-supplemented group (500 mg/day, n = 24). The intervention was administered for 12 weeks. Peripheral blood samples were collected at baseline and after 12-week intervention, to measure inflammatory (tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and matrix metalloproteinase (MMP)-9) and anti-inflammatory (IL-4 and TGF-β) markers.

Results

Forty-five patients completed the study. After 12 weeks of intervention, the TNF-α levels (P = 0.003) decreased significantly in the CoQ10 group. Subjects in the CoQ10 group had significantly lower IL-6 levels (P = 0.037), compared to the placebo group. CoQ10 supplementation also resulted in decreased serum levels of MMP-9 as compared to the placebo group (P = 0.011). However, CoQ10 supplementation did not alter the IL-4 and TGF-β levels (P = 0.16 and P = 0.81, respectively).

Discussion

CoQ10 supplementation at a dosage of 500 mg appears to decrease the inflammatory markers (TNF-α, IL-6, and MMP-9) in patients with MS.     

Effect of selenium supplementation on HIV-1 RNA detection in breast milk of Tanzanian women

ObjectiveSelenium supplementation for women infected with HIV may increase genital shedding of HIV-1, however, to our knowledge, no studies have examined the effect on viral shedding in breast milk. The aim of this study was to determine the effect of selenium supplementation on HIV-1 RNA detection in breast milk of HIV-infected women.MethodsHIV-infected pregnant women enrolled at 12 to 27 wk gestation in a randomized, double-blind, placebo-controlled trial of daily selenium (200 μg as selenomethionine) had cell-free HIV-1 RNA quantified in breast milk at 4 to 9 wk postpartum. All participants received high-dose multivitamins containing vitamin B complex, C, and E as standard of care.ResultsThe proportion of women with detectable (>50 copies/mL) HIV-1 RNA in breast milk appeared to be increased in the selenium group (36.4%) compared with those in the placebo group (27.5%) among the total cohort (N = 420), but results were borderline statistically significant (relative risk [RR], 1.32; 95% confidence interval [CI], 1.00–1.76; P = 0.05). In secondary analyses, the proportion of women with detectable HIV-1 RNA in breast milk was significantly greater in the selenium group (37.8%) compared with placebo group (27.5%) among women who did not receive highly active antiretroviral therapy (HAART; RR, 1.37; 95% CI, 1.03–1.82; P = 0.03). This relationship was primarily due to a significant effect of selenium among primiparous women (RR, 2.24; 95% CI, 1.30–3.86; P < 0.01), but not multiparous women (RR, 1.14; 95% CI, 0.81–1.59; P = 0.54) (P-value for interaction = 0.02). Too few women received HAART in this study (n = 12) to establish the effect of selenium supplementation.ConclusionsSelenium supplementation appears to increase HIV-1 RNA detection in breast milk among primiparous women not receiving HAART. Safety studies among pregnant women on HAART need to be conducted before administering selenium-containing supplements.     

Effects of daily quercetin-rich supplementation on cardiometabolic risks in male smokers

Limited information from human studies indicates that dietary quercetin supplementation influences blood lipid profiles, glycemic response, and inflammatory status, collectively termed cardiometabolic risks. We tested the hypothesis that quercetin-rich supplementation, derived from onion peel extract, improves cardiometabolic risk components in healthy male smokers in a randomized, double blinded, placebo-controlled parallel design. Randomly assigned subjects were instructed to take either the placebo (n = 43) or 100 mg quercetin capsules each day (n = 49) for 10 weeks. Anthropometric parameters and blood pressure were measured, and blood lipids, glucose, interleukin-6, and soluble vascular cell adhesion molecule-1 (sVCAM-1) were determined at baseline and after 10 weeks of quercetin supplementation. Quercetin-rich supplementation significantly reduced serum concentrations of total cholesterol (P < 0.05) and LDL-cholesterol (P < 0.01), whereas these effects were not shown in the placebo group. Furthermore, significant increases were observed in serum concentrations of HDL-cholesterol both in the placebo (P < 0.005) and quercetin-rich supplementation group (P < 0.001); however, changes in HDL-cholesterol were significantly greater in subjects receiving quercetin-rich supplementation than the placebo. Both systolic (P < 0.05) and diastolic blood pressure (P < 0.01) decreased significantly in the quercetin-rich supplementation group. Glucose concentrations decreased significantly after 10 weeks of quercetin-rich supplementation (P < 0.05). In contrast, no effects of quercetin-rich supplementation were observed for the inflammatory markers-IL-6 and sVCAM-1. Daily quercetin-rich supplementation from onion peel extract improved blood lipid profiles, glucose, and blood pressure, suggesting a beneficial role for quercetin as a preventive measure against cardiovascular risk.     

Beneficial effects of aged garlic extract and coenzyme Q10 on vascular elasticity and endothelial function: The FAITH randomized clinical trial

ObjectiveAged garlic extract (AGE) is associated with a significant decrease in atherosclerotic plaque progression and endothelial function improvement. Similarly, coenzyme Q10 (CoQ10) has significant beneficial effects on endothelial function. A stressful lifestyle is a well-known risk factor for the presence and progression of atherosclerosis. This study investigated the effect of AGE plus CoQ10 on vascular elasticity measured by pulse-wave velocity (PWV) and endothelial function measured by digital thermal monitoring (DTM) in firefighters.MethodsSixty-five Los-Angeles County firefighters who met the eligibility criteria were enrolled in this placebo-controlled, double-blinded randomized trial. The firefighters were randomized to four tablets of AGE (300 mg/tablet) plus CoQ10 (30 mg/tablet) or placebo. The participants underwent quarterly visits and 1-year follow-up. PWV and DTM were measured at baseline and at the 1-year follow-up.ResultsThere were no significant differences in age, cardiovascular risk factors, PWV, and DTM between the AGE/CoQ10 and placebo groups at baseline (P > 0.5). At 1-y, PWV and DTM significantly improved in the AGE/CoQ10 compared with the placebo group (P < 0.05). After an adjustment for cardiovascular risk factors and statin therapy, the mean decrease in vascular stiffness (PWV) was 1.21 m/s in the AGE/CoQ10 compared with the placebo group (P = 0.005). Similarly, the mean increase in the area under the temperature curve, the DTM index of endothelial function, was 31.3 in the AGE/CoQ10 compared with the placebo group (P = 0.01).ConclusionThe combination of AGE and CoQ10 was independently associated with significant beneficial effects on vascular elasticity and endothelial function in firefighters with high occupational stress, highlighting the important role of AGE and CoQ10 in atherosclerotic prevention of such individuals.     

Impact of Leucine Supplementation on Exercise Training Induced Anti-Cardiac Remodeling Effect in Heart Failure Mice

Leucine supplementation potentiates the effects of aerobic exercise training (AET) on skeletal muscle; however, its potential effects associated with AET on cardiac muscle have not been clarified yet. We tested whether leucine supplementation would potentiate the anti-cardiac remodeling effect of AET in a genetic model of sympathetic hyperactivity-induced heart failure in mice (α_2A/α_2CARKO). Mice were assigned to five groups: wild type mice treated with placebo and sedentary (WT, n = 11), α_2A/α_2CARKO treated with placebo and sedentary (KO, n = 9), α_2A/α_2CARKO treated with leucine and sedentary (KOL, n = 11), α_2A/α_2CARKO treated with placebo and AET (KOT, n = 12) or α_2A/α_2CARKO treated with leucine and AET (KOLT, n = 12). AET consisted of four weeks on a treadmill with 60 min sessions (six days/week, 60% of maximal speed) and administration by gavage of leucine (1.35 g/kg/day) or placebo (distilled water). The AET significantly improved exercise capacity, fractional shortening and re-established cardiomyocytes’ diameter and collagen fraction in KOT. Additionally, AET significantly prevented the proteasome hyperactivity, increased misfolded proteins and HSP27 expression. Isolated leucine supplementation displayed no effect on cardiac function and structure (KOL), however, when associated with AET (KOLT), it increased exercise tolerance to a higher degree than isolated AET (KOT) despite no additional effects on AET induced anti-cardiac remodeling. Our results provide evidence for the modest impact of leucine supplementation on cardiac structure and function in exercised heart failure mice. Leucine supplementation potentiated AET effects on exercise tolerance, which might be related to its recognized impact on skeletal muscle.     

Effects of phylloquinone supplementation on lipid profile in women with rheumatoid arthritis: a double blind placebo controlled study

BACKGROUND/OBJECTIVES

Rheumatoid arthritis (RA) is associated with an excess mortality from cardiovascular disease which is likely attributed to an atherogenic lipid profile. Among nutritional factors vitamin K has been recently focused as a pivotal nutrient in improvement of lipid related markers. Thus, this study was designed to determine the effects of vitamin K on lipid profile in this disease.

SUBJECTS/METHODS

Fifty eight patients with definitive RA were participated in the present double blind placebo controlled study. They were randomly allocated into two groups to receive vitamin K₁ as phylloquinone [10 mg/day] (n = 30) or placebo pills (n = 28), for eight weeks. In order to control the effects of probable confounders dietary intakes, anthropometric measurements including weight and height, clinical status using disease activity score-28 (DAS-28), physical activity and anxiety status were evaluated at baseline. Moreover, serum levels of lipid related markers including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) were measured at baseline and at the end of intervention.

RESULTS

There were no significant differences between the two groups regarding any of the baseline characteristics. After adjusting for some relevant confounders, in comparison between two groups, we observed no significant changes in lipid related markers at the end of intervention. Also, there was no significant difference between before and after intervention values within groups (P > 0.05).

CONCLUSIONS

Function of vitamin K₁ in lipid profile modification remains still controversial. This study showed that vitamin K₁ has no effect on lipid profile in women with rheumatoid arthritis. Further studies with a longer follow-up are required to determine the effects of vitamin K on atherogenic lipid profile.     

Soy,Soy Isoflavones,and Protein Intake in Relation to Mortality from All Causes,Cancers, and Cardiovascular Diseases: A Systematic Review and Dose–Response Meta-Analysis of Prospective Cohort Studies

ObjectiveWe conducted a systematic review and dose–response meta-analysis of prospective studies to summarize findings on the associations between intakes of soy, soy isoflavones, and soy protein and risk of mortality from all causes, cancers, and cardiovascular diseases.MethodsOnline databases were systematically searched to identify relevant articles published earlier than May 2018. We applied restricted cubic splines using random-effects analysis to assess dose–response associations. Between-study heterogeneity was assessed by I² value and Cochrane Q test. Potential publication bias was assessed by visual inspection of funnel plots and Begg regression test.ResultsIn total, 23 prospective studies with an overall sample size of 330,826 participants were included in the current systematic review and the meta-analysis. Soy/soy products consumption was inversely associated with deaths from cancers (pooled relative risk 0.88, 95% CI 0.79 to 0.99; P=0.03; I²=47.1%, 95% CI 0.0% to 75.4%) and cardiovascular diseases (pooled effect size: 0.85, 95% CI 0.72 to 0.99; P=0.04; I²=50.0%, 95% CI 0.0% to 77.6%). Such significant associations were also observed for all-cause mortality in some subgroups of the included studies, particularly those with higher quality. In addition, higher intake of soy was associated with decreased risk of mortality from gastric, colorectal, and lung cancers as well as ischemic cardiovascular diseases. Participants in the highest category of dietary soy isoflavones intake had a 10% lower risk of all-cause mortality compared with those in the lowest category. We also found that a 10-mg/day increase in intake of soy isoflavones was associated with 7% and 9% decreased risk of mortality from all cancers and also breast cancer respectively. Furthermore, a 12% reduction in breast cancer death was indicated for each 5-g/day increase in consumption of soy protein. However, intake of soy protein was not significantly associated with all-cause and cardiovascular diseases mortality.ConclusionsSoy and its isoflavones may favorably influence risk of mortality. In addition, soy protein intake was associated with a decreased risk in the mortality of breast cancer. Our findings may support the current recommendations to increase intake of soy for greater longevity.     

High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification

Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures.