Evidencia del manejo de miopatías asociadas a estatina con coenzima Q10 / Evidence for the management of myopathies associated with statin with coenzyme Q10

Introducción: La incidencia de eventos cardiovasculares fatales es muy elevada y el tratamiento con estatinas es vital para reducir este riesgo en muchos pacientes, sin embargo, sus efectos adversos sobre el músculo esquelético dificultan la adherencia o la continuación del mismo. Se ha propuesto la suplementación de coenzima Q10 para revertir mialgias asociadas a el empleo de estatinas. Los ensayos clínicos que se realizaron en los últimos 10 años obtuvieron resultados contrapuestos. El objetivo de este trabajo es revisar la evidencia sobre la eficacia del empleo de suplementos de coenzima Q10 en para mitigar las miopatías causadas por las estatinas. Metodología: Se realizó una búsqueda sistemática de la literatura publicada hasta Julio de 2020. Las bases de datos consultadas fueron MEDLINE y SCOPUS. También se consultaron instituciones como la Agencia Española del Medicamento y Productos Sanitarios (AEMPS), la European Medicines Agency (EMA) y la Food and Drug Administration (FDA). Resultados: La etiología de las mialgias asociadas a estatinas sigue siendo desconocida y la evidencia encontrada en los ensayos clínicos y metaanalisis obtuvieron conclusiones dispares. La European Medicine Agency (EMA) solo considera el empleo de suplementos en síndrome de deficiencia primaria de coenzima Q10, mientras en Reino Unido el National Institute for Health and Care Excellence (NICE) y el National Institute of Health (NIH) no recomiendan el empleo de estos suplementos para tratar mialgias asociadas al empleo de estatinas. Conclusiones: El conjunto de los estudios analizados no consiguió una evidencia unánime para poder recomendar este empleo de suplementos de coenzima Q10 de modo confiable. Se necesitan estudios mejor diseñados que aporten reproducibilidad y robustez a futuros ensayos clínicos. (AU)

Introduction: The incidence of fatal cardiovascular events is very high and statin treatment is vital to reduce this risk in many patients, however, its adverse effects on skeletal muscle make it difficult to adhere or continue it. Coenzyme Q10 supplementation has been proposed to reverse myalgia associated with the use of statins. The clinical trials carried out in the last 10 years obtained conflicting results. The aim of the present work is to review the evidence on the efficacy of the use of coenzyme Q10 supplements in mitigating myopathies caused by statins. Methodology: A systematic review of the published literature until July 2020 was undertaken. The searched databases were MEDLINE and SCOPUS. Institutions such as the Agencia Española del Medicamento y productos Sanitarios (AEMPS), European Medicines Agency (EMA) and Food and Drug Administration were also consulted. Results: The etiology of statin-associated myalgias remains unknown, and the evidence found in clinical trials and meta-analysis drew disparate conclusions. The European Medicine Agency (EMA) only considers the use of supplements in primary coenzyme Q10 deficiency syndrome, while in the United Kingdom the National Institute for Health and Care Excellence (NICE) and the National Institute of Health (NIH) do not recommend the use of these supplements to treat myalgias associated with the use of statins. Conclusions: The set of studies analyzed did not obtain unanimous evidence to be able to reliably recommend this use of coenzyme Q10 supplements. Better designed studies that provide reproducibility and robustness to future clinical trials are needed. (AU)

Avaliação dos efeitos da coenzima Q10 utilizada como coadjuvante local e/ou sistêmica ao tratamento mecânico da periodontite experimental em ratos tratados com nicotina / Evaluation of the effects of coenzyme Q10 as local and/or systemic adjuvant to mechanical treatment of experimental periodontitis in rats treated ith nicotine

O propósito do estudo foi avaliar a efetividade da raspagem e alisamento radicular (RAR) associado à coenzima Q10 (CQ10) administrada localmente e/ou sistemicamente no tratamento da periodontite experimental (PE) em ratos tratados sistemicamente com nicotina (NIC). 128 ratos (Wistar) foram divididos em oito grupos (n=16). Durante todo o período experimental, os animais receberam duas injeções subcutâneas diárias de 3mg/kg de hemissulfato de nicotina ou solução salina (SS) na região dorsal, com 12 horas de intervalo entre elas, começando nos 30 dias que antecederam à indução da PE. Após 15 dias da indução da PE, o protocolo de RAR foi realizado bem como o tratamento coadjuvante local e/ou sistêmico com CQ10, com e sem tratamento com a NIC, sendo: SS-PE-RAR e NIC-PE-RAR: irrigação subgengival com SS; SS-PE-RAR/Q10L e NIC-PE-RAR/Q10L: irrigação subgengival com 1ml solução de CQ10; SS-PE-RAR/Q10S e NIC-PE-RAR/Q10S: gavagem gástrica diária com 120 mg de CQ10; SS-PE-RAR/Q10LS e NIC-PE-RAR/Q10LS: irrigação subgengival com 1ml solução de CQ10 e gavagem gástrica diária com 120 mg de CQ10. As eutanásias foram realizadas 7 e 28 dias após tratamento. As peças coletadas foram processadas com desmineralização para as análises histopatológica, histométrica e imunoistoquímica para detecção de TRAP. Os dados foram submetidos ao teste paramétrico Anova two-way e pós-teste de Tukey. O nível de significância adotado foi de 5% (p≤0,05). Na análise histopatológica, pode-se observar que os grupos NIC-PE-RAR-Q10L E NIC-PE-RAR-Q10LS apresentaram tecidos periodontais com aspecto de normalidade, com preservação da inserção conjuntiva e de região de furca preservada aos 7 e 28 dias, de modo distinto do grupo NIC-PE-RAR e NIC-PE-RAR-Q10S em ambos os períodos. Na análise histométrica, pode-se observar maior porcentagem de osso na furca (POF) (p≤0,05) nos grupos NIC-PE-RAR-Q10L, NIC-PE-RAR-Q10S e NIC-PERAR-Q10LS em comparação com o grupo NIC-PE-RAR em ambos os períodos e também com o grupo SS-PE-RAR aos 28 dias. Pode-se observar menor número de células TRAP positivas (p≤0,05) no grupo NIC-PE-RAR-Q10L quando comparado aos grupos SS-PE-RAR E NIC-PE-RAR aos 7 dias e no grupo NIC-PE-RAR-Q10LS quando comparado aos mesmos grupos aos 28 dias. Conclui-se que RAR associado à CQ10 utilizada local e local/sistemicamente no tratamento da PE em ratos tratados sistemicamente com nicotina foram efetivas mostrando resultados favoráveis nas análises histopatológica, histométrica e imunoistoquímica(AU)

The aim of this study was to evaluate the effectiveness of scaling and root planing (SRP) combined with adjunctive local and/or systemic administration of coenzyme Q10 (CQ10) for the treatment of experimental periodontitis (EP) in rats systemically treated with nicotine (NIC). 128 Wistar rats were divided into 8 groups (n=16). Throughout the experiment, animals received two subcutaneous injections of either 3mg/kg nicotine hemissulfate or physiological saline solution (PSS) with 12 h interval between them. These injections were initiated 30 days prior EP induction. 15 days after EP induction, the protocol for SRP was performed together (or not) with local and/or systemic adjunctive CQ10 administration in animals treat with either NIC or PSS, as described: PSS-EP-SRP and NIC-EP-SRP: subgingival irrigation with PSS; PSS-EP-SRP/Q10L and NIC-EP-SRP/Q10L: subgingival irrigation with 1ml of CQ10 solution; PSS-EP-SRP/Q10S and NIC-EP-SRP/Q10S: daily gastric gavage with 120 mg of CQ10; PSS-EP-SRP/Q10LS and NIC-EP-SRP/Q10LS: subgingival irrigation with 1ml of CQ10 solution and daily gastric gavage with 120 mg of CQ10. The euthanasia was performed at 7 and 28 days after treatment. The specimens were collected and processed for histopathologic, histometric and immunochemical for of TRAP analyzes. The data were submitted to the two-way ANOVA and Tukey's post-test. The level of significance adopted was 5% (p≤0.05). In the histopathological analysis, it can be observed that the NIC-PE-RAR-Q10L and NIC-PE-RAR-Q10LS groups presented periodontal tissues with normal aspect, preserving the conjunctival insertion and furca region preserved at 7 and 28 days, differently from the NIC-PE-RAR and NIC-PE-RAR-Q10S groups in both periods. In histometric analysis, a higher percentage of bone in furca (PBF) (p≤0.05) can be observed in the NIC-PE-RAR-Q10L, NIC-PE-RAR-Q10S and NIC-PE-RAR-Q10LS groups compared to the NIC-PE-RAR group in both periods and also with the SS-PE-RAR group at 28 days. A lower number of TRAPpositive cells (p≤0.05) can be observed in the NIC-PE-RAR-Q10L group when compared to the SS-PE-RAR and NIC-PE-RAR groups at 7 days and in the NIC-PE-RAR-Q10LS group when compared to the same groups at 28 days. It was concluded that RAR associated with CQ10 used locally and locally/systemically in the treatment of EP in rats treated systemically with NIC were effective, showing favorable results in histopathological, histometric and immunohistochemical analyses(AU)

Benefits of micronutrient supplementation on nutritional status, energy metabolism, and subjective wellbeing.

INTRODUCTION: The human body, particularly the brain, requires energy, stored in the form of adenosine triphosphate. Energy metabolism during cellular respiration is dependent on the presence of multiple micronutrients, which act as essential components, coenzymes, or precursors at every stage. An adequate supply of multiple micronutrients is vital for efficient energy production. However, micronutrient intakes below the recommended dietary allowance are common, even in industrialized countries. Intakes of vitamins A, D, E, folate, iron, zinc, and selenium are suboptimal across all age groups. Suboptimal micronutrient levels have been shown to contribute to low energy levels, physical and mental fatigue, and impaired cognitive performance and wellbeing - symptoms frequently present in the general population. When supplemented in combination in well-conducted trials, multiple micronutrients ± coenzyme Q10 reduced oxidative stress in chronic fatigue syndrome; in healthy people they increased cerebral blood-flow hemodynamic response, energy expenditure, and fat oxidation; reduced mental and physical fatigue; improved the speed and accuracy of cognitive function during demanding tasks; and reduced stress. The results from these clinical trials suggest that even in industrialized countries, where adults might be assumed to have a healthy, balanced diet, there is a rationale to supplement with multiple micronutrients, including coenzyme Q10, to improve nutritional status, support energy metabolism, and improve subjective wellbeing.

INTRODUCCIÓN: El cuerpo humano, particularmente el cerebro, requiere energía, almacenada en forma de adenosina trifosfato. El metabolismo de la energía durante la respiración celular depende de la presencia de múltiples micronutrientes, que actúan como componentes esenciales, coenzimas o precursores en cada etapa. Un aporte adecuado de múltiples micronutrientes es vital para una producción eficiente de energía. Sin embargo, la ingesta de micronutrientes inferior a la recomendada es frecuente, incluso en los países industrializados. Las ingestas de vitaminas A, D, E, folato, hierro, zinc y selenio son subóptimas en todos los grupos de edad. Se ha demostrado que las situaciones subóptimas en relación con diversos micronutrientes contribuyen a tener niveles bajos de energía, fatiga física y mental, y deterioro del rendimiento cognitivo y el bienestar, síntomas presentes a menudo en la población general. Sin embargo, cuando se suplementa en ensayos bien controlados, con una combinación de diversos micronutrientes ± coenzima Q10, se constata una reducción del estrés oxidativo en el síndrome de fatiga crónica y, en las personas sanas, se observa un aumento de la respuesta hemodinámica del flujo sanguíneo cerebral, el gasto energético y la oxidación de la grasa; una reducción de la fatiga mental y física; una mejora de la velocidad y la precisión de la función cognitiva durante la realización de tareas exigentes, y una reducción del estrés. Los resultados de estos ensayos clínicos sugieren que, incluso en los países industrializados, donde se podría suponer que los adultos tienen una dieta saludable y equilibrada, hay motivos para complementarla con múltiples micronutrientes, incluida la coenzima Q10, con el fin de mejorar el estado nutricional, respaldar el metabolismo energético y mejorar el bienestar subjetivo.

Coenzima Q10versus vitamina D en el manejo de las mialgias asociadas a estatinas / Coenzyme Q10 versus vitamin D when handling myalgias associated to statins

Introducción: Las estatinas han mostrado ser una herramienta esencial en la prevención de eventos cardiovasculares, sin embargo, sus efectos adversos sobre el músculo esquelético conocidos como SAMS (Statin-Associated Muscle Symptoms) son frecuentes y motivan la falta de adherencia al tratamiento. Es necesario superar esta barrera con nuevas estrategias, se ha sugerido en diferentes estudios que la suplementación de vitamina D o de coenzima Q10 (CoQ10) podrían revertir este inconveniente. El objetivo de este trabajo es revisar y comparar la evidencia disponible sobre CoQ10 y la vitamina D como posibles candidatos para el manejo de las SAMS. Método: Se ha realizado una búsqueda bibliográfica de la literatura, las bases de datos consultadas fueron Medline a través de PubMed y Scopus. Resultados: Los ensayos clínicos que evaluaron la suplementación de CoQ10 con este fin obtuvieron conclusiones dispares, la suplementación oral aumentó las concentraciones séricas, pero no se ha confirmado con claridad que este incremento se transfiera al tejido musculo-esquelético ya que pocos ensayos emplearon biopsias, además, cuando se emplearon arrojaron resultados contrapuestos. Respecto a la vitamina D, destacaron estudios transversales y retrospectivos en los que se evidenció que la hipovitaminosis D se asocia a exacerbación de estas miopatías asociadas, en cambio, los ensayos que valoraron la suplementación no obtuvieron una evidencia unánime. Conclusión: No se pueden recomendar suplementos de CoQ10 de modo confiable para tratar SAMS. El estatus de vitamina D al inicio de la terapia con estatinas es un buen marcador de riesgo y mejora el pronóstico de las miopatías asociadas, en cambio, se necesitan más ensayos clínicos controlados con placebo para contrastar la utilidad en suplementación.(AU)

Introduction: Statins have shown to be an essential tool in the prevention of cardiovascular events. However, their adverse effects on skeletal muscle are common and lead to lack of adherence to treatment. Different studies suggest that vitamin D or coenzyme Q10 supplementation could reverse this problem. The aimof this work is to review and compare the available evidence on coenzyme Q10and vitamin D as possible candidates for the management of statin-related myalgias. Method: A bibliographic search of literature was conducted, databases consulted were Medline through Pubmed and Scopus. Results: Clinical trials that evaluated coenzyme Q10 supplementation obtained disparate results. Oral supplementation increased coenzyme Q10 serum concentrations, but it has not been confirmed clearly that this increase is transferred to muscular-skeletal tissue, since few trials used biopsies, and when applied, opposing results were obtained. With regard to vitamin D, some cross-sectional and retrospective studies stand out. They showed hypovitaminosis D is associated with statin-related myalgias exacerbation. However, trials that assessed its supplementation did not obtain unanimous evidence. Conclusion: Coenzyme Q10 supplements cannot be recommended reliably to treat statin-related myalgias. Vitamin D status at the beginning of statin therapy is a good risk marker and improves statin-related myalgias prognosis, but more placebo-controlled clinical trials are needed to prove its supplementation usefulness.(AU)

Benefits of micronutrient supplementation on nutritional status, energy metabolism, and subjective wellbeing / Beneficios de la suplementación con micronutrientes sobre el estado nutricional, el metabolismo energético y el bienestar subjetivo

The human body, particularly the brain, requires energy, stored in the form of adenosine triphosphate. Energy metabolism during cellular respiration is dependent on the presence of multiple micronutrients, which act as essential components, coenzymes, or precursors at every stage. An adequate supply of multiple micronutrients is vital for efficient energy production. However, micronutrient intakes below the recommended dietary allowance are common, even in industrialized countries. Intakes of vitamins A, D, E, folate, iron, zinc, and selenium are suboptimal across all age groups. Suboptimal micronutrient levels have been shown to contribute to low energy levels, physical and mental fatigue, and impaired cognitive performance and wellbeing – symptoms frequently present in the general population. When supplemented in combination in well-conducted trials, multiple micronutrients ± coenzyme Q10 reduced oxidative stress in chronic fatigue syndrome; in healthy people they increased cerebral blood-flow hemodynamic response, energy expenditure, and fat oxidation; reduced mental and physical fatigue; improved the speed and accuracy of cognitive function during demanding tasks; and reduced stress. The results from these clinical trials suggest that even in industrialized countries, where adults might be assumed to have a healthy, balanced diet, there is a rationale to supplement with multiple micronutrients, including coenzyme Q10, to improve nutritional status, support energy metabolism, and improve subjective wellbeing. (AU)

El cuerpo humano, particularmente el cerebro, requiere energía, almacenada en forma de adenosina trifosfato. El metabolismo de la energía durante la respiración celular depende de la presencia de múltiples micronutrientes, que actúan como componentes esenciales, coenzimas o precursores en cada etapa. Un aporte adecuado de múltiples micronutrientes es vital para una producción eficiente de energía. Sin embargo, la ingesta de micronutrientes inferior a la recomendada es frecuente, incluso en los países industrializados. Las ingestas de vitaminas A, D, E, folato, hierro, zinc y selenio son subóptimas en todos los grupos de edad. Se ha demostrado que las situaciones subóptimas en relación con diversos micronutrientes contribuyen a tener niveles bajos de energía, fatiga física y mental, y deterioro del rendimiento cognitivo y el bienestar, síntomas presentes a menudo en la población general. Sin embargo, cuando se suplementa en ensayos bien controlados, con una combinación de diversos micronutrientes ± coenzima Q10, se constata una reducción del estrés oxidativo en el síndrome de fatiga crónica y, en las personas sanas, se observa un aumento de la respuesta hemodinámica del flujo sanguíneo cerebral, el gasto energético y la oxidación de la grasa; una reducción de la fatiga mental y física; una mejora de la velocidad y la precisión de la función cognitiva durante la realización de tareas exigentes, y una reducción del estrés. Los resultados de estos ensayos clínicos sugieren que, incluso en los países industrializados, donde se podría suponer que los adultos tienen una dieta saludable y equilibrada, hay motivos para complementarla con múltiples micronutrientes, incluida la coenzima Q10, con el fin de mejorar el estado nutricional, respaldar el metabolismo energético y mejorar el bienestar subjetivo. (AU)

The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes / Estado antioxidante da coenzima Q10 e da vitamina E em crianças com diabetes tipo 1

Abstract Objective: The purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. Method: This case-control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. Results: Children with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p < 0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p < 0.05). The platelet redox status showed a negative correlation with the A1c % levels (r = −0.31; p = 0.022) and the duration of type 1 diabetes (r = −0.35, p = 0.012). Conclusion: Patients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress.

Resumo Objetivo: Avaliar o estado antioxidante da vitamina E no plasma e da coenzima Q10 no plasma e intracelular em crianças com diabetes tipo 1. Método: Este estudo caso-controle realizado em com 72 crianças com diabetes tipo 1 comparadas por idade, sexo e etnia de 58 crianças saudáveis. As crianças diabéticas foram divididas em dois grupos de acordo com sua hemoglobina glicosilada (A1c %): grupos de controle glicêmico bom e baixo. Todas as crianças foram submetidas a anamnese total, exame clínico e laboratorial para hemograma completo, A1c %, colesterol no plasma, triglicerídeos e níveis de vitamina E e níveis de coenzima Q10 no plasma, eritrócitos e plaquetas. Resultados: As crianças com baixo controle glicêmico mostraram nível de vitamina E no plasma significativamente maior, coenzima Q10, triglicerídeos, lipoproteína de baixa densidade, proporção da circunferência da cintura/estatura e níveis de colesterol e menor nível de lipoproteína de alta densidade e estado redox da coenzima Q10 em comparação aos com bom controle glicêmico e com o grupo de controle (p < 0,05). A coenzima Q10 no plasma mostrou correlação positiva com a duração da diabetes tipo 1, triglicerídeos, colesterol, vitamina E e A1c % e correlação negativa com a idade do grupo diabético (p < 0,05). O estado redox das plaquetas mostrou correlação negativa com os níveis de A1c % (r = -0,31; p = 0,022) e a duração da diabetes tipo 1 (r = -0,35, p = 0,012). Conclusão: Os pacientes com diabetes tipo 1, principalmente mal controlados, apresentaram aumento nos níveis de vitamina E no plasma e coenzima Q10 e redução no estado redox das plaquetas da coenzima Q10 que podem indicar aumento do estresse oxidativo.

The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes.

OBJECTIVE: The purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. METHOD: This case-control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. RESULTS: Children with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p<0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p<0.05). The platelet redox status showed a negative correlation with the A1c % levels (r=-0.31; p=0.022) and the duration of type 1 diabetes (r=-0.35, p=0.012). CONCLUSION: Patients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress.

A utilização da coenzima Q10 adjunta à terapia periodontal básica na periodontite crônica / The use of coenzyme Q10 accompanies basic periodontal therapy in chronic periodontitis

A porção inflamatória da resposta imunoinflamatória é mediada por moléculas oxidativas que causam degradação de colágeno e danos às células periodontais. Uma disbiose nessa resposta leva a periodontite. Essas moléculas oxidativas podem ser neutralizadas pela coenzima Q10 (CoQ10), sendo um composto produzido pelo corpo, e apresenta duas formas moleculares, na forma oxidada chamada de Ubiquinona e na reduzida denominada de Ubiquinol. O Ubiquinol é a molécula que confere propriedade antioxidante a esse composto. O objetivo desse estudo é apresentar uma revisão de literatura sobre o uso adjunto da CoQ10 na terapia periodontal básica de pacientes com periodontite crônica. Para tal, foi realizada uma revisão de literatura de ensaios clínicos controlados de pacientes com diagnóstico de periodontite crônica cujo tratamento consistia em raspagem e alisamento radicular (RAR) e CoQ10 adjunta (grupo teste) em comparação a RAR isolado ou associado a um placebo (grupo controle). Os parâmetros periodontais avaliados foram índice de placa (IP), índice gengival (IG), profundidade de bolsa (PB) e nível clínico de inserção (NIC). Foram obtidos 5 estudos e 3 deles não relataram respostas estatisticamente significantes para nenhum parâmetro periodontal avaliado. Entretanto, nos outros dois estudos verificaram-se melhoras estatisticamente significantes para IG e IP após 3 meses e 4 semanas respectivamente utilizando-se CoQ10 adjunta. Após análise dos resultados, pode-se concluir que o uso da CoQ10 adjunta à terapia periodontal básica em paciente com periodontite crônica apresentou melhoras estatisticamente significantes, somente para IG, quando usada em forma de suplementação oral e somente IP quando usada em gel intrabolsa. (AU)

The inflammatory portion of the immune-inflammatory response is mediated by oxidative molecules, which cause collagen degradation and damage to periodontal cells. A dysbiosis in this response leads to periodontitis. These oxidative molecules can be neutralized by coenzyme Q10 (CoQ10), which is a compound produced by the body, and has two molecular forms, in the oxidized form called Ubiquinone and in the reduced form called Ubiquinol. Ubiquinol is the molecule that confers the antioxidant property to this compound. The purpose of this study is to present a literature review on CoQ10 adjunctive use in basic periodontal therapy of patients with chronic periodontitis. A literature review of controlled clinical trials of patients diagnosed with chronic periodontitis, whose treatment consisted of scaling and root planing (SRP) and adjunct CoQ10 (test group) compared to SRP alone or with a placebo associated. The periodontal parameters evaluated were: plaque index (PI) and gingival index (GI), pocket depth (PD) and clinical attachment level (CAL). Five studies were obtained, of which 03 did not report statistically significant responses for any periodontal parameter evaluated. The other two studies showed statistically significant improvements in GI after 3 months of use, and PI after 4 weeks using CoQ10, respectively. After analyzing the results, it can be concluded that the use of CoQ10 adjunct to basic periodontal therapy in patients with chronic periodontitis showed statistically significant improvements, only for GI, when used as oral supplementation, and only PI when applied in intrapocket gel. (AU)

[Regulation of the expression of coenzyme Q-synthesis complex during ageing]. / La expresión del complejo de síntesis de coenzima Q es regulada durante el envejecimiento.

INTRODUCTION: Coenzyme Q is an essential component in the activity of the mitochondrial electron transport chain. Its synthesis involves, at least, a complex of ten different proteins. In this study, an attempt is made to determine the evolution of the expression of the genes involved in coenzyme Q synthesis during mouse ageing. MATERIAL AND METHODS: The messenger RNA (mRNA) of different organs, such as brain, liver, kidney and skeletal muscle from young (8 months), mature (18 months), and old (24 months) mice was extracted by using Trizol and was then analysed by real time PCR (qPCR) using specific primers for all the known components of the coenzyme Q-synthesis complex (COQ genes). RESULTS: Liver showed the highest age-dependent changes in mRNA levels of the different components of Q-synthesis complex, affecting the extent of the variation as well as the significance of the change. In most of the cases, mRNA levels of the different components were higher in mature animals compared to young and old animals. When mRNAs of young and old animals were compared, only minor reductions of mRNA levels were found. Kidney showed a pattern similar to that found in liver as regards the changes in expression, although with lower increases in mature animals than those observed in the liver. Brain and skeletal muscle showed low variations, with muscle being the tissue with less changes, although a pattern similar to that found in liver and kidney was found, with slight increases in mature animals. DISCUSSION: The results of this study indicate that ageing is an important factor affecting COQ gene expression, but its effect depends on the organ, and that mature animals show higher levels of mRNA than young and old animals. Taken into consideration the importance of coenzyme Q in cell metabolism and ageing, a more detailed study is needed to understand the gene regulation of the coenzyme Q-synthesis mechanisms during ageing.

Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects / Coenzima Q10 e marcadores pró-inflamatórios em crianças com síndrome de Down: aspectos clínicos e bioquímicos

Abstract: Objective: Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. Methods: Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. Results: Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014). Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p = 0.002), while coenzyme Q10 was significantly decreased (p = 0.002). Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. Conclusion: Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

Resumo: Objetivo: Foram relatadas evidências de estresse oxidativo em indivíduos com a síndrome de Down. Há um interesse cada vez maior na contribuição do sistema imunológico na síndrome de Down. O objetivo deste estudo é avaliar a coenzima Q10 e marcadores pró-inflamatórios selecionados, como interleucina 6 e o fator de necrose tumoral α, em crianças com a síndrome de Down. Métodos: Foram inscritas neste estudo de caso-controle 86 crianças (5-8 anos) de duas instituições públicas. No momento da amostragem, os pacientes e os controles não sofriam de doença aguda ou crônica e não recebiam terapia ou suplementos. Foram medidos os níveis de interleucina 6, fator de necrose tumoral α, coenzima Q10, glicemia de jejum e quociente de inteligência. Resultados: Foram incluídas em oito meses (janeiro-agosto 2014) 43 crianças com síndrome de Down e 43 controles. Em comparação com o grupo de controle, os pacientes com síndrome de Down mostraram aumento significativo na interleucina 6 e no fator de necrose tumoral α (p = 0,002), ao passo que a coenzima Q10 apresentou significativa redução (p = 0,002). Além disso, o índice de massa corporal e a glicemia de jejum eram significativamente maiores nos pacientes. Houve uma correlação significativamente positiva entre os níveis de coenzima Q10 e do quociente de inteligência, bem como entre a interleucina 6 e o fator de necrose tumoral α. Conclusão: Os níveis de interleucina 6 e o fator de necrose tumoral α em crianças mais novas com síndrome de Down podem ser usados como biomarcadores, refletem o processo neurodegenerativo neles. A coenzima Q10 pode ter um papel como bom suplemento em crianças com síndrome de Down para melhorar os sintomas neurológicos.

Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects.

OBJECTIVE: Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. METHODS: Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. RESULTS: Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014). Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p=0.002), while coenzyme Q10 was significantly decreased (p=0.002). Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. CONCLUSION: Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

The qualitative effects of resveratrol and coenzyme Q10 administration on the gluteus complex muscle morphology of SJL/J mice with dysferlinopathy / Efectos cualitativos de la administración de resveratrol y coenzima Q10 en la morfología del complejo muscular glúteo de ratones SJL/J con disferlinopatía

Dysferlinopathy is a form of muscular dystrophy affecting muscles of the shoulder and pelvic girdles, resulting from inheritance of a mutated dysferlin gene. The encoded dysferlin protein is proposed to be involved in sarcolemmal vesicle fusion with a disrupted plasma membrane; however, with defective protein function these vesicles accumulate beneath the disruption site but are unable to fuse with it and reseal the membrane, thus rendering the membrane repair mechanism defective. The SJL/J mouse model presents with characteristics much like the commonest human condition. Immune modulators have long been under study in the maintenance of muscle health in muscular dystrophies. Such supplementary treatment would ideally suppress inflammation, preventing the immune response toward degenerating muscle from causing additional muscle fiber death, and thus provide a mechanism by which to prolong the life of muscle fibers with inherently defective healing apparatus. For this purpose the anti-inflammatory supplement resveratrol and the membrane-protective supplement coenzyme Q10 were administered separately and in combination to experimental animals to determine their effectiveness in possible therapy of dysferlinopathy. The findings of this study report that low doses of resveratrol and coenzyme Q10 supplementation in exclusivity were unable to afford much protection to muscle fibers at the tissue level. High doses of coenzyme Q10 proved more effective in reducing attenuating inflammation; and combination treatment with resveratrol and coenzyme Q10 provided not only the membrane-protective effects of coenzyme Q10, but also the anti-inflammatory effects of resveratrol which failed to materialize at sufficient levels in exclusive administration.

Disferlinopatía es una forma de distrofia muscular que afecta a los músculos de los hombros y cintura pélvica, resultado de la herencia y mutación del gen de la distrofina. Sugerimos que la proteína codificada distrofina que integra la estructura sarcolemal con una membrana plasmática interrumpida, que al presentar una proteína defectuosa, las estructuras se acumulan debajo del sitio de alteración sin lograr fundirse con éste y cerrar la membrana afectando el mecanismo de reparación. El modelo de ratón SJL / J se presenta con características muy similares a una condición humana común. Los inmunomoduladores han sido objeto de estudio en el mantenimiento de la salud muscular en las distrofias musculares. Este tipo de tratamiento suplementario puede ser ideal para suprimir la inflamación, en la prevención de la respuesta inmune en la degeneración muscular causando la muerte adicional de fibra muscular, y al mismo tiempo proporcionar, un mecanismo con el cual prolongar la vida útil de aquellas fibras musculares con el aparato de sanación comprometido. Para ello, el Resveratrol suplemento anti-inflamatorio y el suplemento protector de membrana coenzima Q10 se administró por separado y en combinación en los animales de laboratorio para determinar su efectividad en el tratamiento de posible disferlinopatía. Los resultados de este estudio indican que el Resveratrol en menor dosis y la coenzima Q 10 administrados como suplementos de manera exclusiva, no demostraron efectos de protección de las fibras musculares a nivel del tejido. Una alta dosis de coenzima Q10 demostró ser más efectiva en la reducción de la inflamación; adicionalmente, el tratamiento combinado de Resveratrol y coenzima Q10 proporcionó efectos protectores de membrana, además de los efectos anti-inflamatorios del Resveratrol cuyo nivel no alcanzó la efectividad suficiente al ser administrado en forma exclusiva.

Coenzyme Q10 and its effects in the treatment of neurodegenerative diseases: [review] / A coenzima Q10 e seus efeitos no tratamento de doenças neurodegenerativas: [revisão]

According to clinical and pre-clinical studies, oxidative stress and its consequences may be the cause or, at least, a contributing factor, to a large number of neurodegenerative diseases. These diseases include common and debilitating disorders, characterized by progressive and irreversible loss of neurons in specific regions of the brain. The most common neurodegenerative diseases are Parkinson's disease, Huntington's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Coenzyme Q10 (CoQ10) has been extensively studied since its discovery in 1957. It is a component of the electron transportation chain and participates in aerobic cellular respiration, generating energy in the form of adenosine triphosphate (ATP). The property of CoQ10 to act as an antioxidant or a pro-oxidant, suggests that it also plays an important role in the modulation of redox cellular status under physiological and pathological conditions, also performing a role in the ageing process. In several animal models of neurodegenerative diseases, CoQ10 has shown beneficial effects in reducing disease progression. However, further studies are needed to assess the outcome and effectiveness of CoQ10 before exposing patients to unnecessary health risks at significant costs.

De acordo com estudos clínicos e pré-clínicos, o estresse oxidativo e suas conseqüências podem ser a causa, ou, no mínimo, o fator que contribui para grande número de doenças degenerativas. Estas doenças incluem problemas comuns e debilitantes, caracterizados por perda progressiva e irreversível de neurônios em regiões específicas do cérebro. As doenças degenerativas mais comuns são doença de Parkinson, de Hutington, de Alzheimer e esclerose amiotrófica lateral. A Coenzima Q10 (CoQ10) tem sido intensamente estudada desde sua descoberta, em 1957. É um componente da cadeia de transporte eletrônico e participa da respiração aeróbica celular, gerando energia na forma de trifosfato de adenosina (ATP). A propriedade da CoQ10 de atuar como antioxidante ou pró-oxidante sugere papel importante na modulação do estado redox celular sob condições fisiológicas e patológicas, desempenhando, também, papel no processo de envelhecimento. Em vários modelos animais de doenças neurodegenerativas, a CoQ10 mostrou efeitos benéficos na redução do curso da doença. Entretanto, há necessidade de estudos adicionais para avaliar o efeito e a eficácia da CoQ10 antes de expor os pacientes a riscos de saúde desnecessários e de alto custo.

Unusual occurrence of intestinal pseudo obstruction in a patient with maternally inherited diabetes and deafness (MIDD) and favorable outcome with coenzyme Q10 / Pseudo-obstrução intestinal em paciente com diabetes mitocondrial que apresentou boa resposta ao tratamento adjunto com coenzima Q10

Maternally inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. This subtype of diabetes is characterized by maternal transmission, young age at onset and bilateral hearing impairment. Besides diabetes and deafness, the main diagnostic features, a wide range of multisystemic symptoms may be associated with the A3243G mutation. Organs that are most metabolically active, such as muscles, myocardium, retina, cochlea, kidney and brain are frequently affected. Gastrointestinal tract symptoms are also common in patients with mitochondrial disease and constipation and diarrhea are the most frequent manifestations. However, there are few prior reports of intestinal pseudo obstruction in MIDD patients. Here we report the case of a patient with MIDD associated with the mtDNA A3243G mutation who developed chronic intestinal pseudo obstruction, and the introduction of Coenzyme Q10 as adjunctive therapy led to a solution of the pseudo obstruction.

Diabetes mitocondrial ou diabetes e surdez de herança maternal (MIDD, acrônimo de maternally inherited diabetes and deafness) é freqüentemente associado à mutação mitocondrial A3243G. Esse subtipo de diabetes é caracterizado por transmissão materna, disacusia neuro-sensorial bilateral e idade precoce de aparecimento. Além do diabetes e da surdez, principais características diagnósticas, outros sintomas em diferentes órgãos podem também associar-se à mutação A3243G. Os órgãos que são metabolicamente mais ativos, tais como músculos, miocárdio, retina, cóclea, rim e cérebro, são freqüentemente afetados. Sintomas do trato gastrintestinal também são comuns em pacientes com doença mitocondrial, sendo diarréia e obstipação as manifestações mais freqüentes. Entretanto, há poucos relatos de pseudo-obstrução intestinal em portadores de diabetes mitocondrial. Este relato descreve o caso de uma paciente com diabetes mitocondrial que apresentou pseudo-obstrução intestinal e que com a introdução de coenzima Q10, como terapia adjunta, teve resolução o quadro.