Risk Assessment of "Other Substances" – Coenzyme Q10

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk of "other substances" in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by NFSA. These risk assessments will provide NFSA with the scientific basis while regulating the addition of “other substances” to food supplements and other foods. "Other substances" are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals t hat have a nutritional and/or physiological effect. It is added mainly to food supplements, but also to energy drinks and other foods. In this series of risk assessments of "other substances", VKM has not evaluated any potential beneficial effects from these substances, only possible adverse effects. The present risk assessment of coenzyme Q10 (CoQ10) is based on previous risk assessments and articles retrieved from a literature search. According to information from NFSA, CoQ10 is an ingredient in food supplements sold in Norway. NFSA has requested a risk assessment of intake of 100 mg/day of CoQ10 in food supplements. CoQ10 (CAS no. 303-98-0) is a naturally-occurring, lipid-soluble compound present in all tissues in humans. Ubiquinone is the totally oxidized form (CoQ10), whereas ubiquinol (CoQ10H2) is the totally reduced form. Meat and fish are the food sources richest in CoQ10. CoQ10 intake from the diet ranges between 3 and 6 mg/day in developed countries. The total body pool of CoQ10 is estimated to be approximately 0.5–1.5 g in an adult. Several studies of CoQ10 (both oxidized and reduced form) have been performed in healthy humans (adults) and animals, showing fairly similar results. The adverse effects reported in a small number of human subjects were generally limited to mild gastrointestinal symptoms such as nausea and stomach upset. In humans, orally ingested CoQ10 was well tolerated at doses up to 900 mg/day (corresponding to 12.9 mg/kg bw per day in a 70 kg adult) over periods up to one month. With regard to animal studies, the lack of adverse effects of CoQ10 doses up to 1200 mg/kg per day in long-term toxicity studies supported and extended the results from the human studies. No studies on children (10 to <14 years) and adolescents (14 to <18 years) were identified. Based on the included literature there was no evidence indicating that age affects tolerance for CoQ10. Therefore, in this risk characterisation the same tolerance as for adults was assumed for these age groups (adjusted for body weight). From a daily dose of 100 mg CoQ10, the daily exposure is 2.3 mg/kg bw for children (10 to <14 years), 1.6 mg/kg bw for adolescents (14 to <18 years), and 1.4 mg/kg bw for adults (≥18 years). For the risk characterization, the values used for comparison with the estimated exposure are 900 mg/day (corresponding to 12.9 mg/kg bw per day in a 70 kg adult) based on human studies (4 weeks) and the no observed adverse effect level (NOAEL) of 1200 mg/kg bw per day based on a long-term toxicity study in rats (52 weeks). The margin of exposure (MOE) approach is used for the rat study; that is the ratio of the NOAEL to the exposure. An acceptable MOE value for a NOAEL-based assessment of CoQ10 based on an animal study is ≥100, which includes a factor 10 for extrapolation from animals to humans, and a factor 10 for interindividual human variation. Comparing the NOAEL from a long-term toxicity study in rats with the estimated exposure for the different age groups, it is unlikely that a daily dose of 100 mg/day of CoQ10 causes adverse health effects in children above 10 years, adolescents and adults. Comparing the dose reported to be well tolerated for healthy adults directly with the estimated exposure, it is unlikely that a daily dose of 100 mg/day of CoQ10 causes adverse health effects in children above 10 years, adolescents and adults. VKM concludes that it is unlikely that a daily dose of 100 mg of CoQ10 from food supplements causes adverse health effects in children (10 to <14 years), adolescents (14 to <18 years) and adults (≥18 years).

Effect of coenzyme Q10 supplementation on serum protein, mineral status, blood picture and immune status in broilers.

In poultry, coenzyme Q10 (CoQ10) is widely used as a feed additive to control mortality due to ascites in broilers. Apart from its use the treatment of a variety of disorders viz., ischemic heart disease, diabetes mellitus, Parkinson’s disease, muscle fatigue and muscle weakness, its supplementation has been reported to be beneficial for cardiovascular disease, chronic heart failure, cancer, migraine, asthma and hypertension. In this study, we investigated the effect of CoQ10 supplementation on serum protein, serum minerals, blood parameters, ascites susceptibility and humoral immune status in broilers fed with different energy levels which influence their productivity, biochemical profile and ascites incidences. The treatment had three levels of CoQ10, namely 0, 20 and 40 mg/kg at normal (NE), low (LE) and high (HE) energy levels in which 2X3 factorial design was followed. The haemoglobin and packed cell volume were not affected (P >0.05) by either energy or CoQ10 levels but the erythrocyte osmotic fragility per cent (EOF %) and blood glucose levels were decreased by CoQ10 supplementation at both 20 and 40 mg/kg. The serum calcium level had significantly (P <0.01) increased with CoQ10 at 40 mg/kg (12.70 vs. 11.58 and 11.98 mg/dL) in NE diet group over the unsupplemented and 20 mg/kg supplemented birds. Compared to the respective unsupplemented groups, CoQ10 @40 mg/kg reduced (P <0.01) the serum total protein (4.69 vs. 5.23 g/dL) and serum albumin (2.46 vs. 2.78 g/dL) in NE group but increased (P <0.01) (4.70 vs. 4.08 g/dL) and (2.59 vs. 2.04 g/dL), respectively in LE group. High energy birds showed significantly (P <0.01) increased serum albumin (2.74 vs. 2.24 g/dL). The humoral immunity against Newcastle Disease (ND titre) was significantly (P <0.01) higher in 21 days of growth period at both the levels of supplementation but on 42 days no significant difference among the groups were observed. It can be concluded that CoQ10 supplementation at 20 mg/kg decreased blood glucose level and increased erythrocytes osmotic stability and hence, could reduce bird’s susceptibility to ascites.

Dioxygen reduction, reduced oxygen species, oxygen toxicity and antioxidants — A commentary.

Molecular oxygen, a diradical, needs intervention of redox metal ions or other radicals to receive electrons for its reduction. The oxygen radicals thus produced are responsible for oxygen toxicity and oxidative stress. But, autoxidation, relevant in ischemia-reperfusion injury, is absent in any discussion on oxygen toxicity. Naturally occurring compounds which prevent formation or action of the reactive oxygen species (ROS) are generally referred as antioxidants. The reduced oxygen species, superoxide, peroxide and hydroxyl radicals, are formed in a variety of systems in the cell and are useful in selective oxidations. Currently, the popular method for assaying ROS with fluorescence of dichlorofluorescein actually measures a hemeprotein-Fe-oxo complex. The Fe-oxyl radicals are the likely oxidants in damaging proteins, nucleic acids and lipids. Such major lesions are normally repaired or replaced in the cells. The antioxidants counter the damaging oxidant actions. Among these, occurring in large concentration, are glutathione and ubiquinol, synthesized in the body and ascorbic acid and α-tocopherol, drawn from the food. A large number of plant-derived phenolic compounds, especially the flavonoid variety, are also absorbed, albeit poorly, from the food. At the natural low concentrations, these compounds show wide ranging biological effects. Increased benefit on increasing them in circulating blood needs individual verification. The polyphenolic compounds demonstrated powerful antioxidant effects in laboratory experiments. But the clinical studies did not support the consequent expectations of countering the oxidative stress, the purported crucial factor in pathology in several diseases. Antioxidant action against ROS causing oxygen toxicity needs to be reassessed. This commentary is a reappraisal of formation and reactivity of ROS in different cells, the active cellular oxidant forms, products of oxidant action on proteins, nucleic acids and lipids as marker of oxidant injury, bulk antioxidants of endogenous and exogenous origin, limited absorption occurrence and functions of polyphenolic classes.

<b>The Bioavailability of Reduced Coenzyme Q10 Water-Dispersive Powder after Single Oral Administration</b> / 日本補完代替医療学会誌

In this study, we showed the bioavailability of ubiquinol (QH) in the form of water-dispersive powder.Two groups of 5 healthy young subjects received single oral administration of 100 mg of QH in the form of a soft capsule containing QH dissolved in safflower oil or 40% water-dispersive powder in the fasting period, and changes in the plasma QH concentration were monitored over time.The water-dispersive powder form of QH exhibited superior bioavailability even when administered in the fasting period.