Vitamin Q-10

7. REFERENCES

7.1 Product specific references

a) Double-blind, mono-preparation trials

A-8610

Skough K; Krossen C; Heiwe S; Theorell H; Borg K:

Effects of resistance training in combination with coenzyme Q10 supplementation in

patients with post-polio: a pilot study.

J Rehabil Med.: 40:9:773-5. (2008)

OBJECTIVE: Coenzyme Q10 supplementation leads to increased muscle metabolism in patients with

post-polio syndrome. The aim of this study was to investigate the effect of resistance training in

combination with oral supplementation with coenzyme Q10 in patients with post-polio syndrome

regarding muscle strength and endurance as well as functional capacity and health-related quality of

life. DESIGN: Parallel randomized, controlled, double-blind pilot study. PATIENTS AND METHODS: A

total of 14 patients (8 women and 6 men) with post-polio syndrome participated in a 12- week muscular

resistance training, 3 days/week. The patients were randomized for oral supplementation with

coenzyme Q10, 200 mg/day, or placebo. Measurements used were: sit-stand- sit test, timed up & go

test, 6-minute walk test, muscle strength measurement by means of dynamic dynamometer and shortform

(SF)-36 questionnaire. RESULTS: Muscle strength, muscle endurance and quality of life

regarding mental health increased statistically significantly in all 14 patients. There was no significant

difference between the coenzyme Q10 and placebo groups regarding muscle strength, muscle

endurance and quality of life. CONCLUSION: There was no effect of coenzyme Q10 supplementation

during resistance training on post-polio syndrome symptoms. Thus, supplementation with coenzyme

Q10 has no beneficial effect on muscle function in patients with post-polio syndrome.

A-8607

Pella D; Fedacko J; Rybar R; Fedackova P et al.:

Coenzyme Q10 and Selenium in Statin Side Effects Treatment. Results of a

Randomised Double-Blind Clinical Study:

Int. Med. CoQ10 Congress, Prague, Czeck Republic.: Sept. 13th: (2008)

Statins are the principal and the most effective class of drugs to reduce serum cholesterol levels and

cardiovascular events in patients with or without coronary artery disease. Inhibition of HMG-CoA

reductase by statins is leading not only to decreased synthesis of cholesterol but is affecting also

synthesis of other substances. Besides positive pleiotropic effects of statins (antiinflammatory,

antithrombotic,antiproliferative and others) there are probably also negative ones, namely inhibition of

geranyl pyrophosphate synthesis and subsequently dekaprenylu4ubensoate which is precursor of

coenzyme Q10. Moreover statins inhibit endogenous synthesis of several selenoproteins (cholesterol,

CoQ10 and already mentioned selenoproteins share the same biosynthetic pathway which is inhibited

by statins). Coenzyme Q10 (ubiquinone, ubidekarenone) is one of the key substances in myocardial

energetic metabolism and for cells membrane stability as well, when deficient, myocytes should be

prone to damage in the form of myopathy or myositis, or even rhabdomyolysis. Selenium play very

important role like antioxidant and its deficiency may lead to the development of arterial hypertension,

cardiomyopathy (Keshan disease), or peripheral muscle disease. Background: Of our double blind,

single centre prospective 3-months study using 2x2 factorial design (CoQ10 200mg/day vs. selenium

200ug/day vs. their combination vs. placebo administered to statin treated patients with mild side

effects but not leading to treatment withdrawal) was to evaluate possible benefits of coenzyme Q10

and selenium supplementation. Methods: We have screened 1, 142 patients treated with statins and

found 60 eligible patients to be enrolled to the study. All patients underwent at the beginning of study

physical examination including measurement of blood pressure, laboratory examination ( plasma level

of CoQ10, lipid profile, liver enzymes, CK, glycaemia, BUN, creatinine, uric acid, sodium and

potassium levels) and echocardiography parameters to determine diastolic function of the left ventricle

(early diastolic velocity E, late diastolic velocity A, isovolumetric relaxation time, deceleration time).

Physical and laboratory examinations were repeated after 1 month and at the end of study.

Echocardiography was performed at the beginning and at the end of the 3 months study. Results:

Baseline plasma level of CoQ10 in placebo group was 0.74±0.31ug/ml and did not change significantly

during the whole study period. Plasma level of CoQ10 in active group increased from baseline

0.81±0.40ug/ml to 3.31±1.75ug/ml at 3 month visit ( statistical difference between placebo and active

group at month 3 was observed; p<0.0001). Muscle pain in active group dissappeared in 15 from 22

patients in comparison with baseline ( in placebo group not only no improvement, but 2 cases of new

onset of muscle pain were confirmed ). Muscle weakness was persistent only in 2 patients from 13 at

baseline visit compared with 8 patients who remain unchanged in placebo group. Fatigue, present at

baseline in 10 patients of active group, was markedly improved in 9 of them (in placebo group

improvement only in two patients). Polyneuropathy was reduced in 11 patients from 13 diagnosed at

baseline visit in the CoQ10 group compared with no change in the placebo one. Two parameters of

diastolic function were significantly improved in CoQ10 treated patients (E/A ratio increased from

0.854±0.27 to 1.080±0.27; p<0.0001) and isovolumetric relaxation time decreased from

101.26±17.63ms to 83.53±10.43ms; p<0.0001) while the third one remain statistically not significant

( deceleration time at baseline 180.43±48.10ms compared with final visit 176.16±36.25ms; p=0.654 ).

No significant change of all these three values in placebo group were observed. Our study confirmed

that blood concentration of selenium in statin treated patients is suboptimal (baseline values

70.42±13ug/L). In active selenium group we have observed increase to 137.12±31.26ug/L (p<0.0001)

at month 3 visit, which was associated with 50 % decrease of myopathy and fatigue incidence and

more than 70 % decrease of polyneuropathy signs and symptoms. In conclusion, our results showed

that supplementation of statin treated patients with coenzyme Q10 and/or selenium diminished

symptoms of myopathy and fatigue which could be associated Additional Author: Potocekova D.

A-8303

Tiano L; Gabrielli O; Carnevali P; Santoro L et al.:

Coenzyme Q10 and oxidative damage in Down Syndrome: Biochemical and clinical

aspects:

5th Conf Int CoQ10 Ass – Prog & Abstr: 57-8 (2007)

Down syndrome (DS) is a chromosomal abnormality (trisomy 21) associated with mental retardation

and Alzheimer-like dementia, characteristic change of the individualÆs phenotype and premature

ageing. Oxidative stress is known to play a major role in this pathology since a gene dose effect leads

to elevated ratio of superoxide dismutase to catalase/glutathione peroxidase compared to controls in

all age categories suggesting that oxidative imbalance contributes to the clinical manifestation of DS.

Hyperuricemia is another feature of DS that has an interesting relationship with oxidative stress since

uric acid represents an important free radical scavenger. However its formation is connected to the

conversion of xantine-dehydrogenase (XDH) to xantine-oxidase (XO) which leads to concomitant

production of free radicals. Here we report that plasma samples from DS patients in pediatric age

despite an increased total antioxidant capacity, largely due to elevated Uric acid content, do not differ

from healthy control plasma samples in terms of susceptibility to peroxidative stimuli. Instead, they

present significantly elevated markers of oxidative damage such as increased allantoin levels and

oxidative DNA damage in peripheral blood lymphocytes, displaying a bimodal distribution in relation to

DNA damage indexes detected by the Comet assay, characterized by a major population of mild

damaged cells and a smaller population of heavy damaged cells. Moreover, Coenzyme Q10

administration for 6 months, at a dosage of 4mg/Kg/die was able to significantly decrease indexes

associated with mild DNA damage detected by the Comet assay (Tail length and Tail migration).

These results, arising from a double blind controlled study on 40 DS patients in pediatric age, indicate

that CoQ10 is able to protect lymphocytes bearing low levels of DNA damage while it does not seem

effective in ameliorating the heavily damaged cells, thus indicating a potential application in preventive

therapy. We aim to verify if CoQ10 supplementation in this pathology is able to produce elevated

antioxidant protection in the plasma (TAC/Dieni) and ostabilizeo purine metabolism. The ongoing

phase of the study is aimed at verifying whether CoQ10 supplementation in these patients is able to

increase the antioxidant protection in plasma and to affect the conversion of uric acid into allantoin.

ADITTIONAL AUTHORS: Padella L, Carlucci A, Mercuri A, Principi F, Littarru GP

A-8048

Lukmann A; Ojamaa M; Veraksitch A; Vihalemm T et al.:

The effects of Coenzyme Q10 in early rehabilitation after acute coronary syndrome:

5th Conf Int CoQ10 Ass – Prog & Abstr: 124-5 (2007)

Aim: To investigate the effect of coenzyme Q10 (CoQ10) on the changes of several functional and

biochemical parameters during early rehabilitation after acute coronary syndrome (ACS). Methods:

Two to four weeks after ACS the patients started with 50-minute exercise therapy sessions three times

a week with an overall length of 12 weeks. 58 patients were randomized into 2 subgroups: 31 patients

received CoQ10 (gelatin capsule form CoQ10 dissolved in soya bean oil, Pharma Nord)100/200 mg

per day (1/7 weeks) and 27 patients received placebo according to the similar scheme. The patients

underwent breath-by-breath bicycle cardiopulmonary testing before and after the rehabilitation

programme, while the functional indices of cardiorespiratory system, the markers of cardiometabolic

risk factors and oxidative stress were measured: peak oxygen consumption and maximal workload,

total cholesterol, HDLcholesterol, LDL-cholesterol, triglycerides, ultra- sensitive C-reactive protein,

conjugated dienes, baseline conjugated dienes, oxidized LDL and human autoantibodies against

oxidized LDL . Results: After administrating the CoQ10 in early rehabilitation after ACS most of the

indices of cardiorespiratory reserve and functional capacity revealed a significant increase. In the study

group the improvement in aerobic capacity was more significant than in the control group. The markers

of cardiometabolic risk and oxidative stress did not demonstrate statistically significant change neither

in the study group nor in the control group. Conclusions: The administration of CoQ10 improves

positively the aerobic capacity of patients after ACS, especially in patients with congestive heart failure.

TYPE: Conference Poster

A-7806

Singh RB; Niaz MA; Kumar A; Sindberg CD; Moesgaard S; Littarru GP:

Effect on absorption and oxidative stress of different oral Coenzyme Q10 dosages

and intake strategy in healthy men.:

Biofactors.: 25:1-4:219-24. (2005)

INTRODUCTION: The effect of various dosages and dose strategies of oral coenzyme Q(10) (Q(100)

administration on serum Q(10) concentration and bioequivalence of various formulations are not fully

known. SUBJECTS AND METHODS: In a randomized, double blind, placebo controlled trial 60 healthy

men, aged 18-55 years, were supplemented with various dosages and dose strategies of coenzyme

Q(10) soft oil capsules (Myoqinon 100 mg, Pharma Nord, Denmark) or crystalline 100 mg Q(10)

powder capsules or placebo. After 20 days blood levels were compared and oxidative load parameters,

malondialdehyde (MDA) and thiobarbituric acid reactive substances (TBARS) were monitored to

evaluate bioequivalence. All the subjects were advised to take the capsules with meals. Blood samples

were collected after 12 hours of overnight fasting at baseline and after 20 days of Q(10) administration.

Compliance was evaluated by counting the number of capsules returned by the subjects after the trial.

RESULTS: Compliance by capsule counting was >90%. Side effects were negligible. Serum

concentrations of Q(10) (average for groups) increased significantly 3-10 fold in the intervention groups

compared with the placebo group. Serum response was improved with a divided dose strategy.

TBARS and MDA were in the normal ranges at baseline. After 20 days intervention in the 200 mg

group TBARS and MDA decreased, but the decrease was only significant for MDA (Fig. 2).

Conclusions: All supplementations increased serum levels of Q(10). Q(10) dissolved in an oil matrix

was more effective than the same amount of crystalline Q(10) in raising Q(10) serum levels. 200 mg of

oil/soft gel formulation of Q(10) caused a larger increase in Q(10) serum levels than did 100 mg.

Divided dosages (2 x 100 mg) of Q(10) caused a larger increase in serum levels of Q(10) than a single

dose of 200 mg. Supplementation was associated with decreased oxidative stress as measured by

MDA-levels. Indians appear to have low baseline serum coenzyme Q(10) levels which may be due to

vegetarian diets. Further studies in larger number of subjects would be necessary to confirm our

findings.

A-7043

Zita C; Overvad K; Hunter DA; Sindberg CD; Moesgaard S; Hunter DA:

Serum coenzyme Q_{10} concentrations in healthy men supplemented with 30 mg or

100 mg coenzyme Q_{10} for two months in a randomised controlled study.

Biofactors: 18:1-4:185-193. (2003)

Serum coenzyme Q10 (Q10) concentrations were evaluated in healthy male volunteers supplemented

with 30 mg or 100 mg Q10 or placebo as a single daily dose for two months in a randomised, doubleblind,

placebo-controlled study. Median baseline serum Q10 concentration in 99 men was 1.26 mg/l

(10%, 90% fractiles: 0.82, 1.83). Baseline serum Q10 concentration did not depend on age, while

borderline significant positive associations were found for body weight and smoking 1-10 cigarettes/d.

Supplementation with 30 mg or 100 mg Q10 resulted in median increases in serum Q10 concentration

of 0.55 mg/l and 1.36 mg/l, respectively, compared with a median decrease of 0.23 mg/l with placebo.

The changes in the Q10 groups were significantly different from that in the placebo group, and the

increase in the 100 mg Q10 group was significantly greater than that in the 30 mg Q10 group. The

change in serum Q10 concentration in the Q10 groups did not depend on baseline serum Q10

concentration, age, or body weight.

A-6314

Zorn B; Virant-Klun I; Osredkar J; Krstic N:

The effects of a double-blind randomized placebo cross-over controlled trial using

coenzyme Q10 (Bio-Quinone Q10)...:

Frankfurt: 2nd Conf. Intl. CoQ10 Assn: 126-127 (2000)

A-6084

Khatta M; Alexander BS; Krichten CM; Fisher ML; Freudenberger R; Robinson SW;

Gottlieb SS:

The effect of coenzyme Q10 in patients with congestive heart failure.:

Ann Intern Med: 132:8:636-40 (2000)

BACKGROUND: Coenzyme Q10 is commonly used to treat congestive heart failure on the basis of

data from several unblinded, subjective studies. Few randomized, blinded, controlled studies have

evaluated objective measures of cardiac performance. OBJECTIVE: To determine the effect of

coenzyme Q10 on peak oxygen consumption, exercise duration, and ejection fraction. DESIGN:

Randomized, double-blind, controlled trial. SETTING: University and Veterans Affairs hospitals.

PATIENTS: 55 patients who had congestive heart failure with New York Heart Association class III and

IV symptoms, ejection fraction less than 40%, and peak oxygen consumption less than 17.0 mL/kg per

minute (or <50% of predicted) during standard therapy were randomly assigned. Forty-six patients

completed the study. INTERVENTION: Coenzyme Q10, 200 mg/d, or placebo. MEASUREMENTS:

Left ventricular ejection fraction (measured by radionuclide ventriculography) and peak oxygen

consumption and exercise duration (measured by a graded exercise evaluation using the Naughton

protocol) with continuous metabolic monitoring. RESULTS: Although the mean (+/-SD) serum

concentration of coenzyme Q10 increased from 0.95+/- 0.62 microg/mL to 2.2+/- 1.2 microg/mL in

patients who received active treatment, ejection fraction, peak oxygen consumption, and exercise

duration remained unchanged in both the coenzyme Q10 and placebo groups. CONCLUSION:

Coenzyme Q10 does not affect ejection fraction, peak oxygen consumption, or exercise duration in

patients with congestive heart failure receiving standard medical therapy.

A-5615

Eriksson JG; Forsen TJ; Mortensen SA; Rohde M:

The effect of coenzyme Q10 administration on metabolic control in patients with type

2 diabetes mellitus:

BioFactors: 9:2-4:315-18 (1999)

A possible relationship between the pathogenesis of type 2 diabetes and coenzyme Q10 (CoQ10) deficiency

has been proposed. The aim of this study was to assess the effect of CoQ10 on metabolic control

in 23 type 2 diabetic patients in a randomized, placebo-controlled trial. Treatment with CoQ10 100

mg bid caused a more than 3-fold rise in serum CoQ10 concentration (p < 0.001). No correlation was

observed between serum CoQ10 concentration and metabolic control. No significant changes in metabolic

parameters were observed during CoQ10 supplementation. The treatment was well tolerated and

did not interfere with glycemic control; therefore CoQ10 may be used as adjunctive therapy in patients

with associated cardiovascular diseases.

A-5614

Munkholm H; Hansen HHT; Rasmussen K:

Coenzyme Q10 treatment in serious heart failure:

BioFactors: 9:2-4:285-89 (1999)

Several noninvasive studies have shown the effect on heart failure of treatment with coenzyme Q10. In

order to confirm this by invasive methods, we studied 22 patients with mean left ventricular (LV)

ejection fraction 26%, mean LV internal diameter 71 mm and in NYHA class 2-3. The patients received

coenzyme Q10 100 mg twice daily or placebo for 12 weeks in a randomized, double- blinded, placebocontrolled

investigation. Before and after the treatment period, a right heart catheterisation was done

including a three minute exercise test. The stroke index at rest and work improved significantly, the

pulmonary artery pressure at rest and work decreased (significantly at rest), and the pulmonary capillary

wedge pressure at rest and work decreased (significantly at one minute work). These results suggest

improvement in LV performance. Patients with congestive heart failure may thus benefit from adjunctive

treatment with coenzyme Q10.

A-5545

Henriksen JE; Andersen CB; Hother-Nielsen O; Vaag A; Mortensen SA; Beck-Nielsen

Impact of ubiquinone (coenzyme Q10) treatment on glycaemic control, insulin requirement

and well-being in patients with Type 1 diabetes mellitus

Diabet Med: 16:4:312-8 (1999)

AIM: To investigate the effect of ubiquinone (coenzyme Q10) on glycaemic control and insulin requirement

in patients with Type 1 diabetes mellitus (DM). METHODS: We investigated 34 patients with

Type 1 DM in a randomized, double-blind, placebo-controlled study. Patients received either 100 mg

Q10 or placebo daily for 3 months. The insulin doses were adjusted according to patients' home measurements

of blood glucose concentrations and reported experience of hypoglycaemia. RESULTS: At

randomization no differences existed between the Q10 and the placebo groups in age, body mass index

(BMI), HbA1c, daily insulin dose or mean daily blood glucose concentration. Serum Q10 concentration

increased in the Q10 group (mean +/- SD: 0.9+/-0.2 vs. 2.0+/-1.0 microg/ml, P<0.005), with no

change in the placebo group (0.9+/-0.3 vs. 0.9+/-0.3 microg/ml, not significant (NS)). Following intervention

no differences existed between the Q10 and the placebo groups regarding HbA1c (7.86+/-0.88

vs. 7.84+/-0.84%), mean daily blood glucose concentrations (8.06+/-1.86 vs. 8.53+/-1.88 mM), mean

insulin dose (52.1+/- 13.2 vs. 52.6+/-21.4 U), hypoglycaemic episodes (2.0+/-1.8 vs. 2.5+/-2.1 episodes/

week), or cholesterol concentrations (4.81+/-0.91 vs. 4.78+/-1.07 mM). Furthermore, no differences

existed in the well- being of the patients reported from a visual analogue scale (physical:

0.67+/-0.21 vs. 0.71+/-0.18, psychological: 0.70+/-0.25 vs. 0.73+/- 0.24). CONCLUSION: Q10 treatment

does not improve glycaemic control, nor does it reduce insulin requirement, and it can therefore

be taken by patients with Type 1 DM without any obvious risk of hypoglycaemia. No major beneficial or

unfavourable effects on the investigated parameters could be demonstrated and no major changes in

the sense of well-being occurred in the patients.

A-4933

Eriksson JG; Forsen TJ; Mortensen SA; Rohde M:

A double-blind study on the effect of Coenzyme Q10 on metabolic control in patients

with type 2 diabetes mellitus:

Boston: 1st Conf. of the Intl. Coenzyme Q10 Assn.: 158-59 (1998)

Treatment with CoQ10 was well tolerated among elderly type 2 diabetic patients, and CoQ10 did not

interfere with the glycemic control. Thus, CoQ10 may be used in diabetics either prophylactically or as

an adjunctive therapy -- especially in association with concomitant diseases like hypertension, coronary

heart disease, and heart failure. CoQ10 is without unfavorable effects on the metabolic parameters assessed,

and it may have potential benefits under optimal conditions of bioavailability and dosage in

type 2 diabetes.

A-4883

Munkholm H; Hansen HHT; Rasmussen K:

Invasive double-blinded placebo-controlled investigation of treatment of congestive

heart failure with coenzyme Q10:

Boston: 1st Conf. of the Intl. Coenzyme Q10 Assn.: 67 (1998)

PURPOSE: To evaluate the effect of coenzyme Q10 (CoQ10) on congestive heart failure. METHOD:

22 patients with left ventricular ejection fraction (LVEF) below 45%, LV internal diameter in diastole of >

60mm And in NYHA class 2-3 received CoQ10 200mg/day or placebo for 3 months. The usual medication

was kept unchanged. The groups were comparable regarding all relevant basal parameters. Before

and after the treatment period, a right heart catheterisation including a 3 minute exercise test was

done. The placebo group showed no significant changes. CONCLUSION: In this setting, CoQ10

200mg/day seemed to improve LV performance in patients suffering from congestive heart failure.

A-4212

Ylikoski T; Piirainen J; Hanninen O; Penttinen J:

The effect of coenzyme Q10 on the exercise performance of cross-country skiers:

Molec Aspects Med: 18:Suppl:s283-s290 (1997)

Coenzyme Q10 supplementation (Bio-Quinone Pharma Nord, 90 mg/day) was studied in a doubleblind

crossover study of 25 Finnish top-level cross-country skiers. With CoQ10 supplementation, all

measured indexes of physical performance (AET, ANT and V02Max) improved significantly. During verum

supplementation, 94% of the athletes felt that the preparation had been beneficial in improving

their performance and recovery time versus only 33% in the placebo periods.

A-4054

Henriksen JE; Andersen CB; Hother-Nielsen O; Vaag A; Beck-Nielsen H:

The effect of ubikinon (coenzyme Q10) on glycaæmic control and well-being in IDDM

patients:

Diabetologia: 39:Suppl 1:A227 (1996)

Several IDDM patients in our outpatient clinic reported independently that they had observed accumulated

hypoglycaemic episodes after initiating treatment with Ubikinon (CoQ 10). Thus, the aim of our

study was to investigate the effect of CoQ1O on glycaemic control and insulin requirement. Thirty-five

IDDM patients were included in a randomised double blinded placebo con trolled study with a run-in

period of four weeks and an intervention period of 12 weeks. Patients received either CoQ1O, 100 mg

daily, or placebo. Insulin doses were adjusted based on patients measurements of home blood glucose

concentrations. At randomisation no differences existed between the CoQ10 and the placebo

groups: Age (35.5 ± 2.0 vs 35.3 ± 2.4 yr), BMI (23.5 ± 0.7 vs 24.0 ± 0.6 kg/m2), HbAlc (8.04 ± 0.19 vs

8.02 ± 0.2 %), daily insulin dose (52.1 ± 3.1 vs 52.4 ± 5.0 U) or mean daily blood glucose concentration

(8.90 ± 0.42 vs 8.96 ± 0.42 mM). Serum CoQ10 concentration increased in the CoQ10 group (0.9 ± 0.1

vs 2.0 ± 0.24, p<0.005) whereas no changes were observed in the placebo group (0.9 ± 0.1 vs 0.9 ±

0.1). Following intervention no differences existed between the CoQ10 and the placebo groups regarding

HbAlc (7.86 ± 0.21 vs 7.84 ± 0.20 %), mean daily blood glucose concentrations (8.06 ± 0.45 vs

8,53 ± 0.46), mean insulin dose (52.4 ± 3.1 vs 52.6 ± 5.3 U), hypoglycaemic episodes (2.0±0.4 vs

2.5±0.5 episodes/week), or cholesterol concentrations (4.81 ± 0.22 vs 4.78 ± 0.26 mM). Furthermore,

no differences existed in the well-being of the patients reported from a visual analog scale (physical:

0.67 ± 0.05 vs 0.69 ± 0.05, mental: 0.70 ± 0.06 vs 0.73 ± 0.06). In conclusion, CoQ10 does not improve

glycaemic control or reduce insulin requirement and can be taken freely by IDDM patients.

However, this study does not indicate that CoQ10 has any beneficial effect on the well-being of the diabetic

patient.

A-3951

Henriksen JE:

Har antioxidanter gunstige effekter på glukoseomsætningen?:

Tidsskrift for Diabetesbehandling: 7:2 Suppl:37-41 (1997)

CONCLUSION: There have only been published a few studies to date that attempt to evaluate the effect

of antioxidants on diabetes patients, be it effect on diabetic complications or effect on glycemic

control. In the coming years, we can look forward to rapidly expanding knowledge in these areas,

knowledge that we hope will clear up many of our current questions. At present, however, there is no

scientific reason to recommend diabetes patients to take antioxidants in addition to the ones they can

consume in a healthy and varied diet. If diabetes patients are motivated by personal convictions to take

antioxidants, however, it does not seem this involves a risk for the development of uncontrollable diabetes

control, and, in particular, it does not seem that such treatment involves a risk of hypoglycemic

episodes.

A-3566

Nylander M; Weiner J; Nordlund M:

A double-blind clinical dose-response study on effects of coenzyme Q10 on gingival

bleeding/periodontal disease in ordinary people

7th Intl Symp on Trends in Biomedicine in Finland: Suppl 8:1-7 (1996)

Sixty ordinary non smoking Swedish adults were included in this double-blind study. One group of 17

subjects received a daily dose of 30 mg CoQl0 in a soft-gel capsule with CoQl0 emulsified in soybean

oil during 10 days. Nineteen subjects received identical capsules with 100 mg CoQlO -in each capsule

(Bio-Quinone, Pharma Nord). The remaining 24 subjects were controls and received identical placebo

capsules without CoQlO. Gingival bleeding was recorded at the start and at the end of the study. The

decrease in gingival bleeding was greatest for the group that was supplemented orally with 100 mg

CoQlO per day and least in the placebo group. There was a statistically significant difference in change

in gingival bleeding points between the 100 mg CoQlO group and the other two groups (30 mg CoQl0

and placebo); one-tailed T-test p<0.05.

A-3432

Serebruany VL; Herzog WR; Atamas SP; Gurbel PA; Rohde M; Mortensen SA; Folkers

Hemostatic changes after dietary coenzyme Q10 supplementation in swine:

J Cardiovasc Pharmacol: 28:175-181 (1996)

Improved cardiovascular morbidity and mortality have been observed in several clinical studies of dietary

supplementation with coenzyme Q1O (CoQ1O). We elucidated the effect of CoQ1O on certain hemostatic

parameters that may influence the progression of heart disease. Twelve Yorkshire swine were

randomized to receive diet supplementation with either CoQ10 or placebo for 20 days. Blood samples

were obtained at baseline and at the end of the feeding period. At the end of the protocol, there were

no significant differences in hemostatic parameters in the placebo group. A significant increase in total

serum CoQ1O level (from 0.39 +/- 0.06 to 0.96 ± 0.04 mcg/ml, p < 0.001) was noted after the feeding

period in the CoQ1O-supplemented group. We observed significant inhibition of ADP-induced platelet

aggregation (-9.9%) and a decrease in plasma fibronectin (-20.2%), thromboxane B2, (TXB2, –

20.6%), prostacyclin ( – 23.2%), and endothelin 1 (ET-1, -17.9%) level. There were no changes in the

plasma concentrations of the natural antithrombotics [antithrombin-III (AT-III), protein S, and protein C)

after CoQ1O supplementation. CoQ1O supplementation in a dose of 200 mg daily is associated with

mild anti aggregatory changes in the hemostatic.profile. Clinical beneficial effects of CoQ1O may be

related in part to a diminished incidence of thrombotic complications.

A-3081

Herzog WR; Atar D; Mortensen SA; Schlossberg ML; Serebruany VL:

Effect of Coenzyme Q10 supplementation on platelet aggregability in swine:

Coenzyme Q: 3:1:5-8 (1996)

We studied the effect of dietary supplementation with Coenzyme Ql0 (CoQl0) on platelet aggregation

(PA) in 16 female Yorkshire swine. The animal population was divided into 3 groups. The experimental

groups received either CoQ10 200 mg twice daily as soft capsules (Bio-Quinone, Pharma Nord, Denmark)

(group A, n=5); 100 mg CoQl0 twice daily (group B, n=5); or placebo as an addition to their usual

diet (group C, n=6). Three time points for PA studies were chosen: baseline, 10 days and 20 days of

CoQl0 or placebo supplementation. PA was induced in venous blood by adding 5 μM ADP to plateletrich

plasma. The results suggest that PA significantly decreases in a dose-dependent manner after 20

days of CoQ10 supplementation. Inhibition of platelet function may be explained by the known antioxidant

properties of CoQ10. Diminished PA resulting from CoQ10 supplementation may contribute to the

observed clinical benefits in patients with cardiovascular diseases

A-3072

Alford C; Service J; Hogan J:

The effects of food supplements (ubiquinone and selenium) on mood and compliance:

Conference Paper abstract: 1 (1996)

The role of health related behaviour based on operant conditioning, whereby behaviour may change as

a result of its consequences, can be examined by subjective assessment. The level of non-adherence

to recommended lifestyle changes, including diet, may be more than 40% (Sarafino, 1990. Health Psychology,

John Wiley) Daily food supplements: ubiquinone 60 mg (Bio-Quinone, Q-10), and a vitamin

complex (A, B6, C, E) with zinc (15 mg) and selenium (Bio-Selenium 100 micrograms), were compared

to placebo and a no-treatment control in a double-blind, parallel groups design with ten subjects (age

range 18-23 years) each assigned to the four groups. Assessments included the Profile of Mood States

(POMS); Visual Analogue Scales (VAS) and the UWIST Mood Adjective Checklist (UWAC) completed

during baseline and at three and five weeks during treatment. Non-adherence was found in 50%

(5/10) of the non-treatment control in comparison to 20% for the placebo and selenium groups, with

100% adherence for the Q10 group. This was partially reflected in mood changes. Significant (P<0.05)

increases in energy were reported after five weeks for selenium, as were decreases in tiredness

(POMS), increased energy was found for both selenium and Q10 with the VAS measure of energy

whilst UWAC indicated similar trends. Results support Benton and Cook's (1990, Pharmacol, 102,

549-550) finding with selenium and suggest improved mood may have a role in compliance to food

supplements. (Abstract, Brit Assn for Psychopharmacology, Cambridge, July, 1996)

A-3013

Andersen CB; Henriksen JE; Hother-Nielsen O; Vaag A; Mortensen SA; Beck-Nielsen

The effect of CoQ10 on blood glucose and insulin requirement in patients with insulin

dependent diabetes mellitus:

9th Intl. Symp. Biomed. and Clin. Aspects of Coenzyme Q: 9:82-83 (1996)

The aim of the study was to investigate the effect of Coenzyme Q10 on blood glucose and insulin

requirement in patients with insulin dependent diabetes mellitus (IDDM). Several IDDM patients reported

independently that they had observed accumulated hypoglycemic episodes and a need for reducing

insulin dose after initiating Q10 treatment, Thus our working hypothesis was that Q10 may have

a blood glucose lowering effect and/or an insulin diminishing effect. 34 patients from our outpatient clinic

were randomized into a double-blind, placebo-controlled trial with an initial run-in period of four weeks

and thereafter an intervention-period of twelve weeks in which one group received capsula Coenzyme

Q10 100 mg each day and the other group received placebo. Insulin dose was adjusted based

on patients' home monitoring of blood glucose. The same target level of glycemic control was used in

each patient in order to avoid accumulated hypoglycemic episodes and to avoid hyperglycemia. No differences

existed between the two groups (placebo and Q10) before randomisation regarding age, duration

of diabetes, body mass index and serum Q10. The glycemic control (HbAlr) were similar in the

groups before treatment, and there was not observed any change in glycemic control during the run-in

period in either of the groups. Following intervention the Q10 group had a two-fold increase in the serum

Q10 concentration. Overall no improvements in glycemic control during the intervention period

were observed (Table 1), and no decreases in total insulin dose were observed. Furthermore, no differences

in glycemic control or in total insulin dose were observed between the Q10 and the placebo

groups following intervention. No differences existed in the number of reported hypoglycemic episodes.

Blood pressure and plasma cholesterol concentration were unchanged and not different between the

groups. Using the visual scale, no differences were observed in physical, or general well-being between

the groups either before or during intervention. In conclusion, Coenzyme Q10 does not improve glycemic

control nor diminish the insulin requirement in patients with insulin dependent diabetes mellitus

and therefore can be taken freely by these without risk of hypoglycemic episodes. On the other hand

no beneficial effect on the parameters investigated in our study was observed following Q10 treatment.

A-2975

Salonen JT; Kaikkonen J; Nyyssonen K; Maijala L; Porkkala-Sarataho E; Salonen R;

Korpela H:

Coenzyme Q10 supplementation and lipoprotein oxidation resistance: a randomized

placebo controlled double blind study in marathon runners

9th Intl. Symp. Biomed. and Clin. Aspects of Coenzyme Q: 9:23 (1996)

Marathon runners were supplemented with either Bio-Quinone Q10 or placebo for three week before a

competition. Level of CoQ10 as well as oxidative resistance in blood lipids was significantly raised before

the run. No effect was seen on exercise induced oxidative stress or sparing of other antioxidants.

No difference was seen in muscular metabolites or muscular damage. Results suggest that Q10 supplementation

might improve oxidative resistance of lipoprotein in sedentary conditions, but does not

appear to influence oxidation of LDL or muscular damage due to exhaustive exercise.

A-1508

Atar D; Mortensen SA; Flachs H; Herzog WR:

Coenzyme Q10 Protects Ischemic Myocardium in an Open-Chest Swine Model.:

Clin Investig: 71:S103-11 (1993)

Myocardial stunning, defined as a reversible decrease in contractility after ischemia and reperfusion,

may be a manifestation of reperfusion injury caused by free oxygen radical damage. The aim of this

study was to test the hypothesis that pretreatment with coenzyme Q10, believed to act as a free radical

scavenger, reduces myocardial stunning in a porcine model. 12 swine were randomized to receive either

oral supplementation with Q10 (200 mg twice daily as soft capsules) or placebo for 20 days. A

normothermic open-chest model was used with short occlusion (8 min) of the distal left descending

coronary artery (LAD) followed by reperfusion. Regional contractile function was measured with epicardial

Doppler crystals in ischemic and non-ischemic segments by measuring thickening fraction of the

left ventricular wall during systole. Stunning time was defined as the elapsed time of reduced contractility

until return to baseline. Concentrations of reduced CoQ10 were measured in blood and homogenized

myocardial tissue, using high- performance liquid chromatography (HPLC). Plasma levels of reduced

coenzyme Q10 (ubiquinol) were higher in swine pretreated with the experimental medication as

compared to placebo (mean 0.45 mg/l versus 0.11 mg/l, respectively). Myocardial tissue concentrations,

however, did not show any changes (mean 0.79 μg/mg dry weight versus 0.74 μg/mg). Stunning

time was significantly reduced in coenzyme Q10 pretreated animals (13.7 ± 7.7 min versus 32.8 ± 3.1

min, P<0.01). In conclusion, chronic pretreatment with coenzyme Q10 protects ischemic myocardium

in an open-chest swine model. The beneficial effect of coenzyme Q10 on myocardial stunning may be

due to protection from free radical mediated reperfusion injury. This protective effect seems to be generated

by a humoral rather than intracellular mechanism.

b) Double-blinded multi-preparation trials

A-8612

Cooper JM; Korlipara LV; Hart PE; Bradley JL; Schapira AH:

Coenzyme Q10 and vitamin E deficiency in Friedreich's ataxia: predictor of efficacy

of vitamin E and coenzyme Q10 therapy.

Eur J Neurol.: 15:12:1371-9. (2008)

BACKGROUND AND PURPOSE: A pilot study of high dose coenzyme Q(10) (CoQ(10))/vitamin E

therapy in Friedreich's ataxia (FRDA) patients resulted in significant clinical improvements in most

patients. This study investigated the potential for this treatment to modify clinical progression in FRDA

in a randomized double blind trial. METHODS: Fifty FRDA patients were randomly divided into high or

low dose CoQ(10)/ vitamin E groups. The change in International Co- operative Ataxia Ratings Scale

(ICARS) was assessed over 2 years as the primary end-point. A post hoc analysis was made using

cross-sectional data. RESULTS: At baseline serum CoQ(10) and vitamin E levels were significantly

decreased in the FRDA patients (P < 0.001). During the trial CoQ(10) and vitamin E levels significantly

increased in both groups (P < 0.01). The primary and secondary end-points were not significantly

different between the therapy groups. When compared to cross-sectional data 49% of all patients

demonstrated improved ICARS scores. This responder group had significantly lower baseline serum

CoQ(10) levels. CONCLUSIONS: A high proportion of FRDA patients have a decreased serum

CoQ(10) level which was the best predictor of a positive clinical response to CoQ(10)/vitamin E

therapy. Low and high dose CoQ(10)/vitamin E therapies were equally effective in improving ICARS

scores.

A-8337

Skesters A; Zvagule T; Larmane L; Rainsford K et al.:

Effects of selenium alone and with antioxidants and ibuprofen mixture in Chernobyl

catastrophe clean-up workers:

Cell Biol Toxicol: 24:Suppl 1:S31 (2008)

CONFERENCE ABSTRACT: On the night of 26 April 1986, the Soviet nuclear accident brought for the

Soviet Union and Europe huge losses of financial and human resources. More than 6,500 male

inhabitants of Latvia of reproductive age were involved in the clean-up and recovery work after the

Chernobyl catastrophe. Consequently, they were exposed to both direct ?-radiation and inhaled or

absorbed toxic radioactive isotopes and volatile heavy metals derived from the reactor melt-down

through their skin, lungs, and gastrointestinal tract. After their homecoming, all clean-up workers (Cup-

w) immediately visited the University Hospital for a full medical examination. The evidence

obtained from studies performed to date suggest that many of the chronic diseases that are being

experienced by the C-up-w, including the recently identified increase of prostate symptoms, prostate or

other neoplasm, are due to the chronic manifestation of long-term oxidative stress (OS). Hence, this

proposal is part of a long-term study in 134 C-up-w of age 43u55 being served. C-upw received

selenium from yeast alone or in combination with antioxidants, coenzyme Q10, ibuprofen, or placebo.

Concentrations of selenium (Se), vitamin E (E), total antioxidant status (TAS), NEFA, triglycerides, lipid

peroxides (LP), intensity of OS were determined. After 1 year of supplementation, results showed that

increased concentrations of Se, E, and TAS, thus improved antioxidative defense of the organism and

some quality of life described parameters. Simultaneously, there were decreased concentrations of LP

and OS. In fact, during the supplementation period, there were decreased needs for prescribed

medicines, including those for joint pain, chronic bronchitis and emphysema, stomach troubles, and

depression. In groups treated for 1 year, there was no incidence of any neoplasia compared to seven

new cases of neoplasia among the survey (control) C-up-w. ADDITIONAL AUTHORS: Silova A,

Rusakova N & Mustafins P FULL TITLE: Effects of selenium alone and with antioxidants and ibuprofen

mixture in Chernobyl catastrophe clean-up workers at risk of developing cancer.

A-8003

Sindberg CD; Littarru G.P.; Moesgaard S; Storm-Henningsen PL:

Bioavailability of Coenzyme Q10 Formulated with Palm Oil is Equivalent with a

Similar Soy Oil Formulation:

5th Conf Int. CoQ10 Ass – Prog & Abstr: 182-84 (2007)

This study investigated bioavailability of coenzyme Q10, comparing two preparations with palm oil and soy

oil respectively. A randomized, double-blind cross-over study was conducted with 12 volunteers. The

volunteers were randomized in two groups recieving coenzyme Q10 preparations containing 100mg

CoQ10 and 400mg soy oil or palm oil respectively each day for two periods of three weeks, with a two

weeks washout in between. In conclusion there was no significant difference in bioavailability of coenzyme

Q10 using the two different preparations and no adverse effects were observed.

A-7942

Cooper JM; Schapira AH:

Friedreich's ataxia: coenzyme Q10 and vitamin E therapy.:

Mitochondrion.: 7 Suppl:S127-35. E (2007)

Since the identification of the genetic mutation causing Friedreich's ataxia (FRDA) our understanding

of the mechanisms underlying disease pathogenesis have improved markedly. The genetic

abnormality results in the deficiency of frataxin, a protein targeted to the mitochondrion. There is

extensive evidence that mitochondrial respiratory chain dysfunction, oxidative damage and iron

accumulation play significant roles in the disease mechanism. There remains considerable debate as

to the normal function of frataxin, but it is likely to be involved in mitochondrial iron handling, antioxidant

regulation, and/or iron sulphur centre regulation. Therapeutic avenues for patients with FRDA are

beginning to be explored in particular targeting antioxidant protection, enhancement of mitochondrial

oxidative phosphorylation, iron chelation and more recently increasing FRDA transcription. The use of

quinone therapy has been the most extensively studied to date with clear benefits demonstrated using

evaluations of both disease biomarkers and clinical symptoms, and this is the topic that will be covered

in this review.

A-7340

Hoenjet KM; Dagnelie PC; Delaere KP; Oosterhof GON; Zambon JV; Oosterhof GO:

Effect of a Nutritional Supplement Containing Vitamin E, Selenium, Vitamin C and

Coenzyme Q10 on Serum PSA in Patients with Hormonally Untreated Carcinoma of

the Prostate: A Randomised Placebo-Controlled Study.

Eur Urol: 47:4:433-40. Ep (2005)

OBJECTIVE:: To assess the effect of a nutritional supplement containing vitamin E, selenium, vitamin

C and coenzyme Q10 on changes in serum levels of PSA in patients with hormonally untreated

carcinoma of the prostate and rising serum PSA levels. METHODS:: Eighty patients were randomised

to receive a daily supplement with either vitamin E, selenium, vitamin C, coenzyme Q10 (intervention

group) or placebo over 21 weeks. Serum levels of PSA were assessed at baseline (-2, -1, 0 weeks)

and after 6, 13, 19, 20 and 21 weeks. Mean changes in log serum level of PSA, testosterone,

dihydrotestosterone, luteinizing hormone and sex hormone binding globulin over 21 weeks between

the verum and the placebo group were compared by analysis of covariance. RESULTS:: Seventy

patients completed the study (36 verum; 34 placebo). Compliance was >90% in all patients. In the

intervention group, plasma levels of vitamin E, selenium and coenzyme Q10 increased significantly

over the 21 weeks study period. No significant differences in serum levels of PSA, testosterone,

dihydrotestosterone, luteinizing hormone or sex hormone binding globulin (p>0.2) were observed

between the intervention and control group. CONCLUSION:: Our results indicate that supplementation

of a combination of vitamin E, selenium, vitamin C and coenzyme-Q10 does not affect serum level of

PSA or hormone levels in patients with hormonally untreated carcinoma of the prostate.

A-7116

Nielsen HG; Skjønsberg OH; Lyberg T:

Antioxidant supplementation and leukocyte expression of reactive oxygen species

(ROS) in endurance-trained athletes.:

Int. Soc. for Exercise & Immunol. Symp.: (2003)

Abstract presented at the International Society for Exercise and Immunology Symposium, 17-19 June

2003, Copenhagen, Denmark.

A-6799

Engelsen J; Nielsen JD; Hansen KFW:

Effekten af coenzym Q10 og Ginkgo biloba på warfarindosis hos patienter i

længerevarende warfarinbehandling:

Ugeskr Læger: 165:18:1868-1871 (2003)

En randomiseret, dobbeltblind, placebokontrolleret undersøgelse af 100 mg coenzym Q10 (Bio-

Quinon) eller 100 mg Ginkgo biloba (Bio-Biloba) i 24 patienter i stabil warfarin behandling.

Undersøgelsen viste, at der ikke er klinisk betydende interaktion mellem Q10 og warfarin eller mellem

Ginkgo biloba og warfarin.

A-6688

Engelsen J; Nielsen JD; Winther K:

Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term

warfarin treated outpatients. A randomised, double blind, placebo-crossover trial.

Thromb Haemost: 87:6:1075-6. (2002)

B-6214

Kaikkonen J:

Coenzyme Q10 – Plasma analysis and role as an antioxidant:

Kuopio University Publications D. MS 194: (1999)

PhD thesis, including the articles A-5565, A-5566, and A-6212.

A-6212

Kaikkonen J; Nyyssonen K; Tomasi A; Iannone A; Tuomainen TP; Porkkala-

Sarataho E; Salonen JT:

Antioxidative efficacy of parallel and combined supplementation with coenzyme Q10

and d-alpha-tocopherol in mildly hypercholesterolemic subjects: a randomized

placebo- controlled clinical study.

Free Radic Res: 33:3:329-40 (2000)

It has been claimed that coenzyme Q10 (Q10) would be an effective plasma antioxidant since it can

regenerate plasma vitamin E. To test separate effects and interaction between Q10 and vitamin E in

the change of plasma concentrations and in the antioxidative efficiency, we carried out a doublemasked,

double-blind clinical trial in 40 subjects with mild hypercholesterolemia undergoing statin

treatment. Subjects were randomly allocated to parallel groups to receive either Q10 (200 mg daily), dalpha-

tocopherol (700 mg daily), both antioxidants or placebo for 3 months. In addition we investigated

the pharmacokinetics of Q10 in a separate one- week substudy. In the group that received both

antioxidants, the increase in plasma Q10 concentration was attenuated. Only vitamin E

supplementation increased significantly the oxidation resistance of isolated LDL. Simultaneous Q10

supplementation did not increase this antioxidative effect of vitamin E. Q10 supplementation increased

and vitamin E decreased significantly the proportion of ubiquinol of total Q10, an indication of plasma

redox status in vivo. The supplementations used did not affect the redox status of plasma ascorbic

acid. In conclusion, only vitamin E has antioxidative efficiency at high radical flux ex vivo. Attenuation of

the proportion of plasma ubiquinol of total Q10 in the vitamin E group may represent in vivo evidence

of the Q10-based regeneration of the tocopheryl radicals. In addition, Q10 might attenuate plasma lipid

peroxidation in vivo, since there was an increased proportion of plasma ubiquinol of total Q10.

A-3235

Kuklinski B:

Wirkung von Antioxidantien unter klinischen Bedingungen:

Vitaminspur: 10:32-35 (1994)

Oxidative stress is the disbalance between radical generators and radical scavengers in favour of the

former. The results of four clinical intervention trials confirm the pathogenic significance of oxidative

stress in alcoholtoxic liver disease, myocardial infarction, diabetic late syndrome and acute pancreatitis.

A distinct improvement of prognosis could be achieved by using adjuvant antioxidant supplementation

(vitamins and trace elements).

A-2398

Kuklinski B; Weissenbacher E; Fahnrich A:

Coenzyme Q10 and Antioxidants in Acute Myocardial Infarction:

Mol Aspects Med: 15s:s143-s147 (1994)

Sixty-one patients admitted with acute myocardial infarction, and a symptom's duration of less than 6

hr were randomized into two groups. Immediately after hospitalization, members of the verum group

(n=32) received 500 μg of selenium (as sodium selenite). Thereafter they received a daily dosage of

100 mg Coenzyme Q10 (Bio-Quinone, Pharma Nord, Denmark) and 100 mg selenium (Bio-Selenium

in the form of l-selenomethion ine) for a period of one year. The control group (n=29) were given matching

placebo preparations. The groups were comparable as with respect to age, sex and medical treatment.

Biochemical parameters showed a reduced concentration of CPK- and ASAT-level in the verum

group during the acute phase (although not statistically significant). None of the patients in the verum

group (i.e. on antioxidative treatment) showed prolongation of the frequency corrected QT-interval.

In the control group, 40 % revealed a prolongation of the QT-interval by more than 449 msec

(p<0.001). There were no significant differences with respect to early complications. During the oneyear

follow-up period after myocardial infarction, six patients (20 %) from the control group died from

re-infarction whereas one patient from the verum group suffered a non-cardiac death.

c) Other product-specific references

A 8874

Elshershari H, Ozer S, Ozkutlu S, Ozme S:

Potential usefulness of coenzyme Q10 in the treatment of idiopathic dilated cardiomyopathy

in children.

Int J Cardiol.:vol 88:no.1:101-2 (2003)

Open pilot trial with 6 children with dilated cardiomyopathy supplemented with 10 mg/kg BW CoQ10 for

up to 16 months. In 5 children fractional shortening and injection fraction was significantly increased.

A-8845

Fu X; Ji R; Dam J:

Acute, subacute toxicity and genotoxic effect of Bio-Quinone Q10 in mice and rats.

Regul Toxicol Pharmacol.: 53:1:1-5. Epub (2009)

In the present study, the acute, subacute and genetic toxicity of Coenzyme Q10 (CoQ10) in the form of

Bio-Quinone (Pharma Nord, Denmark) was assessed. LD(50) of CoQ10 by oral treatment was greater

than 20g/kg body weight in both female and male mice. Genotoxicity was assessed in mice by Ames

test in Salmonella typhimurium strains TA97, TA98, TA100 and TA102, by bone marrow micronucleus

test and sperm abnormality. Thirty-day subacute toxicity was conducted with oral daily dose at 0, 0.56,

1.13 and 2.25g/kg body weight in rats. No significant changes in body weight, food intake, behavior,

mortality, hematology, blood biochemistry, vital organ weight, sperm abnormality, mutagenicity and

micronucleus formation were observed and no clinical signs or adverse effects were detected by

administration of CoQ10. These results support the safety of CoQ10 for oral consumption.

A-8843

Zmitek J; Smidovnik A; Fir M; Prosek M; Zmitek K; Walczak J; Pravst I:

Relative bioavailability of two forms of a novel water-soluble coenzyme Q10.

Ann Nutr Metab.: 52:4:281-7. Epu (2008)

BACKGROUND: Coenzyme Q10 (CoQ10) is a naturally occurring compound that plays a fundamental

role in cellular bioenergetics and is an effective antioxidant. Numerous health benefits of CoQ10

supplementation have been reported, resulting in growing demands for its use in fortifying food. Due to

its insolubility in water, the enrichment of most food products is not easily achievable and its in vivo

bioavailability is known to be poor. Water solubility was increased significantly with the use of an

inclusion complex with beta-cyclodextrin. This complex is widely used as Q10Vital in the food industry,

while its in vivo absorption in humans has not previously been studied. METHODS: A randomized

three-period crossover clinical trial was therefore performed in which a single dose of CoQ10 was

administered orally to healthy human subjects. The pharmacokinetic parameters of two forms of the

novel CoQ10 material were determined and compared to soft-gel capsules with CoQ10 in soybean oil

that acted as a reference. RESULTS: The mean increase of CoQ10 plasma concentrations after

dosing with Q10Vital forms was determined to be over the reference formulation and the area under

the curve values, extrapolated to infinity (AUC(inf)), were also higher with the tested forms; statistically

significant 120 and 79% increases over the reference were calculated for the Q10Vital liquid and

powder, respectively. CONCLUSIONS: The study revealed that the absorption and bioavailability of

CoQ10 in the novel formulations are significantly increased, probably due to the enhanced water

solubility.

A-8684

Mancini A; De Marinis L; Littarru GP; Balercia G:

An update of Coenzyme Q10 implications in male infertility: biochemical and

therapeutic aspects.

Biofactors.: 25:1-4:165-74. (2005)

This review is focused upon the role of coenzyme Q(10) in male infertility in the light of a broader issue

of oxidative damage and antioxidant defence in sperm cells and seminal plasma. Reactive oxygen

species play a key pathogenetic role in male infertility besides having a well- recognized physiological

function. The deep involvement of coenzyme Q(10) in mitochondrial bioenergetics and its antioxidant

properties are at the basis of its role in seminal fluid. Following the early studies addressing its

presence in sperm cells and seminal plasma, the relative distribution of the quinone between these two

compartments was studied in infertile men, with special attention to varicocele. The reduction state of

CoQ(10) in seminal fluid was also investigated. After the first in vitro experiments CoQ(10) was

administered to a group of idiopathic asthenozoospermic infertile patients. Seminal analysis showed a

significant increase of CoQ(10) both in seminal plasma and in sperm cells, together with an

improvement in sperm motility. The increased concentration of CoQ(10) in seminal plasma and sperm

cells, the improvement of semen kinetic features after treatment, and the evidence of a direct

correlation between CoQ(10) concentrations and sperm motility strongly support a cause/effect

relationship. From a general point of view, a deeper knowledge of these molecular mechanisms could

lead to a new insight into the so-called unexplained infertility.

A-8338

Westermarck T; Sauka M; Selga G; Skesters A et al.:

Effects of cocktail antioxidant supplementation on oxidative stress in aids:

Cell Biol Toxicol: 24:Suppl 1:S55-S56 (2008)

CONFERENCE ABSTRACT: Infection of HIV/AIDS is a worldwide problem of increasing magnitude.

Epidemiological studies have shown an inverse relationship between antioxidant intake and the

incidence of the disease. Nutritional problems in patients with HIV/AIDS may be due to several

mechanisms working independently or synergistically. The most effective role the clinician can play in

the nutritional care of these patients is close surveillance of nutritional complications over time and with

evolving medical therapy. Twenty- four Latvian male volunteers were HIV-infected outpatients (age 35,

3▒0.5). None of the screened subjects had C4 T cell counts less than 200 cells in microliter of blood,

none had active opportunistic infections or malignancies, and all were readily mobile. Ten uninfected

control males were similar in age to the HIV-infected group. HIV-infected subjects were treated

additionally with Coenzyme Q10 (CoQ10), L-Carnitine 500 mg/day, Bio-Selenium + Zinc that contains:

A-vitamin 1,000 ╡g, B6-vitamin 2.2 mg, Vitamin C 90 mg, Vitamin E 15 mg, Zinc 15 mg,and selenium

(Organic) 100 ╡g, each for 6 weeks. Significant decrease of fMLP- stimulated PMNL

chemiluminescence (p<0.05) confirms the antioxidative properties. Serum concentration of selenium

increased after CoQ10 treatment. Monitoring antioxidant enzymes and other metabolic changes in

patients with HIV infection is recommended. The supplementation of antioxidants is worth applying to

HIV patients. ADDITIONAL AUTHORS: Abdulla M, Atroshi F

A-8281

Figuero E; Soory M; Cerero R; Bascones A:

Oxidant/antioxidant interactions of nicotine, Coenzyme Q10, Pycnogenol and

phytoestrogens in oral periosteal fibroblasts and MG63 osteoblasts.

Steroids.: 71:13-14:1062-72. E (2006)

BACKGROUND: There is a growing awareness that oxidative stress may play a role in periodontal

disease. The aim of this investigation was to evaluate potential oxidant/antioxidant interactions of

nicotine with antioxidants (Coenzyme Q10 (CoQ), Pycnogenol and phytoestrogens in a cell culture

model. METHODS: Duplicate incubations of human periosteal fibroblasts and osteoblasts were

performed with 14C-testosterone as substrate, in the presence or absence of CoQ (20 microg/ml),

Pycnogenol (150 microg/ml), and phytoestrogens (10 and 40 microg/ml), alone and in combination with

nicotine (250 microg/ml). At the end of a 24-h incubation period, the medium was solvent extracted and

testosterone metabolites were separated by thin-layer chromatography and quantified using a

radioisotope scanner. RESULTS: The incubations of osteoblasts and periosteal fibroblasts with CoQ,

Pycnogenol or phytoestrogens stimulated the synthesis of the physiologically active androgen DHT,

while the yields of DHT were significantly reduced in response to nicotine compared to control values

(p<0.001 for phytoestrogens). The combination of nicotine with CoQ, Pycnogenol or phytoestrogens

increased the yields of DHT compared with incubation with nicotine alone in both cell types.

CONCLUSION: This investigation suggests that the catabolic effects of nicotine could be reversed by

the addition of antioxidants such as CoQ or Pycnogenol and phytoestrogens.

A-8003

Sindberg CD; Littarru G.P.; Moesgaard S; Storm-Henningsen PL:

Bioavailability of Coenzyme Q10 Formulated with Palm Oil is Equivalent with a

Similar Soy Oil Formulation:

5th Conf Int. CoQ10 Ass – Prog & Abstr: 182-84 (2007)

This study investigated bioavailability of coenzyme Q10, comparing two preparations with palm oil and

soy oil respectively. A randomized, double-blind cross-over study was conducted with 12 volunteers.

The volunteers were randomized in two groups recieving coenzyme Q10 preparations containing

100mg CoQ10 and 400mg soy oil or palm oil respectively each day for two periods of three weeks, with

a two weeks washout in between. In conclusion there was no significant difference in bioavailability of

coenzyme Q10 using the two different preparations and no adverse effects were observed.

A-7942

Cooper JM; Schapira AH:

Friedreich's ataxia: coenzyme Q10 and vitamin E therapy.:

Mitochondrion.: 7 Suppl:S127-35. E (2007)

Since the identification of the genetic mutation causing Friedreich's ataxia (FRDA) our understanding

of the mechanisms underlying disease pathogenesis have improved markedly. The genetic abnormality

results in the deficiency of frataxin, a protein targeted to the mitochondrion. There is extensive evidence

that mitochondrial respiratory chain dysfunction, oxidative damage and iron accumulation play

significant roles in the disease mechanism. There remains considerable debate as to the normal function

of frataxin, but it is likely to be involved in mitochondrial iron handling, antioxidant regulation, and/

or iron sulphur centre regulation. Therapeutic avenues for patients with FRDA are beginning to be explored

in particular targeting antioxidant protection, enhancement of mitochondrial oxidative phosphorylation,

iron chelation and more recently increasing FRDA transcription. The use of quinone therapy has

been the most extensively studied to date with clear benefits demonstrated using evaluations of both

disease biomarkers and clinical symptoms, and this is the topic that will be covered in this review.

A-7354

Soongswang J; Sangtawesin C; Durongpisitkul K; Laohaprasitiporn D; Nana A;

Punlee K; Kangkagate C:

The Effect of Coenzyme Q10 on Idiopathic Chronic Dilated Cardiomyopathy in

Children.:

Pediatr Cardiol: 26:361-366 (2005)

The objective of this study was to assess the effect of coenzyme Q10 (CoQ10) as supplementation to

conventional antifailure drugs on quality of life and cardiac function in children with chronic heart failure

due to dilated cardiomyopathy (DCM). The study was an open-label prospective study performed in

two of the largest pediatric centers in Thailand from August 2000 to June 2003. A total of 15 patients

with idiopathic chronic DCM were included, with the median age of 4.4 years (range, 0.6-16.3).

Presenting symptoms were congestive heart failure in 12 cases (80%), cardiogenic shock in 2 cases

(13.3%), and cardiac arrhythmia in 1 case (6.7%). Sixty-one percent of patients were in the New York

Heart Association functional class 2 (NYHA 2), 31% in NYHA 3, and 8% in NYHA 4. Cardiothoracic

ratio from chest x-ray, left ventricular ejection fraction, and left ventricular end diastolic dimension in

echocardiogram were 0.62 (range, 0.55-0.78), 30% (range, 20-40), and 5.2 cm (range, 3.8-6.5),

respectively. CoQ10 was given at a dosage of 3.1 ? 0.6 mg/kg/day for 9 months as a supplementation

to a fixed amount of conventional antifailure drugs throughout the study. At follow-up periods of 1, 3, 6,

and 9 months, NYHA functional class was significantly improved, as was CT ratio and QRS duration at

3 and 9 months follow-up with CoQ10 when compared to the baseline and post-discontinuation of

CoQ10 at 9 months (range, 4.8-10.8). However, when multiple comparisons were taken into

consideration, there was no statistical significant improvement. In addition to the conventional

antifailure drugs, CoQ10 may improve NYHA class and CT ratio and shorten ventricular depolarization

in children with chronic idiopathic DCM.

A-7129

Balercia G; Mosca F; Mantero F; Boscaro M; Mancini A; Ricciardo-Lamonica G;

Littarru G:

Coenzyme Q(10) supplementation in infertile men with idiopathic

asthenozoospermia: an open, uncontrolled pilot study.

Fertil Steril: 81:1:93-8. (2004)

OBJECTIVE: To clarify a potential therapeutic role of coenzyme Q(10) (CoQ(10)) in infertile men with

idiopathic asthenozoospermia. DESIGN: Open, uncontrolled pilot study. PATIENT(S): Infertile men

with idiopathic asthenozoospermia. INTERVENTION(S): CoQ(10) was administered orally; semen

samples were collected at baseline and after 6 months of therapy. MAIN OUTCOME MEASURE (S):

Semen kinetic parameters, including computer-assisted sperm data and CoQ(10) and

phosphatidylcholine levels. RESULT(S): CoQ(10) levels increased significantly in seminal plasma and

in sperm cells after treatment. Phosphatidylcholine levels also increased. A significant increase was

also found in sperm cell motility as confirmed by computer-assisted analysis. A positive dependence

(using the Cramer's index of association) was evident among the relative variations, baseline and after

treatment, of seminal plasma or intracellular CoQ(10) content and computer-determined kinetic

parameters. CONCLUSION(S): The exogenous administration of CoQ(10) may play a positive role in

the treatment of asthenozoospermia. This is probably the result of its role in mitochondrial

bioenergetics and its antioxidant properties.

A-7120

Hodges SJ; Gill K; Walsh T; Rawlinson A et al.:

Human gingival crevicular fluid levels of coenzyme Q10.:

3rd Conference of the International Coenzyme Q10 Association: 77-78 (2002)

Abstract presented at the 3rd Conference of the Internat- ional Coenzyme Q10 Association, 22-24

November, London, UK.

A-7108

Turunen M; Wehlin L; Sjoberg M; Lundahl J; Dallner G; Brismar K; Sindelar PJ:

beta2-Integrin and lipid modifications indicate a non- antioxidant mechanism for the

anti-atherogenic effect of dietary coenzyme Q10.

Biochem Biophys Res Commun: 296:2:255-60. (2002)

Dietary supplementation with coenzyme Q (CoQ) has been proposed to have anti-atherogenic effects

by virtue of its antioxidant capacity. To investigate this question, the leukocyte status of 5 males and 5

females (52-68 years) was evaluated before and after supplementation with 200mg CoQ/day for 5 and

10 weeks. CoQ was selectively taken up by mononuclear cells and alpha-tocopherol increased in

polynuclear and mononuclear cells. The expression of beta2- integrin CD11b and complement

receptor CD35 on the plasma membrane of resting and stimulated monocytes was significantly

decreased upon dietary CoQ. Fatty acid and aldehyde analysis revealed that there was a selective

increase of arachidonic acid and plasmalogens in only mononuclear cells. These selective lipid

changes are not consistent with a general improvement in antioxidant status and indicate that CoQ

most likely inhibits a phospholipase A2. Thus, these results strongly suggest that the anti- atherogenic

effects of CoQ be mediated by other mechanisms beside its antioxidant protection.

A-6914

Sunesen VH; Weber C; Holmer G:

Lipophilic antioxidants and polyunsaturated fatty acids in lipoprotein classes:

distribution and interaction.:

Eur J Clin Nutr: 55:2:115-23. (2001)

OBJECTIVE: To study the lipoprotein distribution of supplemented coenzyme Q10 (CoQ10), vitamin E,

and polyunsaturated fatty acids (PUFA). DESIGN: Balanced three- period crossover study. SETTING:

University research unit. SUBJECTS: Eighteen apparently healthy free-living non- smoking volunteers

(nine women, nine men), mean age 26 +/- 3 y, recruited among the university students; no dropouts.

INTERVENTIONS: Three supplementation periods of 10 days: 100 mg/day CoQ10, 350 mg/day Dalpha-

tocopherol, and 2 g/day concentrated fish oil. Fasting venous blood samples were collected

twice before the first period and then after each period. Plasma and isolated lipoproteins were

analysed for cholesterol, triacylglycerol, alpha- and gamma-tocopherol, CoQ10, and fatty acid

composition. RESULTS: Significant (P < 0.05) increase in CoQ10 and alpha-tocopherol occurred in all

lipoprotein classes after supplementation. CoQ10 was primarily incorporated into low-density

lipoprotein (LDL). alpha-tocopherol and fish oil n-3 PUFAs had similar patterns. They were equally

distributed between LDL and high-density lipoprotein (HDL), with a smaller part in VLDL. The total sum

of PUFA was unchanged following all supplementations, but fish oil increased the amount of n-3 fatty

acids at the expense of n-6 fatty acids. CONCLUSION: Lipoprotein distribution of CoQ10 is markedly

different from that of alpha-tocopherol, suggesting that they may be metabolised by distinct routes.

alpha-Tocopherol is distributed similarly to n-3 fatty acids, thus providing protection on location for the

oxidatively labile PUFAs.

A-6898

Horstink MW; van Engelen BG:

The effect of coenzyme Q10 therapy in Parkinson disease could be symptomatic.:

Arch Neurol: 60:8:1170-2 (2003)

A-6887

Lankin VZ; Tikhaze AK; Kukharchuk VV; Konovalova GG; Pisarenko OI; Kaminnyi

AI; Shumaev KB; Belenkov YN:

Antioxidants decreases the intensification of low density lipoprotein in vivo

peroxidation during therapy with statins.

Mol Cell Biochem: 249:1-2:129-40. (2003)

The oxidative modification of low density lipoprotein (LDL) is thought to play an important role in

atherogenesis. Drugs of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase

inhibitors (statins) family are usually used as a very effective lipid-lowering preparations but they

simultaneously block biosynthesis of both cholesterol and ubiquinone Q10 (coenzyme Q), which is an

intermediate electron carrier in the mitochondrial respiratory chain. It is known that reduced form of

ubiquinone Q10 acts in the human LDL as very effective natural antioxidant. Daily per os administration

of HMG-CoA reductase inhibitor simvastatin to rats for 30 day had no effect on high-energy

phosphates (adenosin triphosphate, creatine phosphate) content in liver but decreased a level of these

substances in myocardium. We study the Cu2+-mediated susceptibility of human LDL to oxidation and

the levels of free radical products of LDL lipoperoxidation in LDL particles from patients with

atherosclerosis after 3 months treatment with natural antioxidants vitamin E as well as during 6 months

administration of HMG-CoA reductase inhibitors such as pravastatin and cerivastatin in monotherapy

and in combination with natural antioxidant ubiquinone Q10 or synthetic antioxidant probucol in a

double-blind placebo- controlled trials. The 3 months of natural antioxidant vitamin E administration

(400 mg daily) to patients did not increase the susceptibility of LDL to oxidation. On the other hand,

synthetic antioxidant probucol during long-time period of treatment (3-6 months) in low-dose (250 mg

daily) doesn't change the lipid metabolism parameters in the blood of patients but their high antioxidant

activity was observed. Really, after oxidation of probucol-contained LDL by C-15 animal lipoxygenase

in these particles we identified the electron spin resonance signal of probucol phenoxyl radical that

suggests the interaction of LDL-associated probucol with lipid radicals in vivo. We observed that 6

months treatment of patients with pravastatine (40 mg daily) or cerivastatin (0.4 mg daily) was followed

by sufficiently accumulation of LDL lipoperoxides in vivo. In contrast, the 6 months therapy with

pravastatin in combination with ubiquinone Q10 (60 mg daily) sharply decreased the LDL initial

lipoperoxides level whereas during treatment with cerivastatin in combination with probucol (250 mg

daily) the LDL lipoperoxides concentration was maintained on an invariable level. Therefore,

antioxidants may be very effective in the prevention of atherogenic oxidative modification of LDL during

HMG-CoA reductase inhibitors therapy.

A-6848

Lankin VZ; Tikhaze AK:

Atherosclerosis as a free radical pathology and antioxidative therapy of this disease.:

Free Radicals, Nitric Oxide and Inflammation: 218-231 (2003)

Full title of source: Free Radicals, Nitric oxide and inflammation: Molecular, Biochemical, and Clinical

Aspects; A Tomasi et al. (eds). IOS Press, 2003

A-6633

Annon: Hungary:

Absence of forbidden substances (doping) in a range of Pharma Nord Products:

Hungarian Nat. Inst. for Sports Hygiene: (2002)

The Doping Control laboratory of the Hungarian National Institute of Sports Hygiene analysed a range

of Pharma Nord's products (Bio-Sport, Bio-Calcium+Mg+Si, Bio-Carnitine, Bio-Chromium, Bio-Fiber,

Bio-Magnesium, Bio-Quinone 10 mg, Bio-Selenium+Zinc, and Bio-Slim) and found them to be free of

any substances on the country's doping list (which is assumed to be equivalent to international lists).

The preparations were considered safe when used as directed, and could be recommended to

athelets.

A-6622

Lister RE:

An open, pilot study to evaluate the potential benefits of coenzyme Q10 combined

with Ginkgo biloba extract in fibromyalgia syndrome.

J Int Med Res: 30:2:195-9. (2002)

An open, uncontrolled study was undertaken to measure the subjective effects of coenzyme Q10

combined with a Ginkgo biloba extract in volunteer subjects with clinically diagnosed fibromyalgia

syndrome. Anecdotal reports from patients with fibromyalgia syndrome have claimed benefits from the

use of these supplements. The aim of this study was to determine if these reports could be

substantiated in a pilot clinical trial. Patient questioning had determined that poor quality of life was a

major factor in the condition and a quality-of-life questionnaire was used to measure potential benefit.

Subjects were given oral doses of 200 mg coenzyme Q10 and 200 mg Ginkgo biloba extract daily for

84 days. Quality of life was measured, using the well- validated Dartmouth Primary Care Cooperative

Information Project/World Organization of Family Doctors (COOP/WONCA) questionnaire that

measures seven different subjective responses, at 0-, 4-, 8-, and 12-week intervals. The subjects were

asked for an overall self-rating at the end of the study. A progressive improvement in the quality-of-life

scores was observed over the study period and at the end, the scores showed a significant difference

from those at the start. This was matched by an improvement in self-rating with 64% claiming to be

better and only 9% claiming to feel worse. Adverse effects were minor. A controlled study is now

planned.

A-6456

Lodi R; Hart PE; Cooper JM; Schapira AHV; Crilley JG; Bradley JL; Blamire AM;

Manners D; Styles P; Schapira AH; Cooper JM:

Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in

patients with Friedreich's ataxia.:

Ann Neurol: 49:5:590-6. (2001)

Friedreich's ataxia (FA) is the most common form of autosomal recessive spinocerebellar ataxia and is

often associated with a cardiomyopathy. The disease is caused by an expanded intronic GAA repeat,

which results in deficiency of a mitochondrial protein called frataxin. In the yeast YFH1 knockout model

of the disease there is evidence that frataxin deficiency leads to a severe defect of mitochondrial respiration,

intramitochondrial iron accumulation, and associated production of oxygen free radicals. Recently,

the analysis of FA cardiac and skeletal muscle samples and in vivo phosphorus magnetic resonance

spectroscopy (31P-MRS) has confirmed the deficits of respiratory chain complexes in these tissues.

The role of oxidative stress in FA is further supported by the accumulation of iron and decreased

aconitase activities in cardiac muscle. We used 31P-MRS to evaluate the effect of 6 months of antioxidant

treatment (Coenzyme Q10 400 mg/day, vitamin E 2,100 IU/day) on cardiac and calf muscle energy

metabolism in 10 FA patients. After only 3 months of treatment, the cardiac phosphocreatine to ATP

ratio showed a mean relative increase to 178% (p = 0.03) and the maximum rate of skeletal muscle

mitochondrial ATP production increased to 139% (p = 0.01) of their respective baseline values in the

FA patients. These improvements, greater in prehypertrophic hearts and in the muscle of patients with

longer GAA repeats, were sustained after 6 months of therapy. The neurological and echocardiographic

evaluations did not show any consistent benefits of the therapy after 6 months. This study demonstrates

partial reversal of a surrogate biochemical marker in FA with antioxidant therapy and supports

the evaluation of such therapy as a disease- modifying strategy in this neurodegenerative disorder.

A-5882

Watson JP; Jones DE; James OF; Cann PA; Bramble MG:

Case report: oral antioxidant therapy for the treatment of primary biliary cirrhosis: a

pilot study

J Gastroenterol Hepatol: 14:10:1034-40 (1999)

BACKGROUND: The symptoms of the chronic cholestatic liver disease primary biliary cirrhosis (PBC),

in particular fatigue and chronic pruritus, adversely affect quality of life and respond only poorly to

treatment. Recent studies have suggested that oxidative stress may play a role in tissue damage in

cholestatic liver disease and may contribute to symptoms, such as fatigue. We have, therefore,

examined, in an open- label pilot study, the therapeutic effects of antioxidant medication on the

biochemistry and symptomatology of PBC. METHODS: Patients were randomized to 3 months

treatment with a compound antioxidant vitamin preparation (Bio-Antox), four tablets daily (n = 11, group

1), or the combination of Bio-Quinone Q10 (100 mg) with Bio- Antox (n = 13, group 2). Biochemical

and symptomatic responses were assessed at 3 months. RESULTS: Significant improvement in both

pruritus and fatigue was seen in the patients in group 2. Mean itch visual analogue score improved

from 2.4 +/- 3.0 to 0.4 +/- 0.7 post therapy (P < 0.05) while mean night itch severity score improved

from 2.6 +/- 1.9 to 1.3 +/- 0.7 (P < 0.05). Nine of 13 of these patients reported less fatigue, while 10/13

showed an improvement in at least one domain of their Fisk Fatigue Severity Score. No significant

improvement in itch and only limited improvement in fatigue were seen in the patients in group 1. No

change in biochemical parameters was seen in either group. CONCLUSIONS: Antioxidant therapy, as

a combination of Bio-Antox and Bio-Quinone Q10, may improve the pruritus and fatigue of PBC. This

combination of therapy should be investigated further in a double-blind, placebo- controlled trial.

A-5617

Hodges S; Hertz N; Lockwood K; Lister R:

CoQ10: could it have a role in cancer management?:

BioFactors: 9:2-4:365-70 (1999)

Coenzyme Q10 or ubiquinone has been shown to have both anti-cancer and immune system enhancing

properties when tested in animals. Preliminary results reported here suggest that it might inhibit

tumourassociated cytokines. Clinical studies conducted with combination therapies of CoQ10 and other

antioxidants are ongoing, but the results are difficult to evaluate owing to the lack of proper control

groups and of initial randomisation. Also on the basis of some anti-cancer effects of antioxidants reported

in the literature, further animal studies and a proper clinical trial of coenzyme Q10 in cancer patients

are needed.

A-4895

Hodges S; Hertz N; Lister R:

CoQ10: does it have a role in cancer management?:

Boston: 1st Conf. of the Intl. Coenzyme Q10 Assn.: 85 (1998)

A-4252

Lunn R; Rawlinson A; Walsh T; Hodges SJ:

Coenzyme Q10 is lower in gingival cervicular fluid in periodontitis:

Conference Paper, Meeting of Society of Nordic Odontology: 1-6 (1997)

Micronutrient concentrations in the periodontal pocket may be important regulators of bacterial growth.

A number of the suspected oral pathogens have an absolute requirement for vitamin K, while more benign

forms use coenzyme Q10 (Co-Q). There is very little information on gingival crevicular fluid (GCF)

levels of micronutrients; indeed, Co-Q has not been measured in this fluid before this study. We collected

GCF using Periopaper strips from one diseased site and one healthy site in each of nine patients

attending periodontology clinics (age range 27 51, pocket depth 5.9 ± 0.3 and 1.5 ± 0.17 (mean ±

sem) for the diseased and healthy sites respectively). The samples were extracted into ethanol and reduced

to dryness under a stream of 02 free nitrogen into a water bath at 50 degrees C. The residues

were reconstituted in ethanol before being subjected to HPLC purification, coupled to electrochemical

detection. Co-Q levels were quantified against authentic external standard material, and the concentration

of Co-Q determined from GCF volumes. The concentration of Co-Q from the diseased site was found

to be 4.5 ± 3.0 microg/ml and from the healthy site 44.8 ± 21.2 microgram/ml (mean ± sem). The

recovery of Co-Q was 71.5 ± 4.8 %. There was a significant difference in Co-Q concentration between

the two ones (p=0.0078). We conclude that, if Co-Q is required to maintain a healthy microflora ecological

in the periodontal pocket, then this state may be compromised in periodontal disease. Supplementation

with different oral doses of Co-Q10 were found to increase GCF levels in proportion to

dosage. From our limited study, it would appear that a 30 mg oral dose contributes maximally to GCF

levels at about two hours after supplementation. Increasing the dose of Co-Q10 raises the levels in the

periodontal pocket for longer. (Conference paper read at the Meeting of the Society of Nordic Odontology

held in Reykjavik, Iceland, 21-23 August 1997.)

A-3772

Serebruany VL; Ordonez JV; Herzog WR; Rohde M; Mortensen SA; Folkers K; Gurbel

PA:

Dietary CoQ10 supplementation alters platelet size and inhibits human vitronectin

(CD51/CD61) receptor expression:

J Cardiovasc Pharmacol: 29:16-22 (1997)

Improved cardiovascular morbidity and mortality have been observed in several clinical studies of dietary

supplementation with coenzyme Q10 (CoQ10, ubiquinone). Several mechanisms have been proposed

to explain the effects of CoQ10, but a comprehensive explanation of its cardioprotective properties

is still lacking. One attractive theory links ubiquinone with the inhibition of platelets. The effect of

COQ10 intake on platelet size and surface antigens was examined in human volunteers. Study participants

received 100 mg of CoQ10 twice daily in addition to their usual diet for 20 days. Receptor

expression was measured by flow cytometry with monoclonal murine anti-human antibodies CD9

(p24), CD42B (Ib), CD41b (IIb), CD61 (IIIa), CD41a (IIb/IIIa), CD49b (VLA-2), CD62p (P selectin),

CD31 (PECAM- 1), and CD5 I /CD61 (vitronectin). An increase of total serum CoQ10 level (from 0.6 ±

0.1 to 1.8 ± 0.3 microgram/ml; p < 0.001) was found at protocol termination. Fluorescence intensity

was higher for the large platelets when compared with the whole platelet population. Significant inhibition

of vitronectin-receptor expression was observed consistently throughout ubiquinone treatment. Re-

duction of platelet size was observed at the end of CoQ10 supplementation. Inhibition of the platelet vitronectin

receptor and a reduction of the platelet size are direct evidence of a link between dietary

CoQ10 intake and platelets. These findings may not be fully explained by the known antioxidant and

bioenergetic properties of CoQ10. Diminished vitronectin-receptor expression and reduced platelet size

resulting from CoQ10 therapy may contribute to the observed clinical benefits in patients with cardiovascular

diseases.

A-3442

Lewin A; Lavon H; Reubinoff B; Abramov Y; Safron A; Shemesh A; Friedler S;

Schenker JG:

The effect of CoQ10 on sperm viability in vitro and on hamster egg penetration assay:

Journal of Assisted Reproduction and Genetics: 12:3:31S (1995)

Coenzyme Q1O has some major functions in the human cells. These comprise reduction of free radicals

and prevention of cell membrane damage, participation in growth and secretion control of the cell,

and control of calcium exchange and intracellular pH through Na/H exchange. However. the main role

of Q10 is transport of electrons and protons in the process of energy production, through ATP synthesis

in the mitochondrial membrane. It is therefore obvious that the whole process of energy production

in the cell depends on the availability of Q10. In the sperm cells, the majority of Q10 is concentrated in

the midpiece mitochondria. so that the energy for sperm movement and all other energy-dependent

processes in the sperm cell also depend on Q10 availability. In an ongoing study, sperm from fertile

and sub-fertile men are evaluated for their viability in vitro and their penetration capacity into zona free

hamster eggs after incubation with various concentrations of Q10 for 24 hours. The effect of Q10 in vitro

on the above parameters and its correlation to fertility will be discussed.

A-3433

Yokoyama H; Lingle DM; Crestanello JA; Kamelgard J; Kott BR; Momeni R; Millili J;

Mortensen SA; Whitman GJ:

Coenzyme Q10 protects coronary endothelial function from ischemia reperfusion

injury via an antioxidant effect:

Surgery: 120:189-196 (1996)

BACKGROUND. Cardiac ischemia reperfusion (I/R) injury causes coronary vascular dysfunction. Coenzyme

Q10 (CoQ), which preserves cardiac mechanical function after I/R, recently has been .recognized

as a free radical scavenger. We hypothesized that CoQ protects coronary vascular reactivity after

I/R via an antioxidant mechanism. METHODS. Rats were pretreated with either CoQ (20 mg/kg intramuscular

and 10 mg/kg intraperitoneal [CoQ group]) or a vehicle (Control) before the experiment.

Isolated perfused rat hearts were subjected to 25 minutes of global normothermic ischemia and 40 minutes

of reperfusion. The reperfusioninduced oxidative burst was directly assessed by lucigenin enhanced

chemiluminescence. Coronary flow was measured at equilibration and after reperfusion with or without

bradykinin, an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-

independent vasodilator. The effect of intracoronary infusion of hydrogen peroxide (H202 0.1 micro

mol/gm body weight given over 5 minutes), simulating the free radical burst after I/R, also was evaluated.

RESULTS. I/R decreased the bradykinininduced change in coronary flow (-5% +/- 4% versus 26 %

± 3 % at equilibration; p < 0.05) and the SNP-induced change (+20 % +/- 6 % versus +56 % ± 5 % at

equilibration; p < 0. 05). The coronary vasculature after H202 infusion revealed similar loss in vasodilatory

responsiveness (+4 % ± 4 % in response to bradykinin, +35 % ± 8 % in response to SNP; p < 0.

05 versus equilibration). Pretreatment with CoQ improved BK-induced vasorelaxation after I/R (+l2% ±

2%; p < 0.05 versus control I/R) or H202 infusion (18 % ± 4 %; p < 0. 05 versus control I/R) but failed

to improve SNP induced vasorelaxation. The CoQ pretreatment decreased the I/R-induced maximal

free radical burst (9.3 ± 0.8 x 10 to the third power cpm versus 11.5 +/- 1.1. x 10 to the third power

cpm; p < 0. 05) during the early period of reperfusion. CONCLUSION. Endothelium-dependent vasorelaxation

is more sensitive than endothelium independent relaxation to I/R injury. Via a direct antioxidant

effect, CoQ preserved endothelium-dependent vasorelaxation by improving tolerance to I/R injury.

A-3365

Lonnrot K; Metsa-Ketela T; Alho H:

The role of coenzyme Q10 in aging: a follow-up study on life-long oral supplementation

Q-10 in rats:

Gerontology: 41:Suppl. 2:109-118 (1996)

The essential role of coenzyme Q – ubiquinone – in biological energy transduction is well established.

Reduced Q – ubiquinol- has also been shown to act as an antioxidant and to decrease the action of

free radicals, which in turn could cause damage to structural lipids or proteins. The accumulation of

lipopigments during aging in several peripheral organs and in the nervous system is considered to be

related to the peroxidation of unsaturated fatty acids. An age-related decline of Q-10 has been suggested

to occur in man and rats. In this study we followed the effects of life-long oral supplementation of

coenzyme Q-10 on the development and life-span and pigment accumulation in peripheral tissues and

the nervous system of laboratory rats. The Q-10 supplemented group showed a significant increase in

Q-10 in plasma and liver, while it was unchanged in other tissues. There was no significant difference

between the two groups in the development and mortality of the animals. No differences were observed

in lipopigment accumulation. Our results indicate that in rats, life-long supplementation of Q-10 has

no beneficial effects on life-span or pigment accumulation.

A-3203

Crestanello JA; Kamelgard J; Lingle DM; Mortensen SA; Rhode M; Whitman GJ:

Elucidation of a tripartite mechanism underlying the improvement in cardiac tolerance

to ischemia by coenzyme Q10 pretreatment.

J Thorac Cardiovasc Surg: 111:2:443-50 (1996)

Coenzyme Q10, which is involved in mitochondrial adenosine triphosphate production, is also a powerful

antioxidant. We hypothesize that coenzyme Q10 pretreatment protects myocardium from ischemia

reperfusion injury both by its ability to increase aerobic energy production and by protecting creatine kinase

from oxidative inactivation during reperfusion. Isolated hearts (six per group) from rats pretreated

with either coenzyme Q10, 20 mg/kg intramuscularly and 10 mg/kg intraperitoneally (treatment) or vehicle

only (control) 24 and 2 hours before the experiment were subjected to 15 minutes of equilibration,

25 minutes of ischemia, and 40 minutes of reperfusion. Developed pressure, contractility, compliance,

myocardial oxygen consumption, and myocardial aerobic efficiency were measured. Phosphorus 31

nuclear magnetic resonance (31P-NMR) spectroscopy was used to determine adenosine triphosphate

and phosphocreatine concentrations as a percentage of a methylene diphosphonic acid standard.

Hearts were assayed for myocardial coenzyme Q10 and myocardial creatine kinase activity at end

equilibration and at reperfusion. Treated hearts showed higher myocardial coenzyme Q10 levels (133

+/- 5 micrograms/gm ventricle versus 117 +/- 4 micrograms/gm ventricle, p < 0.05). Developed pressure

at end reperfusion was 62% +/- 2% of equilibration in treatment group versus 37% +/- 2% in control

group, p < 0.005. Preischemic myocardial aerobic efficiency was preserved during reperfusion in treatment

group (0.84 +/- 0.08 mm Hg/(microliter O2/min/gm ventricle) vs 1.00 +/- 0.08 mm Hg/(microliter

O2/min/gm ventricle) at equilibration, p = not significant), whereas in the control group it fell to 0.62 +/-

0.07 mm Hg/(microliter O2/min/gm ventricle, p < 0.05 vs equilibration and vs the treatment group at reperfusion.

Treated hearts showed higher adenosine triphosphate and phosphocreatine levels during

both equilibration (adenosine triphosphate 49% +/- 2% for the treatment group vs 33% +/- 3% in the

control group, p < 0.005; phosphocreatine 49% +/- 3% in the treatment group vs 35% +/- 3% in the

control group, p < 0.005) and reperfusion (adenosine triphosphate 18% +/- 3% in the treatment group

vs 11% +/- 2% in the control group, CTRL p < 0.05; phosphocreatine 45% +/- 2% in the treatment

group vs 23% +/- 3% in the control group, p < 0.005). Creatine kinase activity in treated hearts at end

reperfusion was 74% +/- 3% of equilibration activity vs 65% +/- 2% in the control group, p < 0.05). Coenzyme

Q10 pretreatment improves myocardial function after ischemia and reperfusion. This results

from a tripartite effect: (1) higher concentration of adenosine triphosphate and phosphocreatine, initially

and during reperfusion, (2) improved myocardial aerobic efficiency during reperfusion, and (3) protection

of creatine kinase from oxidative inactivation during reperfusion.

A-3139

Alho HE:

The relation of plasma and CSF antioxidants:

Meeting abstract: 1 (1994)

Abstract of a paper presented at the 77th Biennial Scientific Meeting of the International Society for

Free Radical Research in Sydney, Australia, November 6-10, 1994. The relation between the levels of

plasma and cerebrospinal fluid (CSF) antioxidants is not well understood. Compared to plasma normal

CSF has a low total peroxyl radical trapping parameter (TRAP), uric acid, vitamin-E and ubiquinone

(Q-10) but high ascorbic acid content. We studied the effects of oral supplementation of vitamin-C

(ASC) and Q-10 on CSF and plasma TRAP and its component concentration in healthy subjects. ASC

and Q-10 were administered 500-1000mg and 100-300mg for four weeks respectively. After two weeks

of supplementation in plasma both ASC and Q-10 increased significantly (with high dose: ASC from 5l

+/- 5 to 75 +/-5.5 μM and Q-10 from 0.6 +/- 0.2 to 2.5 +/- 0.4 μM) while the TRAP value remained unchanged.

In CSF only ASC increased (from 197 +/-10 to 252 +/- 16 μM) but the Q-10 and TRAP remained

unchanged. It is possible that while plasma ubiquinone is mainly bound to LDL it does not pass

blood brain barrier and oral supplementation has no effects on human CSF Q-10 content.

A-3086

Nylander M; Weiner J; Ruokonen I; Laakso J:

Plasma levels of Coenzyme Q10 before and after supplementation: a bioavailability

study:

Coenzyme Q: 3:1:25-32 (1996)

A group of 146 Swedish adults, average age 60 (range 21-98), were supplemented orally with 60 mg

CoQ10 daily for 10 days. On the first and last day of the study, blood samples were taken before

breakfast. The test grou stayed in the same hotel and ate two vegetarian meals pe day. A subgroup of

36 subjects had been vegetarian for long time. Before suppl., a statistically significant (s.s. correlation

was found between the plasma levels of CoQ10 and total cholesterol (p<0.001). There was also

significant positive correlation between age and CoQ10 (p<0.005) and between age and total

cholesterol (p<0.05) The vegetarians had s.s. lower (p<0.001) levels of total cholesterol (5.7 mmol/l) as

compared to non-vegetarians (6,8 mmol/i). There was no significant difference in CoQl0 levels

between vegetarians and non-vegetarians before supplementation. Average levels of CoQ10 in plasma

increased significantly from 1.12 micro mol/l (Std. dev. 0.40, Range 0.51-2.54) to 1.88 micro mol/l (Std.

dev. 0.65, Range 0.76-3.71) after supp) The relationship between the available variables was further

studied in a multivariate analysis with the difference in CoQ10 plasma levels before and after suppl. as

dependent variable and sex, age, vegetarianism, CoQ10 levels before suppl. and total cholesterol

before suppl. as the independent variables. This analysis showed a positive and significant effect of

total cholesterol before suppl. (p<0.05) and a positive significant effect of vegetarianism (p<0.05). The

effect of sex was not statistically significant (p = 0.15). There was no effect of age The strongest

response to supplementation was shown by the subjects with lower basal levels. There was a s.s.

correlation between levels of CoQ10 and total cholesterol also after the suppl. time (p<0.001).

A-3040

Lockwood K; Moesgaard S; Hanioka T; Folkers K:

ANICA – Adjuvant Nutritional Intervention in Cancer: Current Status (poster):

Poster, 9th Intl. Symp. Biomed. & Clin. Aspects on CoQ10: 1-9 (1996)

Poster presented at the 9th International Symposium on Biomedical and Clinical Aspects of Coenzyme

Q10 in Ancona, Italy, May 16-19,1996.

A-2993

Lewin A:

The effect of coenzyme Q10 on sperm motility:

9th Intl. Symp. Biomed. and Clin. Aspects of Coenzyme Q: 9:47 (1996)

Coenzyme Q10 (CoQ10) has some major functions in the human cells. These comprise reduction of

free radicals, participation in growth and secretion control of the cell, and control of calcium exchange

and intracellular pH. However, the main role of CoQ10 is transport of electrons and protons in the mitochondrial

membrane. For this, CoQ10 has specific ligation sites to various dehydrogenases, such as

NADH- and Succinate-, from which it collects electrons for the oxydative process. By transport of protons,

it creates an electrochemical gradient across mitochondrial membranes, so allowing the

production of ATP. It is therefore obvious that the whole process of energy production in the cell depends

on the availability of CoQ10. In sperm cells, the majority of Q10 is concentrated in the midpiece

mitochondria, so that the energy for sperm movement and all other energy-dependent processes in the

sperm cell also dependent on Coenzyme Ql0 availability. In the present study, sperm samples from infertile

couples were evaluated for motility before and after incubation with various CoQ10 concentrations.

CoQ10 powder was dissolved in Dimethyl-Sulphoxide (DMSO) and added to HAM'S-F10 culture

medium to reach final concentration of 5 micromol/L and 50 micromol/L CoQ10. After motility evaluation,

the sperm samples were divided in 4 parts and incubated for 24 hours in HAM's solution alone, in

HAM's solution with the various concentrations of CoQ10, or in HAM's solution with DMSO alone. While

no difference in motility was observed in the samples with normal motility, an increase in motility was

observed in the sperm from asthenospermic men. Further studies in vivo are needed to establish the

role of CoQ10 supplementation on sperm motility and fertilizing capacity.

A-2987

Serebruany VL; Ordonez JV; Herzog WR; Rohde M; Mortensen SA; Folkers K;

Gurbel PA:

Dietary CoQ10 supplementation alters platelet size and inhibits human vitronectin

(CD51/CD61) receptor expression:

9th Intl. Symp. Biomed. and Clin. Aspects of Coenzyme Q: 9:37 (1996)

Healthy volunteers received 100 mg CoQ10/day for 20 days. Receptor expression and antibodies vere

measured. Total serum Q10 increased significantly. Significant inhibition of vitronectin receptor

expression was observed in addition to a reduction of platelet size. These findings may not fully be

explained by the known antioxidant and bioenergetic properties of CoQ10. The obser- ved changes

may contribute to the clinical benefits in patients with cardiovascular diseases. (see also document

A-3772)

A-2649

Alleva R; Tomasetti M; Littarru GP; Folkers K; Curatola G; Battino M:

The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density

lipoprotein subfractions.:

Proc Natl Acad Sci U S A: 92:20:9388-91 (1995)

The aim of our study was to investigate the relationships between the levels of coenzyme Q10

(CoQ10) and vitamin E and the levels of hydroperoxide in three subfractions of low density lipoproteins

(LDL) that were isolated from healthy donors. LDL3, the densest of the three subfractions, has shown

statistically significant lower levels of CoQ10 and vitamin E, which were associated with higher hydroperoxide

levels when compared with the lighter counterparts. After CoQ10 supplementation (Bio-Quinone,

Pharma Nord, Denmark), all three LDL subfractions had significantly increased CoQ10 levels. In

particular, LDL3 showed the highest CoQ10 increase when compared with LDL1 and LDL2 and was

associated with a significant decrease in hydroperoxide level. These results support the hypothesis that

the CoQ10 endowment in subfractions of LDL affects their oxidizability, and they have important implications

for the treatment of disease.

A-2614

Mizuno M; Quistorff B; Theorell H; Theorell M et al.:

Effects of Peroral Ingestion of Coenzyme Q10 om 31p-MRS detected Skeletal Musc-

le Energy Metabolism in Post-Polio In.:

3. Sci. Meet., Eur. Soc. Magn. Res. Med. Biol.: (1995)

Abstract presented at the 12. annual meeting; European Society for Magnetic Resonance in Medicine

and Biology, Nice, France, Aug. 19. – 25., 1995. Coenzyme Q10 supplementation has demonstrated

an improvement of oxidative energy metabolism, i.e. a decreased Pi/PCr ratio at rest and during

exercise, in mitochondrial myopathies. The study evaluated the possibility of the same effect in postpolio

patients and healthy controls. 5 subjects were supplemented for six months with 90 mg

CoQ10/day. The post-polio subjects showed a progressive decrease in resting Pi/PCr, less pronounced

end-exercise intra- muscular acidosis and faster resynthesis of PCr during recovery.

A-2612

Sindberg CD:

Research in Nutritional Intervention:

Workshop, Pharma Nord Research, Kolding `95: (1995)

Abstracts and Proceedings from Pharma Nord Research Konference "Research in Nutritional Intervention"

held May 19.-21. 1995 at Hotel Koldingfjord, Kolding, Denmark.

A-2611

Mortensen SA (ed.); Remme WJ (ed.); Sindberg CD:

Pharma Nord Satellite Symposium on The Role of Coenzyme Q10 in Ischemia and

Heart Failure:

Heart Failure `95, Europ Soc Cardiol: (1995)

Collection of Abstracts from Pharma Nord Satellite Symp. at "Heart Failure `95" in Amsterdam April 1.-

4. 1995.

A-2589

Lockwood K; Moesgaard S; Yamamoto T; Folkers K:

Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases.:

Biochem Biophys Res Commun: 212:1:172-7 (1995)

Over 35 years, data and knowledge have internationally evolved from biochemical, biomedical and clinical

research on vitamin Q10 (coenzyme Q10; CoQ10) and cancer, which led in 1993 to overt complete

regression of the tumors in two cases of breast cancer. Continuing this research, three additional

breast cancer patients also underwent a conventional protocol of therapy which included a daily oral

dosage of 390 mg of vitamin Q10 (Bio-Quinone of Pharma Nord) during the complete trials over 3-5

years. The numerous metastases in the liver of a 44-year-old patient "disappeared," and no signs of

metastases were found elsewhere. A 49-year-old patient, on a dosage of 390 mg of vitamin Q10, revealed

no signs of tumor in the pleural cavity after six months, and her condition was excellent. A 75-

year-old patient with carcinoma in one breast, after lumpectomy and 390 mg of CoQ10, showed no

cancer in the tumor bed or metastases. Control blood levels of CoQ10 of 0.83-0.97 and of 0.62 micrograms/

ml increased to 3.34-3.64 and to 3.77 micrograms/ml, respectively, on therapy with CoQ10

for patients A-MRH and EEL.

A-2414

Folkers K; Moesgaard S; Morita M:

A One Year Bioavailability Study of Coenzyme Q10 with 3 Months Withdrawal Period:

Mol Aspects Med: 15s:s281-s285 (1994)

Twenty-one healthy subjects received oral Coenzyme Q10 supplementation in soft capsules of 30 mg

t.i.d. for 9 months (Bio-Quinone, Pharma Nord, Denmark), followed by a withdrawal period of 3 months.

Blood samples were taken before start of supplementation, after 3 and 9 months of supplementa-

tion, and finally after 3 months withdrawal. Average blood Coenzyme Q10 concentration increased

from about 1 mg/l before supplementation to about 2 mg/l after 3 and 9 months of supplementation,

and returned to the pretreatment level after withdrawal. The rise of Coenzyme Q10 concentration was

statistically significant (p<0.001, t-test).

A-2413

Weis M; Mortensen SA; Rassing MR; Møller-Sonnergaard J; Poulsen G; Rasmussen

SN:

Bioavailability of Four Oral Coenzyme Q10 Formulations in Healthy Volunteers:

Mol Aspects Med: 15s:s273-s280 (1994)

The bioavailability of four different Coenzyme Q10 (CoQ) formulations was compared in ten healthy volunteers

in a four-way randomised cross-over trial. The included formulations were: A hard gelatine

capsule containing 100 mg of CoQ with 400 mg of Emcompress(R). Three soft gelatine capsules containing:

100 mg of CoQ with 400 mg of soy bean oil (Bio-Quinone(R)); 100 mg of CoQ with 20 mg of

polysorbate 80, 100 mg of lecithin and 280 mg of soy bean oil; and 100 mg of CoQ with 20 mg of polysorbate

80 and 380 mg of soy bean oil, respectively. The result suggests that the soy bean oil suspension

of CoQ (Bio-Quinone(R)) has the highest bioavailability. A difference in the basic AUC and

AUC after p.o. administration of CoQ was observed with respect to sex. A characteristic two-peak pattern

was observed at the concentration vs. time profile.

A-2408

Lockwood K; Moesgaard S; Hanioka T; Folkers K:

Apparent Partial Remission of Breast Cancer in 'High Risk' Patients Supplemented

with Nutritional Antioxidants, Essential Fatty Acids and Coenzyme Q10

Mol Aspects Med: 15s:s231-s240 (1994)

Thirty-two typical patients with breast cancer, aged 32-81 years and classified 'high risk' because if tumor

spread to the lymph nodes in the axilla, were studied for 18 months following an Adjuvant Nutritional

Intervention in Cancer protocol (ANICA protocol). The nutritional protocol was added to the surgical

and therapeutic treatment of breast cancer, as required by regulations in Denmark. The added treatment

was a combination of nutritional antioxidants (Vitamin C: 2850 mg, Vitamin E: 2500 iu, ß-carotene

32.5 iu, selenium 387 μg plus secondary vitamins and minerals), essential fatty acids (1.2 g gamma

linolenic acid and 3.5 g n-3 fatty acids) and Coenzyme Q10 (90 mg per day). (All nutritional preparations

supplied by Pharma Nord, Denmark) The ANICA protocol is based on the concept of testing the

synergistic effect of those categories of nutritional supplements, including vitamin Q10, previously

having shown deficiency and/or therapeutic value as single elements in diverse forms of cancer, as

cancer may be synergistically related to diverse biochemical dysfunctions and vitamin deficiencies. Biochemical

markers, clinical condition, tumor spread, quality of life parameters and survival were followed

during the trial. Compliance was excellent. The main observations were: (1) none of the patients

died during the study period. (the expected number was four.) (2) none of the patients showed signs of

further distant metastases. (3) quality of life was improved (no weight loss, reduced use of pain killers).

(4) six patients showed apparent partial remission.

A-2393

Weber C; Jakobsen TS; Mortensen SA; Paulsen G; Hølmer G:

Effect of Dietary Coenzyme Q10 as an Antioxidant in Human Plasma:

Mol Aspects Med: 15s:s97-s102 (1994)

A human study including 22 volunteers was conducted to investigate the antioxidative effect in blood of

dietary Coenzyme Q10 supplementation (Bio-Quinone, Pharma Nord, Denmark). The levels of a-tocopherol,

ascorbic acid, lipid peroxidation (measured as TBARS) and the redox status of CoQ10 (reduced

CoQ10/total CoQ10) were measured in plasma as markers for the antioxidative status once a

week during the study period. To introduce an increased oxidative stress, a fish oil supplementation

was given. The levels of a-tocopherol and ascorbic acid and the redox status did not change upon

CoQ10 supplementation, while the level of TBARS decreased. The decrease in TBARS might be ascri-

bed to an antioxidative effect of the supplied CoQ10. The constant redox level of CoQ10 during the

CoQ10 supplementation shows that the exogenous CoQ10 is reduced during absorption and subsequent

incorporation into lipoproteins, which is a prerequisite for its antioxidative function. The fish oil

supplementation resulted in a higher TBARS level and a lower a-tocopherol level, but the redox level of

CoQ10 was unchanged. In conclusion, the CoQ10 supplementation resulted in a higher plasma level of

reduced CoQ10 and a lower TBARS level, but sparing of other plasma antioxidants (i.e. ascorbic acid

and a-tocopherol) was not observed.

A-2195

Weber C; Sejersgard Jakobsen T; Mortensen SA; Paulsen G; Hølmer G:

Antioxidative effect of dietary coenzyme Q10 in human blood plasma:

Internat J Vit Nutr Res: 64:311-315 (1994)

The effect of an oral dose of 90 mg/day coenzyme Q10 on the antioxidative status in 22 healthy young

subjects (9 men and 13 women) was investigated before and after induction of an oxidative stress by

fish oil supplementation. The levels of oxidised and reduced coenzyme Q10, alpha tocopherol, ascorbate,

TBARS and the fatty acid composition of phospholipids were determined in plasma. The total

amount of plasma coenzyme Q10 increased significantly from 0.7 +/- 0.1 micromol/l before supplementation

to 1.7 +/ 0.3 micromol/l after one week of supplementation while the redox status (reduced

CoQ10/total CoQ10) remained constant, even during a following fish oil supplementation. The level of

TBARS decreased during the first 2 weeks of CoQ10 ingestion while the content of alpha tocopherol

increased in the second week and ascorbate did not change. The decrease of TBARS and the presence

of the majority of the orally supplemented CoQ10 in the reduced form in plasma seem to indicate an

antioxidative role of CoQ10 in blood plasma.

A-1956

Gardner A:

Coenzyme Q10 and diabetes mellitus: A 72-year-old man taking CoQ10 on his own

accord could quit insulin injections:

8th. Int. Symp. Biomed. and Clin. Aspects of CoQ10: 69 (1993)

A-1850

Lockwood K; Moesgaard S; Folkers K:

Partial and complete regression of breast cancer in patients in relation to dosage of

coenzyme Q10:

Biochem Biophys Res Commun: 199:3:1504-8 (1994)

Relationships of nutrition and vitamin to the genesis and prevention of cancer are increasingly evident.

In a clinical protocol, 32 patients having -"high-risk" breast cancer were treated with antioxidants, fatty

acids, and 90 mg of CoQ10. Six of the 32 patients showed partial tumor regression. In one of these 6

cases, the dosage of CoQ10 was increased to 390 mg. In one month, the tumor was no longer palpable

and in another month, mammography confirmed the absence of the tumor. Encouraged, another

case having verified breast tumor, after nonradical surgery and with verified residual tumor in the tumor

bed was treated with 300 mg CoQ10. After 3 months, this patient was in excellent clinical condition and

there was no residual tumor tissue. The bioenergetic activity of CoQ10, expressed as hematological or

immunological activity, may be the dominant but not the sole molecular mechanism causing the regression

of breast cancer.

A-1510

Mortensen SA:

Perspectives on Therapy of Cardiovascular Diseases with Co Q10.:

Clin Investig: 71:S116-23 (1993)

A defective myocardial energy supply – due to lack of substrates and/or essential cofactors and a poor

utilization efficiency of oxygen – may be a common final pathway in the progression of myocardial di-

seases of various etiologies. The vitamin-like, essential substance Coenzyme Q10 (CoQ10) has a key

role in the oxidative phosphorylation. A biochemical rationale for using CoQ10 as a therapy in heart disease

was been established years ago by Folkers and associates; however, this has been further

strengthened by investigations of viable myocardial tissue from the author's series of 45 patients with

various cardiomyopathies. Myocardial tissue levels of CoQ10 determined by HPLC were found significantly

lower in groups with more advanced heart failure (NYHA classes III and IV) compared with those

patients in the milder stages of heart failure. Furthermore, the tissue CoQ10 deficiency was significantly

restored by oral therapy, 100 mg CoQ10 daily (dissolved in soy-bean oil and administered in soft gelatine

capsules). In a series of 40 patients with heart failure of various origin at Rigshospitalet nearly

two thirds revealed clinical improvement, most pronounced in patients with dilated cardiomyopathy.

Double-blind placebo-controlled trials have definitely confirmed that coenzyme Q10 has a place as adjunctive

treatment in heart failure with beneficial effects on the clinical outcome, the patients' physical

activity, and their quality of life. The positive results have been above and beyond the clinical status obtained

from treatment with traditional principles – including angiotensin-converting enzyme inhibitors.

A-1302

Nylander M:

Kliniska effekter pa parodontalt status efter kostsupplementering med ubiquinon, coensym

Q10:

Biomed: 4:6-11 (1991)

Six people with varying degree of periodontosis were given a daily oral supplement of 30-100 mg of

ubiquinone (Bio-Quinone, Pharma Nord) for 6-12 weeks. The results indicate that ubiquinone can attenuate

the degree of bleeding tendency and/or inflammation of the gingiva in individuals showing periodontosis.

Time needed of supplementation for therapeutic effect varied individually.

A-1016

Kuklinski B; Pietschmann A:

Oxidativer Stress und Altern:

Z Geriatrie: 4:224-246 (1991)

Review: Oxidative stress and the aging process. A description of the involvement of oxidative stress

during aging. Antioxidants and their specific effects are presented. Epidemiological investigations in

Germany revealed an undersupply with nutritional anti- oxidants. The highest deficit could be found in

selenium, an essential trace element for radical scavenger enzymes. This may lead to a deficiency in

vitamin E. Oxidative stress activates the cascade of arachidonic acid, as well as inducing inflow of intracellular

calcium. These changes on a subcellular level, contribute to immunodisturbances and enhancement

of cancer- and atherogenesis.

7.2 Selected references

A-1217 Lücker PW, Wetzelsberger N, Hennings G, Rehn D:

Pharmacokinetics of coenzyme ubidecarenone in healthy volunteers;

Biomed. and clin. aspects of coQ10 1984 4, pp. 143-151

A-1304 Tomono Y, Hasegawa J, Seki T, Motegi K et al.: Pharmacokinetic

study of deuterium-labelled coenzyme Q10 in man; Int Jin Pharmacol

Ther Toxicol 1986 24, no. 10, pp. 536-41

A-1338 Lenaz G, Fato R, Castelluccio C, Castelli GP et al.: Coenzyme Q

saturation kinetics of mitochondrial enzymes: theory, experimental

aspects and biomedical implications; Biomed. and clin. aspects of

coQ10 1991 6, pp. 11-18

A-1348 Packer L, Kagan V, Serbinova E: Participation of ubiquinones in

membrane antioxidation: direct radical scavenging or tocepherol

recycling?; Biomed. and clin. aspects of Q10 1991 6, pp. 115-124

A-1395 Yamabe H, Fukuzaki H: The beneficial effect of coQ10 on the

impaired aerobic function in middle aged women without organic

disease; Biomed. and clin. aspects of Q10 1991 6, pp. 535-540

A-1433 Kalen A, Appelkvist EL, Dallner G: Age-related changes in the lipid

compositions of rat and human tissues.; Lipids 1989 24, no. 7, pp.

579-84

A-1505 Karlsson J, Diamant B, Theorell H, Folkers K: Ubiquinone and

Alpha-Tocopherol in Plasma; Means of Translocation or Depot.; Clin

investig 1993 71, pp. S84-91

A-1508 Atar D, Mortensen SA, Flachs H, Herzog WR: Coenzyme Q10

Protects Ischemic Myocardium in an Open-Chest Swine Model.; Clin

Investig 1993 71, pp. S103-11

A-1510 Mortensen SA: Perspectives on Therapy of Cardiovascular Diseases

with Co Q10.; Clin Investig 1993 71, pp. S116-23

A-1512 Lampertico M, Comis S: Italian Multicenter Study on the Efficacy

and Safety of CoQ10 as Adjuvant Therapy in Heart Failure.; Clin

Investig 1993 71, pp. S129-33

A-1515 Jameson S: Statistical Data Support Prediction of Death within Six

Months on Low Levels of Coenzyme Q10 and Other Entities.; Clin

Investig 1993 71, pp. S137-9

A-1852 Folkers K: Critique of 30 years of research on hematopoietic and

immunological activities of CoQ10 and potentiality for ...; Med Chem

Res 1992 2, pp. 48-60

A-1864 Glavind L, Moe D, Klausen B, Diamant B: Effekt af ubiquinon

(coenzyme Q10) pa marginal parodontitis; Tandlægebladet 1994 98,

no. 6, pp. 287-292

A-1929 McRee JT, Morita M, Folkers K: Reduction of microflora in

periodontal disease by therapy with coenzyme q10 and vitamin B6;

8th. Int. Symp. Biomed. and Clin. Aspects of CoQ 1993, pp. 40

A-1955 Kontush A, Hubner C, Finckh B, Kohlschutter A et al.:

Supplementation with ubiquinol-10 protects low density lipo- protein

against lipid peroxidation more efficiently than...; 8th. Int. Symp.

Biomed. and Clin. Aspects of CoQ 1993, pp. 68

A-2398 Kuklinski B, Weissenbacher E, Fähnrich A: Coenzyme Q10 and

Antioxidants in Acute Myocardial Infarction; Mol Aspects Med 1994

15s, pp. s143-s147

A-2402 Romagnoli A, Oradei A, Destito C, Iacocagni A et al.: Protective

Role IN VIVO of Coenzyme Q10 during Reperfusion of Ischemic

Limbs; Mol Aspects Med 1994 15s, pp. s177-s185

A-2403 Bargossi AM, Grossi G, Fiorella PL, Gaddi A et al.: Exogenous

CoQ10 Supplementation Prevents Plasma Ubiquinone Reduction

Induced by HMG-CoA Reductase Inhibitors; Mol Aspects Med 1994

15s, pp. s187-s193

A-2409 Hanioka T, Tanaka M, Ojima M, Shizukuishi S: Effect of Topical

Application of Coenzyme Q10 on Adult Periodontitis; Mol Aspects

Med 1994 15s, pp. s241-s248

A-2413 Weis M, Mortensen SA, Rassing MR, Møller-Sonnergaard J et al.:

Bioavailability of Four Oral Coenzyme Q10 Formulations in Healthy

Volunteers; Mol Aspects Med 1994 15s, pp. s273-s280

A-2414 Folkers K, Moesgaard S, Morita M: A One Year Bioavailability

Study of Coenzyme Q10 with 3 Months Withdrawal Period; Mol

Aspects Med 1994 15s, pp. s281-s285

A-2415 Baggio E, Gandini R, Plancher AC, Passeri M et al.: Italian

Multicenter Study on the Safety and Efficacy of Coenzyme Q10 as

Adjunctive Therapy in Heart Failure; Mol Aspects Med 1994 15s, pp.

s287-s294

A-2496 Spigset O: Reduced effect of warfarin caused by ubidecarenone

:letter:; Lancet 1994 344, no. 8933, pp. 1372-3

A-2632 Mancini A, De Marinis L, Oradei A, Littarru GP et al.: Coenzyme

Q10 concentrations in normal and pathological human seminal fluid.;

J Androl 1994 15, no. 6, pp. 591-4

A-2649 Alleva R, Tomasetti M, Littarru GP, Folkers K et al.: The roles of

coenzyme Q10 and vitamin E on the peroxidation of human low

density lipoprotein subfractions.; Proc Natl Acad Sci U S A 1995 92,

no. 20, pp. 9388-91

A-2849 Chello M, Mastroroberto P, Romano R, Bevacqua E et al.:

Protection by coenzyme Q10 from myocardial reperfusion injury

during coronary artery bypass grafting.; Ann Thorac Surg 1994 58,

no. 5, pp. 1427-32

A-2891 Okamoto T, Fukui K, Nakamoto M, Kishi T et al.: Serum levels of

coenzyme Q10 and lipids in patients during total parenteral nutrition.;

J Nutr Sci Vitaminol (Tokyo) 1986 32, no. 1, pp. 1-12

A-2971 Stocker R: Inhibition of radical initiated LDL oxidation by ubiquinol

10. A protective role for CoQ in atherogenesis?; 9th Intl. Symp.

Biomed. and Clin. Aspects of Coenzyme Q 1996 9, pp. 16-17

A-2987 Serebruany VL, Ordonez JV, Herzog WR, Rohde M et al.: Dietary

CoQ10 supplementation alters platelet size and inhibits human

vitronectin (CD51/CD61) receptor expression; 9th Intl. Symp.

Biomed. and Clin. Aspects of Coenzyme Q 1996 9, pp. 37

A-3203 Crestanello JA, Kamelgard J, Lingle DM, Mortensen SA et al.:

Elucidation of a tripartite mechanism underlying the improvement in

cardiac tolerance to ischemia by coenzyme Q10; J Thorac

Cardiovasc Surg 1996 111, no. 2, pp. 443-50

A-3432 Serebruany VL, Herzog WR, Atamas SP, Gurbel PA et al.:

Hemostatic changes after dietary coenzyme Q10 supplementation in

swine; J Cardiovasc Pharmacol 1996 28, pp. 175-181

A-3433 Yokoyama H, Lingle DM, Crestanello JA, Kamelgard J et al.:

Coenzyme Q10 protects coronary endothelial function from ischemia

reperfusion injury via an antioxidant effect; Surgery 1996 120, pp.

189-196

A-3566 Nylander M, Weiner J, Nordlund M: A double-blind clinical doseresponse

study on effects of CoQ10 on gingival bleeding/periodontal

disease in ordinary; 7th Intl Symp on Trends in Biomedicine in

Finland 1996 Suppl 8, pp. 1-7

A-3882 Thomas SR, Neuzil J, Stocker R: Cosupplementation with

coenzyme Q prevents the prooxidant effect of alpha-tocopherol and

increases the resistance of L; Arterioscler Thromb Vasc Biol 1996 16,

no. 5, pp. 687-96

A-4054 Henriksen JE, Andersen CB, Hother-Nielsen O, Vaag A et al.: The

effect of ubikinon (coenzyme Q10) on glycaæmic control and well-

being in IDDM patients; Diabetologia 1996 39, no. Suppl 1, pp. A227

A-4192 Soja AM, Mortensen SA: Treatment of congestive heart failure with

coenzyme Q10 illuminated by meta-analyses of clinical trials; Molec

Aspects Med 1997 18, no. Suppl, pp. s159-s168

A-4198 Lewin A, Lavon H: The effect of coenzyme Q10 on sperm motility

and function; Molec Aspects Med 1997 18, no. Suppl, pp. s213-s219

A-4212 Ylikoski T, Piirainen J, Hanninen O, Penttinen J: The effect of

coenzyme Q10 on the exercise performance of cross-country skiers;

Molec Aspects Med 1997 18, no. Suppl, pp. s283-s290

A-4252 Lunn R, Rawlinson A, Walsh T, Hodges SJ: Coenzyme Q10 is

lower in gingival cervicular fluid in periodontitis; Conference Paper,

Meeting of Society of Nordic Odontology 1997, pp. 1-6

A-4524 Iwamoto Y, Watanabe T, Okamoto H, Folkers K et al.: Clinical

effect of coenzyme Q10 on periodontal disease; Biomed. and Clin.

Aspects of Coenzyme Q 1981 3, pp. 109-119

A-4748 Nakamura R, Littarru GP, Folkers K, Wilkinson EG: Study of

CoQ10 enzymes in gingiva from patients with periodontal disease

and evidence for a deficiency of Q10; Proc Natl Acad Sci U S A 1974

71, no. 4, pp. 1456-60

A-5545 Henriksen JE, Andersen CB, Hother-Nielsen O, Vaag A et al.:

Impact of ubiquinone (coenzyme Q10) treatment on glycaemic

control, insulin requirement and well-being in patients with; Diabet

Med 1999 16, no. 4, pp. 312-8

A-5614 Munkholm H, Hansen HHT, Rasmussen K: Coenzyme Q10

treatment in serious heart failure; BioFactors 1999 9, no. 2-4, pp.

285-89

A-5615 Eriksson JG, Forsén TJ, Mortensen SA, Rohde M: The effect of

coenzyme Q10 administration on metabolic control in patients with

type 2 diabetes mellitus; BioFactors 1999 9, no. 2-4, pp. 315-18

A-5776 Barbieri B, Lund B, Lundstrom B, Scaglione F: Coenzyme Q10

administration increases antibody titer in hepatitis B vaccinated

volunteers--a single blind placebo-co; Biofactors 1999 9, no. 2-4, pp.

351-7

A-5821 Overvad K, Diamant B, Mortensen SA, Stender S et al.:

Coenzyme Q10 in health and disease [Review]; Eur J Clin Nutr 1999

53, pp. 764-70

A-5918 Denny N, Chapple I, Matthews JB: Antioxidant and antiinflammatory

effects of Coenzyme Q10: a preliminary study; Journal

of Dental Research 1999 78, no. 2, pp. 543

A-6084 Khatta M, Alexander BS, Krichten CM, Fisher ML et al.: The effect

of coenzyme Q10 in patients with congestive heart failure.; Ann Intern

Med 2000 132, no. 8, pp. 636-40

B-6214 Kaikkonen J: Coenzyme Q10 - Plasma analysis and role as an

antioxidant; Kuopio University Publications D. MS 194 1999

A-6278 Gille G, Hung S-T, Janetzky B, Rausch W-D: Neuroprotective

effects of a novel Q10 preparation on the dopaminergic system in

vitro; Frankfurt: 2nd Conf. Intl. CoQ10 Assn. 2000, pp. 51-52

A-6286 Blatt T, Stab F, Schreiner V, Wittern K-P: CoQ10, an effective

endogenous antioxidant and energizer in human skin; Frankfurt; 2nd

Conf. Intl. CoQ10 Assn. 2000, pp. 67

A-6314 Zorn B, Virant-Klun I, Osredkar J, Krstic N: The effects of a

double-blind randomized placebo cross-over controlled trial using

coenzyme Q10 (Bio-Quinone Q10)...; Frankfurt: 2nd Conf. Intl.

CoQ10 Assn 2000, pp. 126-127

A-6343 Zita C, Mortensen SA, Sindberg CD, Hunter DA et al.: Coenzyme

Q10 concentrations in serum of healthy men ingesting Bio-Quinone

30 mg Q10 or Myoqinon 100 mg Q10...; Frankfurt: 2nd Conf. Intl.

CoQ10 Assn. 2000, pp. 186

A-6344 Mosca F, Balercia G, Mantero F, Littarru GP et al.: Effects of

coenzyme Q10 supplementation on some biochemical parameters

and on sperm motility in a group of...; Frankfurt: 2nd Conf. Intl.

CoQ10 Assn. 2000, pp. 187

A-6617 Rozen TD, Oshinsky ML, Gebeline CA, Bradley KC et al.: Open

label trial of coenzyme Q10 as a migraine preventive.; Cephalalgia

2002 22, no. 2, pp. 137-41.

A-6688 Engelsen J, Nielsen JD, Winther K: Effect of coenzyme Q10 and

Ginkgo biloba on warfarin dosage in stable, long-term warfarin

treated outpatients. A randomi; Thromb Haemost 2002 87, no. 6, pp.

1075-6.

A-6887 Lankin VZ, Tikhaze AK, Kukharchuk VV, Konovalova GG et al.:

Antioxidants decreases the intensification of low density lipoprotein in

vivo peroxidation during therapy with statins; Mol Cell Biochem 2003

249, no. 1-2, pp. 129-40.

A-6898 Horstink MW, van Engelen BG: The effect of coenzyme Q10

therapy in Parkinson disease could be symptomatic.; Arch Neurol

2003 60, no. 8, pp. 1170-2

A-7059 Turunen M, Olsson J, Dallner G: Metabolism and function of

coenzyme Q.; Biochim Biophys Acta 2004 1660, no. 1-2, pp. 171-99.

A-7172 Rundek T, Naini A, Sacco R, Coates K et al.: Atorvastatin

decreases the coenzyme Q(10) level in the blood of patients at risk

for cardiovascular disease and stroke.; Arch Neurol 2004 61, no. 6,

pp. 889-92.

A-7185 Shults CW, Flint Beal M, Song D, Fontaine D: Pilot trial of high

dosages of coenzyme Q10 in patients with Parkinson's disease.; Exp

Neurol 2004 188, no. 2, pp. 491-4.

A-7227 Damian MS, Ellenberg D, Gildemeister R, Lauermann J et al.:

Coenzyme Q10 combined with mild hypothermia after cardiac arrest:

a preliminary study.; Circulation 2004 110, no. 19, pp. 3011-6. Ep

A-7234 Singh RB, Neki NS, Kartikey K, Pella D et al.: Effect of coenzyme

Q10 on risk of atherosclerosis in patients with recent myocardial

infarction.; Mol Cell Biochem 2003 246, no. 1-2, pp. 75-82.

A-7249 Silver MA, Langsjoen PH, Szabo S, Patil H et al.: Effect of

atorvastatin on left ventricular diastolic function and ability of

coenzyme Q(10) to reverse that dysfu; Am J Cardiol 2004 94, no. 10,

pp. 1306-10.

A-7324 Sandor PS, Di Clemente L, Coppola G, Saenger U et al.: Efficacy

of coenzyme Q10 in migraine prophylaxis: a randomized controlled

trial.; Neurology 2005 64, no. 4, pp. 713-5.

A-7354 Soongswang J, Sangtawesin C, Durongpisitkul K,

Laohaprasitiporn D et al.: The Effect of Coenzyme Q10 on

Idiopathic Chronic Dilated Cardiomyopathy in Children.; Pediatr

Cardiol 2005 26, pp. 361-366

A-7372 Dallner G, Stocker R:. Coenzyme Q10; Encyclopedia of Dietary

Supplements 2005,121-131

A-7507 Hart PE, Lodi R, Rajagopalan B, Bradley JL et al.: Antioxidant

treatment of patients with Friedreich ataxia: four-year follow-up.; Arch

Neurol 2005 62, no. 4, pp. 621-6.

A-7563 Muller T, Buttner T, Gholipour AF, Kuhn W: Coenzyme Q10

supplementation provides mild symptomatic benefit in patients with

Parkinson's disease.; Neurosci Lett. 2003 341, no. 3, pp. 201-4.

A-7564 Chan A, Reichmann H, Kogel A, Beck A et al.: Metabolic changes

in patients with mitochondrial myopathies and effects of coenzyme

Q10 therapy.; J Neurol. 1998 245, no. 10, pp. 681-5.

A-7574 Rosenfeldt F, Marasco S, Lyon W, Wowk M et al.: Coenzyme Q10

therapy before cardiac surgery improves mitochondrial function and

in vitro contractility of myocard; J Thorac Cardiovasc Surg. 2005 129,

no. 1, pp. 25-32.

A-7575 Rosenfeldt F, Marasco S, Lyon W, Wowk M et al.: Coenzyme Q10

therapy before cardiac surgery improves mitochondrial function and

in vitro contractility of myocard; J Thorac Cardiovasc Surg. 2005 129,

no. 1, pp. 25-32.

A-7581 Golomb BA, Kane T, Dimsdale JE: Severe irritability associated

with statin cholesterol-lowering drugs.; QJM. 2004 97, no. 4, pp.

229-35.

A-7625 Belardinelli R, Mucaj A, Lacalaprice F, Solenghi M et al.:

Coenzyme Q10 and exercise training in chronic heart failure.; Eur

Heart J. 2006 27, no. 22, pp. 2675-81. E

A-7633 de Lau LM, Koudstaal PJ, Hofman A, Breteler MM: Serum

cholesterol levels and the risk of Parkinson's disease.; Am J

Epidemiol. 2006 164, no. 10, pp. 998-1002.

A-7636 Ikematsu H, Nakamura K, Harashima S, Fujii K et al.: Safety

assessment of coenzyme Q10 (Kaneka Q10) in healthy subjects: a

double-blind, randomized, placebo-controlled tri; Regul Toxicol

Pharmacol. 2006 44, no. 3, pp. 212-8

A-7742 Rosenfeldt FL, Haas SJ, Krum H, Hadj A et al.: Coenzyme Q10 in

the treatment of hypertension: a meta-analysis of the clinical trials.; J

Hum Hypertens. 2007 21, no. 4, pp. 297-306. E

A-7743 Caso G, Kelly P, McNurlan MA, Lawson WE: Effect of coenzyme

q10 on myopathic symptoms in patients treated with statins.; Am J

Cardiol. 2007 99, no. 10, pp. 1409-12. E

A-7813 Hathcock JN, Shao A: Risk assessment for coenzyme Q10

(Ubiquinone).; Regul Toxicol Pharmacol. 2006 45, no. 3, pp. 282-8.

Epu

A-7814 Galpern WR, Cudkowicz ME: Coenzyme Q treatment of

neurodegenerative diseases of aging.; Mitochondrion. 2007 7 Suppl

1, pp. S146-53. E

A-7821 Tavintharan S, Ong CN, Jeyaseelan K, Sivakumar M et al.:

Reduced mitochondrial coenzyme Q10 levels in HepG2 cells treated

with high-dose simvastatin: A possible role in stati; Toxicol Appl

Pharmacol. 2007, pp. .

A-7835 Tiano L, Belardinelli R, Carnevali P, Principi F et al.: Effect of

coenzyme Q10 administration on endothelial function and

extracellular superoxide dismutase in patients ; Eur Heart J. 2007, pp.

A-7870 Edwards IR, Star K, Kiuru A: Statins, neuromuscular degenerative

disease and an amyotrophic lateral sclerosis-like syndrome: an

analysis of ; Drug Saf. 2007 30, no. 6, pp. 515-25.

A-7883 Haruna M, Matsuzaki M, Tanizaki T, Sekine K et al.: Increased

serum coenzyme Q10 during pregnancy correlates to birth weight;

5th Conf Int CoQ10 Ass - Prog & Abstr 2007, pp. 108-9

A-7939 Pepe S, Marasco SF, Haas SJ, Sheeran FL et al.: Coenzyme Q10

in cardiovascular disease.; Mitochondrion. 2007 7 Suppl, pp.

S154-67. E

A-7942 Cooper JM, Schapira AH: Friedreich's ataxia: coenzyme Q10 and

vitamin E therapy.; Mitochondrion. 2007 7 Suppl, pp. S127-35. E

A-8028 Miles MV, Patterson BJ, Chalfonte-Evans ML, Horn PS et al.:

Coenzyme Q10 (Ubiquinol-10) Supplementation Improves Oxidative

Imbalance in Children With Trisomy 21.; Pediatr Neurol. 2007 37, no.

6, pp. 398-403.

A-8049 Hidaka T, Fujii K, Funahashi I, Fukotimi N et al.: Overview of

safety assessment of coenzyme Q10 (CoQ10): Animal and human

data; 5th Conf Int CoQ10 Ass - Prog & Abstr 2007, no. J12-038, pp.

73-4

A-8058 Teran E: Coenzyme Q10 supplementation during pregnancy and

later development of preeclampsia; 5th Conf Int CoQ10 Ass - Prog &

Abstr 2007, no. J11-034, pp. 65-7

A-8059 Littarru GP, Tiano L: Bioenergetic and antioxidant properties of

coenzyme Q10: recent developments.; Mol Biotechnol. 2007 37, no.

1, pp. 31-7.

A-8064 Yamasaki M, Kitagawa T, Chujo H, Koyanagi N et al.:

Physiological Difference between Free and Triglyceride-type

Conjugated Linoleic Acid on the Immune Function of C57BL/6N ; J

Agric Food Chem 2004 52, pp. 3644-48

A-8164 Horvath R, Schneiderat P, Schoser BG, Gempel K et al.:

Coenzyme Q10 deficiency and isolated myopathy.; Neurology. 2006

66, no. 2, pp. 253-5.

A-8252 Roffe L, Schmidt K, Ernst E: Efficacy of coenzyme Q10 for

improved tolerability of cancer treatments: a systematic review.; J

Clin Oncol. 2004 22, no. 21, pp. 4418-24.

A-8287 Mizuno K, Tanaka M, Nozaki S, Mizuma H et al.: Antifatigue effects

of coenzyme Q10 during physical fatigue.; Nutrition. 2008 24, no. 4,

pp. 293-9. Epu

A-8316 Deguchi S, Fujii K, Kurihara T: The Effect of the Reduced Form of

Coenzyme Q10 (Ubiquinol, Kaneka QH) on QoL Improvement in the

Elderly; Journal of Clinical Therapeutics & Medicines 2008 24, no. 3,

pp. 233-8

A-8389 Cooke M, Iosia M, Buford T, Shelmadine B et al.: Effects of acute

and 14-day coenzyme Q10 supplementation on exercise

performance in both trained and untrained individu; J Int Soc Sports

Nutr. 2008 5, pp. 8.

A-8423 Baumann L: How to prevent photoaging?; J Invest Dermatol. 2005

125, no. 4, pp. xii-xiii.

A-8463 Trushina E, McMurray CT: Oxidative stress and mitochondrial

dysfunction in neurodegenerative diseases.; Neuroscience. 2007

145, no. 4, pp. 1233-48. E

A-8482 Hershey AD, Powers SW, Vockell AL, Lecates SL et al.:

Coenzyme Q10 deficiency and response to supplementation in

pediatric and adolescent migraine.; Headache. 2007 47, no. 1, pp.

73-80.

A-8580 Chen RS, Huang CC, Chu NS: Coenzyme Q10 treatment in

mitochondrial encephalomyopathies. Short-term double-blind,

crossover study.; Eur Neurol. 1997 37, no. 4, pp. 212-8.

A-8607 Pella D, Fedacko J, Rybar R, Fedackova P et al.: Coenzyme Q10

and Selenium in Statin Side Effects Treatment. Results of a

Randomised Double-Blind Clinical Study; Int. Med. CoQ10 Congress,

Prague, Czeck Republic. 2008 Sept. 13th

A-8612 Cooper JM, Korlipara LV, Hart PE, Bradley JL et al.: Coenzyme

Q10 and vitamin E deficiency in Friedreich's ataxia: predictor of

efficacy of vitamin E and coenzyme Q10 ; Eur J Neurol. 2008 15, no.

12, pp. 1371-9.

A-8667 Bhagavan HN, Chopra RK, Craft NE, Chitchumroonchokchai C et

al.: Assessment of coenzyme Q10 absorption using an in vitro

digestion-Caco-2 cell model.; Int J Pharm. 2007 333, no. 1-2, pp.

112-7. Epu

A-8684 Mancini A, De Marinis L, Littarru GP, Balercia G: An update of

Coenzyme Q10 implications in male infertility: biochemical and

therapeutic aspects.; Biofactors. 2005 25, no. 1-4, pp. 165-74.

A-8779 Bhagavan HN, Chopra RK: Coenzyme Q10: absorption, tissue

uptake, metabolism and pharmacokinetics.; Free Radic Res. 2006

40, no. 5, pp. 445-53.

A-8810 Molyneux SL, Florkowski CM, George PM, Pilbrow AP et al.:

Coenzyme Q10: an independent predictor of mortality in chronic

heart failure.; J Am Coll Cardiol. 2008 52, no. 18, pp. 1435-41.

A-8835 Teran E, Hernandez I, Nieto B, Tavara R et al.: Coenzyme Q10

supplementation during pregnancy reduces the risk of preeclampsia.;

Int J Gynaecol Obstet. 2009 105, no. 1, pp. 43-5. Epub

A-8849 Hamilton SJ, Chew GT, Watts GF: COENZYME Q10 IMPROVES

ENDOTHELIAL DYSFUNCTION IN STATIN-TREATED TYPE 2

DIABETIC PATIENTS.; Diabetes Care 2009 32, no. 5, pp. 810-2

A-8868 Kon M, Tanabe K, Akimoto T, Kimura F et al.: Reducing exerciseinduced

muscular injury in kendo athletes with supplementation of

coenzyme Q10.; Br J Nutr. 2008 100, no. 4, pp. 903-9. Epu

A-8874 Elshershari H, Ozer S, Ozkutlu S, Ozme S: Potential usefulness of

coenzyme Q10 in the treatment of idiopathic dilated cardiomyopathy

in children.; Int J Cardiol 2003 88 101-2

A-8876 Safarinejad MR. Efficacy of coenzyme Q10 on semen parameters,

sperm function and reproductive hormones in infertile men; J Urol

2009 182 237-48

A-8878 Draeger A, Monastyrskaya K, Mohaupt M, Hoppeler H, et al.:

Statin therapy induces ultrastructural damage in skeletal muscle in

patients without myalgia.; J Pathol 2006 210 94-102

Liv til svigtende hjerter med Q10