診療と新薬・第 53 巻

第 5 号（2016 年 5 月）

45 （413）

THE EFFECTS OF COENZYME Q10 ON VITAL SIGN AND SYMPTOMSIN HEALTHY WOMEN WITH HYPOTENSION― A RANDOMIZED PLACEBO-CONTROLLED STUDY ―Masatomo NAJIMA1), Mitsuhiko MUNEKATA2) and Ryosuke KOBAYASHI3)
1) JACTA (Japan Clinical Trial Association)
2) OZ Clinic
3) CLIQUE

Abstract
Objective: Coenzyme Q10 is ubiquitous in the body of most animals. It is an essential
cofactor in mitochondrial oxidative phosphorylation, and is necessary for adenosine
triphosphate production. Coenzyme Q10 has the function which improves the balance of
cardiac output and peripheral circulation. In this study, we examined the eﬀect of Coenzyme
Q10 on blood pressure, heart rate, skin surface temperature and subjective symptoms inhealthy volunteers with hypotension.
Methods: A randomized, double-blind, placebo-controlled study was conducted on 32 womenwith hypotension. Subjects were randomly allocated to group A or B. Subjects in group A
and B ingested Coenzyme Q10 and placebo for 12 weeks, respectively. As a primary
outcome, blood pressure, heart rate, skin surface temperature, and subjective symptoms
that arise from hypotension were evaluated in each group. Safety was also evaluated basedon a diary kept by the subjects.
Results: A total 29 subjects completed the study. There were signiﬁcant diﬀerences in theamount of change in systolic blood pressure, skin surface temperature, and dizziness scores
between group A and B. No adverse events were observed.
Conclusion: Daily ingestion of Coenzyme Q10 showed a favorable eﬀect on systolic bloodpressure, skin surface temperature, and dizziness without any adverse events.
Key words: coenzyme Q10, hypotension, low blood pressure

1. INTRODUCTION
Coenzyme Q10 (CoQ10), also known as ubiquinone, isubiquitous in the body of most animals. It is an essential
cofactor in mitochondrial oxidative phosphorylation, andis necessary for adenosine triphosphate (ATP)p r od u c t i o n . I t i s e n d o g e n o u s l y s y n t h e s i z e d v i amevalonate pathway, and some is obtained from food 1).
Although CoQ10 is produced in the human body, it
decreases gradually by aging and the amount of CoQ10 of
the octogenarian is estimated half of the quantity
produced in the 20 s 2). Physiologically, CoQ10 is vital forthe proper transferal of electrons within the
mitochondrial oxidative respiratory chain, whose mainfunction is ATP 3). Additionally, CoQ10 has demonstrated
activity in preventing lipid peroxidation as an antioxidant
scavenger and an indirect stabilizer of calcium channels
to decrease calcium overload 4)5). Clinically, CoQ10 has thefunction to improve the balance of cardiac output 6) andperipheral circulation 7). Ingestion of CoQ10 may stimulate
heart function 8), assist contraction and increase thevolume of circulating blood to the whole body 9). In Japan,
CoQ10 was approved as a metabolic cardiotonic drug for
medical treatment and has been prescribed for mild tomoderate symptoms of heart failure 10). Since CoQ10 was
approved as food due to the revision of Pharmaceutical
Law in 2001, the CoQ10 supplement has been expected tohave a beneficial effect on health such as fatigue
reduction 11) and improvement of physical activity 12). We
assumed the possibility that these effects of CoQ10
improve the symptoms that arise from hypotension. In
this study, we examined the effect of CoQ10 on bloodpressure, skin surface temperature, and subjective
symptoms in healthy volunteers with hypotension. As weknow, this is the ﬁrst report to evaluate the function of
CoQ10 on symptoms that arise from hypotension.

2. METHOD
2.1. Trial Design
A randomized, placebo-controlled, double-blind study was
conducted to evaluate efficacy and safety of CoQ10 inhealthy subjects with the aid of fund from CLIQUE(Osaka) at JACTA ( Japan Clinical Trial Association,
Tokyo). The study period was 12 weeks, from 1 Nov.
2015 to 24 Jan. 2016. This study was conducted inaccordance with the ethical principles of the declarationof Helsinki. The study protocol was approved by theinstitutional review board of Pharmaceutical Law

46 （414）

診療と新薬・第 53 巻

Table 1Term
Item

第 5 号（2016 年 5 月）

Schedule for the study
Screening

Informed consent
Selection and/or allocation
blood pressure/heart rateskin surface temperature
subjective symptoms
Ingestion of test foods
Log

Test period (12 w)

Pre Trial
Test

Week 4

Week 8

Week 12

●
●
●

●
●
●

●
●
●

●
●
●

●
●

←――――――――――――――――→←――――――――――――――――→● : Implementation↔ : Daily practice during the test period

Wisdoms (Tokyo). Written informed consent was
obtained from all subjects.
The allocation of the test product to the subjects was
carried out by the person in charge of allocation. The
allocation list was sealed and strictly controlled in a safe
deposit box of JACTA until the end of the study.
2.2. Subjects
Healthy female subjects who met all inclusion criteria anddid not meet any exclusion criteria were enrolled in thisstudy. All of the subjects in this study were public
volunteers via monitor bank of Stephens & Associates,
Inc.
2.2.1. Inclusion criteria
Healthy female subjects with systolic blood pressure
between 100 and 120 mmHg.
2.2.2. Exclusion criteria(1) Subjects who were undergoing treatment of bloodpressure;(2) Subjects who were taking drugs or supplements forblood pressure;(3) Subjects who were pregnant, lactating, or likely to
become pregnant during the study;(4) Subjects who were considered unsuitable toparticipate by the principle investigator.
2.3. Randomization
Recruited subjects were 50 women. Subjects who fulﬁlled
eligibility criteria were 32 women. The inclusion criteria
were judged by the principle investigator. The allocation
was pre-assigned on the basis of randomized numbers. All
subjects were sequentially allocated to Group A (n=16)
and B (n=16) based on a random number table. Subjects
in Group A ingested CoQ10 and subjects in Group B
ingested the placebo for 12 weeks.
2.4. Description of study products and blinding
The test food, CoQ10 and placebo were prepared by
CLIQUE. The amount of daily intake is 3 tablets (1 tablet
weighs 280 mg, therefore 3 tablets weigh 840 mg). The
compositions of CoQ10 were Coenzyme Q10, Vitamin C,
Vitamin B1, etc., while Placebo was mainly consisted ofcellulose. Both tablets were indistinguishable inappearance, color, smell and taste. All involved wereblinded.
2.5. Experimental procedures
2.5.1. Experimental protocol
The time schedule of the study is shown in Table 1.
Systolic and diastolic blood pressure (SBP/DBP), heartrate, and skin surface temperature were measured at thebaseline and every 4 weeks in both groups. Bloodpressure and heart rate was measured using an
automated sphygmomanometer UDEX-i (Elquest
Corporation, Chiba). Skin surface temperature wasmeasured using thermography FLIR-i5 (FKIR Systems,Inc.). In addition, to evaluate subjective symptoms, aquestionnaire survey was performed at the baseline andevery 4 weeks in each group.
Subjects were instructed as follows: to take theassigned foods as indicated; to maintain their usual
lifestyles and habits; to avoid excessive amounts of food,drink or alcohol; to maintain a daily record of lifestylefactors such as all the food items or number of steps they
took for the day during the test period; and to send thediary to the study coordinator every Friday by mobile
email.
2.5.2. Outcome(1) Primary outcome
A change in blood pressure, heart rate, skin surface
temperature, and subjective symptoms were evaluated as
primary outcomes. For evaluating these variables,
chronological change in each group and intergroupdiﬀerence was assessed every 4 weeks during the study.
A questionnaire included the following 10 items;
dizziness, vertigo, headache, fatigue, stiff shoulders,
palpitation/dyspnea, ringing in the ears and numbness.
Each item has 5-choices that scored from 0 to 4, withlower scores indicating a better result.
(2) Secondary outcome
Safety was evaluated using a diary kept by the subjects
which was recorded lifestyle habits and adverse events
during the study period.

診療と新薬・第 53 巻

第 5 号（2016 年 5 月）

47 （415）

Assessed for eligibility (n = 50)

Enrollment

Excluded (n = 18)¨ Not meeting inclusion criteria (n = 18)〔out of range in SBP (100‑120 mmHh)〕¨ Declined to participate (n = 0)
¨ Other reasons (n = 0)

Randomized (n = 32)
Group B

Group A

Allocation
Allocated to CoQ10 (n = 16)¨ Received allocated intervention (n = 16)¨ Did not receive allocated (n = 0)

Allocated to placebo (n = 16)¨ Received allocated intervention (n = 16)¨ Did not receive allocated intervention (n = 0)

Follow-Up
Lost to follow-up (n = 0)

Lost to follow-up (n = 0)
Discontinued intervention (n = 1)
〔declined to participate for physical condition〕

Discontinued intervention (n = 2)
〔declined to participate for physical condition〕

AnalysisAnalysed (n = 14)¨ Excluded from analysis (n = 0)

Analysed (n = 15)¨ Excluded from analysis (n = 0)

Fig. 1 Flow diagram of subject disposition

2.6. Data analysis
The full analysis set principle was adopted in the present
study and no sample size design was used. Data wereexpressed as mean ± SD. For blood pressure, heart rateand skin surface temperature, changes from the baselinein the same group were assessed using the paired t-test.
Student s t-test was used for intergroup comparisons ofchanges from the baseline. For subjective symptoms,
changes from baseline in the same group were assessedusing the Wilcoxon signed-rank test. The Mann-Whitney s
U test was used for intergroup comparisons of changes
from the baseline. Student s t-test was used to compare
subject backgrounds between groups. Statistical analyses
were performed using Statcel 3 (Yanai, 2011). The
results were considered signiﬁcant at the < 5 ％ level inthe two-sided test.

3. RESULTS
3.1. Subject s ﬂow and characteristics
50 subjects were recruited and 32 subjects who fulﬁlled
eligibility were enrolled in the study (Fig. 1). 32 subjects

Table 2 Subjects characteristics
Item

Unit

CoQ10

Placebo

Subjects *
Age

−
years

14
36.1 ± 9.6

1537.6 ± 8.3* Number of subjects
mean ± SD

were allocated to CoQ10 (n=16) and Placebo (n=16). 2
subjects in CoQ10 and 1 subject in Placebo withdrew
during study period. Thus, 14 and 15 subjects completed
the study. The mean age was 36.1 ± 9.6 and 37.6 ± 8.3 in
CoQ10 and Placebo, respectively (Table 2).
3.2. Eﬃcacy
Table 3 shows chronological change in blood pressure,heart rate, and skin surface temperature. SBP
signiﬁcantly increased within normal range at week 12 in
CoQ10, whereas it decreased significantly at week 4 inPlacebo. There was a signiﬁcant diﬀerence in change in
SBP at week 4 and week 12 between groups. For DBP,

48 （416）

診療と新薬・第 53 巻

Table 3

第 5 号（2016 年 5 月）

Chronological change in vital sign
ValuesItem

SBP (systolicblood pressure)

DBP (diastolicblood pressure)Heart rate

Skin surface
temperature

Unit

mmHg

mmHg

beats/
minutedegreeCelsiusTime point

P-value
CoQ10 (n ＝ 14)

Placebo (n ＝ 15)

Baseline
Week 4
ChangeWeek 8ChangeWeek 12
Change107.9 ± 5.9
108.6 ± 7.6
0.7 ± 4.7
108.9 ± 6.4
1.0 ± 2.8
109.8 ± 6.3 *1.9 ± 2.5

108.5 ± 5.9
103.1 ± 8.5 *− 5.3 ± 7.0
103.7 ± 9.4− 4.8 ± 10.8
103.0 ± 11.1 †Baseline
Week 4
ChangeWeek 8ChangeWeek 12
Change74.3 ± 5.6
71.6 ± 9.7− 2.7 ± 7.4
69.4 ± 8.5 **− 4.9 ± 5.1
70.6 ± 9.8 †− 3.6 ± 7.5

73.1 ± 5.970.1 ± 7.9− 2.9 ± 7.1
70.8 ± 7.8− 2.3 ± 8.5
68.5 ± 9.2 *− 4.6 ± 7.9

Baseline
Week 4
ChangeWeek 8ChangeWeek 12
Change79.8 ± 9.8
76.4 ± 8.2− 3.4 ± 9.976.5 ± 10.1
− 3.3 ± 11.8
76.9 ± 8.9− 2.9 ± 10.3

75.8 ± 8.7
70.0 ± 8.0 **− 5.8 ± 7.3
73.5 ± 7.3− 2.4 ± 10.3
75.0 ± 9.4− 0.8 ± 9.1

Baseline
Week 4
ChangeWeek 8ChangeWeek 12
Change30.9 ± 1.4
31.1 ± 1.0
0.2 ± 1.2
31.4 ± 0.8
0.5 ± 1.0
31.6 ± 0.8 *0.7 ± 1.1

31.2 ± 2.7
30.5 ± 2.5− 0.7 ± 2.8
29.3 ± 2.9 **− 1.9 ± 2.3
30.0 ± 2.5− 1.2 ± 3.1− 5.5 ± 10.3

0.011 #
0.061 ‡
0.016 #

0.925
0.338
0.742

0.455
0.832
0.573

0.268
＜ 0.00 ##0.003 ##

Values are expressed as the mean ± SD.
†

p ＜ 0.1, * p ＜ 0.05, ** p ＜ 0.01 against baseline.

‡p ＜ 0.1, # p ＜ 0.05, ## p ＜ 0.01 between group diﬀerences in change from baseline.

there was no significant difference in the amount ofchange between groups. Heart rate showed no signiﬁcantchange between groups. Skin surface temperaturesignificantly rose at week 12 in CoQ10, whereas itshowed a signiﬁcant falling at week 8 in Placebo. There
was a significant difference in the amount of change inskin surface temperature at week 8 and week 12 between
groups.
Table 4 shows chronological change in subjective
symptom scores. The dizziness score significantly
decreased at week 8 and 12 in CoQ10, but not in Placebo.
There was a signiﬁcant diﬀerence in change of dizzinessscores at week 12 between groups. As well as changes of
CoQ10 showed the decreasing trend in headache at week
12 and in stiff shoulders at week 8 as compared toPlacebo. Moreover decreasing trends were seen in scoresof fatigue and stiff shoulders in CoQ10 (at week 12 andweek 8, respectively). There were no signiﬁcant changes
in other items in both groups.
3.3. Safety
There were no problematic changes in all parameters or
any adverse events during the study.

4. DISCUSSION
We conducted a randomized, placebo-controlled, doubleblind study for examining the eﬃcacy of CoQ10 on vitals i g n a n d s u b j e c t i ve s y m p t o m s i n s u b j e c t s w i t hhypotension. All subjects were classified healthy. This
study revealed the following new findings; CoQ10
improved dizziness with rising SBP within normal range
and skin surface temperature also rose in subjects withhypotension.

診療と新薬・第 53 巻

第 5 号（2016 年 5 月）

49 （417）

Table 4 Chronological change in scores of questionnaire on symptoms
Scores
Item

1

2

3

4

5

6

7

8

Dizziness

VertigoHeadache

FatigueStiﬀ shoulders

Palpitation/
Dyspnea

Ringing in theears

Numbness

Time points

P-value
CoQ10 (n ＝ 14)

Placebo (n ＝ 15)

Baseline
Week 4
ChangeWeek 8ChangeWeek 12
Change0.6 ± 0.6
0.3 ± 0.5 †− 0.4 ± 0.6
0.2 ± 0.4 *− 0.4 ± 0.6
0.1 ± 0.4 *− 0.5 ± 0.7

0.9 ± 0.9
0.9 ± 0.9
0.0 ± 0.5
0.9 ± 0.9
0.1 ± 0.3
1.0 ± 0.9
0.1 ± 0.5

Baseline
Week 4
ChangeWeek 8ChangeWeek 12
Change0.4 ± 0.5
0.2 ± 0.4
− 0.1 ± 0.4
0.2 ± 0.4
− 0.1 ± 0.5
0.1 ± 0.4
− 0.2 ± 0.4

0.5 ± 0.6
0.3 ± 0.6
− 0.1 ± 0.5
0.3 ± 0.6
− 0.1 ± 0.5
0.4 ± 0.6
− 0.1 ± 0.6

Baseline
Week 4
ChangeWeek 8ChangeWeek 12
Change0.6 ± 0.8
0.6 ± 0.8
− 0.1 ± 0.6
0.5 ± 0.8
− 0.1 ± 0.5
0.4 ± 0.6
− 0.2 ± 0.6

0.6 ± 1.1
0.7 ± 1.0
0.1 ± 0.4
0.7 ± 0.9
0.1 ± 0.5
0.9 ± 0.8
0.3 ± 0.6

Baseline
Week 4
ChangeWeek 8ChangeWeek 12
Change0.9 ± 0.9
0.7 ± 0.8
− 0.1 ± 0.7
0.6 ± 0.7
− 0.2 ± 1.0
0.4 ± 0.6 †− 0.4 ± 0.8

0.9 ± 0.8
0.9 ± 0.8
0.0 ± 0.8
0.9 ± 0.7
0.0 ± 0.8
1.0 ± 0.8
0.1 ± 1.0

Baseline
Week 4
ChangeWeek 8ChangeWeek 12
Change1.8 ± 1.2
1.9 ± 1.6
0.1 ± 0.7
1.3 ± 1.4 †− 0.5 ± 0.9
1.4 ± 1.3
− 0.4 ± 0.9

1.5 ± 1.3
1.5 ± 1.1
− 0.1 ± 0.7
1.7 ± 1.2
0.1 ± 0.7
1.5 ± 1.2
0.0 ± 0.9

Baseline
Week 4
ChangeWeek 8ChangeWeek 12
Change0.3 ± 0.5
0.6 ± 0.8 †0.3 ± 0.5
0.5 ± 0.7
0.2 ± 0.6
0.4 ± 0.5
0.1 ± 0.6

0.7 ± 0.7
0.5 ± 0.7
− 0.1 ± 0.9
0.5 ± 0.5
− 0.2 ± 0.7
0.3 ± 0.5 †− 0.4 ± 0.7

Baseline
Week 4
ChangeWeek 8ChangeWeek 12
Change0.1 ± 0.4
0.2 ± 0.4
0.1 ± 0.5
0.1 ± 0.3
− 0.1 ± 0.5
0.1 ± 0.3
− 0.1 ± 0.5

0.3 ± 0.8
0.1 ± 0.3
− 0.3 ± 0.6
0.0 ± 0.0
− 0.3 ± 0.8
0.1 ± 0.4
− 0.2 ± 0.9

Baseline
Week 4
ChangeWeek 8ChangeWeek 12
Change0.2 ± 0.8
0.4 ± 0.8
0.1 ± 0.4
0.1 ± 0.3
− 0.1 ± 0.5
0.1 ± 0.5
− 0.1 ± 0.3

0.1 ± 0.3
0.2 ± 0.4
0.1 ± 0.4
0.1 ± 0.3
0.0 ± 0.4
0.3 ± 0.6
0.2 ± 0.7

Scores are expressed as the mean ± SD.
†
p ＜ 0.1, * p ＜ 0.05 against pre-ingestion.
‡p ＜ 0.1, # p ＜ 0.05 between group diﬀerences in change from baseline.

0.239
0.067 ‡
0.028 #

1.000
0.965
0.585

0.419
0.275
0.074 ‡

0.727
0.556
0.150

0.631
0.081 ‡
0.239

0.295
0.132
0.121

0.256
0.570
0.983

0.965
0.743
0.383

50 （418）

診療と新薬・第 53 巻

Main Findings
CoQ10 improved dizziness with rising SBP within normal
range in subjects with hypotension. Regarding CoQ10, a
lot of functions were reported. However, as we know
these ﬁndings have not been reported so far. Although it
is diﬃcult to determine the causing factor in this study,
possible causes include improving hemodynamics,
peripheral blood circulation, and oxidative stress.
(1) Rising SBP and DizzinessAlthough various factors cause dizziness, orthostatic
hypotension is common in adults and it is often
accompanied by dizziness 13). In the majority of cases,
orthostatic hypotension is caused by multiple factors
including, age-related physiologic change; a decline inbaroreflex sensitivity and parasympathetic function,
impaired α1-adrenergic vasoconstriction, decreased
cardiac and venous compliance, and so on 14). Based on
CoQ10 s wide-ranging cellular properties, the potential
treatment for numerous conditions was reported. A
number of randomized controlled trials showed evidence
in which CoQ10 improved several clinical parameters
related to congestive heart failure 15)-20). In this study, aslight but significant rise in SBP was found in subjects
that suggested CoQ10. As a background for rising SBP,
we assumed improvement of hemodynamics which wascaused by CoQ10. Then this hemodynamic condition
might positively aﬀect dizziness via the improvement oforthostatic hypotension. Therefore, improvement of
hemodynamics by CoQ10 might be one of possible reason
for improving dizziness.
(2) Rising skin surface temperature
Skin surface temperature significantly rose in subjects
ingesting CoQ10. Watts, et al. reported CoQ10
supplementation improved flow-mediated dilation of thebrachial artery and the mechanism was assumed to haveincreased the endothelial release of nitric oxide due toimprovement on vascular oxidative stress 21). CoQ10 has
demonstrated activity in preventing lipid peroxidation as
an antioxidant scavenger and an indirect stabilizer of thecalcium channels to decrease calcium overload 4)5) .
Considering the above, the improvement of peripheral
blood circulation via anti-oxidative stress might havecaused the rising skin surface temperature to rise.
Secondary Findings
Safety was evaluated as a secondary outcome in thisstudy. Even though CoQ10 is for medical use, no absolutecontraindications are known 10) and the rate of drug
related adverse events is only 1.46％ . Even in this study,
there was no adverse event or problematic changes inmeasured variables during study.
General Information
CoQ10 is found in the highest concentrated tissues withhigh energy turnover such as the heart, brain, liver andkidney 22). As mentioned above, CoQ10 is a ubiquitouscompound vital to a number of activities related to energy
metabolism, and decreases gradually by aging and the

第 5 号（2016 年 5 月）

amount of CoQ10 of the octogenarian are estimated halfof the quantity produced in the 20 s 2) . Therefore,
supplementation of CoQ10 for aging induced malfunctions
is rational. Based on Comprehensive Survey of Living
Conditions 2010 conducted by the Ministry of Health,
Labor and Welfare, prevalence rate of dizziness was 3.04
％ and sensitivity to cold in extremity was 3.94％ in total
women observed in this study and those percentages
increased with age 23). Consequently this means millions of
women are suffering from these symptoms in Japan.
Improvement of dizziness and skin surface temperature
by CoQ10 might contribute to the well-being of womenwith these symptoms.
Limitations
There were some limitations regarding this study
including the sample size, results of DBP and subjective
questionnaire results. Wilst the investigation achieved
significant improvements in the results of SBP, it isunsure as to the cause of no improvement in DBP. In
addition, even though important information was acquired
from questionnaire, some answers caused in significant
results. Therefore, a more objective approach with
suﬃcient sample size could improve invaluable to gaining
more solid results.

5. CONCLUSION
Daily ingestion of CoQ10 showed a favorable effect on
SBP, skin surface temperature, and dizziness in healthy
women with hypotension without any adverse events.
CoQ10 might contribute to the well-being of women withhypotension.
CONFLICT OF INTEREST
All parts of this study were funded by CLIQUE. All authors state that the
study was conducted in the absence of any other relationship that could beinterpreted as a conﬂict of interest.

REFERENCES
1) Molyneux SL, Young JM, Florkowski CM, et al. Coenzyme Q10: Is aclinical role and a case for measurement? Clin Biochem Rev. 2008; 29:
71-82.
2) Kalén A, Appelkvist EL, Dallner G. Age-related changes in the lipid
compositions of rat and human tissues. Lipids. 1989; 24: 579-84.
3) Bonakdar RA, Guarneri E. Coenzyme Q10. Am Fam Physician. 2005;
72: 1065-70.
4) Sugiyama S, Kitazawa M, Ozawa T, et al. Anti-oxidative effect ofcoenzyme Q10. Experentia. 1980; 36: 1002-3.
5) Nayler WG. The use of coenzyme Q10 to protect ischemic heart
muscle. In: Yamamura Y, Folkers K, Ito Y, eds. Biomedical andclinical aspects of coenzyme Q. Vol. 2. Amsterdam: Elsevier, 1980;
409-25.
6) Tanaka J, Tominaga R, Yoshitoshi M, et al. Coenzyme Q10: Theprophylactic effect on low cardiac output following cardiac valve
replacement. Ann Thorac Surg. 1982; 33: 145-51.
7) Gao L, Mao Q, Cao J, et al. Effect of coenzyme Q10 on vascularendothelial function in humans: a meta-analysis of randomized
controlled trials. Aterosclerosis 2012; 221: 311-6.
8) Tiano L, Belardinelli R, Carnevali P, et al. Effect of coenzyme Q10
administration on endotherial function and extracellular superoxide
dismutase in patients with ischaemic heart diseases: a double-blind,randomized controlled study. Eur heart J. 2007; 28: 2249-55.
9) Belardinelli R, Muçaj A, Lacalaprice F, et al. Coenzyme Q10 improves

診療と新薬・第 53 巻
contractility of dysfunctional myocardium in chronic heart failure.
Biofactors. 2005; 25: 137-45.
10) Neuquinon. package insert ver13. Eisai Co., Ltd. (http://www.eisai.
jp/medical/products/di/EPI/NEQ̲T-ST-C-G̲EPI.pdf)
11) Castro-Marrero J, Cordero MD, Segundo MJ, et al. Does oralcoenzyme Q10 plus NADH supplementation improve fatigue andbiochemical parameters in chronic fatigue syndrome? Antioxid Redox
Signal. 2015; 22: 679-85.
12) Cooke M, Iosia M, Buford T, et al. Effects of acute and 14-day
coenzyme Q10 supplementation on exercise performance in bothtrained and untrained individuals. J Int Soc Sports Nutr. 2008; 5: 8.
13) Miller ER 3rd, Appel LJ. High prevalence but uncertain clinicalsigniﬁcance of orthostatic hypotension without symptoms. Circulation.
2014; 130: 1772-4.
14) Arnold AC, Shibao C. Current concepts in orthostatic hypotension
management. Curr Hypertens Rep. 2013; 15: 304-12.
15) Morisco C, Trimarco B, Condorelli M. Effect of coenzyme Q10
therapy in patients with congestive heart failure: a long-term
multicenter randomized study. Clin Investig 1993; 71(suppl 8): S1346.
16) Hofman-Bang C, Rehnqvist N, Swedberg K, et al. Coenzyme Q10 as
an adjunctive in the treatment of chronic congestive heart failure. The
Q10 study group. J Card Fail. 1995; 1: 101-7.

第 5 号（2016 年 5 月）

51 （419）17) Baggio E, Gandini R, Plauncher AC, et al. Italian multicenter study on
the safety and eﬃcacy of coenzyme Q10 as adjunctive therapy in heart
failure. CoQ10 Drug Surveillance Investigators. Mol Aspects Med.
1994; (15 suppl): S287-94.
18) Soja AM, Mortensen SA. Treatment of congestive heart failure withcoenzyme Q10 illuminated by meta-analysis of clinical trials. Mol
Aspescts Med. 1997; 18 suppl: S159-68.
19) Khatta M, Alexander BS, Krichten CM, et al. The eﬀect of coenzyme
Q10 in patients with congestive heart failure. Ann Intern Med. 2000;
132: 636-40.
20) Watson PS, Scalia GM, Galbraith A, et al. Lack of eﬀect of coenzyme
Q on left ventricular function in patients with congestive heart failure.
J Am Coll Cardiol. 1999; 33: 1549-52.
21) Watts GF, Playford DA, Croft KD, et al. Coenzyme Q(10) improves
endothelial dysfunction of the brachial artery in Type II diabetes
mellitus. Diabetologia. 2002; 45: 420-6.
22) Tran MT, Mitchell TM, Kennedy DT, et al. Role of coenzyme Q10 inchronic heart failure, angina, and hypertension. Pharmacotherapy.
2001; 21: 797-806.
23) Comprehensive Survey of Living Conditions 2010. Ministry of Health,Labour and Welfare. (http://www.mhlw.go.jp/toukei/saikin/hw/
k-tyosa/k-tyosa10/toukei.html)