Shokri-Mashhadi, N.
et al., 2021 [118][208]
|
Randomized,
double-blind,
placebo-controlled,
prospective study
|
44 patients with
type 2 diabetes
|
0, 8 mg/day
|
8 weeks
|
Decrease plasma levels of MDA and IL-6 (p < 0.05) and decrease the expression level of miR-146a, associated with inflammatory markers (fold change: −1/388) (p < 0.05).
|
Brown, R.D. et al., 2021 [100][193]
|
Kawamura A. et al., 2021 [108][201]
|
Randomized,
double-blind,
placebo-controlled, crossover study
|
Randomized controlled
Open-label, prospective study
12 recreationally trained male cyclists 27.5 ± 5.7 years,
VO2peak: 56.5 ± 5.5 mL⋅kg |
26 healthy male −1⋅min−1,
subjectsWmax: 346.8 ± 38.4 W
|
0, 12 mg/day
|
N/A
(1 mg AX/100 g salmon) *
7 days
|
|
10 weeks
Completion time of the 40-km cycling time trial improved by 1.2 ± 1.7% with AX supplementation, from 70.76 ± 3.93 min in the placebo condition to 69.90 ± 3.78 min in the AX condition (mean improvement time = 51 ± 71 s, p = 0.029, g = 0.21).
|
Higher resting oxygen consumption after training in the intervention group only (p < 0.05). Serum carbonylated protein level as an oxidative stress marker tended to be lower immediately after exercise than before exercise in the intervention group only (p = 0.056). (See Table 2. for other outcomes.) Whole body fat oxidation rate was also greater in the AX group between 39–40 km (+0.09 ± 0.13 g⋅min−1, p = 0.044, g = 0.52) and respiratory exchange ratio was lower (−0.03 ± 0.04, p = 0.024, g = 0.60).
|
|
Talbott I. et al., 2018 [101][194]
|
|
Kato T. et al.,
2020 [119][209]
| Randomized,
double-blind,
placebo-controlled, prospective study
|
Open-label,
prospective study
28 recreational runners
(42 ± 8 years)
|
|
16 patients with
systolic heart failure
0, 12 mg/day
|
12 mg/day *
8 weeks
|
3 months
Reduced average heart rate at submaximal endurance intensities (aerobic threshold, AeT and anaerobic threshold, AT), but not at higher “peak” intensities.
|
| Increased left ventricular ejection fraction (LVEF) from 34.1 ± 8.6% to 38.0 ± 10.0% |
| ( | p | = 0.031) and 6-min walk distance increased from 393.4 ± 95.9 m to 432.8 ± 93.3 m
( p = 0.023). Significant relationships were observed between percent changes in dROM level and those in LVEF.
|
Klinkenberg L.J. et al., 2013 [102][195]
|
Randomized,
double-blind,
|
Chan K. et al.,
2019 [120][210]
| placebo-controlled
prospective study
|
Randomized controlled
Open-label, prospective study
32 well-trained male cyclists
25 ± 5 years,
V˙O2 |
54 patients with
type 2 diabetes peak = 60 ± 5 mL·kg−1·min−1,
Wmax = 5.4 ± 0.5 W·kg−1
|
0, 20 mg/day *
|
0, 6, 12 mg/day
4 weeks
|
8 weeks
N.S; effect on exercise-induced cardiac troponin T release (p = 0.24), changes in antioxidant capacity markers (trolox equivalent antioxidant capacity, uric acid, and malondialdehyde). Markers of inflammation (high-sensitivity C-reactive protein) and exercise-induced skeletal muscle damage (creatine kinase).
|
| Increased plasma AX levels and decreased fasting plasma glucose and HbA1c levels. |
| In 12 mg AX group, reduced in plasma triglyceride, total chol and LDL levels. |
| Lowered changes in plasma IL-6 and TNF-α levels and plasma vWF level and higher changes in AT-III level. In 12 mg AX group, decreased changes in plasma FVII and PAI-1 levels.
|
Res T. et al.,
2013 [103][196]
|
Takami M. et al.,
2019 [121][211]
|
Randomized,
double-blind,
placebo-controlled,
prospective study
|
|
Open-label,
prospective study
32 trained male cyclists or triathletes 25 ± 1 years,
V˙O2peak = 60 ± 1 mL·kg−1·min−1,
Wmax = 395 ± 7 W
|
20 healthy young male subjects
0, 20 mg/day
|
c.a, 4.5 mg/day * from salmon
4 weeks
|
N.S; total plasma antioxidant capacity (p = 0.90) or attenuated malondialdehyde levels
(p = 0.63). Whole-body fat oxidation rates during submaximal exercise (from 0.71 +/− 0.04 to 0.68 ± 0.03 g⋅min−1 and from 0.66 ± 0.04 to 0.61 ± 0.05 g⋅min−1 in the placebo and AX groups, respectively; p = 0.73), time trial performance (from 236 ± 9 to 239 ± 7 and from 238 ± 6 to 244 ± 6 W in the placebo and AX groups, respectively; p = 0.63).
|
| 4 weeks |
|
| Higher carbohydrate oxidation during rest in the post-training than that in the pre-training only in the antioxidant group. More decreased levels of serum insulin and HOMA-IR after training were observed in the antioxidant group than in the control group. |
(See Table 2. for other outcomes.)
|
Djordjevic B. et al., 2011 [104][197]
|
|
Mashhadi N.S. et al., 2018 [122][163]
| Randomized,
Double-blind,
|
Randomized, placebo-controlled,
prospective study
|
double-blind,
placebo-controlled, prospective study
32 male elite soccer players
|
|
44 participants with type 2 diabetes
0, 4 mg/day
|
0, 8 mg/day
90 days
|
8 weeks
Changes in elevated O2-¯ concentrations after soccer exercise were statistically significant only in the placebo group (exercise × supplementation effect, p < 0.05); TAS values decreased significantly only in the placebo group after exercise (p < 0.01).
After intervention, total SH group content increased (21% and 9%, respectively), and the effect of AX was marginally significant (p = 0.08).
Basal SOD activity was significantly reduced in both the placebo and AX groups at the end of the study (main training effect, p < 0.01). Post-exercise CK and AST levels were significantly lower in the AX group than in the placebo group (p < 0.05)
|
| Increased the serum adiponectin concentration, reduced visceral body fat mass ( | p | < 0.01), serum triglyceride and VLDL chol concentrations, systolic blood pressure, fructosamine concentration ( | p | < 0.05) and marginally reduced the plasma glucose concentration (p = 0.057).
|
Earnest C.P. et al.,
2011 [105][198]
|
Randomized,
double-blind,
placebo-controlled, |
Canas J. A. et al.,
2017 [121][211]
|
prospective study
|
Randomized,
double-blind,
placebo-controlled,
prospective study
14 amateur endurance-trained subjects 18–39 years,
V˙O2peak = 52.84 ± 3.5 mL·kg−1·min−1,
W |
20 children with simple obesity
(BMI > 90%) max = 330 ± 26 W
|
0, 4 mg/day
|
500 μg/day * (MCS)
28 days
|
6 months
Improved performance in the 20-km cycling time trial in the AX group (n = 7, −121 s; 95% CI, −185, −53), but not in the placebo group (n = 7, −19 s; 95% CI, −84, 45).
AX group significantly increased power output (20 W; 95% CI, 1, 38), whereas the placebo group did not (1.6 W; 95% CI, −17, 20). N.S; carbohydrate, fat oxidation and blood indices indicative of fuel mobilization.
|
| Mixed-carotenoid supplementation (MCS) increased β-carotene, total adiponectin, and high-molecular-weight adiponectin in plasma compared with placebo; MCS decreased BMI z-score, waist-to-height ratio, and subcutaneous adipose tissue compared with placebo. AX was used as a part of MCS. |
|
Bloomer, R.J. et al., 2005 [106][199]
|
Takemoto M. et al.,
2015 [123][212 |
Randomized,
placebo-controlled,
prospective study
|
20 resistance trained male subjects (25.1 ± 1.6 years)
|
0, 4 mg/day *
|
3 months
|
N.S; Muscle soreness, creatine kinase (CK), and muscle performance were measured before and through 96-h post-eccentric exercise
|
]
|
Case report
|
1 Werner syndrome patient
|
12 mg/day *
|
6 months
|
Improved blood transaminase concentrations before AX intervention and 3 and 6 months after initiation were: AST 40 IU/L, 41 IU/L, and 20 IU/L; ALT 69 IU/L, 62 IU/L, and 34 IU/L; GGT 38 IU/L, 41 IU/L, and 35 IU/L; and cholinesterase 360 IU/L, 366 IU/L, and 331 IU/L, respectively.
Liver-to-spleen Hounsfield units on CT were 0.41 before AX initiation, 0.71 at 3 months, and 0.94 at 6 months. No significant changes after AX intervention in hyaluronic acid, a marker of liver fibrosis; high-sensitivity C-reactive protein, a marker of inflammation; and MDA-modified LDL.
|
Sawaki K. et al.,
2002 [107][200]
|
Ni Y. et al.,
2015[95][108]
|
Randomized
double-blind
placebo-controlled,
prospective study
|
16 healthy adult |
Randomized,
single-blind,
placebo-controlled,
prospective study
male subjects
|
0, 6 mg/day
|
|
12 NASH patients4 weeks
|
|
12 mg/day
|
24 weeksIn the AX group, the serum lactate concentration after 2 min of activity (1200 m run) was significantly lower than that in the control group.
|
|
| Improved steatosis ( | p | < 0.05), marginally improved lobular inflammation ( | p = 0.15) and NAFLD activity score (p = 0.08)
|
<Subjects: healthy subjects>
|
Choi H.D. et al.,
2011 [38][40]
|
Randomized,
double-blind,
placebo-controlled,
prospective study
|
27 overweight subjects
(BMI >25.0 kg/m2)
|
0, 20 mg/day
|
12 weeks
|
Decreased LDL chol and ApoB.
(See Table 1. For other outcomes.)
|
Kawamura A. et al., 2021 [108][201]
|
Yoshida H. et al.,
2010 [124][161]
|
Randomized
controlled
|
Randomized,
ouble-blind, open-label,
prospective study
|
placebo-controlled,
26 healthy male subjects
|
N/A
(1 mg AX/100 g salmon) *
|
prospective study
10 weeks
|
|
61 non-obese subjects with fasting serum triglyceride of 120–200 mg/dL and without diabetes and hypertension
|
0, 6, 12, 18 mg/day
|
12 weeks
The skeletal muscle mass was higher after training than before training in both control and intervention groups (p < 0.05). Increased maximal voluntary contraction after training in the intervention group (p < 0.05), but not significantly increased in the control group. (See Table 3 for other outcomes.)
|
| Multiple comparison: triglycerides were significantly decreased by 12 and 18 mg/day and HDL-cholesterol was significantly increased by 6 and 12 mg. Serum adiponectin was increased by AX (12 and 18 mg/day), and changes in adiponectin were positively correlated with changes in HDL-chol. |
|
Fleischmann C. et al., 2019 [109][202]
|
Randomized,
double-blind,
placebo-controlled,
prospective study
|
22 healthy subjects
|
Satoh A. et al.,
2009 [125][213]
|
Open-label,
prospective study
|
20 subjects at risk for developing metabolic syndrome
(from 127 healthy subjects)
|
0, 12 mg/day
|
4, (8, 20) mg/day
30 days
|
4 weeks.
Decreased raise in blood lactate caused by the VO2 Max test; AX group (9.4 ± 3.1 and 13.0 ± 3.1 mmole⋅L−1 in the AX and placebo groups, respectively p < 0.02).
Change in oxygen uptake during recovery (−2.02 ± 0.64 and 0.83 ± 0.79% of VO2 Max in the AX and placebo group, respectively, p = 0.001). N.S; anaerobic threshold or VO2 Max. physiological or biochemical differences in the heat tolerance test (HTT) (2 h walk at 40 °C, 40% relative humidity.
|
| When subjects who met the diagnostic criteria for metabolic syndrome in Japan (SBP ≥ 130 mmHg, DBP ≥ 85 mmHg, TG ≥ 150 mg/dL, FG ≥ 100 mg/dL) at the start of the study were selected from 4 mg group, significant decreased in SBP( | p | < 0.01). On the other hand, there was no significant decrease in DBP. Reduced TG after treatment (218 mg/dL) than the baseline value (292 mg/dL), marginally reduced fasting glucose after the intervention ( | p | < 0.1).
|
Takami M. et al.,
2019 [110] |
Uchiyama A. et al., 2008 [126][162] [203]
|
Open-label,
prospective study
|
Open-label, prospective study
20 healthy young male
subjects
|
c.a, 4.5 mg/day * from salmon
|
|
17 subjects at risk for developing metabolic syndrome4 weeks
|
|
8 mg twice day
|
3 months
Increased maximum workload by training in both groups (p = 0.009), and increased oxygen consumption during exercise in the antioxidant group only (p = 0.014).
There were positive correlations between maximum workload and fat (r = 0.575, p = 0.042) and carbohydrate oxidations (r = 0.520, p = 0.059) in the antioxidant group.
(See Table 3 for other outcomes.)
|
| Significant decreases plasma HbAlc ( | p | = 0.0433) and TNF-α levels ( | p | = 0.0022) and increase adiponectin concentration (p = 0.0053). N.S: body weight, BMI and waist circumference.
|
Imai A. et al.,
2018 [111][204]
|
Randomized,
double-blind,
|
Fukamauchi M. et al., 2007 [127][214]
| placebo-controlled,
crossover study
|
Randomized,
double-blind,
placebo-controlled,
prospective study
42 healthy subjects
|
32 healthy subjects
0, 6 mg/day *
|
4 weeks
|
0, 6 mg/day
Elevated PCOOH levels during mental and physical tasks were attenuated by AX supplementation. Improved recovery from mental fatigue compared with the placebo. No differences were found between AX and the placebo in other secondary outcomes, such as subjective feelings, work efficiency, and autonomic activity.
|
| 6 weeks |
|
| Synergistic effects of AX intake (12 mg/day, 6 weeks) and aerobic exercise (walking) were studied. AX contributed to reduction of body fat and suppressed the increase in blood lactate level after exercise. |
|
Hongo N. et al.,
2017 [112][205]
|
Randomized,
|
Kim Y.K. et al.,
2004 [48][50]
| double-blind
placebo-controlled,
prospective study
|
Open-label,
prospective study
39 healthy subjects
|
|
15 healthy postmenopausal female subjects0, 12 mg/day *
|
|
0, 2, 8 mg/day
12 weeks
|
8 weeks
Intent-to-treat (ITT) analysis; fatigue after physical and mental stress was significantly lower in the AX group than in the placebo at week 8; the change in POMS Friendliness was significantly higher in the AX group than in the control group at week 8; the rate of change in BAP values at week 12 was not significantly different between the AX and control groups. The rate of change in BAP values at week 12 was not significantly different between the AX group and the control.
|
| Increase HDL-chol levels in 2 mg and 8 mg group increased significantly after 8 weeks from 50.6 ± 5.8 to 60.4 ± 7.1 mg/dL, 44.4 ± 10.7 to 49.4 ± 2.7 mg/dL respectively ( | p | < 0.05). In the 2 mg group, triglyceride decreased significantly from 171.6 ± 67.4 mg/dL to 145.8 ± 5.1 mg/dL ( | p | < 0.05).
(See Table 1. For other outcomes.)
|
Malmstena C.L.L. et al., 2008 [113][206]
|
Randomized,
double-blind,
placebo-controlled,
prospective study
|
40 young healthy subjects
(17–19 years)
|
0, 4 mg/day
|
3 months
|
Increased average number of knee bending (squats) increased by 27.05 (from 49.32 to 76.37, AX group) vs. 9.0 (from 46.06 to 55.06, placebo subjects), p = 0.047.
|
Tajima T. et al.,
2004 [114][207]
|
Randomized,
double-blind,
placebo-controlled,
crossover study
|
18 healthy subjects
(35.7 ± 4 years)
|
0, 5 mg/day
|
2 weeks
|
Increased in CVRR and HF/TF (Heart rate variability) were significant during exercise at 70% maximum heart rate (HRmax) intensity (p < 0.05). Also, after the AX supplementation, decreased minute ventilation (VE) during exercise at 70% HRmax (p < 0.05). Decreased LDL cholesterol (chol) (p < 0.05) and respiratory quotient after exercise.
|
<Subjects: elderly subjects>
|
Liu S.Z. et al.,
2021 [115][189]
|
Randomized,
double-blind,
placebo-controlled,
prospective study
|
42 elderly subjects
(65–82 years)
|
0, 12 mg/day *
|
12 weeks
|
In endurance training (ET), specific muscular endurance was improved only in the AX group (Pre 353 ± 26 vs. Post 472 ± 41) and submaximal graded exercise test duration was improved in both groups (placebo 40.8 ± 9.1% vs. AX 41.1 ± 6.3%).
The increase in fat oxidation at low intensity after ET was greater in AX (placebo 0. 23 ± 0.15 g vs. AX 0.76 ± 0.18 g), and was associated with reduced carbohydrate oxidation and improved exercise efficiency in men, but not in women.
|
Liu S.Z. et al.,
2018 [116][190]
|
Randomized
double-blind,
placebo-controlled,
prospective study
|
42 elderly subjects
(65–82 years)
|
0, 12 mg/day *
|
12 weeks
|
Administration of AX increased maximal voluntary force (MVC) by 14.4% (± 6.2%, p < 0.02), tibialis anterior muscle size (cross-sectional area, CSA) by 2.7% (± 1.0%, p < 0.01), and specific impulse increased by 11.6% (MVC/CSA, ± 6.0%, p = 0.05), respectively, whereas placebo treatment did not alter these characteristics (MVC, 2.9% ± 5.6%; CSA, 0.6% ± 1.2%; MVC/CSA, 2.4 ± 5.7%; all p > 0.6).
|
Fujino H. et al.,
2016 [117][191]
|
Randomized,
double-blind,
placebo-controlled,
prospective study
|
29 community-dwelling healthy elderly subjects
(80.9 ± 1.5 years.)
|
0, 12 mg/twice a day *
|
3 months
|
Decrease in d-ROM values with AX group (p < 0.01), but not the placebo group; the AX group had a therapeutic effect on 6-min walking distance compared with the placebo group (p < 0.05).
AX group had an increase in distance and number of steps in the 6-min walking test compared with the placebo group. Furthermore, the rate of increase in blood lactate levels after walking was lower in the AX group than in the placebo group (p < 0.01).
|