Journal Article | Others

January 19, 2020



Sophia Z. Liu, Amir S. Ali, Matthew D. Campbell, Kevin Kilroy, Eric G. Shankland1, Baback Roshanravan, David J. Marcinek & Kevin E. Conley

Introduction

Age is characterized by a progressive loss of mobility, with muscle wasting (sarcopenia) and reduced endurance as key factors in this exercise intolerance.

Exercise training has been the gold standard for slowing or reversing sarcopenia.

Recent evidence indicates that dietary supplements may lead to improvements in both strength and endurance, which is a combination of adaptations that have not been possible with a traditional training program alone.5,6

Astaxanthin is a natural product with both antioxidant and anti-inflammatory properties 9–12 that has been found to increase strength and endurance.

Astaxanthin accumulates in tissues of animals in the food chain, such as salmon, that feeds on the marine algae, Haematococcus pluvialis 9 and is estimated to have been consumed at levels of 6 mg per day in populations with a salmon-based diet.15


Clinical Significance

Evidence for the beneficial impact of AX on old muscle comes from a pilot study in mice found that AX accumulated in muscle with feeding and was associated with elevated muscle quality after exercise training on a treadmill.

Building on this pilot study there are a few studies that shows beneficial impact of AX in elderly humans.

Objectives

To test a dietary formulation of astaxanthin, vitamin E, and zinc in combination with exercise training as an approach to elevate mobility, endurance, and strength in the elderly.6,8

To test the hypothesis that this astaxanthin-based formulation in combination with a functionally based exercise training program would activate improvements in both endurance and muscle strength, thereby providing a single approach to reverse loss of mobility and muscle properties in the elderly.

 

Methods

Pilot study

Twenty-nine-month-old male mice were treated with either 300 mg/(kg×day) astaxanthin (n = 10, Astareal, Inc. Moses Lake, WA, USA) or standard chow alone (n = 9).

The AX dose was determined for mice by scaling22 from the level found to be effective in rat studies.23

Exercise training occurred 3×/week on a 20° inclined treadmill at 10 m/min for 5 min at the start reaching 15 min in the final 4 weeks of training.

In vivo muscle force of the gastrocnemius was measured as the maximum twitch and tetanic force during electric stimulations (200 Hz for 300 ms) at baseline and at 8 weeks in anaesthetized mice as described.24

The quadriceps muscle was frozen at the end of training to determine the level of astaxanthin.


Human study

Randomized, double-blind, placebo-controlled study was conducted at the University of Washington Medical Center and the Fred Hutchison Cancer Research Center.

Adults age 65–85 years old were recruited through public lectures, mailers, posted advertisements, and referrals from prior studies.

A total of 365 subjects were phone screened; 58 subjects enrolled in the study and were randomly assigned to groups.

Each subject had a physical examination, resting and exercise electrocardiogram, and blood testing to ensure that they were healthy and free from orthopedic and neuromuscular problems.


Treatment and dosing

The dietary formulation consisted of astaxanthin (12 mg), tocotrienol (10 mg), and zinc (6 mg; Astamed, Bellevue, WA) and was ingested as two capsules per day.

Additional components included in the formulation were Tocotrienols (vitamin E) and zinc.


Randomization and blinding

The subjects were assigned to the two treatment groups by an individual not associated with the study.

 A random number generator provided the assignments.

Copies of the codes were held in separate locations that were not accessible to the investigators.

The assignment of the individual subjects to the treatment groups was not known to the participants or to the investigators until the study was completed.


Exercise training

The 12-week training program met 3× per week with a 10 min warm-up before and 5–10 min cool down period at the end of each session.

Treadmill training involved walking at ~1.3 m/sec with periods at a high treadmill incline of 9–12% grade (interval training) separated by periods of low incline walking at 5–7% grade (recovery).

Magnetic resonance imaging

Tibialis anterior (TA) muscle cross-sectional area (CSA) was determined from magnetic resonance images.

Five slices of each right limb were analyzed with NIH Image software.

Single muscle test: isometric ankle dorsiflexion

The TA muscle strength and contractile properties were determined on the right leg using a custom-built isometric exercise apparatus.

The subject performed a maximal voluntary contraction (MVC) using ankle dorsiflexion for ~5 sec by pulling on a strap that secured the foot to a force transducer platform.


Statistical analysis

An unpaired Student’s t-test was used to evaluate treatment vs. placebo in the pilot mouse study.

For the human study, a paired, 2-tailed t-test (pre-training vs. post-training change) was used with significance assigned at α = 0.05 (P < 0.05).


Results

Pilot study

The level of astaxanthin in muscle after the 8-week exercise program was significantly elevated in the AX (236.7 ± 123.4 ng/g, n = 4) vs. the placebo (9.2 ± 9.2 ng/g, n = 6) treatment group.

Specific force (maximum twitch force/muscle cross-sectional area) was significantly greater in AX vs. placebo-treated mice after training (P < 0.004, Table 2).


Human study

Increased interval stage exercise time demonstrates that the subjects in both treatment groups could exercise longer (greater time) and at a higher intensity (higher % grade) after training.

Walking distance in the 6 min walk also significantly improved by ~8% in both groups with training (Figure 2B, Table S3).

A significant change in human muscle strength, as measured by MVC (Δ14.4 ± Δ6.2% mean ± SEM, P < 0.02), is shown for the AX treatment group alone.

The TA muscle CSA (Δ2.7 ± Δ1.0%) also only increased in the AX treatment group (both image analysers found CSA differences at P < 0.01).

The ratio of these measures provides the muscle specific force (MVC/CSA), which trended to a higher value (Δ11.6 ± Δ6.1%, P = 0.053) in the AX treatment group alone.

No significant change in muscle properties was found in the placebo treatment group (MVC, Δ2.9% ± Δ5.6%; CSA, Δ0.6% ± Δ1.2%; MVC/CSA, Δ2.4 ± Δ5.7%; P > 0.6 for all).


Conclusion

Functionally based exercise training combined with a formulation of natural anti-inflammatory and antioxidant compounds improved muscle strength and size in elderly subjects more than exercise training alone without sacrificing the improvements in walking distance and endurance that typically accompany endurance training.

These results suggest that the potential for strength and endurance improvements in elderly muscle is realized when natural products that promote adaptation are combined with exercise training incorporating both resistance and aerobic components.

The end result is an approach involving functional exercise and a dietary formulation that can improve endurance, strength, and function to remedy the deficits associated with sarcopenia that limit mobility in the elderly.

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