Antioxidants for Vascular and Muscle Health During Inactivity

Overseen By Joel D Trinity, PhD

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: Joel Trinity

Must not be taking: Anticoagulants, Antioxidants, Corticosteroids, others

Disqualifiers: Cardiac abnormalities, Diabetes, Hypertension, Obesity, others

Compensation: Varies

Number of Visits: 1

Duration: 5 days

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two antioxidant supplements, MITO-AO and PB-125, to determine if they help maintain muscle and blood vessel health during inactivity, such as bed rest, which is common in older adults. The goal is to understand how inactivity contributes to muscle weakening and poor blood flow, which can worsen with age. Researchers aim to find ways to protect muscle and vascular health, potentially reducing the risk of issues like muscle loss and hospital readmissions. Individuals aged 65 to 85, who are generally healthy and not dealing with serious heart or metabolic issues, might be suitable for this study. As an unphased trial, it offers participants the chance to contribute to important research that could lead to better health outcomes for older adults.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must stop taking dietary supplements 4 weeks before starting the study. If you are on anticoagulant therapy or mitochondrial targeted antioxidants, you cannot participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that antioxidants like MITO-AO, which target mitochondria, are under study for their effects on blood vessel health. These antioxidants may support heart health by focusing on mitochondria, the energy centers in cells. Although specific safety details for MITO-AO remain incomplete, antioxidants are generally considered safe for people.

PB-125, a mix of plant extracts, has some studies providing safety information. It is believed to support overall health by activating Nrf2, a protein that protects cells from stress. These studies have not shown major side effects, but detailed safety data specific to PB-125 trials is limited.

Both MITO-AO and PB-125 appear safe based on general use and the nature of antioxidants and plant-based supplements. However, more specific trial data is needed to confirm their safety in this context. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments, MITO-AO and PB-125, because they tackle muscle and vascular health in a novel way, especially during periods of inactivity like bed rest. Unlike traditional treatments that often focus on improving blood flow or exercise, these supplements aim to support the body's bioenergetics directly at the cellular level, even when blood flow and oxygen supply are restricted. MITO-AO and PB-125 are unique because they specifically target mitochondrial function and antioxidant pathways, potentially offering a new approach to maintaining muscle health in older adults. While standard care might involve physical therapy or medications that improve circulation, these treatments could provide benefits without the need for activity, which is particularly beneficial for those who are temporarily immobilized.

What evidence suggests that this trial's treatments could be effective for vascular and muscle health during inactivity?

This trial will compare the effects of the supplements MITO-AO and PB-125 on muscle and blood vessel health during inactivity. Research has shown that MITO-AO, which participants in this trial may receive, is an antioxidant that works in the mitochondria, potentially improving heart and blood vessel health by reducing oxidative stress. Meanwhile, PB-125, another treatment option in this trial, may boost muscle health by affecting the Nrf2 pathway, which helps the body manage stress and inflammation. Studies suggest that PB-125 can enhance mitochondrial function and help maintain muscle health. These treatments might help older adults recover better and reduce muscle and blood vessel issues during periods of inactivity. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for older adults aged 65-85 with good cognitive health (MOCA score ≥26) and normal kidney function. They must not be on a weight-loss diet, have a BMI over 35, or smoke. Those with recent cancer treatment, heavy smoking history, drug/alcohol abuse, or who exercise regularly are excluded.

Inclusion Criteria

Ability to sign informed consent

Montreal cognitive assessment (MOCA) exam score greater-than or equal to 26

Free-living, prior to admission

Exclusion Criteria

My kidney function is very low or I have kidney disease/failure.

Inability to abstain from smoking for duration of study

My thyroid and sugar levels are under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either MITO-AO, PB-125, or placebo during a 5-day bed rest to assess vascular and skeletal muscle function

5 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MITO-AO
• PB-125

Trial Overview

The study tests the effects of bed rest combined with antioxidants (MITO-AO and PB-125) versus placebo on vascular and muscle function in aging individuals. It includes passive leg movements and strength tests to understand how oxidative stress contributes to dysfunction during inactivity.

How Is the Trial Designed?

Group I: PB-125 Experimental Treatment 5 Interventions

Healthy older adult subjects ages 65-75 will take the supplement PB-125 during a 5 day bed rest and will be assessed for vascular function independent of metabolism with passive leg movement (PLM), skeletal muscle bioenergetics independent of vascular constraints (i.e. blood flow and O2 supply) with phosphorous magnetic resonance spectroscopy (P-MRS), and skeletal muscle bioenergetics under normal blood flow and O2 supply.

Group II: MITO-AO Experimental Treatment 5 Interventions

Healthy older adult subjects ages 65-75 will take the supplement MITO-AO during a 5 day bed rest and will be assessed for vascular function independent of metabolism with passive leg movement (PLM), skeletal muscle bioenergetics independent of vascular constraints (i.e. blood flow and O2 supply) with phosphorous magnetic resonance spectroscopy (31P-MRS), and skeletal muscle bioenergetics under normal blood flow and O2 supply.

Group III: Placebo Placebo Group 5 Interventions

Healthy older adult subjects ages 65-75 will take placebo during a 5 day bed rest and will be assessed for vascular function independent of metabolism with passive leg movement (PLM), skeletal muscle bioenergetics independent of vascular constraints (i.e. blood flow and O2 supply) with phosphorous magnetic resonance spectroscopy (P-MRS), and skeletal muscle bioenergetics under normal blood flow and O2 supply.

Who Is Running the Clinical Trial?

Joel Trinity

Lead Sponsor

Trials

1

Recruited

70+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study involving 20 healthy older adults, 6 weeks of oral supplementation with the mitochondrial-targeted antioxidant MitoQ significantly improved endothelial function, as indicated by a 42% increase in brachial artery flow-mediated dilation compared to placebo.

MitoQ was well tolerated and also reduced aortic stiffness and plasma oxidized LDL levels, suggesting its potential as a therapeutic strategy for age-related vascular dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults. Rossman, MJ., Santos-Parker, JR., Steward, CAC., et al.[2022]

Eccentric exercise leads to significant impairments in microvascular function, as evidenced by delayed and blunted blood flow responses in the exercised muscle, which were not improved by antioxidant or beetroot juice supplementation.

The study suggests that these impairments may be due to structural changes in the microvasculature rather than oxidative stress or nitric oxide availability, indicating a need for further investigation into the underlying mechanisms affecting blood flow regulation after eccentric exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impaired microvascular reactivity after eccentric muscle contractions is not restored by acute ingestion of antioxidants or dietary nitrate. Larsen, RG., Thomsen, JM., Hirata, RP., et al.[2021]

A study on muscle immobilization over 14 days showed that it leads to significant muscle atrophy and increased production of reactive oxygen species (ROS), which contribute to oxidative stress and muscle damage.

Using a mitochondrial-targeted antioxidant (SS-31) effectively reduced ROS production and prevented muscle atrophy, highlighting the role of mitochondria in muscle health during periods of inactivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondrial-targeted antioxidants protect skeletal muscle against immobilization-induced muscle atrophy. Min, K., Smuder, AJ., Kwon, OS., et al.[2021]

Chronic exposure to stretch-shortening contractions (SSCs) in young rats helped prevent oxidative stress and improved their ability to scavenge hydrogen peroxide, indicating a protective effect of exercise against oxidative damage.

In older rats, however, SSCs did not alleviate oxidative stress, and instead, increased levels of malondialdehyde and hydrogen peroxide were observed, suggesting that aging may enhance vulnerability to oxidative stress despite some improvements in antioxidant capacity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of age and glutathione levels on oxidative stress in rats after chronic exposure to stretch-shortening contractions. Hollander, MS., Baker, BA., Ensey, J., et al.[2021]

Acute intake of the mitochondrial-targeted antioxidant MitoQ significantly improved vascular endothelial function and increased superoxide dismutase levels in patients with peripheral artery disease (PAD), based on a study involving 11 participants.

MitoQ also enhanced walking capacity and delayed the onset of claudication, suggesting it may effectively restore mitochondrial function and improve overall leg performance in PAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute mitochondrial antioxidant intake improves endothelial function, antioxidant enzyme activity, and exercise tolerance in patients with peripheral artery disease. Park, SY., Pekas, EJ., Headid, RJ., et al.[2021]

In a study involving 12 healthy volunteers (6 young and 6 older), the administration of an antioxidant cocktail significantly improved muscle blood flow and oxidative capacity during exercise in older adults, suggesting that oxidative stress contributes to age-related declines in muscle function.

The antioxidant treatment did not affect muscle perfusion or recovery in younger individuals, indicating that the benefits of antioxidants on muscle function may be more pronounced in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antioxidants and aging: NMR-based evidence of improved skeletal muscle perfusion and energetics. Wray, DW., Nishiyama, SK., Monnet, A., et al.[2021]

Antioxidants, specifically vitamin C and tempol, significantly increased the muscle microvascular oxygen partial pressure (Pmv(O(2))) in aged rats, improving oxygen delivery during muscle contractions.

While antioxidants elevated Pmv(O(2)), they also reduced muscle blood flow and oxygen consumption during contractions, leading to decreased force production, suggesting a complex interaction between oxidative stress and muscle performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of antioxidants on contracting spinotrapezius muscle microvascular oxygenation and blood flow in aged rats. Herspring, KF., Ferreira, LF., Copp, SW., et al.[2013]

An antioxidant cocktail consisting of polyphenols, omega-3, vitamin E, and selenium effectively prevented muscle deterioration and oxidative stress during bedrest in a study involving 20 healthy male subjects.

The treatment not only normalized key metabolic processes and protein levels associated with muscle health but also enhanced the antioxidant defense response, indicating its potential as a nutritional intervention for counteracting disuse-induced muscle atrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrosative Redox Homeostasis and Antioxidant Response Defense in Disused Vastus lateralis Muscle in Long-Term Bedrest (Toulouse Cocktail Study). Blottner, D., Capitanio, D., Trautmann, G., et al.[2021]

This study utilized C2C12 myoblast and myotube cell cultures to investigate age-related changes in reactive oxygen and nitrogen species (RONS) signaling, finding that aged cells exhibited significantly increased levels of reactive oxygen species and lipid peroxidation, indicating oxidative stress in older muscle cells.

Among nine dietary polyphenols tested, only kaempferol and resveratrol effectively reduced multiple markers of RONS signaling in aged muscle cells, suggesting their potential as therapeutic agents to promote healthy skeletal muscle function in the context of aging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologically-obtainable polyphenol exposures modulate reactive oxygen and nitrogen species signaling in the C2C12 model of skeletal muscle ageing. Hayes, N., Fogarty, M., Sadofsky, L., et al.[2023]

In a study of six older men with mild hypertension, a 6-week aerobic exercise program significantly reduced both systolic and diastolic blood pressure and improved vascular function, as measured by flow-mediated vasodilation (FMD).

However, acute antioxidant supplementation (vitamins C and E, and alpha-lipoic acid) after exercise negated these benefits, returning blood pressure to hypertensive levels and blunting improvements in vascular function, indicating that combining exercise with antioxidant supplements may be counterproductive for cardiovascular health in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral antioxidants and cardiovascular health in the exercise-trained and untrained elderly: a radically different outcome. Wray, DW., Uberoi, A., Lawrenson, L., et al.[2022]

Citations

1.

link.springer.com

link.springer.com/article/10.1007/s00421-009-1260-x

Impact of inactivity and exercise on the vasculature in ...

We examine evidence that inactivity and exercise have direct effects on both vasculature function and structure in humans.

2.

dom-pubs.onlinelibrary.wiley.com

dom-pubs.onlinelibrary.wiley.com/doi/pdf/10.1111%2Fdom.14669

targeted antioxidants on glycaemic control, cardiovascular ...

Aim: To investigate the effects of mitochondrial-targeted antioxidants (mitoAOXs) on glycaemic control, cardiovascular health, and oxidative ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7749226/

Sedentary Behaviors, Physical Inactivity, and ...

In the past few decades, the pharmacological management of cardiovascular diseases (CVD) has improved dramatically.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11162984/

Effect of Exercise Prior to Sedentary Behavior on Vascular ...

The findings of this research suggest that prior exercise may prevent the impairment of vascular health parameters caused by sedentary behavior.

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S2667137922000091

Pharmacological significance of MitoQ in ameliorating ...

Mitoquinone attenuates vascular calcification by suppressing oxidative stress and reducing apoptosis of vascular smooth muscle cells via the Keap1/NRF2 pathway.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8163660/

Mitochondrial contributions to vascular endothelial dysfunction ...

This review outlines the role of mitochondria in vascular function and discusses the ramifications of mitochondrial dysfunction on vascular health.

7.

dom-pubs.onlinelibrary.wiley.com

dom-pubs.onlinelibrary.wiley.com/doi/pdf/10.1111/dom.14669

targeted antioxidants on glycaemic control, cardiovascular ...

Aim: To investigate the effects of mitochondrial-targeted antioxidants (mitoAOXs) on glycaemic control, cardiovascular health, and oxidative ...

8.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/33249505/

Cardiovascular health and mitochondrial function: testing ...

This study evaluSated whether mitochondrial oxidative capacity, as assessed by phosphorus magnetic resonance spectroscopy, was associated with ...

9.

translational-medicine.biomedcentral.com

translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04369-z

Mitochondrial dysfunction: roles in skeletal muscle atrophy

Mitochondria play important roles in maintaining cellular homeostasis and skeletal muscle health, and damage to mitochondria can lead to a ...

10.

sciencedirect.com

sciencedirect.com/science/article/pii/S016748892400051X

The mitochondrial link: Phthalate exposure and ...

This review will examine the potential link among phthalates and their effects on the mitochondria, permissive of CVD development.