Comparing the Effects of Aerobic & Resistance Exercises and Vitamins D & E on Oxidative Stress & Inflammatory Markers Among Patients with Depression

Summary

Depression has been ranked as the fourth leading contributor to disability globally. As per data provided by the World Health Organization (WHO), depression affects approximately 3.8% of the global population, constituting approximately 280 million individuals worldwide, with an annual suicide-related mortality of 700,000 people GHDx 2023). Women are 50% more affected with depression as compared to men. Approximately 27.4% have experienced symptoms associated with anxiety and depression in Pakistan. The increasing prevalence and yearly occurrence influenced by the COVID-19 have compelled us to reevaluate the significance of mental well-being. Furthermore, based on the latest data, there has been an increase of 53.2 million cases of depressive disorder worldwide, indicating a growth of 27.6% throughout this pandemic. The prevalence of depression is uniform in both developed and economically challenged nations, independent of cultural background, origin, or ethnicity. Depression has various forms which include major depressive disorder (MDD), bipolar disorder (manic depression), persistent depressive disorder (dysthymia), and seasonal affective disorder (SAD). In the present time, MDD is the leading cause of global disability, contributing to 7.5% of years lived with a disability. (YLD) worldwide, with an estimated annual cost surpassing $US 1 trillion.

The primary etiology of MDD is disturbances in neurotransmitters and neuroendocrine regulation, accompanied by a complex interaction of genetic and environmental factors. In addition to these factors, increasing attention has been directed towards understanding the pathophysiology of MDD through the relationship between oxidative stress and inflammation. Essential enzymatic antioxidants, particularly Glutathione Peroxidase (GPx) and Superoxide Dismutase (SOD), play a crucial role in moderating oxidative stress. Oxidative stress arises from an imbalance between the generation of reactive oxygen species (ROS) and the body's capacity to counteract them. Studies indicate a tendency for reduced GPx and SOD activity in individuals with MDD, leading to heightened oxidative stress.

Furthermore, the involvement of pro-inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF) and Interleukin-6 (IL-6), in the inflammatory processes associated with depression is noteworthy. Persistent inflammation is associated with the activation of the kynurenine pathway, triggering the production of neurotoxic metabolites that may contribute to observed neurobiological changes in MDD. Elevated levels of TNF and IL-6, key immune response mediators, are observed in individuals with depression. These cytokines influence neurotransmitter metabolism, disrupt the blood-brain barrier, and activate microglia, spreading neuro-inflammation. The bidirectional interplay between oxidative stress and inflammation establishes a cyclically reinforcing paradigm, amplifying the neurobiological substrates of depression.. Moreover, deficiencies in various vitamins and minerals are significantly associated with Major Depressive Disorder (MDD), including vitamin D and E. Vitamin D and its metabolite calcitriol may act as a defense mechanism for the brain, guarding against the depletion of dopamine and serotonin whereas vitamin E has an antidepressant-like effect.

The management of major depressive disorder encompasses diverse treatment approaches, comprising pharmacological, psychotherapeutic, interventional, and lifestyle modifications, such as incorporating exercise and dietary changes. While the current antidepressants are more effective than placebos in adults with MDD, limitations of antidepressant treatment include a prolonged therapeutic time lag required for the clinical betterment of depressive symptoms and various side effects linked to their usage. These side effects frequently lead to treatment discontinuation by patients. Consequently, adjunctive treatments may play a crucial role in managing this disorder, particularly in cases of treatment resistance.

Engaging in regular exercise exerts a beneficial impact on symptoms commonly associated with depression. The consistent practice of physical activity positively influences various physiological aspects, encompassing neurotransmitter levels, neurotrophic factors, hormonal balance, immune modulation, sleep quality, and cognitive functions. This comprehensive influence collectively provides substantial evidence for the therapeutic effectiveness of exercise in alleviating depressive symptoms. Hence, the objective of the current study is to investigate the outcomes of aerobic and resistance exercises in conjunction with vitamin supplementation on individuals diagnosed with Major Depressive Disorder (MDD).

Conditions

• Depression Disorders

Interventions

OTHER

Aerobic Exercises + Vitamin E

For aerobic exercise, patient will perform cycling. The patient will perform stationary bike with an intensity of 60-85% of MHR by using Karvonean formula for duration of 30 minutes for 4 days/ week. Participants will be advised by the physical therapist to sit on a cycle ergometer with back supported, hands holding the handle bar and feet firmly placed on the pedals. The imprint of FITT protcol by ACSM for aerobic exercise will be as follows, Frequency: 4 days/week Intensity: 60-85% of MHR Time: 30 minutes Type: Stationary bike

OTHER

Resistance Exercises + Vitamin E

The strength training protocol will focus on 10 major muscles of the body. The sessions will be performed for 4 days per week, lasting approximately 30 minutes. The training will be divided in a systematical manner, on first- and third-day participant will perform strength training of upper limb and abdominal muscles that include: Biceps, Triceps, Pectoralis Major, Deltoid, and abdominal muscles. On second and fourth day, participant will perform strength training of lower back and lower limb muscles that include: Latissimus Dorsi, Abdominals, Back Extensors, Hamstrings, Quadriceps and Calf. The intensity of the weight bearing exercises will be calculated using 1 Repetition Maximum (RM) method. The protocol will be divided as follows: 2 days the participant will perform exercises for upper limb and 2 days, patient will perform exercises for lower limb.

OTHER

Aerobic Exercises + Vitamin D

For aerobic exercise, patient will perform cycling. The patient will perform stationary bike with an intensity of 60-85% of MHR by using Karvonean formula for duration of 30 minutes for 4 days/ week. Participants will be advised by the physical therapist to sit on a cycle ergometer with back supported, hands holding the handle bar and feet firmly placed on the pedals. The imprint of FITT protcol by ACSM for aerobic exercise will be as follows, Frequency: 4 days/week Intensity: 60-85% of MHR Time: 30 minutes Type: Stationary bike

OTHER

Resistance Exercises + Vitamin D

The strength training protocol will focus on 10 major muscles of the body. The sessions will be performed for 4 days per week, lasting approximately 30 minutes. The training will be divided in a systematical manner, on first- and third-day participant will perform strength training of upper limb and abdominal muscles that include: Biceps, Triceps, Pectoralis Major, Deltoid, and abdominal muscles. On second and fourth day, participant will perform strength training of lower back and lower limb muscles that include: Latissimus Dorsi, Abdominals, Back Extensors, Hamstrings, Quadriceps and Calf. The intensity of the weight bearing exercises will be calculated using 1 Repetition Maximum (RM) method. The protocol will be divided as follows: 2 days the participant will perform exercises for upper limb and 2 days, patient will perform exercises for lower limb.

Sponsors & Collaborators

• Ziauddin University

  lead OTHER

Principal Investigators

• Erum Tanveer · Ziauddin University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

FACTORIAL

Eligibility

Min Age

25 Years

Max Age

35 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-09-02

Primary Completion

2025-08-05

Completion

2025-08-05

Countries

• Pakistan

Study Locations