Oxidative stress and gut-brain axis identified as key contributors to ADHD development, highlighting potential dietary interventions.
Study: Investigating the Impact of Nutrition and Oxidative Stress on Attention Deficit Hyperactivity Disorder. Image Credit: PeopleImages.com - Yuri A/Shutterstock.com
In a recent review published in Nutrients, researchers investigated the influence of oxidative stress (OS) in attention deficit hyperactivity disorder (ADHD) development.
Introduction
ADHD is a childhood neurodevelopmental disease marked by difficulty paying attention, impulsive behavior, and hyperactivity. The disease is associated with various mental problems, addictions, accidents, and comorbidities such as anxiety and depression.
Heredity plays a vital role in ADHD development. Non-genetic factors such as oxidative stress also contribute to ADHD symptoms.
Gut microbes regulate oxidative stress and systemic inflammation, influencing mental health. Diet can influence microbiota, hence altering brain function and cognitive symptoms.
About the review
In the present systematic review, researchers determined whether oxidative stress (OS) contributes to attention deficit hyperactivity disorder (ADHD) development. They also explored the mediating effects of the gut-brain axis (GBA) and diet on ADHD.
The researchers searched PubMed, Google Scholar, and ScienceDirect databases for studies determining associations between oxidative stress, GBA, diet, and ADHD, published in English until July 2024. Exclusions were letters, case reports, comments, expert opinions, summaries, conference abstracts, book chapters, and unpublished findings.
The researchers used narrative synthesis to analyze 46 from 4,462 records, excluding 1,370 duplicates, 53 in non-English languages, and other records by article type.
Oxidative stress contributes to ADHD
Oxidative stress is crucial for developing and experiencing ADHD symptoms. OS is a biological state defined by an imbalance of oxidants and antioxidants.
Excess free radicals such as reactive oxygen species (ROS) or antioxidant deficiency can disrupt central nervous system (CNS) enzymes and impair neurotransmitter receptor functioning. Oxidative stress causes neuroinflammation and damage to cell components such as proteins, lipids, and deoxyribonucleic acid (DNA).
OS disrupts cellular signaling and gene expression, reduces protein function, and causes cell death or apoptosis. Iron catalyzes the processes that cause oxidative stress. ADHD is associated with iron deficiency.
Studies report elevated malondialdehyde (MDA) and melatonin levels in ADHD children. In contrast, antioxidants like catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) are significantly lower in ADHD serum. ADHD individuals also exhibit a lower total antioxidant status (TOS) than controls.
Influence of the gut microbiome on ADHD
An excess of harmful bacteria or a reduction in the abundance of beneficial bacteria in the gut contributes to ADHD. The GBA maintains a robust bidirectional relationship between the neurological tissues and gut microorganisms.
Gut microorganisms influence host metabolism through tissue interactions using microbiota-derived signals and metabolites. Gut microorganisms secrete compounds such as serotonin and short-chain fatty acids (SCFA), which affect brain activity.
Probiotics are living microbes present in fermented foods and dietary supplements. In ADHD patients, they reduce gut pH, prevent harmful organisms from colonizing the gut, and modulate the immune response.
Animal studies report that probiotics can improve the gut microbiome composition and increase the levels of tryptophan precursors and serotonin. Furthermore, probiotics help restore intestinal equilibrium and maintain intestinal barrier integrity.
Effects of diet on ADHD risk
Healthy diets, like the Mediterranean diet, high in fruits, vegetables, legumes, grains, and unsaturated and monounsaturated fats, have been thought to minimize ADHD risk.
Dietary ingredients activate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and phase II detoxifying genes and enzymes to provide powerful antioxidant and anti-inflammatory capabilities. The enzymes include heme oxygenase-1 (HO-1), thioredoxin (Trx), heat shock protein 70 (Hsp70), and sirtuin-1 (Sirt1).
Hormetic nutrients include polyphenols, vitamins, probiotics, and polyunsaturated fatty acids (PUFAs), which lower OS via activating intracellular antioxidants. Dietary polyphenols and probiotics work together to minimize inflammation caused by changes in the gut microbiota, which has a favorable effect on the GBA.
Polyphenols in blueberries, grapes, Hidrox olive extract, saffron, and Hericium erinaceus mushroom stimulate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and modify gut bacteria, lowering neuroinflammation and improving cognitive performance.
Manganese is a crucial cofactor that promotes macronutrient metabolism, cognitive function, and antioxidant defense. Magnesium, found in many plant diets, is essential for brain function. Zinc is an important antioxidant that regulates immunological function, protein synthesis, DNA synthesis, cell division, and melatonin metabolism.
Iron is essential for oxygen transportation, dopamine generation, and brain function. Diets high in zinc, magnesium, manganese, and iron can decrease ADHD symptoms. Selenium inhibits oxidative damage, but copper increases the chance of ADHD.
Vitamins B2, B6, B9, B12, and D help reduce free radicals and oxidative stress. Fish oil contains omega-3 polyunsaturated fatty acids (PUFA), which improve neurotransmitter activity and reduce ADHD symptoms.
Conclusion
The review reveals that oxidative stress and GBA are primary factors in ADHD pathogenesis, particularly in adults with comorbidities. Healthy diets could restore gut microbial balance and provide antioxidants that reduce oxidative stress in ADHD.
Future studies on the therapeutic potential of modulating oxidative stress in ADHD could facilitate more targeted interventions that would lower ADHD disease burden and improve the standard of care for affected individuals.
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