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. In a latest published 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.
Oxidative stress contributes to ADHD
Oxidative stress is defined by an imbalance of oxidants and antioxidants and it seems crucial for developing and experiencing ADHD symptoms. Excess free radicals such as reactive oxygen species (ROS) or antioxidant deficiency can disrupt central nervous system enzymes and impair neurotransmitter receptor functioning. Oxidative stress causes neuroinflammation and damage to cell components such as proteins, lipids and DNA. It disrupts cellular signaling and gene expression, reduces protein function, and causes cell death or apoptosis. Iron catalyzes the processes that cause oxidative stress. ADHD may be 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 GABA, 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 Nrf2 transcription factor 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), quinone oxido-reductase (NQO-1) and sirtuin-1 (Sirt1). Hormetic nutrients include polyphenols, some vitamins, probiotics, and polyunsaturated fatty acids (PUFAs), which lower oxidative stress 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, pomace 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 oligoelement that promotes macronutrient metabolism, cognitive function, and antioxidant defense. 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. Selenium inhibits oxidative damage, but copper increases the chance of ADHD. Diets high in zinc, magnesium, manganese and iron can decrease ADHD symptoms. Vitamins B2, B6, B9, B12 and D help reduce free radicals and oxidative stress as well.
Fish oil contains omega-3 fatty acids, which improve neurotransmitter activity and reduce ADHD symptoms. Therefore, 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.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Visternicu M et al. Nutrients 2024, 16(18):3113;
Panpetch J et al. J Pers Med. 2024; 14(7):739.
Gonçalves CL et al. Life Sci. 2024; 337:122357.