Anti-oxidant and Anti-inflammatory additions for Cognition and Mental Health Novel therapeutic strategies that attenuate neuroinflammation and protect neurons against oxidative stress are important for delaying neuroprogression in various disorders. A diet rich in antioxidants may partially contribute to the alleviation of symptoms - use of specific diets rich in antioxidants and anti-inflammatory components may lower cognitive decline and neuroprogression. Decreased antioxidant capacity correlates with cognitive deficits and depression, with depression, anxiety-like behaviour and memory impairment being associated with increased oxidative stress and inflammation. There are often synergistic antioxidant/anti-inflammatory effects through the use of anti-oxidant combinations. Accumulating evidence implicates free radical-mediated pathology, altered antioxidant capacity, neurotoxicity and inflammation in neuropsychiatric disorders. To what extent these contribute to specific clinical symptomatology of these complex and debilitating psychiatric ailments remains to be determined. Some suggested therapeutic options: - polyphenols - melatonin, sulforaphane, and N-acetylcysteine (NAC) - Vitamin C A neuroprotective strategy proposes natural antioxidant molecules as an alternative form of treatment for the prevention of neurological pathologies. Polyphenols Examples include hesperidin, a flavanone glycoside found abundantly in citrus fruit which has neuroprotective effect and synaptogenic action on the central nervous system, partially mediated through astrocytes. It was able to improve memory in healthy adult mice by two main mechanisms: directly, by inducing synapse formation and function between hippocampal and cortical neurons; and indirectly, by enhancing the synaptogenic ability of cortical astrocytes It also has additional antidepressant properties via its anti-oxidant and anti-inflammatory activities, the enhancement of neurogenesis (chronic treatment with low dose hesperidin resulted in an increase in hippocampal brain-derived neurotrophic factor (BDNF) levels), and changes in the levels of monoamines in the brain. Melatonin 1 - neuroprotective - anti-inflammatory and antioxidant agent (increased expression of antioxidant enzymes) - Improves sleep quality - Preliminary studies suggest it may improve sleep and reduce restricted repetitive behaviours in ASD - In psychotic disorders: augmentative antipsychotic actions, mitigating the risk of tardive dyskinesias, curbing metabolic syndrome N-acetylcysteine - robust effects on neurogenesis - modulation of inflammatory pathways - modulation of synaptic release of glutamate in cortico-subcortical brain regions and also indirect effects on dopamine (increased dopamine release) - may counteract neurodegenerative and psychiatric disease: may assist in treatment of schizophrenia, bipolar disorder and depression through decreasing oxidative stress and reducing glutamatergic dysfunction - reverses mitochondrial dysfunction - some studies suggest effectiveness of NAC therapy requires more extended intervention ( ⩾ 24 weeks) 2 - Small-to-moderate reductions in depressive symptoms across various psychiatric diagnoses - Some studies have shown that NAC significantly improves cognitive function in patients with neurological or psychiatric diseases, but the clinical relevance of the effects is still unclear. - Limited by rapid metabolism orally, low bioavailability of its free form (<10%) - the achieved plasma and tissue concentration is at a low level Vitamin C Ascorbic acid produces a fast therapeutic response with low toxicity and high tolerance with the potential to elevate mood as well as reduce distress and anxiety. Anti-excitotoxic, anti-stress, neuromodulatory and neurotrophic properties are claimed with modulation of of some neurotransmitter systems including dopamine, norepinephrine, serotonin, glutamatergic and cholinergic systems. It is a neuroprotective compound against neurotoxicants and neurodegenerative diseases. Studies suggest supplementation reduces stress-induced cortisol release. It improves behavioural and biochemical alterations in psychiatric disorders, including schizophrenia, anxiety, major depressive disorder, and bipolar disorder. - protects the neuron against oxidative stress, alleviates inflammation, regulates neurotransmission, affects neuronal development and controls epigenetic function. - improved neurogenesis and synaptic plasticity: regulate positively stem cell generation and proliferation, improves neuronal differentiation of precursor cells, promotes adult hippocampal neurogenesis - may change the course of neurological diseases and display potential therapeutic roles. - Some clinical studies reported that ascorbic acid could counteract the increase in stress hormones and subjective perceptions of stress condition. For example, the increase in cortisol levels was blunted by ascorbic acid (3 g/day for 5 days), suggesting that ascorbic acid can be used to limit the effects of stress hormones - Older individuals treated with ascorbic acid (1 g/day for 8 weeks) showed a 71% decrease 3 in mood symptoms, and a 51% decrease in psychologic stress - Schizophrenic patients treated with ascorbic acid (1 g/day for 3 weeks) presented remission of depressive symptoms - Ascorbic acid treatment for 3 months induced the remission of depressive symptoms in fifty depressive patients presenting acute episodes. - SSRIs augmented with ascorbic acid (1 g/day, for 6 months) ameliorated the symptoms of depressive children. There seems to be a better response of antidepressants in combination with ascorbic acid in some studies - Sustained-release of a high-dose of ascorbic acid (3 x 1000 mg/day for 14 days), reduced the subjective response to psychological stress - Systematic reviews indicated that high-dose of ascorbic acid was effective in reducing mental disorders, including anxiety See more: Unusual Bioactive Compounds with Antioxidant Properties in Adjuvant Therapy Supporting Cognition Impairment in Age-Related Neurodegenerative Disorders https://doi.org/10.3390/ijms221910707 The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trialsz https://doi.org/10.1002/wps.20672 4