How ascorbic acid soothes the brain
Beyond immune support
Vitamin C (ascorbic acid) is best known for its immune-enhancing effects – from reducing the severity and duration of the common cold, to supporting the health of individuals with HIV/AIDS, to reducing the histamine response seen in allergies and asthma,,, to even potentially reducing the risk of many kinds of cancer.
Antioxidants [like vitamin C] do more than just support immunity; they also are crucial for mental health.
Vitamin C largely supports immune health by serving as an essential antioxidant and enzyme cofactor in the body. But antioxidants do more than just support immunity; they also are crucial for mental health. Ascorbic acid, furthermore, plays a crucial role in a myriad of metabolic pathways, with effects in virtually every organ system of the body, including the brain. In fact, the nutrient has been shown to help not only with depression and anxiety, but also with addictions and chronic drug/alcohol use through several different effects:
Vitamin C to correct nutritional deficiency
Patients with major depression as well as those entering therapy for drug addiction have been shown to have low vitamin C (plasma ascorbic acid) levels. In fact, over 74% of individuals entering treatment for drug addiction had clinical signs of nutrient deficiency according to one study, with this group being at particular risk of deficiency in the antioxidant-related vitamins – namely A, E, and, of course, C.
Vitamin C as an antioxidant
Oxidative damage likely compromises mental health by altering the fluidity of cellular membranes, leading to problems with the mitochondria, the organelles within every cell that generate ATP (energy).,, It’s likely for this reason that psychiatric disorders like anxiety,, depression,,, bipolar disorder,, panic disorder,, obsessive-compulsive disorder (OCD), and schizophrenia are associated with higher levels of oxidative stress., Oxidative stress goes hand-in-hand with inflammation, and thus higher levels of pro-inflammatory markers like C-reactive protein (CRP) have also been observed in those with these conditions.,,, In fact, there’s some argument that anti-depressants work at least in part by means of their anti-inflammatory and antioxidant effects.,
Psychiatric disorders like anxiety, depression, bipolar disorder, panic disorder, obsessive-compulsive disorder (OCD), and schizophrenia are associated with higher levels of oxidative stress and inflammation.
Multiple animal studies show that ascorbic acid reduces depressive behavior and decreases oxidative stress., In humans, vitamin C has been shown in multiple randomized, double-blind, placebo-controlled trials (RDBPCTs) to help with both depression and anxiety in patients of various ages.,,
Vitamin C recycles glutathione
In addition to being at higher risk of vitamin C deficiency, chronic alcohol users are also more likely to be significantly deficient in another major antioxidant: glutathione., This is no coincidence: in addition to improving the overall antioxidant protection capacity in the body, vitamin C also influences glutathione concentrations in the blood. In fact, 500 mg of vitamin C supplemented daily was shown in one study to increase mean red blood cell glutathione levels by almost 50% after just two weeks.
Vitamin C helps the body cope with stress
As a water-soluble vitamin, vitamin C is stored in many tissues throughout the body, with the highest concentrations being in the adrenal glands. Sitting atop the kidneys, the adrenal glands produce cortisol, the hormone that helps us have the energy and mental/emotional resilience we need to cope with stress. The adrenal glands secrete ascorbic acid into the plasma in response to adrenocorticotropic hormone (ACTH) – the same brain signal that triggers the adrenals to put out cortisol. An important component of the hypothalamic-pituitary-adrenal (HPA) axis, ACTH is produced in response to biological stress – whether physical or psychological.
The more stress we experience, the more our adrenal glands pump out ascorbic acid, and the more likely we are to become deficient in the nutrient.
This means the more stress we experience, the more our adrenal glands pump out ascorbic acid, and the more likely we are to become deficient in the nutrient. Vitamin C, furthermore, is a necessary cofactor in the reactions that make norepinephrine from dopamine in the adrenal glands and the nervous system., Vitamin C is therefore likely to be useful in settings of stress.
Vitamin C modulates dopamine and glutamate in the brain
The balance of glutamate (an excitatory neurotransmitter) and gamma-aminobutyric acid (GABA) (a calming amino acid) plays an important role in brain health. Higher glutamate and/or lower GABA concentrations tip the brain’s balance in favor of activated, agitated, and excited states, as are seen with poor sleep quality, depression, anxiety,, ADHD, and addiction.
The glutamatergic and dopaminergic systems are involved in drug tolerance and withdrawal, especially with respect to alcohol and opiate drugs. Vitamin C has been shown to modulate the actions of dopamine and glutamate in the brain – another mechanism by which it may support mental health and offset addictive behavior., Vitamin C has thus been used clinically for offsetting addictive cravings, whether for food, tobacco, stimulants, alcohol, opiates, or other substances.
In a study exploring morphine addiction, rats were placed in a setting in which they could administer the drug to themselves by pressing a lever. The rats that received ascorbic acid throughout the study on average took fewer “hits” of morphine over the course of the 12-day exposure period and had fewer morphine withdrawal signs (MWS). This study – and a similar one conducted nine years prior – suggests that vitamin C supplementation may prevent both the development of drug tolerance and the likelihood of physical dependence.
Vitamin C supplementation may prevent both the development of drug tolerance and the likelihood of physical dependence.
In a study conducted in humans addicted to heroin, oral supplementation with vitamin C (at a dose of 300 mg per kg of body weight per day) and vitamin E (5 mg per kg of body weight per day) ameliorated withdrawal symptoms in both inpatients and outpatients.
In another trial conducted at the Haight-Ashbury Free Clinic in San Francisco, 1,000 to 3,000 mg of buffered vitamin C taken daily was found to significantly offset withdrawal symptoms in patients seeing to detoxify from stimulants and opiates. One third of the 60 patients reported that 70% or more of their acute withdrawal symptoms abated when taking buffered vitamin C during the active detox phase of the program; half reported at least 60% relief. Aftercare clients (those already finished with active detox phase at the start of the study) reported even greater benefits, with a median relief of 90% of symptoms.
It has also been suggested that alkalinizing substances – like the high levels of ionized calcium or magnesium packed within buffered vitamin C supplements – play a significant role in promoting health and detoxification.
Sources of vitamin C
Vitamin C can be found in fresh citrus fruits, strawberries, cantaloupe and currants. Fresh vegetables, like Brussels sprouts, lettuce, cabbage, peas, collard greens, and asparagus are likewise good sources. Vitamin C supplements are also readily available for both children and adults in a variety of preparations.
Some people find that taking vitamin C supplements at therapeutic doses can cause gastrointestinal upset and loose stools. Reducing the dosage to “bowel tolerance” and then gradually increasing is likely to help in such situations. Gastrointestinal side effects are also less likely to occur with buffered vitamin C products.
The many mechanisms by which vitamin C supports the brain, mood, and neurological health, coupled with the reasonable cost of this nutrient, makes choosing vitamin C, well, a no-brainer.
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 Pauling L. How to Live Longer and Feel Better. New York: W.H. Freeman and Company; 1986:118-21.
 Cathcart RF 3rd. Vitamin C in the treatment of acquired immune deficiency syndrome (AIDS). Med Hypotheses. 1984 Aug;14(4):423-33.
 Levine MA, Pollard HB. Hydrocortisone inhibition of ascorbic acid transport by chromaffin cells. FEBS Lett. 1983;158(1):134-8.
 Hatch GE. Asthma, inhaled oxidants, and dietary antioxidants. Am J Clin Nutr. 1995 Mar;61(3 Suppl):625S-30S.
 Bielory L, et al. Asthma and vitamin C. Ann Allergy. 1994 Aug;73(2):89-96.
 Block G. Epidemiologic evidence regarding vitamin C and cancer. Am J Clin Nutr. 1991 Dec;54(6 Suppl):1310S-4S.
 Khanzode SD, et al. Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors. Redox Rep. 2003;8(6):365-70.
 Nazrul Islam SK, et al. Nutritional status of drug addicts undergoing detoxification: prevalence of malnutrition and influence of illicit drugs and lifestyle. Br J Nutr. 2002 Nov;88(5):507-13.
 Nazrul Islam SK, et al. Serum vitamin E, C and A status of the drug addicts undergoing detoxification: influence of drug habit, sexual practice and lifestyle factors. Eur J Clin Nutr. 2001 Nov;55(11):1022-7.
 Tsuboi H, et al. Depressive symptoms are independently correlated with lipid peroxidation in a female population: comparison with vitamins and carotenoids. J Psychosom Res. 2004 Jan;56(1):53-8.
 Jou SH, et al. Mitochondrial dysfunction and psychiatric disorders. Chang Gung Med J. 2009;32(4):370-9.
 Allen J, et al. Mitochondria and mood: mitochondrial dysfunction as a key player in the manifestation of depression. Front Neurosci. 2018 Jun 6;12:386.
 Vaváková M, et al. Markers of oxidative stress and neuroprogression in depression disorder. Oxid Med Cell Longev. 2015;2015:898393.
 Bouayed J, et al. Oxidative stress and anxiety: relationship and cellular pathways. Oxid Med Cell Longev. 2009 Apr-Jun;2(2):63-7.
 Michel TM, et al. The role of oxidative stress in depressive disorders. Curr Pharm Des. 2012; 18(36):5890-9.
 Black CN, et al. Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology. 2015;51:164-75.
 Moylan S, et al. Oxidative & nitrosative stress in depression: why so much stress? Neurosci Biobehav Rev. 2014;45:46-62.
 Berk M, et al. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev. 2011 Jan; 35(3):804-17.
 Andreazza AC, et al. Oxidative stress markers in bipolar disorder: a meta-analysis. Journal of Affective Disorders. 2008;111(2-3):135-44.
 Ersoy MA, et al. Role of oxidative and antioxidative parameters in etiopathogenesis and prognosis of panic disorder. Int J Neurosci. 2008 Jul;118(7):1025-37.
 Gul IG, et al. The effect of agoraphobia on oxidative stress in panic disorder. Psychiatry Investig. 2013 Dec;10(4):317-25.
 Kandemir H, et al. Oxidative imbalance in child and adolescent patients with obsessive compulsive disorder. J Psychiatr Res. 2013 Nov; 47(11):1831-4.
 Ng F, et al. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008 Sep;11(6):851-76.
 Smaga I, et al. Oxidative stress as an etiological factor and a potential treatment target of psychiatric disorders. Part 2. Depression, anxiety, schizophrenia and autism. Pharmacol Rep. 2015 Jun;67(3):569-80.
 Pasco JA, et al. Association of high-sensitivity C-reactive protein with de novo major depression. Br J Psychiatry. 2010;197(5):372-7.
 Dowlati Y, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67(5):446-57.
 Kim YK, et al. Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder. J Affect Disord. 2007 Dec;104(1-3):91-5.
 Vogelzangs N, et al. Anxiety disorders and inflammation in a large adult cohort. Transl Psychiatry. 2013 Apr 23;3:e249.
 Dinan TG. Inflammatory markers in depression. Curr Opin Psychiatry. 2009;22(1):32-6.
 Caiaffo V, et al. Anti-inflammatory, antiapoptotic, and antioxidant activity of fluoxetine. Pharmacol Res Perspect. 2016;4(3):e00231.
 Moretti M, et al. Ascorbic acid treatment, similarly to fluoxetine, reverses depressive-like behavior and brain oxidative damage induced by chronic unpredictable stress. J Psychiatr Res. 2012 Mar;46(3):331-40.
 Moretti M, et al. Protective effects of ascorbic acid on behavior and oxidative status of restraint-stressed mice. J Mol Neurosci. 2013 Jan;49(1):68-79.
 de Oliveira IJ, et al. Effects of oral vitamin C supplementation on anxiety in students: a double-blind, randomized, placebo-controlled trial. Pak J Biol Sci. 2015 Jan;18(1):11-8.
 Amr M, et al. Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. Nutr J. 2013 Mar;12:31.
 Mazloom Z, et al. Efficacy of supplementary vitamins C and E on anxiety, depression and stress in type 2 diabetic patients: a randomized, single-blind, placebo-controlled trial. Pak J Biol Sci. 2013 Nov 15;16(22):1597-600.
 Loguercio C, et al. Ethanol consumption, amino acid and glutathione blood levels in patients with and without chronic liver disease. Alcohol Clin Exp Res. 1999 Nov;23(11):1780-4.
 Loguercio C, et al. Determination of plasma alpha-glutathione-S-transferases in chronic alcohol abusers: relationship with alcohol intake and liver involvement. Alcohol Alcohol. 1998 Jul-Aug;33(4):366-72.
 Johnston CS, et al. Vitamin C elevates red blood cell glutathione in healthy adults. Amer Jour Clin Nutr. 1 July 1993;58(1):103-5.
 Patak P, et al. Vitamin C is an important cofactor for both adrenal cortex and adrenal medulla. Endocr Res. 2004 Nov;30(4):871-5.
 Padayatty SJ, et al. Human adrenal glands secrete vitamin C in response to adrenocorticotrophic hormone. Am J Clin Nutr. 2007 Jul; 86(1):145-9.
 May JM, et al. Ascorbic acid efficiently enhances neuronal synthesis of norepinephrine from dopamine. Brain Res Bull. 2013 Jan;90:35-42.
 Fleming PJ, Kent UM. Cytochrome b561, ascorbic acid, and transmembrane electron transfer. Am J Clin Nutr. 1991 Dec; 54(6 Suppl):1173S-8S.
 Petroff OA. GABA and glutamate in the human brain. Neuroscientist. 2002 Dec;8(6):562-73.
 Gottesmann C. GABA mechanisms and sleep. Neuroscience. 2002;111(2):231-9.
 Pehrson AL, Sanchez C. Altered γ-aminobutyric acid neurotransmission in major depressive disorder: a critical review of the supporting evidence and the influence of serotonergic antidepressants. Drug Des Devel Ther. 2015;9:603-24.
 Meyerhoff DJ, et al. Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality. Sleep. 2014;37(5):893-900.
 Rosso IM, et al. Insula and anterior cingulate GABA levels in posttraumatic stress disorder: preliminary findings using magnetic resonance spectroscopy. Depress Anxiety. 2014;31(2):115-23.
 Gilgun, JF. The NEATS: A Child & Family Assessment. Printed by CreateSpace, 2011.
 Siggins GR, et al. Glutamatergic transmission in opiate and alcohol dependence. Ann NY Acad Sci. 2003 Nov; 1003:196-211.
 Aghajanian GK, et al. Opiate withdrawal increases glutamate and aspartate efflux in the locus coeruleus: an in vivo microdialysis study. Brain Res. 1994 Feb 4; 636(1):126-30.
 Alaei H, Esmaeily M. Low doses of ascorbic reduced withdrawal syndrome sign in rats. J Gazvin University. 2001;5:24-9.
 Garcia MM, et al. Morphine induction of c-fos expression in the rat forebrain through glutamatergic mechanisms: role of non-n-methyl-D-aspartate receptors. Neuroscience. 2003; 119(3):787-94.
 Mahboobeh T, et al. The effect of vitamin C on morphine self-administration in rats. Adv Biomed Res. 2014;3:178.
 Alaei H, et al. Ascorbic acid decreases morphine self-administration and withdrawal symptoms in rats. Pathophysiology. 2005 Sep; 12(2):103-7.
 Evangelou A, et al. Ascorbic acid (vitamin C) effects on withdrawal syndrome of heroin abusers. In Vivo. 2000 Mar-Apr;14(2):363-6.
 Newmeyer J, et al. Efficacy of buffered ascorbate compound (BAC) in the detoxification and aftercare of clients involved in opiate and stimulant abuse. From the Haight-Ashbury Free Medical Clinic. 1983 Jul:1-5.
 Minich DM, Bland JS. Acid-alkaline balance: role in chronic disease and detoxification. Altern Ther Health Med. 2007 Jul-Aug;13(4):62-5.
 Marz R. Vitamin C. In: Medical Nutrition from Marz. 2nd ed. Portland, OR: Omni-Press; 2002.