Appendix D - Vitamin C Use in Withdrawal and Medication Side-effects

Vitamin C - Withdrawal and Medication Side-effects

Vitamin C, also known as ascorbic acid, is a water-soluble vitamin. Unlike most mammals, humans cannot synthesize vitamin C. Therefore, we must obtain vitamin C through our diet.1

Vitamin C is the antiscorbutic or anti-scurvy vitamin. Although scurvy was first described during the Crusades and commonly plagued early explorers and voyagers, the specific relationship between scurvy, citrus foods, and ascorbic acid was not established until the 20th century. The antiscorbutic factor was isolated and named hexuronic acid in 1928 by Szent-Gyorgyi, who found it in adrenal tissue, orange, and cabbage. In 1932 both he and C. Glenn King demonstrated that hexuronic acid was vitamin C.2

Natural vs. Synthetic Vitamin C
Natural and synthetic L-ascorbic acid are chemically identical and there are no known differences in their biological activities or bioavailabilities.3

Effective Dosing
Dr. Robert Cathcart, in treating over 9000 patients with large doses of vitamin C, found effective doses to be proportionate to the stress or toxicity experienced which were in turn proportionate to the amount of oral ascorbic acid tolerated by the patient without producing diarrhea. This increased bowel tolerance phenomenon serves not only to indicate the amount which should be taken but indicates the unsuspected and astonishing magnitude of the potential use that the body has for ascorbate under stressful conditions. Cathcart named the process of determining optimum dose as titrating to bowel tolerance. “The patient tries to TITRATE between that amount which begins to make him feel better and that amount which almost but not quite causes diarrhea.”4

Drug Withdrawal
Ascorbate, administered in high oral doses has been observed to relieve pain and reduce opioid use in cancer patients. In vitro studies have also shown that antioxidants, such as vitamin C, may, at high concentrations, inhibit endogenous opioid degrading enzymes and increase endorphin levels. The most recent study, conducted in 2000, has demonstrated that high oral doses (300 mg/kg bw/day [approximately 20 g/d]) of vitamin C were able to substantially reduce withdrawal symptoms in heroin abusers.5 Libby and Stone (1977) successfully demonstrated the same effect twenty three years earlier.6

Mania and Psychosis
Dr. Abram Hoffer observed early in his career two cases of psychosis which resolved with vitamin C within three days on as little as 3g/day and as much as 1g/waking hour.7 These individuals did have other medical conditions, but the change was clear and distinct.  In 1963, Milner reported statistically significant improvement in the depressive, manic, and paranoid symptom-complexes, together with an improvement in overall personality functioning, was obtained using vitamin C.8  Naylor et al. conducted a double-blind placebo controlled cross-over trial in 1981 which provided further evidence of vitamin C efficacy.  Both manic and depressed patients showed that a single 3g dose significantly improved symptoms compared to placebo.9 

Agitation and Stress
Individuals in stress, shock, surgery, trauma and critical illness have a drastic reduction of circulating plasma ascorbate; and 3g doses per day are required to restore normal ascorbate concentrations and improve outcome.10,11

Tardive Akathisia and Dyskinesia
Akathisia and dyskinesia are related disorders that frequently appear after long-term or high-dose use of antipsychotic drugs.12 Tardive akathisia involves painful feelings of inner tension and anxiety and a compulsive drive to move the body. Tardive dyskinesia is characterized by repetitive, involuntary, purposeless movements. Hypersensitivity of certain dopamine receptors12 and dopamine inhibition of certain mitochondrial enzymes13 appear to play a role in the development and progression of these drug- induced disorders, as well as Parkinson’s disease. Vitamin C is able to prevent the dopaminergic impairment of mitochondrial enzymes14; and in a small study, six patients experienced a reduction in tardive symptoms with a combination of vitamin E and C.15

Chemical Forms and pH
Sodium ascorbate can be obtained both as the pure crystalline powder and as 1g tablets. The crystalline powder is very soluble in liquids and has a slight salt taste. A level teaspoon weighs about 3g. A solution of sodium ascorbate has a pH of slightly over 7.6
Ascorbic acid can also be obtained as pure crystalline powder or as 1g tablets. While also quite soluble in water, it has a sour taste. A solution of ascorbic acid has a pH of about 3.6


3. Gregory JF, 3rd. Ascorbic acid bioavailability in foods and supplements. Nutr Rev. 1993;51(10):301-303.
4. Cathcart RF. Vitamin C, titrating to bowel tolerance, anascorbemia, and acute induced scurvy. Med Hypotheses. 1981 Nov;7(11):1359-76.
5. Evangelou A, Kalfakakou V, Georgakas P, Koutras V, Vezyraki P, Iliopoulou L, Vadalouka A. Ascorbic acid (vitamin C) effects on withdrawal syndrome of heroin abusers. In Vivo. 2000 Mar-Apr;14(2):363-6.
6. Libby AF, Stone I. The hypoascorbemia - kwashiorkor approach to drug addiction therapy: a pilot study. Australas Nurses J. 1978 Jan-Feb;7(6):4-8, 13. PMID: 418764
7. Hoffer, Dr. Abram. Clinical Procedures in Treating Terminally Ill Cancer Patients with Vitamin C. Journal of Orthomolecular Medicine. 1991;6.3.4
8. Milner G. Ascorbic acid in chronic psychiatric patients—a controlled trial. B J Psych. 1963;109:294-299.
9. Naylor GJ, Smith AH. Vanadium: a possible aetiological factor in manic depressive illness. Psychol Med. 1981 May;11(2):249-56.
10. Berger MM. Vitamin C requirements in parenteral nutrition. Gastroenterology. 2009 Nov;137(5 Suppl):S70-8.
11. McGregor GP, Biesalski HK. Rationale and impact of vitamin C in clinical nutrition. Curr Opin Clin Nutr Metab Care. 2006 Nov;9(6):697-703.
12. Jones HM, Pilowsky LS. Dopamine and antipsychotic drug action revisited. Br J Psychiatry. 2002 Oct;181:271-5.
13. Przedborski S, Jackson-Lewis V, Muthane U, Jiang H, Ferreira M, Naini AB, Fahn S. Chronic levodopa administration alters cerebral mitochondrial respiratory chain activity. Ann Neurol. 1993 Nov;34(5):715-23.
14. Przedborski S, Jackson-Lewis V, Fahn S. Antiparkinsonian therapies and brain mitochondrial complex I activity. Mov Disord. 1995 May;10(3):312-7.
15. Michael N, Sourgens H, Arolt V, Erfurth A. Severe tardive dyskinesia in affective disorders: treatment with vitamin E and C. Neuropsychobiology. 2002;46 Suppl 1:28-30.