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Letter to the Editor

Psychosis Resulting From Herbs Rather Than Nutrients

L. Eugene Arnold, MD; Mary A. Fristad, PhD; Barbara L. Gracious, MD; Jeanette M. Johnstone, PhD; Bonnie J. Kaplan, PhD; Charles W. Popper, MD; and Julia J. Rucklidge, PhD

Published: April 28, 2016

See reply by Wong et al

Psychosis Resulting From Herbs Rather Than Nutrients

To the Editor: The very useful case report by Wong et al1 illustrates the potential harm of psychosis resulting from concurrent administration of over 50 ingredients, including 18 unregulated herbal agents, 19 digestive enzymes, 6 probiotic strains, and other over-the-counter substances. This is a valuable cautionary message, but the title and abstract lead readers astray. Instead of using specific language to identify the offending agents as herbs, the authors use the general term dietary supplements, an erroneous rubric often used in marketing herbs. By publishing evidence for an adverse herbal interaction with the term dietary supplements, this article inadvertently leads readers (many of whom read only the title and abstract) to believe that this case demonstrates harm from consumption of nutrients fundamental for human health.

Without careful reading of the full text and Table 1, readers will not recognize that only 4 of the > 50 ingredients this patient consumed were minerals or vitamins (chromium, vitamin B6, folate, vitamin B12). And, given that the patient’s B12 levels, when tested, were in the low normal range, resulting in treatment with cyanocobalamin 1,000 μg, there is good reason to suspect that even these few nutrients were not very bioavailable or had trivial physiologic impact.

It is unlikely that the patient’s psychosis resulted from the direct or combined effects of minerals, vitamins, enzymes, or probiotics. Rather, it is most likely that the patient’s physical and mental impairments resulted from the concurrent use of 18 botanicals, each with its own complex, nonspecific, and largely unmapped pharmacologic actions.

Humans have evolved to need dietary nutrients such as minerals and vitamins for the function of every mitochondrion (and hence every cell) of our brains and bodies. In contrast, there is no evidence of evolutionary need of herbs. In fact, physiologically active herbs could be more accurately described as crude drugs that have been misclassified as dietary supplements (eg, St John’s wort, tobacco, marijuana, coca leaf, and poppies are plant parts with psychoactive chemicals).

The signatories to this letter have contributed to the rapidly growing empirical literature demonstrating mental health benefits from nutrients (not herbs)2-8 as well as establishing safety of these nutrients,9 even when multiple nutrients are used in combination. It concerns us that the nonspecific use of the term dietary supplements could prejudice interpretation of the scientifically valid studies on nutritional approaches to treating psychiatric conditions. In addition to our own work, there is a large literature supporting the association between dietary patterns and mental health in population studies,10 and a new international society of scientists has formed to study this area (International Society for Nutritional Psychiatry Research;

If the title and abstract of the report had accurately specified that it was primarily about the risk of the concurrent use of multiple unregulated botanical substances, there would be no confusion. Given the present situation, we respectfully ask that a correction be issued.


1. Wong MK, Darvishzadeh A, Maler NA, et al. Five supplements and multiple psychotic symptoms: a case report. Prim Care Companion CNS Disord. 2016;18(1):doi:10.4088/PCC.15br01856. doi:10.4088/pcc.15br01856.

2. Rucklidge JJ, Kaplan BJ. Broad-spectrum micronutrient formulas for the treatment of psychiatric symptoms: a systematic review. Expert Rev Neurother. 2013;13(1):49-73. PubMed doi:10.1586/ern.12.143

3. Popper CW. Single-micronutrient and broad-spectrum micronutrient approaches for treating mood disorders in youth and adults. Child Adolesc Psychiatr Clin N Am. 2014;23(3):591-672. PubMed doi:10.1016/j.chc.2014.04.001

4. Kaplan BJ, Rucklidge JJ, McLeod K, et al. The emerging field of nutritional mental health: inflammation, the microbiome, oxidative stress, and mitochondrial function. Clinical Psychological Science. 2015;3(6):964-980. doi:10.1177/2167702614555413

5. Frazier EA, Fristad MA, Arnold LE. Feasibility of a nutritional supplement as treatment for pediatric bipolar spectrum disorders. J Altern Complement Med. 2012;18(7):678-685. PubMed doi:10.1089/acm.2011.0270

6. Vesco AT, Lehmann J, Gracious BL, et al. Omega-3 supplementation for psychotic mania and comorbid anxiety in children. J Child Adolesc Psychopharmacol. 2015;25(7):526-534. PubMed doi:10.1089/cap.2013.0141

7. Gordon HA, Rucklidge JJ, Blampied NM, et al. Clinically significant symptom reduction in children with attention-deficit/hyperactivity disorder treated with micronutrients: an open-label reversal design study. J Child Adolesc Psychopharmacol. 2015;25(10):783-798. PubMed doi:10.1089/cap.2015.0105

8. Fristad MA, Young AS, Vesco AT, et al. A randomized controlled trial of individual family psychoeducational psychotherapy and omega-3 fatty acids in youth with subsyndromal bipolar disorder. J Child Adolesc Psychopharmacol. 2015;25(10):764-774. PubMed doi:10.1089/cap.2015.0132

9. Simpson JSA, Crawford SG, Goldstein ET, et al. Systematic review of safety and tolerability of a complex micronutrient formula used in mental health. BMC Psychiatry. 2011;11:62. PubMed doi:10.1186/1471-244X-11-62

10. Jacka FN, Mykletun A, Berk M. Moving towards a population health approach to the primary prevention of common mental disorders. BMC Med. 2012;10(1):149. PubMed doi:10.1186/1741-7015-10-149

11. Sarris J, Logan AC, Akbaraly TN, et al. International Society for Nutritional Psychiatry Research. Nutritional medicine as mainstream in psychiatry. Lancet Psychiatry. 2015;2(3):271-274. PubMed doi:10.1016/S2215-0366(14)00051-0

L. Eugene Arnold, MDa

Mary A. Fristad, PhDa

Barbara L. Gracious, MDa

Jeanette M. Johnstone, PhDb

Bonnie J. Kaplan, PhDc

Charles W. Popper, MDd

Julia J. Rucklidge, PhDe

aOhio State University, Columbus

bOregon Health & Science University, Portland

cDepartment of Pediatrics, University of Calgary, Calgary, Canada

dMcLean Hospital, Belmont, and Harvard Medical School, Boston, Massachusetts

eUniversity of Canterbury, Christchurch, New Zealand

Potential conflicts of interest: Dr Arnold has received research funding from Curemark, Forest, Lilly, Neuropharm, Novartis, Noven, Shire, Supernus, YoungLiving, National Institutes of Health, and Autism Speaks; has consulted or been on advisory boards for Arbor, Gowlings, Ironshore, Neuropharm, Novartis, Noven, Organon, Otsuka, Pfizer, Roche, Seaside Therapeutics, Sigma Tau, Shire, Tris Pharma, and Waypoint; and has received travel support from Noven. Dr Fristad has received honoraria from American Occupational Therapy Association and Physicians Postgraduate Press, Inc, and royalties from Guilford Press, American Psychiatric Press, and Child & Family Psychological Services, Inc. Drs Gracious, Johnstone, Kaplan, Popper, and Rucklidge report no conflicts of interest related to the subject of this letter.

Funding/support: None.

Published online: April 28, 2016.

Prim Care Companion CNS Disord 2016;18(2):doi:10.4088/PCC.16l01940

© Copyright 2016 Physicians Postgraduate Press, Inc.

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