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Happy Gut: Happy Brain
Beyond improving mental health, resolving Clostridia overgrowth is essential to restoring gastrointestinal health. Dysbiosis leads to severe damage of intestinal tissue leading to poor dietary absorption and digestion, reduced immunity, and greater risk of allergy. Furthermore, suppression of favorable bacteria contributes to intestinal dysfunction by inhibiting their synthesis of beneficial byproducts. The presence of elevated HPHPA does not rule out additional perpetrators of intestinal dysfunction; food allergies are frequent contributors in virtually every psychiatric condition, requiring minimal to drastic dietary changes.3
My thirty years of clinical experience suggests a significant number of children and adults with ADHD, anxiety, autism, and schizophrenia, particularly those with gastrointestinal symptoms will test high for urinary HPHPA. A number of clinical reports and published data corroborate the importance of assessing elevated HPHPA across the spectrum of psychiatric illness, warranting its routine inclusion in lab assays for patients displaying these risk factors. When urinary HPHPA concentrations exceed 180 mmol/ml of creatine, my first line strategy is always a multi-strain, high-dose probiotic in doses of at least 200 billion CFUs per day; often 600 CFUs per day is required.3
In many cases, reintroducing commensal bacteria with a multi-strain, high-dose probiotic over a period of two to three months is enough to overcome the bacterial imbalance and realign the gut-brain axis. Individuals who do not respond to probiotics in the expected time may require a Clostridia-specific antibiotic to create an optimal environment for probiotics to take effect. In most patients requiring adjunct antibiotics, vancomycin in a 30-day pulsing protocol (1 day on; 2 days off) is sufficient to eliminate Clostridia and jumpstart recovery with probiotic treatment. In addition to restoring homeostasis of the microbiome, resolving Clostridia overgrowth often increases the efficacy of other necessary supplementations or medications.3
The Power of the Organic Acids Test and Probiotics
A 25-year-old adult male with a history of atopy, including multiple food allergies and a diagnosis of celiac disease, dry eye, and asthma arrived at my office after a referral for generalized anxiety and major depression. This patient had been in therapy and psychiatric treatment for over a decade and responded poorly to multiple prescription medications. His struggles with mental health began in high school and college, which seemed to align with severe gastrointestinal symptoms and disordered eating behaviors and, which the patient said, correlated with a highly stressful, demanding period of time. In recent years, the patient's symptoms had escalated to more significant issues with anger, rage attacks, panic, and self-harm. An organic acids test confirmed elevated HPHPA as the primary culprit. A prescription for a multi-strain, high-dose probiotic liberated this patient from years of suffering and removed barriers to success in his young life. This case emphasizes the array of debilitating physical and mental effects that HPHPA can inflict.
I regularly find elevated HPHPA in children with ADHD and autism, and frequently begin immediately with the organic acids test, especially in patients disposed to aggression, angry outbursts, and impulsivity. One patient, a four-year-old boy, was brought into my office by his mother with stereotypical ADHD symptoms that were characterized by many incidences of anger and violence towards others and pets. He often experienced "sensory overload" that triggered tantrums and impulsive, abnormal behaviors, followed by feelings of remorse. Not surprisingly, these episodes resulted in significant problems at home and school. Stimulant medications were ineffective and brought adverse side effects. His urinary HPHPA level, along with several other indicators from the organic acids test, was markedly elevated. A prescription of a multi-strain, high-dose probiotic and restriction of dairy from his diet resolved much of his symptoms and aggression and supported the return to a normal developmental track.
These are two cases that show the profound effect of elevated HPHPA on psychiatric symptoms and the astonishing transformation that can occur in response to simple and straightforward treatments. The HPHPA levels in the organic acids test represents one of the most highly valuable diagnostic tools available to mental health practitioners. Its utility for confirming intestinal dysbiosis has implications for many psychiatric conditions.2,6 Restoring balance to the microbiome can lay the foundation for psychological healing. Psychiatry can no longer be called the measureless medicine. As psychiatrists and mental health clinicians, we understand how to utilize concepts of functional medicine and orthomolecular medicine. We can provide objective personalized treatment to alleviate the pain and anguish of mental illness. I believe testing for HPHPA has the potential to alleviate an inconspicuous source of mental health symptoms and support patients on a road to recovery.
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1. Greenblatt J, To W. Breakthrough Depression Solution: Mastering Your Mood with Nutrition, Diet & Supplementation. Sunrise River Press; 2016.
2. Shaw W. Clostridia Bacteria in the GI Tract Affecting Dopamine and Norepinephrine Metabolism. In Greenblatt, JM and Brogan, K. (Ed.), Integrative Therapies for Depression: Redefining Models for Assessment, Treatment and Prevention. Boca Raton, FL: CRC Press; 2015; pp.31-48.
3. Greenblatt J, Gottlieb B. Finally Focused: The Breakthrough Natural Treatment Plan for ADHD That Restores Attention, Minimizes Hyperactivity, and Helps Eliminate Drug Side Effects. Harmony; 2017.
4. Carding S, et al. Dysbiosis of the gut microbiota in disease. Microbial Ecology in Health and Disease. 2015; 26(1), 26191.
5. Sarkar A, et al. Psychobiotics and the Manipulation of Bacteria–Gut–Brain Signals. Trends in Neurosciences. 2016; 39(11), 763–781.
6. Shaw W. Usefulness of HPHPA marker in a wide range of neurological, gastrointestinal, and psychiatric disorders. 2015. Great Plains Laboratory website. www.greatplainslaboratory.com/articles-1/2015/11/13/usefulness-of-hphpa-marker-in-a-wide-range-of-neurologicalgastrointestinal-and-psychiatric-disorders. Accessed 30 June 2018.
7. Armstrong M, Shaw K. The occurrence of (−)-β-m-hydroxy- phenylhydracrylic acid in human urine. J Biol Chem. 1957; 225: 269–278.
8. Shaw W, Kassen E, Chaves E. Increased urinary excretion of analogs of Krebs cycle metabolites and arabinose in two brothers with autistic features. Clinical Chemistry. 1995; 41(8): 1094-1104.
9. Shaw W. Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia. Nutritional Neuroscience, 2010; 13(3): 135-143.
Dr. James M. Greenblatt, MD, is chief medical officer and vice president of medical services at Walden. He provides medical management, leadership and oversight of Walden's eating disorder and psychiatric programs in Massachusetts and Connecticut. Dr. Greenblatt is board-certified in child and adult psychiatry.
He received his medical degree and completed his adult psychiatry residency at George Washington University in Washington, DC. He completed a fellowship in child and adolescent psychiatry at Johns Hopkins Medical School. In addition, Dr. Greenblatt is a clinical faculty member in the psychiatry department at Tufts Medical School as well as the Geisel School of Medicine at Dartmouth College in New Hampshire.
He lectures extensively throughout the United States and Canada on integrative therapies for mental health. . Dr. Greenblatt is the author of six books including one textbook and books on depression, eating disorders and ADHD. His latest book is on Integrative Therapies for Alzheimer's disease, exploring the research on nutritional lithium. Dr. Greenblatt is the founder of Psychiatry Redefined, a healthcare education training program for integrative psychiatry.
He can be reached at: Walden Behavioral Care, 9 Hope Avenue, Suite 500, Waltham, Massachusetts, 02453; 781-647-2901. For more information on Dr. Greenblatt please visit www.jamesgreenblattmd.com.