Mental Health

Integrative Therapies for Obsessive Compulsive Disorder

James Greenblatt, MD

While it is human nature to occasionally ruminate or overanalyze important decisions, these thought patterns normally dissipate quickly freeing us of those fleeting moments of inner turmoil.  However, for those suffering from Obsessive Compulsive Disorder (OCD), letting go of repetitive thoughts is not so effortless.  Relentless ideas, impulses, or images inundate the brain leaving the individual mentally imprisoned to an existence of recurrent, irrational thought patterns.  These senseless obsessions often drive the individual to perform ritualistic behaviors or compulsions, in an effort to temporarily relieve their anxiety.  Sufferers stagger through life with a sense of pure powerlessness against their disorder; fully aware that the behavior is abnormal, yet unable to stop.

Psychotropic medications such as selective serotonin reuptake inhibitors (SSRI’s) and Anafranil and cognitive behavioral therapy are the conventional treatment options for Obsessive Compulsive Disorder. Sadly, the likelihood of complete recovery from OCD has not been shown to exceed 20% and relapse is quite common.  Inadequate treatment and limited biomedical options contribute to the high relapse rate as conventional medicine does not address underlying nutritional deficiencies or the root cause. Though unlikely to be caused by deficiencies alone, addressing vital nutrient depletions is a critical aspect of treating OCD since certain vitamins, minerals, and amino acids significantly impact serotonin neurotransmission.  Specifically, natural therapies including: 5-HTP, niacin (B3), pyridoxal-5-phosphate (B6), folate (5-MTHF), vitamin C, zinc, magnesium, inositol, and taurine are important to serotonin synthesis.  Therefore, the combination of aforementioned nutrients taken in therapeutic dosages should be part of integrative treatment approach for Obsessive Compulsive Disorder.

The fourth most common psychiatric illness in the United States, Obsessive Compulsive Disorder or “OCD” onset typically occurs by adolescence usually between the ages of 10-24, with one third of all cases appearing by age 15. In fact, OCD is said to be more common than asthma and diabetes (Schwartz, 1997). Despite its prevalence, it is often under diagnosed and under treated with more than half of those suffering receiving no treatment at all for their condition.  Gender does not affect susceptibility, as men and women are equally affected by this detrimental disorder. 

To fully grasp the inner workings of OCD, consider Jeffrey Schwartz’s description of “Brain Lock” (Schwartz, 1997) where four key structures of the brain become locked together sending false messages that the individual cannot interpret as false.  The brain is made up of two structures called the caudate nucleus and the putamen, which can be compared to a gearshift in a car.  According to Schwartz, “The caudate nucleus works like an automatic transmission for the front, or thinking part, of the brain…the putamen is the automatic transmission for the part of the brain that controls body movements… the caudate nucleus allows for the extremely efficient coordination of thought and movement during everyday activities.  In a person with OCD, however, the caudate nucleus is not shifting gears properly, and messages from the front part of the brain get stuck there.  In other words, the brain’s automatic transmission has a glitch.  The brain gets ‘stuck in gear’ and can’t shift to the next thought” (Schwartz, 1997).

It is clear that enhancing serotonin neurotransmission through psychotropic medications helps the brain “shift into gear” so to speak.   But what exactly causes this glitch that leads to serotonin deficiency syndrome? A number of factors including genes, diet, stress, neurotoxins, and inflammation are responsible for inadequate serotonin synthesis.  Amino acid availability for neurotransmitter synthesis is dependent upon certain digestive enzymes, and their activation is dependent on hydrochloric acid.  Without sufficient amino acid availability, neurotransmitter synthesis will suffer.  Specifically, availability of the essential amino acid L-tryptophan is required for serotonin production.  Because serotonin synthesis depends on the availability of L-tryptophan and essential cofactors including vitamin B3, folate (5-MTHF), vitamin B6, and zinc, serotonin levels will be less than optimal if any of the required building blocks are deficient.  The process of serotonin synthesis starts when L-tryptophan is converted into 5-hydroxytryptophan with the help of tryptophan hydroxylase (a vitamin B3 dependent enzyme), which requires 5-MTHF.  5-hydroxytryptophan (5-HTP) then converts to serotonin with the aid of decarboxylase, vitamin B6 dependent enzymes, and zinc.

Supplemental 5-hydoxytryptophan (5-HTP) can be beneficial for individuals as it essentially bypasses the need for L-tryptophan availability.  Easily crossing the blood brain barrier, 5-HTP works like a targeted missile directly increasing brain serotonin levels.  It does not require a transport molecule for crossing the blood brain barrier, and unlike L-tryptophan, it is shunted from incorporation into proteins and niacin conversion (Birdsall, 1998).  What’s more, promising research indicates that the therapeutic effect of 5-HTP compared to fluoxetine (Prozac), is actually equal (Jangid et al., 2013). Antidepressant effects are experienced in as little as two weeks with 5-HTP; effectively treating individuals with varying degrees of depression (Jangid et al., 2013).There has been four research studies looking at 5-HTP supplements specifically for OCD. Clinicians around the globe, for more than twenty years, have had success with amino precursors including 5-HTP for the treatment of OCD. I recommend starting all patients with 50 mg of 5-HTP and titrate slowly every 2 weeks up to a maximum of 200 mg per day. Side effects of 5-HTP include nausea, irritability, and possible anxiety.

In addition to the influence of digestive health on serotonin synthesis, absorption of vital minerals specifically zinc and magnesium, are also impacted by Hydrochloric Acid (HCL) availability.  Thus, if HCL and digestive enzyme production is low, mineral deficiencies will likely follow.  This is worth noting because optimal levels of zinc and magnesium are imperative to maintaining healthy serotonin levels, while moderating the activity of glutamate receptors. As stated previously, zinc is an important coenzyme required for decarboxylase activation and the conversion of 5-HTP to serotonin.  Magnesium also plays an essential role, aiding the conversion process of L-tryptophan to serotonin.

In addition to zinc and magnesium, folate plays a critical role in serotonin neurotransmission.  Specifically, the enzyme responsible for converting L-tryptophan to 5-HTP, requires 5-MTHF, also known as “L-Methylfolate.”  Without sufficient folate, L-tryptophan will struggle to convert to 5-HTP.  Research on depression and folate is extensive; hundreds of studies support the relationship between folate and depression.  Thus, it is imperative to consider folate status when treating OCD.   Specifically, low folate levels are associated with increased incidence of depression, poor response to antidepressants, and higher relapse rates.  Because dietary sources of folate are heat labile and easily oxidized (more than 50% is oxidized during food processing) folate malabsorption and deficiency is quite prevalent in our society.  To make matters worse, individuals taking certain medications such as anticonvulsants, oral contraceptives, antacids, antibiotics, and Metaformin are at increased risk of deficiency. 

Individuals that possess genetic polymorphisms in the gene coding for the methylenetetrahydrofolate reductase (MTHFR) gene are at high risk for low folate status due to reduced ability to convert folic acid to its active form. Folic acid requires a four step transformation process to be converted to L-methylfolate, where dietary folate requires three steps.  MTHFR polymorphisms reduce efficiency of this transformation process; severely impacting conversion of folic acid to L-methylfolate.  Since L-methylfolate is the active absorbable form of folate that crosses the blood brain barrier for use, inability to properly convert dietary or supplemental folic acid may cause folate deficiency (Lewis et al., 2006).

Inositol has proven particularly effective for SSRI resistant patients as well.  Specifically, OCD patients experiencing lack of response to SSRI’s or clomipramine have been examined.  There are research studies demonstrating dosages of 18/gms of inositol per day was effective in OCD treatment.  Improvement in symptoms had been reported at 6 weeks of treatment with no reported side effects (Fux et al., 1996).  A promising finding, inositol is an effective natural therapy for OCD treatment when taken on its own.  It is particularly helpful to individuals who are unresponsive to conventional SSRI treatment.  However, at this time use of inositol as an augmentation agent to improve SSRI function has not been proven effective (Fux et al., 1999).

Inositol’s effect on treatment resistant patients is likely due to its role in the neurotransmission process.  Operating as a secondary messenger, it enhances the sensitivity of serotonin receptors on the postsynaptic neuron using signal transduction.  Upon binding to its receptor, messages from serotonin are then translated into signals that are expressed through behaviors such as positive mood, relaxation, and reduced obsessions.  Due to its role in serotonin signaling, patients resistant to SSRI treatment may not necessarily have an issue with serotonin synthesis but rather decreased receptor sensitivity.

Controlled trials of inositol have confirmed therapeutic effects in a wide spectrum of psychiatric illnesses generally treated with SSRI’s including: OCD, Major Depressive Disorder, Panic Disorder, and Bulimia.  In particular, children exhibiting OCD symptoms have shown considerable life altering improvements with inositol treatment. For instance, “S.M.” a socially withdrawn, 11 year old child who obsessively feared fire and contamination, transformed into a “completely different child” with inositol treatment.  Similarly, “P.J.”, treated with inositol and 5-HTP, showed significant improvement in OCD symptoms.  A third clinical case, “C.K.” had suffered immensely with severe adverse side effects to Celexa and Prozac including aggressive thoughts of self-harm.  Upon treatment with inositol, no side effects were reported and minimal improvement was even displayed.  Even though research studies suggest 18 grams of Inositol per day, I start all patients with OCD on approximately 3 grams of Inositol per day (1/2 Tsp. 3 times per day).this minimizes GI side effects including bloating and nausea. If needed, Inositol dosages can be titrated up slowly with most patients responding below 12 grams per day.

Improving serotonin production and neurotransmission is integral to boosting serotonin levels and combating symptoms of OCD.  However, preventing over-activity of neurotransmitters should also be considered.  Taurine is an essential amino acid and precursor to GABA, an inhibitory neurotransmitter.  A regulatory agent, GABA helps maintain healthy serotonin levels and reuptake.  Widely known for its calming effect, taurine’s therapeutic use for anxiety and depression treatment has been explored.  In one study, animals fed a high taurine diet for 4 weeks exhibited anti-depressive behavior (Caletti, 2015).  Furthermore, a study on mice indicated a reduction in anxiety where taurine was administered 30 minutes before anxiety tests (Kong et al., 2006).  Though taurine does not directly target serotonin production, it is still worth noting as its inhibitory effect may reduce racing thoughts associated with anxiety disorders such as OCD.

Based on extensive scientific evidence supporting the relationship of aforementioned nutrients to serotonin production, as well as decades of clinical experience, I developed SeroPlus (   SeroPlus is a nutritional supplement to help patients with OCD and depression.   The formula provides serotonin building blocks including therapeutic doses of 5-HTP (direct precursor to serotonin), Inositol, and Taurine in addition to vital cofactors magnesium, vitamin C, pyridoxal-5- phosphate (activated B6), and Metafolin® (activated folate). Inositol elevates sensitization of serotonin receptors while taurine maintains healthy sympathetic nervous system tone and moderates serotonin activity and reuptake.  The formula also includes niacin and zinc picolinate which enhance availability of 5-HTP by reducing the amount of 5-HTP used for activation and absorption of these nutrients.  Synergistically, these ingredients work effectively together to optimize serotonin production and restore healthy serum levels of common deficiencies contributing to abnormalities in serotonin neurotransmission.

As with any psychiatric illness, treating OCD is complex and requires a comprehensive multi-prong approach beyond basic SSRI prescriptions and behavioral therapy.  Although directly enhancing serotonin production through natural therapies such as 5-HTP as well as correcting underlying B3, B6, zinc, magnesium, folate, and inositol deficiencies is at the heart of integrative treatment there are a number of alternative factors that may be contributing to the cause. Low levels of B12, DHA, and vitamin D must be addressed. 

A prisoner to their own thoughts, OCD sufferers are frustrated and searching for alternative treatment options.  The complex etiology of OCD includes genetics, inflammation, and the dysfunction of serotonin synthesis.  While SSRI’s may enhance serotonin synthesis, a number of OCD patients do not experience long term results.  Thus, identifying key nutrient depletions and replenishing them through dietary modification and supplementation is essential to increasing chances of long term recovery. 

James M. Greenblatt, MD, is the author of Finally Focused: The Breakthrough Natural Treatment Plan for ADHD (Harmony Books, 2017). He currently serves as Chief Medical Officer and Vice-President of Medical Services at Walden Behavioral Care, and he is an Assistant Clinical Professor of Psychiatry at Tufts University School of Medicine and Dartmouth Geisel School of Medicine. An acknowledged expert in integrative medicine, Dr. Greenblatt has lectured throughout the United States on the scientific evidence for nutritional interventions in psychiatry and mental illness. For more information, visit


  1. Birdsall. (1998). 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. Aug; 3(4): 271-80.

  2. Caletti. (2015). Antidepressant dose of taurine increases mRNA expression of GABAA receptor α2 subunit and BDNF in the hippocampus of diabetic rats. Behav Brain Res. 2015 Apr 15; 283:11-5.

  3. Fux et al. (1996). Inositol treatment of obsessive-compulsive disorder. Am J Psychiatry, Vol 153(9) 1219-1221.

  4. Fux et al. (1999). Inositol versus placebo augmentation of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder: a double blind cross-over study. International Journal of Neuropsychopharmacology 2, 193-195.

  5. Jangid et al. (2013) Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian J Psychiatr. Feb;6(1):29-34

  6. Kong. (2006). Effect of taurine on rat behaviors in three anxiety models. Pharmacol Biochem Behav. Feb; 83(2):271-6.

  7. Milner. (1963). Ascorbic acid in chronic psychiatric patients. Brit J Psychiatr 109; 294-299.

  8. Schwartz, Jeffrey M. Brain Lock: Free Yourself from Obsessive-Compulsive Behavior . Harper Perennial; 1st edition, 1997.

Magnesium: The Missing Link in Mental Health?

by James Greenblatt, MD

Chief Medical Officer at Walden Behavioral Care in Waltham, MD
Assistant Clinical Professor of Psychiatry at Tufts University School of Medicine and Dartmouth College Geisel School of Medicine

Magnesium is a cofactor in more than 325 enzymatic reactions—in DNA and neurotransmitters; in the bones, heart and brain; in every cell of the body. Unfortunately, a deficiency of this crucial mineral is the most common nutritional deficiency I see in my practice as an integrative psychiatrist. Fortunately, supplementation with magnesium is the most impactful integrative treatment I use, particularly in depression and attention deficit hyperactivity disorder (ADHD).

Why is magnesium deficiency so common, and why is restoring the mineral so essential to mental and emotional well-being and behavioral balance? The rest of this article addresses those two questions, and presents aspects of my therapeutic approach.

Magnesium Deficiency

 The population is deficient in magnesium—found abundantly in whole grains, beans and legumes, nuts and seeds, and leafy greens, as well as cocoa and molasses—for several reasons.

Soil depletion. Intensive agricultural practices rob the soil of magnesium and don’t replace it. As a result, many core food crops—such as whole grains—are low in magnesium. A recent paper in Crop Journal put it this way: Magnesium’s “importance as a macronutrient ion has been overlooked in recent decades by botanists and agriculturists, who did not regard Mg deficiency in plants as a severe health problem. However, recent studies have shown, surprisingly, that Mg contents in historical cereal seeds have markedly declined over time, and two thirds of people surveyed in developed countries received less than their minimum daily Mg requirement.” [1]  

Food processing. Magnesium is stripped from foods during food processing. For example, refined grains—without magnesium-rich germ and bran—have only 16% of the magnesium of whole grains. [2]

Stress. Physical and emotional stress—a constant reality in our 24/7 society—drain the body of magnesium. In fact, studies show inverse relationships between serum cortisol and magnesium—the higher the magnesium, the lower the cortisol. Stress robs the body of magnesium—but the body must have magnesium to respond effectively to stress.

Other factors. Many medications—such as medications for ADHD—deplete magnesium. So does the intake of alcohol, caffeine and soft drinks.

The result: In 1900, the average intake of magnesium was 475 to 500 mg daily. Today, it’s 175 to 225 mg daily. Which means that only one-third of adult Americans get the daily RDA for magnesium—320 mg for women, and 420 mg for men. (And many researchers consider the RDA itself inadequate.)  And that magnesium deficit causes deficits in health. Magnesium deficiency has been cited as contributing to atherosclerosis, hypertension, type 2 diabetes, obesity, osteoporosis and certain types of cancer. [4] But detecting that deficiency in laboratory testing is difficult, because most magnesium in the body is stored in the skeletal and other tissues. Only 1% is in the blood, so plasma levels are not a reliable indicator. That means a “normal” magnesium blood level may exist despite a serious magnesium deficit. An effective therapeutic strategy: Assume a deficit is present, and prescribe the mineral along with other appropriate medical and natural treatments. That’s particularly true if the patient has symptoms such as anxiety, irritability, insomnia and constipation, all of which indicate a magnesium deficiency.

The Mind Mineral

Some of the highest levels of magnesium in the body are found in the central nervous system, with studies dating back to the 1920s showing how crucial magnesium is for a balanced brain…

It’s known, for example, that magnesium interacts with GABA receptors, supporting the calming actions of this neurotransmitter. Magnesium also keeps glutamate—an excitatory neurotransmitter—within healthy limits. Patients with higher magnesium levels also have healthy amounts of serotonin in the cerebrospinal fluid. And the synthesis of dopamine requires magnesium.

In summary, the body needs magnesium to create neurotransmitters (biosynthesis) and for those neurotransmitters to actually transmit. Magnesium also acts at both the pituitary and adrenal levels. In the pituitary gland, it modulates the release of ACTH, a hormone that travels to the adrenal glands, stimulating cortisol release. In the adrenal gland, it maintains a healthy response to ACTH, keeping cortisol release within a normal range. As a result, magnesium is a must for maintaining the homeostasis of the HPA axis. Given all these key mechanisms of action, it’s not surprising that a lack of the mineral can produce psychiatric and other types of problems. The patient may have: Difficulty with memory and concentration. Depression, apathy and fatigue. Emotional lability. Irritability, nervousness and anxiety. Insomnia. Migraine headaches. Constipation. PMS. Dysmenorrhea. Fibromyalgia. Autism. ADHD. Fortunately, studies show that magnesium repletion—restoring normal levels of the mineral—produces positive changes in mood and cognition, healthy eating behavior, healthy stress responses, better quality of sleep, and better efficacy of other modalities, such as medications. Let’s look at two areas in which magnesium supplementation is particularly effective: Depression and ADHD.


A cross-sectional, population-based data set—the National Health and Nutrition Examination Survey—was used to explore the relationship of magnesium intake and depression in nearly 9,000 US adults. Researchers found significant association between very low magnesium intake and depression, especially in younger adults. [5] And in a recent meta-analysis of 11 studies on magnesium and depression, people with the lowest intake of magnesium were 81% more likely to be depressed than those with the highest intake. [6] In a clinical study of 23 senior citizens with depression, low blood levels of magnesium and type 2 diabetes, magnesium was compared to the standard antidepressant medication imipramine (Tofranil)—one group received 450 mg of magnesium daily and one group received 50 mg of imipramine. After 12 weeks, depression ratings were equally improved in both groups. [7] In my practice, I nearly always prescribe magnesium to a patient with diagnosed depression. You can read more about the integrative approach to depression in Integrative Therapies for Depression: Redefining Models for AssessmentTreatment and Prevention (CRC Press), which I co-edited, and in Breakthrough Depression Solution: Mastering Your Mood with Nutrition, Diet & Supplementation (Sunrise River Press, 2nd Edition).

Attention Deficit Hyperactivity Disorder

Magnesium deficiency afflicts 90% of all people with ADHD and triggers symptoms like restlessness, poor focus, irritability, sleep problems, and anxiety. These symptoms can lessen or vanish one month after supplementation starts. Magne­sium can also prevent or reverse ADHD drug side effects. That’s why all of my ADHD patients get a prescription for magnesium. For adolescents, I typically prescribe 200 mg, twice daily. For children 10 to 12, 100 mg, twice daily. For children 6 to 9, 50 mg, twice daily. Typically, I recommend magnesium glycinate, using a powdered product. I describe my entire approach to magnesium and ADHD (and to the disorder’s overall integrative treatment) in my book Finally Focused: The Breakthrough Natural Treatment Plan for ADHD That Restores AttentionMinimizes Hyperactivity, and Helps Eliminate Drug Side Effects. (Forthcoming from Harmony Books in May 2017)

Dosage and Form

I have found that 125 to 300 mg of magnesium glycinate at meals and a bedtime (four times daily) produces clinically significant benefits in mood. (This form of magnesium is gentle on the digestive tract.) 200 to 300 mg of magnesium glycinate or citrate before bed supports sleep onset and duration through the night. You can also find magnesium in powder or liquid form, which are effective alternatives to capsules, particularly for children with ADHD. Ways to increase the bioavailability of magnesium include: Supplementing with vitamin D3, which increases cellular uptake of the mineral. Vitamin B6 also helps magnesium accumulate in cells. Taking the mineral in divided doses instead of a single daily dose. Taking it with carbohydrates, with improves absorption from the intestine. And taking an organic form, such as glycinate or citrate, which improves absorption by protecting the mineral from antagonists in the digestive tract. Avoid giving magnesium in enteric-coated capsules, which decreases absorption in the intestine.

Magnesium oxide is poorly absorbed and tends to cause loose stools. Magnesium-l-threonate has been shown to readily cross the blood-brain barrier, and animal studies show that it supports learning ability, short and long-term memory and brain function, I don’t typically prescribe it, however, because of its higher cost, and the clinical effectiveness of other forms. The therapeutic response to magnesium typically takes several weeks, as levels gradually increase in the body.


[1] Guo W., et al. Magnesium deficiency in plants: An urgent problem. The Crop Journal, Volume 4, Issue 2, April 2016, Pages 83-91.



[4] Volpe, SL. Magnesium in Disease Prevention and Overall Health. Advances in Nutrition, 2013 May; 4(3): 378S-383S.

[5] Tarleton EK, at al. Magnesium Intake in Depression in Adults. Journal of the American Board of Family Medicine, 2015 Mar-Apr;28(2):249-56.

[6] Li B, et al. Dietary magnesium and calcium intake and risk of depression in the general population: A meta-analysis. Australian and New Zealand Journal of Psychiatry, 2016 Nov 1. [Epub ahead of print].

[7] Barragan-Rodriquez L, et al. Efficacy and safety or oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial. Magnesium Research, 2008 Dec;21(4):218-23.

The Little Lauded Benefits of Lithium

Heather Getz

While most know lithium as a drug (or the title of a popular song by 90's grunge band, Nirvana), it's also an element (a salt) that occurs naturally and is present in our drinking water here in the United States in varying amounts, depending on where you live. While it seems it's not being talked about much, there is a great deal of evidence in the scientific community that even very small doses of lithium may be beneficial to mental health. Several studies have shown it to be effective in many areas, from reducing rates of suicide and dementia to treating bipolar disorder (see below for a list of studies).

Dr. Nassir Ghaemi, professor of psychiatry at Tufts University School of Medicine said, "Lithium is, by far the most proven drug to keep neurons alive, in animals and in humans, consistently and with many replicated studies". So why aren't more people in the mainstream or even integrative and alternative medicine groups giving it serious consideration? Dr. Peter D. Kramer, clinical professor of psychiatry at Brown University suggested that mainstream doctors may "distrust low-dose supplements as somehow ineffective or like homeopathy" and that the alternative medicine crowd "may shun it because – though it's a salt found in groundwater – lithium already has an identity as a powerful, marketed medication for mental illness".

There has been a considerable amount of research done on the effects of both naturally occurring lithium (in tap water) and on dietary supplementation on a variety of mental health disorders. You may review some of that research and decide whether lithium supplementation is a possible treatment for any of your patients.

Clinical References

  • Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr (2002) 21(1):14-21.
  • Dawson EB. The relationship of tap water and physiological levels of lithium to mental hospital admission and homicide in Texas, in Schrauzer & Klippel, Eds. Lithium in Biology and Medicine. Cambridge, VCH, 1991:169-188.
  • Schrauzer GN, Shrestha KP. Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions. Biol Trace Elem Res (1990) 25(2):105-113.
  • Schrauzer GN, de Vroey E. Effects of nutritional lithium supplementation on mood: A placebo-controlled study with former drug users. Biol Trace Elem Res (1994) 40(1):89-101.
  • Nunes MA, Viel TA, Buck HS. Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease. Curr Alzheimer Res (2013) 10(1):104-107.
  • Forlenza OV, Diniz BS, Radanovic M, et al. Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial.Br J Psychiatry (2011) 198(5):351-356.
  • Straten G, Saur R, Laske C, et al. Influence of lithium treatment on GDNF serum and CSF concentrations in patients with early Alzheimer's disease. Curr Alzheimer Res (2011) 8(8):853-859.
  • Leyhe T, Eschweiler GW, Stransky E, et al. Increase of BDNF serum concentration in lithium treated patients with early Alzheimer's disease. J Alzheimers Dis (2009) 16(3):649-656.
  • Nierenberg A, Friedman E, Bowden C, et al. Lithium treatment moderate-dose study (LiTMUS) for bipolar disorder: A randomized comparative effectiveness trial for optimized personalized treatment with and without lithium. The American Journal of Psychiatry (2013) 170(1):102-110
  • Geddes, J, Miklowitz D. Treating of bipolar disorder. The Lancet (2013) 381(9878):1672 – 1682 doi:10.1016/S0140-6736(13)60857-0
  • Cipriani A, Hawton K, Stockton S, Geddes J. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ (2013) 346:f3646 doi:
  • Other reference for article:

    Fels, Anna (2014 September 14). Should We All Take a Bit of Lithium? The New York Times. Retrieved from

The Role of Diet and the Gut in Mental Health

Terri Hirning

While the traditional mental health model focuses on brain function, neurotransmitters and potentially pharmaceutical medications, the ever burgeoning integrative mental health field understands there is more to it than that. Even mainstream media is starting to get the hint. Our gut influences our mind, emotions, cognition and mental health more than we've given it credit for in recent history. Whether we want to focus on the role food allergies play on mental health (1), (2) or how the gut-brain axis impacts our mental health (3), or even how the microbiome shapes our mental functioning (4) we can see the trend in research confirming what many integrative physicians and clinicians know: the gut matters

When we talk about the gut, we must cover diet. Some literature even suggests that a debilitating mental health disorder like Alzheimer's now be called "Type 3 Diabetes" (5) because of its links to certain kinds of foods and a generally poor diet. What is causing the alarming trend of food allergies, food sensitivities and the increase in auto-immune conditions? Is it GMO's? Is it Glyphosate (the herbicide used in products like Monsanto's Roundup)? Is it the prevalence of processed grains in our diets now? It may be all of thesethings, or none of these things, but as physicians and clinicians, the data suggests we take a closer look at our patients' diets and here are some things to consider:

Is there an underlying food allergy or multiple allergies? This can be an easy and yet very powerful place to start. Research shows that food allergies can indeed cause manifestations of mental health disorders. Running a simple IgG food allergy test from the Great Plains Laboratory, which also includes markers for Candida (harmful fungus in the gut) can be a great first step. More mainstream information on the treatment of Celiac disease can be also helpful in finding its connections to many mental health disorders like dementia, seizures, schizophrenia, etc.(6), and one does not have to be diagnosed with Celiac disease to be sensitive and reactive to gluten.

What about healthy gut function and microbiome population? Our microbiome is sensitive to our diets, and quickly reactive to changes. Looking at potential gut dysbiosis and the levels of beneficial flora in the gut is very important. An organic acids test will show you a wide range of metabolic markers, including several for bacteria (like Clostridia) and fungus (like Candida albicans) in the gut. If a patient has high levels of these, a course of treatment can be started to rid them of these invaders, possibly including dietary restrictions (like a low sugar, low carb diet) and adding helpful antibacterial or antifungal supplements. Then, to assess the beneficial bacteria in the gut, you may want to run a comprehensive stool analysis. This will help determine whether a patient needs to add a high-quality probiotic supplement to their diet and possibly increase his/her intake of probiotic-rich and fermented foods like kefir and sauerkraut.

Today's mental health disorders are very complex. Their treatment requires a well-rounded look at the many factors impacting the body and brain, including diet, lifestyle, the microbiome, and more. When an integrative approach is used and these many factors considered when creating a treatment plan, time and time again we see improvements in functioning and a reduction in clinical symptoms.

Clinical References:

  • Jackson J1, Eaton W2, Cascella N3, Fasano A4, Santora D5, Sullivan K6, Feldman S6, Raley H7, McMahon RP6, Carpenter WT Jr6, Demyanovich H6, Kelly DL8.Gluten sensitivity and relationship to psychiatric symptoms in people with schizophrenia Schizophr Res. (2014) Oct 10. pii: S0920-9964(14)00511-8. doi: 10.1016/j.schres.2014.09.023.
  • Genuis SJ1, Lobo RA2. Gluten sensitivity presenting as a neuropsychiatric disorder . Gastroenterol Res Pract. (2014);2014:293206. doi: 10.1155/2014/293206.
  • Nemani K1, Hosseini Ghomi R2, McCormick B3, Fan X3. Schizophrenia and the gut-brain axis. Prog Neuropsychopharmacol Biol Psychiatry. (2014) Sep 19;56C:155-160. doi: 10.1016/j.pnpbp.2014.08.018.
  • Severance EG1, Yolken RH2, Eaton WW3. Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling. Schizophr Res. (2014) Jul 14. pii: S0920-9964(14)00319-3. doi: 10.1016/j.schres.2014.06.027.
  • De la Monte S, Wands J. Alzheimer's Disease Is Type 3 Diabetes–Evidence Reviewed. J Diabetes Sci Technol. (2008) 2(6): 1101–1113.
  • Velasquez-Manoff Moises (2014 October 12). Can Celiac Disease Affect the Brain? The New York Times. Retrieved from:

Usefulness of HPHPA marker in a wide range of neurological, gastrointestinal, and psychiatric disorders

William Shaw, Ph.D.

The dysbiosis marker 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), the predominant dihydroxyphenylpropionic acid isomer in urine, is also measured in the Organic Acids Test offered by The Great Plains Laboratory. This marker was proven by Dr. William Shaw to be due to a combination of human metabolism and the metabolism by a group of Clostridia species, including but not limited to C. difficile. 

HPHPA has been one of the most useful clinical markers in recent medical history. Treatment with metronidazole, vancomycin, or high doses of probiotics of individuals with high urinary values has led to significant clinical improvements or remissions of psychosis.

The biochemical role of Clostridia in altering brain neurotransmitters is due to the fact that Clostridia metabolites inactivate dopamine beta-hydroxylase, leading to an excess production of brain dopamine and reduced levels of the neurotransmitter norepinephrine. Excess dopamine is associated with abnormal or psychotic behavior. This imbalance can be demonstrated in the Organic Acids Urine Test by observing the ratio of the major dopamine metabolite, homovanillic acid (HVA), to that of the major norepinephrine metabolite, vanillylmandelic acid (VMA) when the Clostridia marker HPHPA is elevated. After treatment with metronidazole or vancomycin, HPHPA values return to normal along with normal ratios of HVA/VMA and normal behavior. 

The highest value of HPHPA was measured in the urine of a young woman with first onset of schizophrenia. Treatment of Clostridia bacteria resulted in loss of auditory hallucinations. In autism, children with gastrointestinal Clostridia commonly exhibit aggressive behavior, agitation, obsessive compulsive behavior, and irritability. They may have very foul stools with diarrhea with mucus in the stools although some individuals may be constipated. Stool testing for Clostridia is usually of limited usefulness since most Clostridia species are considered probiotics or beneficial. There are about 100 species of Clostridia that are commonly found in the gastrointestinal tract. Only seven of these species are producers of HPHPA including C. sporogenes, C.botulinum, C. caloritolerans, C. angenoti, C. ghoni, C.bifermentans, C. difficile, and C. sordellii while C. tetani,C. sticklandii, C. lituseburense, C. subterminale, C.putifaciens, C. propionicum, C. malenomenatum, C.limosum, C. lentoputrescens, C. tetanomorphum, C.coclearium, C. histolyticum, C. aminovalericum, and C.sporospheroides do not produce compounds that are converted to HPHPA.

The same article by Dr. Shaw indicates that 3,4-dihydroxyphenylpropionic acid (DHPPA) is a marker for beneficial bacteria in the gastrointestinal tract such as Lactobacilli, Bifidobacteria, and E. coli. The exception is one species of Clostridia orbiscindens that can convert the flavanoids luteolin and eriodictyol, that occur only in a relatively small food group that includes parsley, thyme, celery, and sweet red pepper to 3,4-dihydroxyphenylpropionic acid. The quantity of C. orbiscindens in the gastrointestinal tract is negligible (approximately 0.1% of the total bacteria) compared to the predominant flora of Lactobacilli, Bifidobacteria, and E. coli (7). DHPPA is an antioxidant that lowers cholesterol, reduces proinflammatory cytokines, and protects against pathogenic bacteria. 2,3-Dihydroxyphenypropionic acid, a different isomer has been claimed to be a metabolite of Pseudomonas species but the literature indicates that this compound is formed by the in vitro action of these species on quinoline, a component of coal tar, a substance missing from the diet of virtually all humans. 


1. 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. Nutr Neurosci. 2010 Jun;13(3):135-43.