Research into treatments for trichotillomania and skin picking has grown steadily over the past decade. Although no one treatment has been found to be effective for everyone, a number of treatment options have shown promise for many people. At this time, management of these behaviors should begin with education about the disorders, followed by consideration of the treatment options listed below. I would also recommend reading both of these articles about available treatments for trichotillomania. I found them extemely helpful.

Expert Consensus Treatment Guidelines for Trichotillomania and Skin Picking

A Beginner’s Guide to Treating Trichotillomania: Separtating Science from Pseudoscience by Alli Mattu (TTM expert)

I have dedicated this page to research about trichotillomania. Here you can learn more about how and why certain treatments are helpful. Knowledge is power…read on 🙂

 Treatments: Supplements

Research shows that nutritional supplements may help mental health including trichotillomania. Lately I have focused on inositol and NAC as I have heard about these supplements in many trichotillomania communities with varied success.

I started taking NAC (N-acetylcysteine) about five months ago and had noticed a slight decrease in my urge to pull.  I take 3- 600mg capsules in the morning and 3-600mg capsules in the evening, giving me a total of 3600mg of NAC. Doses between 1200-3600mg may be helpful according to this article.

I recently added inositol to increase the benefits of NAC.  It is generally agreed that a large dose is needed for inositol to be effective with trich. I worked my way up to 18g per day. I do this by mixing 3 teaspoons or 1 tablespoon of inositol in water 3 times a day. I have found the Jarrow brand powder dissolves best. It is available on amazon for a reasonable price. I mix it with warm water as it dissolves better that way. You can add it to fruit juice or other sweetened drinks.  I simply mix the powder with ~3 oz. of warm water and drink it plain as it has a mild sweet taste that I actually like.

N-acetylcysteine for Trichotillomania, Skin Picking, and Nail Biting
Jon E. Grant, MD, JD, MPH
University of Minnesota, Department of Psychiatry
TLC Scientific Advisory Board Member
Foreword by TLC Staff
Reprinted from InTouch, Issue #55, © 2009

This article is informational and may not be of use to everyone. If you decide to try NAC on a trial basis, please work with your health care provider to determine if it is appropriate for your body. It is VERY important that you do not mix chemicals, whether they are natural or synthetic or a combination, without a full and complete understanding of the potential interactions. ****Note: As a result of Dr. Grant’s research, TLC has funded a study on the efficacy of NAC for pediatric trichotillomania. We expect to present the results at the 2011 National Conference.

In 2009 , TLC reported on the publication of Dr. Jon Grant’s study, published in the July, 2009 issue of the Archives of General Psychiatry, on the effectiveness of N-acetylcysteine (NAC) as a pharmacological treatment for trichotillomania, skin picking and nail biting. In his report, Dr. Grant wrote that 56% of the subjects experienced a significant reduction in symptoms of these behaviors.
These findings are exciting for a number of reasons. There is now another readily available tool for treating trichotillomania, skin picking and nail biting. Pharmacology studies for trich and related behaviors are rare, and the results of this study are so promising, it will likely lead to more research in the field. Ideally, larger and more complex studies that test a greater sample of patients for a longer duration will be funded. (Note: in issue #54 of InTouch, TLC reported on the funding of a double-blind, placebo-controlled trial of NAC for childhood trichotillomania through TLC’s donor-funded Research Grant Program).
This research is also noteworthy because it is one of the first studies of compulsive behaviors to examine the role of glutamate (a chemical that triggers excitement) rather than serotonin, a naturally occurring chemical most commonly linked to compulsive behavior.

What is N-acetylcysteine?
N-acetylcysteine is an amino acid which can be found at nutrition and health food stores. This supplement affects levels of glutamate in a specific area of the brain, making it easier for patients to decrease unwanted behavior. For that reason, Dr. Grant believes glutamate modulators such as N-acetylcysteine may be applicable to other disorders, addictions, and compulsive behaviors.

Will it work for me?
The study showed that NAC significantly reduced the symptoms of trichotillomania compared to a placebo. 56% of subjects reported “much or very much improved” on NAC compared to 16% on placebo (sugar pill or inert substance). Significant improvement was initially noted after 9 weeks of treatment.
“This study, the first to our knowledge that examines the efficacy of a glutamatergic agent in the treatment of trichotillomania, found that N-acetylcysteine demonstrated statistically significant reductions in trichotillomania symptoms,” wrote Dr. Grant. It is important to note that 44% of the participants in this study failed to respond to the amino acid, and that this was a relatively small study.
As the researchers note, “Cognitive Behavior Therapy has shown benefit for trichotillomania and should be considered in conjunction with pharmacotherapies.”
While N-acetylcysteine was well tolerated by participants in this study, it is always important to discuss taking dietary supplements with your own physician.
What’s next?
Dr. Grant and his team hope their study will lead to further research into the effectiveness of N-acetylcysteine at higher dosages, studies of its use in the long-term treatment of trichotillomania, and its effectiveness in treating patients with various manifestations of the disorder. “As effective treatments for hair pulling emerge, it becomes increasingly important that physicians and mental-health care providers screen for trichotillomania to provide timely treatment,” they wrote in their report.

Read more from Dr. Grant:
Why is this study significant?
Although behavioral therapy has shown benefit for trichotillomania, the use of medications has generally been disappointing. One possible reason is that all of the medications previously studied (clomipramine [Anafranil], fluoxetine [Prozac]) work largely by affecting the neurochemical serotonin. The findings from this study suggest that using medication that targets the neurochemical glutamate may prove more beneficial in controlling the symptoms of trichotillomania.

Limitations of the study?
Although it was the largest randomized, controlled clinical trial performed on trichotillomania, with 50 people, it is still an incredibly small number of people. Also, people pull for many different reasons and may have different biological aspects to their pulling. NAC helped in just about half of the people and so it is hardly a magical pill. The study did not combine NAC with behavioral therapy and it is strongly suggested that anyone taking NAC also use behavioral therapy. In addition, the study was only 12 weeks in duration so it is not clear how long people need to take NAC if it is helpful.

Are there side effects or other problems with NAC?
The subjects in our study did not have problems on NAC. We used a capsule form of the supplement. There is a liquid available from pharmacies but it causes significant side effects and should not be used for this purpose. Side effects reported in the literature have included: nausea, indigestion, headache and abdominal pain. Other issues with NAC include that it should not be used in people with asthma as it may worsen that condition (this is interesting given that it actually helps people with bronchitis). Also, because of the way NAC works in the body, many people recommend supplemental zinc, copper and other trace minerals as well as taking two to three times the typical amount of vitamin C. These recommendations are based on people taking NAC over an “extended period” and, because the scientific literature is unclear what that actually means, it is probably best to take NAC with a multiple vitamin plus vitamin C.
People should be cautioned that although NAC is an amino acid and thereby appears safe, people should always ask their doctors before starting the supplement. In addition, just because something may be good for you in small doses does not mean that more is better or safe.

Could the results apply to skin picking and nail biting?
In my opinion they can. We published a small case series describing the benefits of NAC in people with skin picking and nail biting. Having said that, we have not yet conducted a controlled study of these behaviors using NAC.
What is the optimal dose of NAC and when during the day should people take it?
The answers are still unclear. For our study, we examined dosing between 1200mg and 2400mg per day. I think some people could benefit from higher doses, up to 3600mg per day, but this has not yet been studied in a controlled manner. Over time I’ve learned to start at 1200mg instead of 600mg because the lower dose helps very few people.
In terms of when to take it, I advise people to divide the dose and take it twice a day, perhaps even closer to the times of day when people pull or pick. For example, I give 1200mg as divided doses of 600mg twice a day. Sometimes my dosing depends upon the timing of the pulling. NAC may only stay in the system for about 8-10 hours. Therefore if they pull all day, I divide it as 600mg in the morning and 600mg around dinner. For some people, it is probably out of the system in 3-5 hours.

Where does someone get NAC?
For our study, we bought the product online from a company named Swanson’s in Fargo, North Dakota. I am not endorsing that company and they did not provide us any discounts or funding for our research. They were able, however, to provide us with documentation of the quality of their product. From my perspective, this is a problem in doing research in this area. Which are the reputable companies and which are not? I don’t know enough about makers of nutraceutical products to recommend particular companies. I would suggest asking your doctors or other clinicians about products and suppliers in your areas or online.

Is NAC helpful and safe for children?
The study we conducted was done only on adults with trichotillomania. I know many people want to be able to help their children who suffer from trichotillomania. A study addressing this question is currently being conducted at Yale University and is sponsored by a research grant from TLC. A definitive answer is still pending.
I have used NAC in some adolescents with trichotillomania or skin picking (who have failed to respond to behavior therapy), and have ultimately used the same doses we studied in the controlled trial (1200-2400mg). It appears safe in these young people.
Should it be used in little children?
I would always recommend first trying behavioral therapy and if that is not successful or only partially successful, then I would talk to the child’s pediatrician before starting NAC. Some research studies in children have based the dose on body weight – often trying to reach a target dose of 60mg/kg/day. Of course, it should be started at a lower dose, say 300mg or 600mg per day. I think discussing this with your pediatrician would be potentially helpful.

Final thoughts:
The interest this study has generated has told me that too many people are struggling with this problem and have seen too little improvement from available treatments. Although this study offers hope for better treatments, keep in mind that about half of the people did not respond. The encouraging message from this study is that perhaps we are learning more about what is happening in the brains of people who pull their hair and that we can and will have even better treatments down the road.
Jon Grant, MD, JD, MPH, is an Associate Professor of Psychiatry at the University of Minnesota, and co-directs a clinic for Impulse Control Disorders at the University of Minnesota Medical Center in Minneapolis, MN. Dr. Grant has written over 100 peer-reviewed articles and book chapters on the phenomenology and pharmacological management of impulse control disorders, particularly pathological gambling, kleptomania, and grooming disorders. He is the author of Stop Me Because I Can’t Stop Myself, a book on impulse control disorders published by McGraw-Hill (2002) (co-authored with Dr. Suck Won Kim), and co-editor (along with Marc Potenza) of two books published by the American Psychiatric Association: Pathological Gambling: A Clinical Guide to Treatment (2004) and A Textbook of Men’s Mental Health (in press). Dr. Grant’s research is funded by the National Institute of Mental Health.


There is currently a clinical trial studying inositol and trichotillomania that is expected to end in May 2015. I am eager to learn the results and will post them here as soon as they are available.  I am also trying inositol and will post my experience on the home page.

Inositol and Trichotillomania

  • Fred Penzel, Ph.D.
  • Reprinted from InTouch Issue 25 © 1997
  • © Trichotillomania Learning Center, Inc. 2008. All Rights Reserved

This article is informational only, and may not be of use to everyone. If you decide to try inositol on a trial basis, please work with your health care provider to determine if it is appropriate for your body. It is VERY important that you do not mix chemicals, whether they are natural or synthetic or a combination, without a full and complete understanding of the potential interactions. Just because a product is “natural” does not mean it is always beneficial!

However, it is also important to note that, over the years, many people have reported that dietary changes and various supplements definitely affect the urges to pull and pick, so perhaps this information may add a bit to your trich “tool-box!”

At the American Psychiatric Association (APA) conference in 1996, a paper was delivered on the treatment of obsessive compulsive disorder with inositol, one of the B-vitamins. It seemed to indicate that this might be a viable treatment for OCD. As someone who treats OCD and related disorders, I am always on the lookout for new approaches. I did some further research, and found that since the early 1970s, a number of papers have been published on the use of inositol in the treatment of OCD, depression, and anxiety. It seems that Inositol is converted by the body to a substance that regulates the action of serotonin within brain cells. Serotonin, as we know, is a brain transmitter chemical that has been implicated in OCD and trich. Not all of these studies were conducted in the most scientific manner, but nevertheless, my curiosity had been piqued.

After several discussions with one of the psychiatrists at my clinic, we looked into its safety and possible interactions with other drugs. It appeared that most people took in an average of about 1 grain of inositol each day in their diets. We discovered that apart from some harmless digestive tract side effects, it appeared to be quite tolerable, and would not interact harmfully with any of the SSRIs our patients were taking for their OCD. At about the same time, (September, 1996) a double-blind placebo-controlled study on the use of high doses of inositol was published in the American Journal of Psychiatry. Dr. Mendel Fux and colleagues in Israel conducted the study. Although it was only a small study involving thirteen individuals, inositol was found to have a significant effect upon the symptoms of OCD. It was shown to work as well and as quickly as the SSRIs Prozac and Luvox. The patients in this study had either not been able to find relief via standard medications, or were unable to tolerate medication side effects. Dosages in the study were built up to 18 grams per day.

The article proved to be the convincer for us. We had a number of OCD patients, who were only getting partial relief from prescription antidepressants, so we decided to suggest the possibility of their trying inositol as an augmenting agent, in addition to what they were already taking. I should mention here that our clinic is a rather busy treatment center, and unfortunately, not really geared toward conducting research, so we really didn’t collect any data on this. I know my learned colleagues will shake their heads at this, and they would be right. In any case, we started to see some positive results among approximately 50% of those who tried it. In most cases, these results ranged from at least mild to moderate relief of symptoms. A few reported even more improvement. We have generally built up our patients over a six-week period, starting with 1 teaspoon (2gms) twice per day, and going as high as 3 teaspoons, three times per day. It turned out that not everyone required the full 18 grams used in the Fux study. One person was seen to improve on just 2 grams daily.

Recently, we began to take a second look at some of our trich patients, some of whom, like the study participants, were unable to get help from medications. A few others were somewhat fearful of medications, and were looking for an alternative. We suggested that they try using the inositol in the same manner as our OCD patients. Since that time, we have seen some positive results in several cases, in both children and adults. I have also received some positive calls from various hair pullers around the country who have heard of inositol, and tried it. Although it was probably not as precise as we would have liked, we based our children’s doses on body weight, figuring roughly that a 40-lb. child could tolerate a maximum dose of up to 6gms. of inositol per day.

I do not believe that inositol is a ‘miracle drug’ for everyone with trich. There are no miracle treatments. I am sharing this information with the readership in hopes that it may help at least some people who have not otherwise been able to get relief, or who are too afraid of prescription medications to try anything. I also decided to write about this because I felt that some people might hear of this through some other sources, and try inositol without any guidance.

Please note the following: This advice is purely informational, and not in any way meant to be a substitute for treatment by a licensed physician. Do not try this, or anything else, without first consulting your physician. If your M.D. has not heard about it, refer them to the American Journal of Psychiatry article and let them decide.

Obviously, before you run out and try anything new, you should always consult your physician. If your physician recommends trying this, you might also want to mention the following information to him or her:

  • It cannot be taken together with Lithium, as it seems to block its action.
  • The chief side effects of inositol are gas and diarrhea. Some people get this for the first few days and then it clears up. Some of those taking it never have this side effect, and some only get it when they take more than a particular amount.
  • I have heard reports that caffeine lowers inositol levels in the body, so if you are a heavy coffee drinker, you might consider cutting down or eliminating this from your diet. Actually, stimulants such as caffeine can sometimes contribute to hair pulling, etc.
  • It should be purchased in powdered form, and taken dissolved in water or fruit juice. It has a sweet taste, and is chemically related to sugar. If you mix it continuously for about 2 minutes, and if it is allowed to stand for about 10 minutes after mixing it, it seems to dissolve better. If it still doesn’t dissolve well (not all brands do), stir it up and drink it quickly before it settles.
  • Inositol is a water-soluble vitamin, so although the doses appear to be large, it will not build up to toxic levels in the body. Whatever the body doesn’t use is excreted. The average person normally takes in about 1 gram of inositol each day via the food they eat.

It can be built up according to the following schedule (1 teaspoon=2 grams, and be sure to use a measuring spoon) for an adult:

  • Week 1 – 1 teaspoon/2x per day
  • Week 2 – 1 teaspoon/3x per day
  • Week 3 – 1.5 teaspoons/3x per day
  • Week 4 – 2 teaspoons/3x per day
  • Week 5 – 2.5 teaspoons/3x per day
  • Week 6 – 3 teaspoons/3x per day

A child can be built up to 3 teaspoons per day over the same six-week period. Dosages for adolescents can be adjusted according to weight. In either case, it is best to allow side effects to be the guide. If they begin to occur, it is not considered wise to increase the dosage unless they subside.

Once a person has reached either the maximum dosage, or the greatest amount they are able to tolerate, it is best to try staying six weeks at that level to see if there is any noticeable improvement. If there is none by the end of that time, it should probably be discontinued. As with any treatment, those who are absolutely positive that it will help are only setting themselves up, and may wind up more than disappointed. Everything works for someone, but nothing works for everyone.

One further note: I know personally of one case where an adolescent with trich was administered a combination of inositol and a substance known as 5-HTP, which is a breakdown product of the amino acid L-Tryptophan. The body manufactures serotonin from 5-HTP, and serotonin is believed to be one of the brain transmitter chemicals implicated in trichotillomania. Taking this is believed to raise serotonin levels in the brain. This adolescent got partial results with inositol, and seemed to get a complete remission of the urge to pull with the addition of 100 mg. of 5-HTP daily. 5-HTP can cause drowsiness, and is usually taken at bedtime. It should never be taken with any prescription antidepressant or herbal products such as St. John’s Wort, as it can cause a very serious condition called serotonergic syndrome.

Again, none of the above is meant to be a substitute for expert medical advice. As with inositol, 5-HTP should not be taken without the supervision of a licensed physician. I find reports such as this rather interesting. Further study is clearly needed. It may have implications for the future treatment of trich.

As an interesting side note, a study was published (Seedat et al, 2001) since this article was written, in which three women with hair pulling and compulsive skin picking were treated with inositol. All three were seen to improve and this improvement was seen to continue through a 16-week follow-up period. Hopefully, there will be further studies on the usefulness of this compound.

Inositol in the Treatment of Trichotillomania and Compulsive Skin Picking


When reading about inositol, I found many connections to methylation.  I think The Flying Publisher Guide to Complementary and Alternative Medicine Treatments in Psychiatry by Stadford et al. does a nice job of explaining the methylation cycle and it’s connection to many areas of mental health including trichotillomania.

The Methylation Cycle

“While nutritional supplementation may seem, at first glance, unlikely to impact mental function as significantly as pharmaceuticals, the picture becomes clearer when we take a look at some of the biochemical pathways that affect psychiatric symptoms. Here we see that nutrients are the building blocks of normal cerebral activity and, without them, necessary neural processes cannot occur.

One example of such biochemical activity is the methylation cycle (Figure 4.1). Methylation refers to the transfer of methyl groups (CH3-a carbon atom bonded to three hydrogen atoms) to and from organic molecules, a process that occurs billions of times in the body each day. This process impacts a broad range of physiological and psychiatric issues. Methylation deactivates noradrenalin, for example, a neurotransmitter associated with cortisol and the stress response. Methylation acts on dopamine, norepinephrine and serotonin to impact, among other things, mood, memory, concentration and sleep.

For the methylation cycle to work properly, the correct substrates, or materials, must be available. Nutrients involved in this activity include folic acid (noted by its derivative tetrahydrofolate, or THF, in Figure 4.1), B6, B12, and SAM-e(shown as SAM in Figure 4.1). As expected, supplementation with each of these nutrients has been found to have some psychiatric benefit and deficiencies have been seen to affect brain performance” (Stadford et al, 47-48).

Figure 4.1-A simplified schematic of the methylation cycle.
Figure 4.1-A simplified schematic of the methylation cycle.

Stadford explains that certain nutrients are needed for the methylation cycle to work properly. Although using all of these could be helpful for some people, I would consider the ideas presented by William Walsh, Ph.D. that undermethylated people are made worse by folic acid and B12, while overmethylated people are helped by it. Therefore it is important to figure out which category of methylation you fall into.

Here trichotillomania is grouped as undermethylated and I fit into this category. In my personal trial I will treat myself as an undermethylated person. I hope to have my blood histamine and absolute basophils tested, but am not sure if my GP or psychiatrist will approve the blood work.

In Walsh’s Commentary on Nutritional Treatment of Mental Disorders he gives a thorough explanation of methylation and it correlation to mental health. He is also the first scientist I have heard who specifically discusses trichotillomania in relationship to undermethylation. For this reason, I am very interested in finding out more about his work. In the following excerpt from his work, I have highlighted the information I found post pertinent to myself.


Effective “markers” for methylation are (1) whole blood histamine (ref. levels 40-70 mcg/dL), available from Quest and LabCorp; (2) Absolute Basophils (ref. levels 30-50), available from Direct Healthcare, Inc in the Chicago area.

Elevated histamine and/or elevated basophils indicate undermethylation. Review of symptoms and medical history can bolster the diagnosis. For example, most undermethylated persons exhibit seasonal allergies, perfectionism, strong wills, slenderness, OCD tendencies, high libido, etc. Overmethylated persons generally exhibit anxiety, absence of seasonal allergies, presence of food/chemical sensitivities, dry eyes, low perspiration, artistic/music interests/abilities, intolerance to Prozac and other SSRI’s, etc.

Conditions associated with undermethylation: Anorexia, Bulemia, shopping/gambling disorders, depression, schizo-affective disorder, delusions, oppositional-defiant disorder, OCD.

Conditions associated with overmethylation: Anxiety/Panic disorders, anxious depression, hyperactivity, learning disabilities, low motivation, “space cadet” syndrome, paranoid schizophrenia, hallucinations. (Oct 3, 2003)

One-carbon (methyl) groups are involved in numerous important biochemical reactions in the body, including genetic expression, neurotransmitter synthesis and metabolism, etc. Methylation (more properly, the methyl/folate ratio) is a major factor in the rate-limiting step (the tetrahydrobiopterin reaction) in the synthesis of serotonin, dopamine, and norepinephrine in the brain. Undermethylated persons tend to be depleted in these 3 neurotransmitters, and the opposite is true for overmethylation.

The SAM cycle in which dietary methionine is converted to SAMe (the primary CH3 donor in the body), and then to homocysteine, is a dominant cascade of reactions in methylation and also is very important in production of glutathione, cysteine, and other aspects of sulfur chemistry.

Most persons with depression, oppositional defiant disorder, OCD, bipolar disorder, or schizophrenia exhibit a genetic abnormality in methylation….. which appears to be central to their illness. Carl Pfeiffer, MD, PhD of Princeton, NJ was a pioneer in this field. (Oct 3, 2003)

About 25 years ago, Dr. Carl Pfeiffer (Princeton, NJ) identified the condition he called “histapenia” or histamine deficiency. After studying the metabolism of more than 20,000 schizophrenics he learned that this  “low histamine” syndrome was common in anxiety, panic disorders, and classical paranoid schizophrenia. His enormous biochemistry database revealed that most histapenics suffered from (1) copper overload and (2) deficiency of folic acid and/or B-12. More importantly, he found that aggressive therapy using folic acid, B-12, and B-3 usually produced dramatic improvements in these persons. Pfeiffer thought the improvements were largely due to elevating histamine levels in the body & brain.

Subsequent research has indicated that the improvements are due to normalizing the methyl/folate ratio. This ratio is important in the BH4 rate-controlling step in catecholamine synthesis (dopamine & norepinephrine). Also, methyl/folate abnormalities can impact genetic expression of many biochemicals. At any rate, too much methyl results in overproduction of DA and NE, and vice versa.

Also, a serious overload of homocysteine (homocysteinuria) can result in symptoms quite identical to paranoid schizophrenia. Folic Acid & B-12 serve to lower HCy levels.

One thing that is absolutely certain is that methionine and/or SAMe usually harm low-histamine (overmethylated persons)….. but are wonderful for high-histamine (undermethylated) persons. The reverse in true for histadelic (undermethylated) persons, who thrive on methionine, SAMe, Ca and Mg….. but get much worse if they take folates & B-12 which can increase methyl trapping.

I guess the bottom line is that undermethylated persons generally exhibit very elevated folate levels…. and these persons get worse if additional folate is given.

This is a fairly complex subject, and some of my medical staff are still struggling with the concept. However, they have the solace of knowing the clinical impact of methylation or folate therapy on persons with specific methylation/histamine disorders.

It’s certainly true that whole blood histamine is compromised by AH treatments (including antigens and many psychiatric medications). We’ve gotten quite proficient in taking these factors into account. Fortunately, the ABC test doesn’t suffer from this disadvantage. Also, the syndromes of over-methylation and under-methylation are well defined…. and a medical history & review of symptoms greatly aids the diagnosis. (Oct 6, 2003)

The generalization that perfume and other chemical sensitivities are associated with overmethylation, low blood histamine, and elevated norepinephaine… is exactly that…a general rule with many exceptions.  However, the correlation seems to be above 90 percent in the case of perfume sensitivity.  Whenever a patient enters our clinic wearing a mask to filter out inhalant chemicals, we immediately suspect the overmethylation syndrome.  The chemical testing usually confirms this diagnosis, but there definitely are a few persons who have severe perfume sensitivity for other reasons.  We’ve evaluated about 19,000 persons, including about 1500 with anxiety disorder or panic disorder.  Hundreds of these patients reported sensitivity to perfumes.  Nearly 90 percent of the perfume-sensitive group were overmethylated, and reported multiple chemical and food sensitivities. usually in the absence of seasonal inhalant allergies.  Perfume sensitivity is a classic symptom of these high nonepinephaine persons, who usually respond beautifully to folate/B-12 therapy [1 Dec -03]

Inositol is especially helpful for undermethylated persons (for example most persons with OCD), but can cause negative side effects in those who are overmethylated. Since Inositol is one of the primary second messengers in neurotransmission, it’s surprising is isn’t more commonly used. It’s especially useful in reducing anxiety and enhancing sleep.

To enhance sleep for a 160 lb person, we usually recommend 650 mg tablets, 1-3 as needed for sleep. Persons who have difficulty falling asleep should take it 30-60 minutes before sleep. Persons whose main problem is waking up in the middle of the night should take it at bedtime.

We’ve often given as much as 3-4 grams/day to undermethylated persons who respond beautifully to Inositol, and these persons take it morning, noon, and evening.

I once gave an invited presentation at a symposium at an APS annual meeting… in which data on megadoses (15-30 g) of Inositol were reported by another speaker. The volume of Inositol used seemed extreme to me, and would present daunting compliance problems. I believe such huge doses of Inositol are unnecessary, if methionine, calcium, B-6, and other nutrients to combat undermethylation are used. However, massive doses of Inositol might be needed if one tries to combat OCD with Inositol alone. 

Regardless of the form of inositol, its use should be started as a trial, with close monitoring of patient. We’ve found that persons who achieve improved sleep after inositol are excellent candidates for taking it throughout the day also. I recommend you be alert for adverse side effects, especially with persons with severe anxiety or panic symptoms

Trichotillomania has been associated with OCD and undermethylation. If you can confirm the presence of undermethylation, the patient should benefit from (1) aggressive doses of l-methionine, calcium, magnesium, along with augmenting nutrients zinc, B-6, Inositol, Vitamin A & C and (2) strict avoidance of folic acid, choline, DMAE, and copper supplements

Aggressive methylation therapy can be very successful, but usually involves a very slow response. Typically, treatment with methionine, calcium, magnesium, B-6, etc requires about 2 months before the patient before any progress is evident — and 6-12 months are required for all of the benefits to be attained. Please note that whole blood histamine is a marker for innate methylation tendency, but is not an indicator of wellness or the degree to which undermethylation has been overcome. Undermethylated patients can become quite well without their histamine lab results changing at all.

One way to speed up the process of recovery is to use SAMe supplements in the beginning. Undermethylated patients usually report nice progress after the first week or two. SAMe is quite expensive, and can be gradually replaced by methionine after a couple of months.

Nearly all severely undermethylated persons have low serotonin levels and present with a history of depression, internal anxiety, and OCD. Many have a history of perfectionism and high accomplishment in the early years.  Unfortunately this population also has a tendency for non-compliance with any treatment.

The late and great Carl Pfeiffer would occasionally resort to use of the anti-histamines Benedryl or Dilantin in high-histamine persons who were slow to respond. Avoidance of folate supplements is essential for most undermethylated persons, an exception being autism.

Some practitioners like to tinker with the SAM cycle to promote conversion of homocysteine to methionine, but this can deplete the cystathione pathway and result in deficiencies of glutathione, cysteine, etc. Some persons have a genetic enzyme weakness which can disrupt the SAM cycle

Undermethylated adults typically require 2,000 – 3,000 mg/day of methionine for several months to see good results. Also, augmenting nutrients such as calcium, magnesium, B-6, and zinc are essential.

TMG generally provides some benefits to undermethylated persons, but tends to make oxidative stress protections worse by diminishing the amount of homocysteine which converts via the cystathione pathway of the SAM cycle.TMG certainly is a promising nutrient for such persons, and adding some cysteine or glutathione can overcome the cystathione pathway deficit.

Personally, I believe the use of SAMe is the quickest way to help an undermethylated, high-histamine person.


SAMe is very promising for undermethylated persons and a bad idea for those who suffer from a genetic tendency for overmethylation. I don’t particularly like the “allopathic” method you referred to which is simply trial & error. SAMe can do great harm if given to the wrong person. I hate going to funerals. (17 Dec, 2002)

The mechanisms of action of SAMe and TMG are quite different. Most of our methyl groups come from dietary methionine. The methionine is converted to SAMe in a reaction with magnesium, ATP, methionine-adenosyl-transferase, and water. SAMe is a relatively unstable carrier of methyl groups and is the primary source of methyl for most reactions in the body. Once the methyl group has been donated, the residual molecule is s-adenosyl-homocysteine which converts to homocysteine. TMG (betaine) is a biochemical which can donate a methyl group to homocysteine, thus converting it back to methionine. The TMG route is secondary to the 5-methyl-tetrahydrofolate/B-12 reaction which the primary route for restoring methionine. Methionine and SAMe supplements directly introduce new methyl groups into the body. TMG can provide a methyl group only to the extent that there is insufficient folate/B-12 to do the job. In some persons, the methylation effect of TMG is very minimal. In addition, persons who are undermethylated have a SAM cycle which is “spinning very slowly”, much like a superhighway with little traffic. The answer for them is NOT to more efficiently convert the small amount of homocysteine to methionine (using TMG), but rather to directly introduce more methionine or SAMe into the body. A small percentage of persons with sufficient dietary methionine cannot efficiently produce SAMe — These persons need supplemental SAMe, and not methionine or TMG and are the exception to the rule. In most other cases, methionine supplements alone are sufficient. TMG is a great way to treat individuals with dangerously high homocysteine levels. TMG can be very useful in augmenting methionine therapy along with B-6/P-5-P , serine, etc. The challenge is to supply enough methyl groups to help the patient, without creating dangerously high levels of homocysteine. Use of TMG is an “insurance policy” against this happening. (Jan 22, 2003)

A quick way to test for need for methylation therapy is to carry out a cautious trial of SAMe. Within a week or two you should have your answer. If she clearly is improving on the SAMs (which is frightfully expensive)….. you can get usually the same benefits (albeit more slowly) using methionine plus calcium, magnesium, and B-6. This should be side-effect free unless (a) the methylation is begun too abruptly or (b) the patient has a rare genetic enzyme disorder which disrupts the SAM cycle. We’ve found that direct methylation is usually more successful than tinkering with the SAM cycle. The primary way humans receive most of their methyl groups is from dietary methionine. It’s often hard to improve on Mother Nature. (Jan 20, 2003)

SAMe is likely to cause great worsening of symptoms, including mania, if given to an OVER-methylated person. The incidence of overmethylation in our patient database of 1,500 bipolar cases is about 18%. Bipolar disorder is not a single condition, but a collection of very different biochemical disorders under the same umbrella diagnosis. SAMe works great for truly undermethylated patients, but all hell breaks out if given to someone who is overloaded (genetically) with methyl groups. The right way to do this is to (a) first determine the person’s innate methylation tendency & then (b) act accordingly. (Jan 31, 2003)

Stadford, D, Vickar, G, Berger, C, & Cass, H. (2012). The flying publisher guide to:

Complementary and alternative medicine treatments in psychiatry (8th ed.). Flying Publisher.

Walsh, W. (2013). Commentary on Nutritional Treatment of Mental. Illinois: Walsh Research  Institute.


I suffered from recurrent strep infections as a child.  The onset of my trichotillomania at age 6 coincided with these infections and I think there is a correlation based on my research of P.A.N.D.A.S.  Here is a good article that explains how Obsessive Compulsive Disorders can be triggered by a phenomenon called “P.A.N.D.A.S”, or Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections.

Obsessive Compulsive Disorders, Obsessive Compulsive Spectrum Disorders, and the P.A.N.D.A.S. Connection

Elizabeth Bryan

As someone who’s been plagued by an Obsessive Compulsive Spectrum Disorder since childhood, I can say it seems hopeless at times. For so long a sufferer feels that what they have isn’t a legitimate ailment and that he is alone in his battle. Thankfully, in recent years, more and more research is being done on Obsessive Compulsive Disorders, and more answers are being found.

Obsessive Compulsive Disorders are the fourth most common psychiatric diagnosis. Sometimes the onset of symptoms is sudden, but more often than not it is a gradual progression. Precipitating events that could spur the onset of an Obsessive Compulsive Disorder can include emotional stress (domestic or job-related), increased levels of responsibility, health problems, and bereavement. According to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, “the essential features of an Obsessive Compulsive Disorder are recurrent obsession or compulsions that are severe enough to be time consuming (i.e.: they take more than an hour per day) or cause marked distress or significant impairment. At some point during the course of the disorder, the person has recognized the obsessions or compulsions are excessive or unreasonable. It’s important to note that this is difficult concerning children because children tend to not realize that their compulsions are excessive or unreasonable while adults do ((1) .).

People develop compulsions by trying to ignore thoughts or impulses, or by trying to neutralize them with other thoughts or actions. Compulsions are mental acts, and include repeating words, ordering things, hand washing, and various other motions. The goal of these compulsions is to prevent or reduce anxiety.

Because Selective Serotonin Reuptake Inhibitors (SSRI’s) such as Prozac, Luvox, Zoloft, and Paxil are effective in controlling Obsessive Compulsive Disorders, it’s believed that serotonin regulation is a part of the cause of OCD. Serotonin is a very important chemical messenger in the brain, and plays a role in a person’s mood, aggression, impulse control, sleep, appetite, body temperature, and pain. Brain imaging studies have depicted various abnormalities in parts of the brains of Obsessive Compulsive Disorder sufferers. These parts include the caudate nucleus, the basil ganglia, the thalamus, orbital cortex, and cingulated gyrus.

Disorders that have the obsessive compulsive symptoms of intrusive, repetitive behaviors are often called OC Spectrum Disorders. Amongst these include Trichotillomania, Monosyruptomatic Hypochondriasis, Body Dismorphic Disorder, and some eating disorders. Other disorders also coexist with Obsessive Compulsive Disorders, and are referred to as Comorbid Disorders. The most common Comorbid Disorder is depression.

Trichotillomania is the chronic, repetitive pulling of bodily hair, most often being from the scalp, eyebrows, eyelashes, and pubic areas. Sufferers feel great anxiety before pulling, and feel a sense of relief after pulling out their hair. While more research needs to be done on Trichotillomania, it is believed to be related to abnormalities in brain function.

Body Dismorphic Disorder is “characterized by preoccupation with a minor bodily defect or imagined defect which is believed to be conspicuous to others” (Pedrick, #1). Repetitive Body Dismorphic Disorder behaviors include mirror checking, grooming, shaving, washing, skin picking, weight lifting, and comparing self with others. Both Trichotillmania and Body Dismorphic Disorder can be treated with medication and cognitive behavior therapy.

It is now widely believed that in many cases Obsessive Compulsive Disorders are triggered by a phenomenon called “P.A.N.D.A.S”, or Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections. This term is used to describe children who have Obsessive Compulsive/”Tic” disorders (such as Tourette’s Syndrome) in which symptoms worsen after a strep infection(2) ..

It’s recently been found that in some children, the natural antibodies developed in their blood to fight a strep infection not only attacked the strep, but also attacked perfectly healthy cells as well, including the basal ganglia region, which controls the body’s motor movements, and it also known to have abnormalities in OCD sufferers. Generally the onset of tics or compulsions is abrupt in P.A.N.D.A.S. cases, and may occur within days, weeks, or months following a strep infection.

Dr. Susan Swedo has been the most prolific researcher of P.A.N.D.A.S., and is the head of the Behavioral Pediatrics Department of the child psychiatry branch of the National Institute of Mental Health. Her department has been studying OCDs and their links to strep infections since 1986. According to Dr. Swedo, if the following criteria are met, a diagnosis of P.A.N.D.A.S. may be made:

1. “The presence of an OCD or tic disorder
2. Pediatric onset of symptoms (age three to pre puberty)
3. Abrupt onset or dramatic exacerbation of symptoms
4. Symptom exacerbation related to a strep infection
5. Neurological abnormalities during the exacerbation periods, which could include unwarranted fears, fidgeting, and difficulty in school” (2) .

Dr. Swedo also notes that if P.A.N.D.A.S. hasn’t occurred by age twelve or thirteen, it most likely never will.

New treatments are being experimented with for P.A.N.D.A.S. In 1999, Dr Swedo reported at the annual meeting of the American Academy of Child and Adolescent Psychiatry that plasmapheresis was successful in treating P.A.N.D.A.S. Dr. Swedo cited a preliminary study in which twenty-eight children were randomly assigned to receive plasmapheresis, intravenous immunoglobulin, or a placebo infusion. Tics declined fifty percent within one month in the plasmapheresis patients and twenty-five percent in the patients who received the immunoglobulin. No change was seen in the placebo group. Obsessive Compulsive Disorder symptoms were reduced by sixty percent with plasmapheresis, by forty-five percent with immunoglobulin, and virtually not at all with the placebo infusion(3) ..

Children treated with plasmapheresis showed greater improvement on global functioning measures, and their total improvement went on for over a month after their treatment. In the children who received the plasmapheresis, brain structures such as the caudate nucleus, basal ganglia, and globus pallidus, which are enlarged during P.A.N.D.A.S. flares, normalized. Dr. Swedo even said in some cases the difference in the size of the caudate nucleus is visible(3) ..

Thankfully, for OCD, OC Spectrum Disorders, and P.A.N.D.A.S. sufferers, more research is being completed everyday. Because significant research has only begun since the late 1980s, what is known now will be considered little in the years to come. The Plasmapheresis treatments now being experimented with look very promising in treating P.A.N.D.A.S. In terms of other OCDs, OC Spectrum Disorders, and Comorbid Disorders, cognitive therapy as well as medications have proved to be very effective. In my own experience with an OC Spectrum Disorder and depression, the combination of the right serotonin medication and therapy have proved very successful in allowing me to go on with my life without worrying about such disorders on a daily basis, as sufferers of these disorders often do.

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