Pyroluria and Orthomolecular Psychiatry

I have previously written about psychomotor patterning – an alleged treatment for developmental delay that was developed in the 1960s. The idea has its roots in the notion of ontogeny recapitulates phylogeny, that as we develop we progress through evolutionary stages. This idea, now largely discredited, was extended to the hypothesis that in children who are developmentally delayed their neurological development could be enhanced if they were made to progress through evolutionary stages. Children were put through hours a day of passive crawling, for example, with the belief that this coax the brain into a normal developmental pathway. The treatment was studied extensively in the 1970s showing that the treatment did not work.

However, those who developed this treatment, Doman and Delecato, did not want to give up on their claim to fame simply because it didn’t work and the underlying concepts were flawed. For the last 40 years they have continued to offer the Doman-Delecato treatment for all forms of mental retardation, surviving on the fringe, all but forgotten by mainstream medicine (except by those with an interest in pathological science).

I was recently asked to look into the claims for a disorder known as pyroluria, and what I found was very similar to the history of psychomotor patterning. There was some legitimate scientific interest in this alleged condition in the 1960s. Studies in the 1970s, however, discredited the hypothesis and it was discarded as a failed hypothesis. The published literature entirely dries up by the mid 1970s. But the originators of the idea did not give up, and continue to promote the idea of pyroluria to this day.

The story is told by Dr. Abram Hoffer himself, the originator of the pyroluria hypothesis. It started with a reasonable idea – since LSD mimics some of the clinical findings of schizophrenia, perhaps we can learn something about the biology of schizophrenia by studying the effects of LSD on the body. He specifically looked at the urine of patients given high doses of LSD before and after treatment. He found an increase in an unknown substance. As Dr. Hoffer recounts:

At first we called it the unknown substance (US), and later the mauve factor because when developed on the paper chromatogram it stained a beautiful mauve. When it was identified we called it, more accurately, kryptopyrrole. We named the disease characterized by large amounts of mauve factor “malvaria,” but Dr. Pfeiffer later gave it the more appropriate term pyrolleuria.

He goes on to recount how he and his team found kyrptopyrrole in the urine of patients who are physically ill, those with depression and other mood disorders, and schizophrenics, but not in healthy controls or recovered schizophrenics. So far this all sounds reasonable. It was later found that kryptopyrrole excretion relates to levels of vitamin B6 and zinc in the body, and therefore schizophrenics can be successfully treated with vitamin supplements.

There is nothing implausible about nutritional or biochemical disorder presenting with psychiatric conditions. In fact, acute intermittent porphyria (also believed by Hoffer to be related to kryptopyrrole) is a known biochemical disorder that presents as acute episodes of psychosis (the movie The Madness of King George relates the story of King George III’s bouts of this disease). Schizophrenia is a debilitating disease and it would certainly be very nice if we could cure it (or even a subset of cases) with a vitamin supplement. That is not, however, how the science turned out. Unfortunately, science does not always conform to what we wish to be true.

Pyroluria (which has various spellings, but this seems to be the most common in current use) did not survive replication. A number of studies in the 1970s failed to confirm the presence of kryptopyrrole in the urine of patients with schizophrenia or prophyria. For example, Gendler et al found no hemopyrrole or kryptopyrrole in the urine of healthy subjects or schizophrenics. Jacobson et al found similar negative results.

The pattern is identical to what I found when I researched psychomotor patterning, a string of negative studies in the 1970s followed by the complete disappearance from the peer-reviewed literature, except in journals dedicated to the now fringe idea. In this case Hoffer decided that he was not the victim of a failed hypothesis, but rather the victim of a conspiracy of mainstream psychiatry that was simply closed to his revolutionary ideas. He founded the journal Orthomolecular Psychiatry, now the Journal of Orthomolecular Medicine – a fringe journal in which he could continue to publish his ideas.

I also looked for research on the related but distinct question of using vitamin B6 to treat schizophrenia. If there were any clinically significant effect it should be easy to demonstrate in clinical trials. I found a few double-blind studies and they show two things: Vitamin B6 has no benefit on psychotic symptoms of schizophrenia, but it may have benefit for motor symptoms – specifically Tardive dyskinesia and Parkinsonism as a side effect of anti-psychotic medication. So B6 does not treat schizophrenia itself, but may reduce the motor side effects of medications used to treat schizophrenia. Perhaps this effect is what has led to anecdotal observations of improvements in schizophrenic patients from B6.

Hoffer, in his telling of the tale, has this revealing passage:

Since schizophrenic patients, most of whom had the factor in their urine, responded better when treated with vitamin B3, I concluded that any psychiatric disease, no matter what they were diagnosed clinically, might also do better with this vitamin. This was confirmed by a large series of open clinical studies. I will not term these studies anecdotal, which has become the politically correct term for denigrating any studies that are not double blind, since all clinical studies depend upon the history or herstory of patients and how they respond, i.e. upon anecdotes. The only difference is that in double blind studies the anecdotes are collected by physicians or others who are blinded by not knowing what treatment is being given. At least this is the theory of this type of procedure. In fact, the vast majority of these studies are so imperfectly blinded that few clinician or nurses have much difficulty deciding whether the patient was on placebo or something more active.

Worshippers of the double blind remind me of the emperor whose nakedness was seen only by a child not yet blinded by tradition. This report by Kraus is an excellent example of the type of anecdotal history which has contributed so much to medicine.

The denigration of double-blind studies and the holding up of anecdotal information as reliable is a sure sign of someone on the fringe, not wishing to listen to the scientific evidence but rather to pick the evidence they want to use because it better suits their theories. We have discussed the weaknesses of anecdotal information many times in the past. Anecdotes are overwhelmed by bias and uncontrolled factors. At best they can be used to generate hypotheses, but not to test them. We need double-blind studies to see if alleged effects are real. There is a kernel of truth in what Hoffer says in that not all studies reported as double-blind are reliable, and imperfect blinding can be a major, and often hidden, weakness of clinical trials. But he misses the point in his criticism.

First I need to point out that the “only difference,” as Hoffer claims, is not that the physicians are blinded – the subjects are also blinded (hence double blind). This is critical to controlling for biasing effects. But also the point here is that while anecdotal reports were positive, well-controlled double blind studies of pyroluria (biochemically and clinically) were negative. You cannot explain this pattern of results with improper blinding. Improper blinding causes false positive results – not false negative results, so Hoffer’s objections make no sense. The better controlled studies were negative, that pattern strongly implies the null hypothesis, in this case that pyroluria does not exist as a legitimate entity and vitamin B6 is not an effective treatment for schizophrenia (although it may help reduce the motor side effects of medication).

The bigger picture here (as with psychomotor patterning) is that it is a fundamentally flawed and failed strategy to essentially take your ball and leave the playground when mainstream science does not support your theory. I guess this also depends on your goals. If your goal is to set up your own clinic and make money treating patients according to your own pet theories, then certainly you can follow the Doman and Delecato pathway. If your goal is to convince the world that your ideas are correct, however, this is the wrong path to take. If your goal is to find the truth and develop treatments that are actually effective and helpful for patients, this is also not the right path to take.

Hoffer has had 40 years to do more and more rigorous research, to produce the data that would convince even a skeptical mainstream scientific community that his ideas are correct. If he truly believes that he is right, then this is the path that would help the most patients by changing the standard of care. Rather, he formed his own fringe journal and fringe community where he can brood about the conspiracy of mainstream psychiatry and rail against the dogma of rigorous scientific research.

Posted in: Neuroscience/Mental Health

Leave a Comment (27) ↓

27 thoughts on “Pyroluria and Orthomolecular Psychiatry

  1. WilliamLawrenceUtridge says:

    Though his legacy of quackery will live on forever, staggering from disreputable journal to disreputable journal like a half-eaten zombie, Hoffer himself died in 2009.

  2. EricG says:

    this idea of forcing children through stages sounds roughly similar to that depicted in the film “Temple Grandin.” Pretty decent movie, for those who haven’t seen it.

    This seems to be a pretty plausible treatment, as the actual Temple Grandin seemed to be merely “quirky” in adulthood. Apparently, she was very low functioning on the autism spectrum as a child. But i suppose something like trisomy23 and autism aren’t the same to begin with…

    Any thoughts?

  3. What the studies showed is that when you compare psychomotor patterning therapy to standard therapy, controlling for time of therapy, there was no difference. Any benefit was the result of simply doing stuff and getting attention from a therapist. The interventions that were specific to patterning had no additional benefit.

    People with developmental delay are delayed, not static. They can improve as they mature, and they do benefit from intervention. Partly they have to achieve through training and practice what comes more easily to most everyone else.

    With patterning, however, children are put through hours a day of passive movement, such as crawling. It is very work intensive. It takes over families, who are promised that their child will not only improve but will be cured. When they are not the family is told they did not work hard enough.

    It’s really quite cruel. Now they are also mixing in orthomolecular stuff and other nonsense, like 100% oxygen to make the brain work better. They are really exploiting and hurting families with their pseudoscience.

  4. windriven says:

    “other nonsense, like 100% oxygen to make the brain work better”

    Retrolental fibroplasia was a plague among infants into the early 50s when it became recognized that hyperoxemia was the cause. Does hyperoxemia have clear negative effects on older children as well?

  5. Chris says:

    Dr. Novella:

    Rather, he formed his own fringe journal and fringe community where he can brood about the conspiracy of mainstream psychiatry and rail against the dogma of rigorous scientific research.

    My, that does sound familiar. I believe there are several other conditions being “ignored by medicine” and other brave maverick doctors that have been covered in this blog.

    I don’t remember seeing any psychomotor patterning in the “Temple Grandin” movie. I saw some intensive speech, reading and other therapies, but nothing that resembled holding on the floor and making her crawl in specific manner.

    A very good book to read about one family’s experience with patterning is No Time for Jello, which is unfortunately out of print. They had to buy lots of equipment, and attend conferences in Philadelphia (which were more like sales meetings). If there were any problems with the program the parents were automatically blamed, not the system.

    The patterning could also cause permanent physical damage, as noted by someone on Usenet you experienced if first hand, Questions about patterning was Re: I feel vindicated:

    I also have wearing of my joints and arthritis, which has been attributed to my being taught to keep a rigid posture and closed in body position to hide the muscle movements typical of CP. This didn’t stop the movements, but what it did do was put the strain on my body. As a result, my bones and joints are aging at about 2 times my chronological age, and I will be much less mobile over the long term because of this. I also deal with pain daily because of this.

  6. DugganSC says:

    I have to say that the part of me schooled in English grammar also recoiled when I saw the phrase “history or herstory”. *shudder* The word “history” has nothing to do with the possessive pronoun, “his”. There is no more need to create gendered versions of it than there is for a woman with the last name of Kaufmann deciding to change it to Kaufwomann or Kaufpersonn.

  7. EricG says:

    very interesting. it sounds much like the diet/autism “therapy” whereif you are “cured” it is the result of the therapy, and if you are not it is because you “did it wrong.” it must be nice to account for a 100% cure rate simply by ignoring the lazy people. something comes to mind about prayers being answered…


    yea, i dont think there was any psychomotor patterning as Dr. Novella has put it. It was more along the lines of the mother forcing behaviors that would ordinarily be learned through the normal course of development, like paying attention when someone is talking to you or introducing yourself upon a first meeting. for most kids, it takes…what…3 patient and restrained corrections from a parent? Temple appeared to require…i don’t know, hundreds maybe?

  8. EricG says:


    not sure what this has to do with this post, but I agree. At some point, i suppose i was convinced that “history” was a rather lame attempt at a portmanteau.

    learning an additional language makes you realize how arbitrary word choices actually are and that most of the english lexicon is derived (or literally borrowed) from latin, greek, french and german anyway. As a caveat, at least the language as it was prior to mass media – clearly english has taken on a life of its own since.

  9. Scott says:

    @ EricG:

    English doesn’t borrow from other languages. It corners them in dark alleys, knocks them out, and goes through their pockets looking for loose grammar.

    (Beautiful quote, though I’m not sure of the origin.)

  10. Chris says:


    what…3 patient and restrained corrections from a parent?

    Even for normal kids it could be more often. I just don’t think Ms. Grandin’s mother spent an entire day doing polite introductions.

    I once asked my younger son how many times I had to ask him to do something before he did it, he actually replied “oh, perhaps five or six times.” He regretted that as I continued to repeat that he had to call HR of his work place about his health insurance card (which he lost), sign up for classes and memorize his social security card*. He told me I was annoying him, then I reminded him that he himself told I had to say things multiple times.

    *Zits cartoon from last week:

  11. EricG says:

    @ scott

    classic, google delivered with a copy and paste. turns out, there is more…you left out the funniest quip!

    ““The problem with defending the purity of the English language is that the English language is as pure as a crib-house whore. It not only borrows words from other languages; it has on occasion chased other languages down dark alley-ways, clubbed them unconscious and rifled their pockets for new vocabulary.””

    James Nicoll

  12. EricG says:

    @ Chris

    epically accurate strip. when i reference Grandin, I’m basically interpreting the dramatic flair for reality, ha. though, the director was quite purposeful in having claire daines, as a matter of obnoxious formality, introduce herself before rambling excitedly to a science professor. whatever it may have been, the message of her story seems to be that her mother spent a great deal of time coaching her social skills to great benefit.

  13. Harriet Hall says:

    Re: purity of language

    The word “man” originally meant “person,” and was used to designate any member of the human race. I claim my status as part of the human race and refuse to be disenfranchised by those who would insist on alternating “he” and “she” and other awkward concessions to political correctness. When I see the word “man” in a context that does not mean “male” I’m willing to take the responsibility to remember that women are included, rather than making it the responsibility of the writer to remind me.

  14. Chris says:

    There is a name for the type of therapy you are describing: pragmatic speech therapy. That, along with “social stories” are commonly used for autistic kids and others.

    Having had a child spend years in speech therapy starting as a nonverbal two year old, I know there is homework to be done. It usually consists of adjusting our behavior (use full but simple sentences, repeat back what the child said but insert the missing words, etc), and generally incorporate it into the day. While it does involve much of the day, it is part of the normal routines of the day and if there is a specific sit-down bit, it does not last more than a few minutes (there is a limit of tolerance). There is no resemblance to the demands required by Doman patterning.

    My son received almost four years of intensive speech therapy from a speech therapy charity, the Scottish Rite Center for Speech and Language Disorders, now called Rite Care. After being accepted as a four year old, we had to attend a group class for several days. After I dropped off my younger son (the one who forgot his SSN) at a friend’s house, my son and I would meet his grandmother at the center. While my mother-in-law and I were taught about language disorders, and how we could help my son with his speech in another room college students studying speech therapy would work with the group of kids. Then after a while we joined the kids and worked with improving our interactive skills.

    There was so much to learn, and I was so glad I was exposed to that before I read Glenn Doman’s absolutely terrible book, What To Do About Your Brain-Injured Child. It is just an advertizement for his institute in Pennsylvania.

  15. Chris says:

    (oops, Dr. Hall posted, I was addressing EricG)

    One thing I learned at the speech/language class was how to elicit speech with wordless books. Some of my favorite include David Wiesner’s Tuesday with frogs flying on lily pads and the “Good Dog, Carl” books. The trick is to get the child to verbalize about the silly situations.

  16. lilady says:

    A well-meaning business colleague of my husband, sent us the Delman-Delecato book…personally “autographed” by both authors. I skimmed through and tossed it, based on the premise of patterning to “cure” a neurologically impaired child. My son had physical therapy 2X weekly for his entire life and I did passive range of motion exercises to prevent contractures for my spastic quadriplegic child.

    Here is an interesting website reviewing a book that debunks the Delman-Delecato “patterning” program:

  17. EricG says:

    I’m glad that you found success, Chris. I can only imagine the BS that one would have to wade through with something as tricky as cognitive/social/speech development in children.

  18. Chris says:

    Success? I hope you mean that we found a place of good information. Because my son is still disabled and has several other issues.

    Though I should mention I was subscribed to Skeptical Inquirer before having children, which did inoculate me against lots of nonsense. And trust me, if having a kid makes someone a target of old wives’ tales, it goes up exponentially for a kid with medical issues.

  19. Chris says:

    Gah, I need a grammar check! Sorry about that I’m running out the door.

  20. autismum says:

    Eric G,
    “it sounds much like the diet/autism “therapy” where if you are “cured” it is the result of the therapy, and if you are not it is because you “did it wrong.” ”
    There’s another reason it sounds like the GF/CF diets used to “treat” autism and that’s that some of the proponents of such diets lacking in grain and dairy claim they are akin to “caveman diets.” That this implies that autistic people are somehow less or inadequately evolved is as offensive as it is stupid.

  21. DW says:

    “I have to say that the part of me schooled in English grammar also recoiled when I saw the phrase “history or herstory”. *shudder* The word “history” has nothing to do with the possessive pronoun, “his”. There is no more need to create gendered versions of it than there is for a woman with the last name of Kaufmann deciding to change it to Kaufwomann or Kaufpersonn.”

    I know this is off topic for this blog and maybe a dead topic now anyway, but I have to interject. You are assuming that there is one “right” or legitimate way for language to evolve; that somehow, it’s all right if new forms evolve out of etymologically related forms, but not if words evolve some other way. That’s not correct. Language evolves in many diverse ways. It seems to you like we can’t replace “history” with “herstory” if the change is based on some misunderstanding of the etymology of the word “history,” but in fact, we jolly well can, and linguistic change occurs that way all the time. Much of lanugage development is a “misunderstanding.” On the other hand, it also seems inevitable that linguistic changes will set some people’s teeth on edge.

    I have no personal attachment to “herstory” and am kind of glad the term never really caught on, but I just wanted to correct the linguistic myths being promoted here.

  22. Linda Rosa says:

    It’s heart-breaking to see patterning still being used. Working in home care, I have seen how cruel patterning can be. Families, already fatigued by providing total care for a loved one, may need to enlist and coordinate neighbors (or church groups) for hours of crawling, which can take up to five adults working together with a hoist. I have had no immediate success in talking about patterning, but it might help families decide to give up on it sooner than they might have otherwise.

  23. Miro says:

    “Improper blinding causes false positive results – not false negative results, so Hoffer’s objections make no sense.”

    Unless, there is a conspiracy!

  24. Great post!
    I have nothing central to add, except that Temple Grandin is awesome.

    I do have yet another tangential comment:

    There is no such thing as a schizophrenic.

    There is such a thing as a person with schizophrenia.

    This is not just “PC” talk.

    This is a way of perceiving your clients. You are treating patients, not symptoms, illnesses, a reimbursement printing press, or the computer monitor.

    When you begin treating patients, versus symptoms, a great deal of the all-too-present complaints about physicians will disappear.

    I think SBM is great, and I assume the physicians who post here have great bedside manner. However, my opinion based on experience as a patient and family member of patients is similar to the view of many that physicians, generally, see us as symptoms, or revenue generating opportunities, or otherwise as some annoying problem to be dealt with as quickly as possible, like the pesky mosquito who must be addressed, but the more quickly dismissed the better.

    ^ today, I am stating this a little more boldly than usual because I have had my bias reconfirmed by the comments in this NYT feature, linked below. If you are a physician who sees patients, read a bunch of these comments.

    We all act like those days are long behind us, now that we are all enlightened and have changed medical education. Those comments indicate otherwise.

    Challenge yourself to never again treat a “diabetic” or a “schizophrenic.”

    I did this a long time ago. It has added awkword phrasing to spoken language, and more keystrokes to typing. Poor, poor me. What misery it has been to be inconvenienced to give dignity to a fellow human being.

  25. MedVsTherapy, I appreciate where your heart is on that issue, but I personally would far rather be called “autistic” than “a person with autism.” By using more words to describe someone’s condition, you are actually drawing more attention to it, rather than having it be just another adjective to describe the individual, and by tiptoeing around it preciously, you are implying that “autistic” ( or diabetic, or schizophrenic, or whatever the patient’s condition) has a negative connotation and should be softened rather than just come out and stated. YMMV, of course, but I know I am not the only person who feels this way.

    For the record, I feel the same way about being called “an artist” rather than “a person who does art.” Being a diabetic or schizophrenic, in an ideal world of course, should be no more stigmatizing to call someone than to say they are an artist or a scientist or an engineer.

  26. EricG says:

    @ chris

    yes of course. through the fervor of different comment strings on all sorts of posts, I kinda lost the crux of your story. In any event, I am glad you have found resources that you can trust.

  27. Chris says:

    Eric, skepticism does serve as consumer protection. Always ask questions from those trying to sell you stuff, especially medical and educational.

Comments are closed.