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Carl Pfeiffer

Side stitch when running or exercising: the anxiety/stress connection (and the pyroluria protocol of zinc and vitamin B6 as a solution?)

August 4, 2023 By Trudy Scott 21 Comments

side stitch and anxiety

If you get a painful side stitch when running or doing other exercise or experienced a side stitch  when you were a kid, you may be as intrigued as I was to learn there is new research that points to an anxiety/stress connection. This cross-sectional observational study was done involving an anonymous survey of one hundred sixty-eight male and female adults who were running at least 10 miles/16 km per week.

The conclusion of this study, Thorn in Your Side or Thorn in Your Head? Anxiety and Stress as Correlates of Exercise-Related Transient Abdominal Pain, is as follows: “anxiety and stress are associated with the presence of ETAP.” A runner’s side stitch is referred to as ETAP i.e. exercise-related transient abdominal pain. The authors mention the fact that this is the first study to reveal this anxiety/stress connection. This is relevant given the numerous recent studies looking for a cause and no definitive solutions.

This research is also really intriguing to me given what Dr. Carl Pfeiffer MD, PhD, identified 50+ years ago in the 1970s i.e. side stitches are common in those with pyroluria/social anxiety. What’s important is the fact that the pyroluria nutrient protocol eases social anxiety and prevents side stitches in my clients. You’ll read feedback from individuals in the community who resonate with this research and the pyroluria connections. I share more about pyroluria below in case it’s new to you and a possible cause of the side stitch pain.

My feedback and feedback from others in the community

I have pyroluria and always got a left side stitch as a kid, in my teens when running and playing squash and in my 20s/30s when running. And then they stopped (and the social anxiety and related symptoms resolved) when I addressed my pyroluria with zinc, B6 and EPO, and a copper-free multi that contains manganese. I see these kinds of results with my clients all the time so a light-bulb went off when I read this new research .

I shared this research and the anxiety/stress/pyroluria connection on Facebook and asked: did you/do you get side stitches when running/exercising? Here is some of the feedback I received, where the pyroluria protocol did help.

Kameka shared this: “I had side stitches as a kid and as an adult. Running was the main exercise that caused it and it was usually the left side. Now that you mention it, I haven’t had them since I started supplementing for pyroluria. Also, my social anxiety is sooo much better as well!”

She did the symptoms questionnaire and the pyroluria urine test (which can give false negative results) and confirmed she takes vitamin B6, zinc, magnesium, and primrose oil.

Bec shared this: “I hated PE at high school for that reason. While everyone was running, I was suffering from side stitches (I think it was my right side) and having breaks. I have pyroluria with lots of symptoms. I do well with zinc and P5P.”

Not everyone reported an improvement with the protocol but many folks resonated with the side stitch/pyroluria connections:

Megan said: “Couldn’t run as a kid. A stitch every time. I can’t recall which side, never really paid too much attention. Looking at the pyroluria symptoms, I think I may have always had it.”

Janie exclaimed: “Oh, boy, did I!” (while distance running). She finds it hard to remember but thinks it may have been on her right side. She also shared that “tests for zinc come back normal, but I have many of the [pyroluria] symptoms, especially the less common ones. I scored high. I always want breakfast but all the other questions fit me like a glove, like pieces of a puzzle with my photo on the box.

My lack of dream recall is another sign. I take 25 mg of methylated B6, but still no dreams. The question regarding being seated in the middle of a restaurant…THAT IS ME!! My throat will feel like it’s closing up, so much tension.”

I explained that most zinc testing is not accurate and that we increase until we get symptom resolution. I also referred her to the pyroluria chapter in my book.

Susie shared this: “Yes I always got side stitches so I gave up running. I suspected pyroluria but not sure if I have it.”

Leah said “I’d say my daughter and I both [had side stitches] more when we were younger. Both socially anxious and pyroluria. Less exercising now too.”

Information if you’re new to pyroluria

Pyroluria is frequently associated with a type of anxiety characterized by social anxiety, avoidance of crowds, a feeling of inner tension, and bouts of depression. People with this problem experience varying degrees of anxiety or fear, often starting in childhood, but they usually manage to cover it up and push through. They tend to build their life around one person, become more of a loner over time, have difficulty handling stress or change, and have heightened anxiety symptoms when under more stress.

Also on the list of symptoms is this one: “Upper abdominal pain on your left side under the ribs or, as a child, having a stitch in your side as you ran.”

Addressing low levels of the mineral zinc and vitamin B6, together with some other nutrients and stress management, are key to addressing these symptoms.

Here is the complete symptoms questionnaire on the blog. This questionnaire can also be found in the pyroluria chapter in my book, The Antianxiety Food Solution. You’ll find the detailed supplement protocol and additional information on how to assess for low zinc and low vitamin B6 in this chapter too.

You can read more about the prevalence and associated conditions here. It’s most often considered a genetic condition but is possibly environmentally triggered too.

There are many pyroluria blog posts where I cover various aspects such as the importance of addressing pyroluria for recovery from MCAS and Lyme, pyroluria and Ehlers Danlos Syndrome, pyroluria and intrusive thoughts and many more. I encourage you to use the search feature on the blog.

A possible cause of the side stitch in pyroluria

Here is an excerpt from a paper published in 1974 by Dr. Pfeiffer and colleagues, Treatment of Pyroluric Schizophrenia Malvaria With Large Doses of Pyridoxine and zinc, describing why the side pain probably occurs:

This 15-year-old upper middle-class patient (now 19 after studying for four years) represents a case of nutrient deficiency in which vitamins (specifically B6) and the trace minerals manganese and zinc were inadequate for the development of normal knee joints and normal brain function.

The deficiency was sufficiently severe at its peak to cause prolonged psychosis, atypical seizures, arthritis, amenorrhea, constipation, and splenic pain. The pain is probably due to hemolytic crisis in which red cell fragments engorge the Kupfer cells of the spleen and liver, extend the capsule, and cause pain. The double deficiency is produced by the formation of KP [kryptopyrroles] which combines with pyridoxal and zinc.

Based on the above and other publications by Dr. Pfeiffer, when the stitch happens on the left side, my understanding is that the pain is in the spleen. And when it happens on the right side, the pain is in the liver area. Most individuals with pyroluria say they felt/feel their side stitch on the left side. Either way it appears to be caused by low zinc, low vitamin B6 and the other nutrients needed by those with pyroluria. And resolved when on the pyroluria protocol.

I would love to see these ETAP researchers take their anxiety/stress research one step further and identify how common pyroluria is in runners who get side stitches and if the pyroluria protocol prevents the side stitches.

My book as a resource and pyroluria supplements

As mentioned above, there is an entire chapter on pyroluria in my book, The Antianxiety Food Solution – How the Foods You Eat Can Help You Calm Your Anxious Mind, Improve Your Mood, and End Cravings, I highly recommend getting it and reading it before jumping in and addressing these deficiencies. And be sure to share it with the practitioner/health team you or your loved one is working with.

Keep in mind that these nutrients are cofactors for making neurotransmitters and are a key part of my protocol when working with individual amino acids.

The book doesn’t include product names (per the publisher’s request) so this blog, The Antianxiety Food Solution Amino Acid and Pyroluria Supplements, lists the pyroluria supplements and amino acids that I use with my individual clients and those in my group programs. You can find them all in my online store.

If you are a practitioner, join us in The Balancing Neurotransmitters: the Fundamentals program. This is also a paid online/virtual program with an opportunity to interact with me and other practitioners who are also using the amino acids and pyroluria protocol.

Thanks to everyone who contributed to the discussion on Facebook. Now I would love to hear from you so I can approach the authors with their feedback and yours too.

Did you get a side stitch as a kid and did it affect your ability to take part in school sports?

Do you still get a side stitch when running or doing other exercises? If yes, does it hold you back and with which exercise?

Did/does the side stitch occur on the left or right side?

And do you have pyroluria? (based on the symptoms questionnaire and/or pyroluria urine test)?

Does the pyroluria protocol prevent your painful side stitches? And had you made the connection to pyroluria/anxiety/stress?

Are you seeing a similar pattern with your kid/s? (pyroluria, side stitch and the protocol helps them too)

If you have questions and feedback please share them here too.

Filed Under: Anxiety, Exercise, Pyroluria Tagged With: anxiety, Carl Pfeiffer, ETAP, exercise, exercise-related transient abdominal pain, exercising, liver, painful side stitch, pyroluria, running, side stitch, social anxiety, spleen, stress, vitamin B6, zinc

Methylation and anxiety: histadelia and histapenia

May 13, 2015 By Trudy Scott 64 Comments

carl pfeiffer nutrition and mental illness

In preparing for the Anxiety Summit I put out a call for questions for my methylfolate interview with Dr. Ben Lynch: How Methylfolate can make you Feel Worse and even Cause Anxiety, and What to do about it  This question was posted on my blog and since it’s a big topic I feel it deserves a separate blog post

This is the question that Paula posted:

If my understanding is correct, William Walsh of the Walsh Research Institute explains that folates of any kind (methylfolate, folic acid, etc) will cause there to be less serotonin activity at the synapse because folates promote the expression of the SERT enzyme which increases serotonin reuptake. He warns that those who are undermethylators should not take folate if they have cognitive/mood issues, as it will make their anxiety or depression worse. Since those with the MTHFR gene defect are likely undermethylators, his advice contradicts Dr Lynch’s advice regarding the use of folate. Could you ask Dr Lynch if he has any opinion regarding this?

Dr. Walsh has treated over 30,000 patients with mental health problems and has one of the largest lab chemistry data bases in the world. It would be great to see the top doctors collaborating on the methylation cycle as it seems to be a large piece of the puzzle for so many people. Maybe a methylation summit? It’s such a complicated and confusing subject and there seems to be some contradictory information out there.

This was my response:

These are excellent questions you bring up!

The terminology can be confusing so I will recap my understanding here:

Undermethylators/high histamine/histadelia = folate not good
Overmethylators or low folate/low histamine/histapenia = folate helps symptoms

This is from the work of Carl Pfeiffer (his book “Nutrition and Mental Illness” is excellent) and is also written about in Joan Matthews Larson’s wonderful book “Depression-Free Naturally” and Eva Edelman’s “Natural Healing for Schizophrenia.”

As you’re aware Dr. Walsh uses this terminology too. His book is “Nutrient Power.” Here is a snippet from a powerpoint of his called The Role of Epigenetics in Mental Health 

Undermethylated mental patients are intolerant to folic acid, but most overmethylated mental patients improve after folic acid supplements.

Folic Acid generates acetylase enzymes that alter histones, promoting expression of SERT and DAT transporter proteins. SERT and DAT enhance reuptake at serotonin and dopamine synapses…. thus reducing NT activity.

For undermethylators, the harmful impact of folic acid at NT synapses greatly exceeds the benefits of normalizing methylation.

So there is a place for methylfolate. I don’t know anything about SERT and DAT transporter proteins so can’t comment on that aspect, but look forward to learning more.

You say “Since those with the MTHFR gene defect are likely undermethylators.” I don’t know that this is a true statement. I would love to see a source for this? It’s certainly not the case with me – I have the MTHFR 1298C defect and have low histamine/histapenia/overmethylation (using the Carl Pfeiffer terminology).

As far as I’m aware Dr Walsh does NOT feel the MTHFR defects play a role in all of this. I hope to learn more and interview him on a future Anxiety Summit.

I have not seen Dr. Lynch write about histapenia and histadelia or the work of Carl Pfeiffer, although some recent comments in this blog  refer to Walsh and Dr. Lynch says he’ll check it out.

Dr. Lynch is not a big fan of the terms overmethylation and undermethylation. And when he talks about overmethylation and undermethylation I think he is referring to the methylation process being more effective/speeding up and being less effective/slowing down within a few days of adding methylfolate supplements.

So I feel we have some terminology differences AND some differences of opinions.

Both Dr. Walsh and Dr. Lynch see amazing results with their patients/clients but I agree with you – I’d love to clear up some of the confusion. I’m going send this question and my answer to Dr. Lynch for our interview next Friday. Since he may need to do some additional prep/research, we may have to do a deeper dive into this question on a future summit. Hopefully he’ll be able to add something to the discussion this time.

I did also interview Yamsina (www.thelowhistaminechef.com) for this summit and she too was not familiar with the work of Carl Pfeiffer so it’s exciting that we can all learn from each other and advance the field.

Finally, this is not all bad because it gets us thinking and asking questions and digging deeper.

Paula then has this follow-up question:

The following quote from this link gave me the impression that the MTHFR mutation usually caused undermethylation, but farther down it also references where Dr Walsh says it’s possible to have MTHFR and not be undermethylated.

In your opinion, do people fall into either an overmethylated or undermethylated status or can you be an undermethylator in certain areas of the methylation cycle and an overmethylator in other areas of the cycle? If someone has some traits of an undermethylator and some traits of an overmethylator, what would you recommend?

Dr. Walsh: Based on my massive chemistry database, about 22% of the population is undermethylated and 8% overmethylated. These are inborn tendencies that usually persist throughout life. Undermethylation usually results from single nucleotide polymorphisms (SNPs) that weaken MTHFR or other enzymes in the methylation cycle. Overmethylation is generally caused by enzyme weaknesses (SNPs) in the SAMe utilization pathways.

What are your thoughts on using genetic testing, such as “23 and Me” to create an individual methylation roadmap/treatment plan.

Dr. Walsh: Genetic testing is quite inexpensive, highly accurate, reliable, and will certainly grow in importance in future years. These tests can already identify predispositions for many disorders such as breast cancer and Alzheimer’s and may soon obsolete the need for pap smears. However the reliability of genetic testing for assessing methylation is quite limited at present.

Identifying SNP weaknesses in MTHFR and other methylation-cycle enzymes does not necessarily mean that individual is undermethylated. There is a “tug-of-war” competition between enzyme SNPs that weaken methylation and SNPs in the SAMe utilization pathway that can produce overmethylation.

I believe you’re right Trudy in saying this is not all bad because it gets everyone thinking and digging deeper. I think both Dr Lynch and Dr Walsh bring invaluable information to the discussion, each adding something that can further illuminate how this complicated process works. Thanks again to you for providing us an opportunity to ask questions.

And this is my response:

This is a perfect summary of Dr Walsh’s approach – thank you!

This part is interesting: “Undermethylation usually results from single nucleotide polymorphisms (SNPs) that weaken MTHFR or other enzymes in the methylation cycle. Overmethylation is generally caused by enzyme weaknesses (SNPs) in the SAMe utilization pathways.” I’d love to know which ones… and then he says “However the reliability of genetic testing for assessing methylation is quite limited at present”

His percentages are also interesting and I would challenge this saying it’s very likely based on the people he has worked with: 22% of the population is undermethylated (high histamine) and 8% overmethylated (low histamine).

When I worked with Julia Ross we saw way more low histamine and that is likely because we worked with more women who seem to be prone to low histamine.

This is also what Carl Pfeiffer found: “These are inborn tendencies that usually persist throughout life” and was my understanding until I started learning from Dr Lynch 2 years ago. Now I’m confused too!

Here is a nice post by Chris Kresser: Methylation – What it is and why should you care. I’m going to paraphrase some of it. He says yes do the 23and me testing but: “genetics do not always predict functional methylation capacity”…”I really believe that we need to be testing both”… “There are different ways to test functional methylation capacity. Doctor’s Data has a methylation panel blood test. Health Diagnostics and Research Institute has a Methylation Pathways Panel that’s good and I tend to use in my practice. Genova has a Complete Hormones profile that, among other things, looks at the ability to convert proliferative estrogen metabolites into less proliferative metabolites, and those conversions are methylation dependent. So if you see poor conversion happening there, that’s a methylation issue. The urine organics acids profile from Genova has some methylation markers, active folate and B12 deficiency. And then a urine amino acids profile can be helpful to look at taurine levels and levels of other metabolites in the methylation cycle.”

This above blog has comments about Dr. Walsh and Dr. Lynch too so they are worth a read.

Of course Dr. Lynch supports the fact that just because you have a defect it doesn’t mean you are affected by it so the additional functional testing makes total sense. And he recommends this additional testing too.

I feel it’s time to mesh the old research and prior work Carl Pfeiffer did, the work Dr. Walsh is doing, Dr. Lynch’s work and the new methylation research. And the wisdom from other practitioners like Chris Kresser and people like you who are digging and reading and asking questions

We clearly all have lots to learn!  I know I don’t have the answers! This topic has been front and center in my mind for awhile so it’s good to get it down in writing here (so thanks Paula, for asking this question!)

I encourage you to listen in to my interview with Dr. Lynch. We talk about this and acknowledge that we all have gaps and that getting together to talk about all this would be an excellent idea!

And finally, please share if you have had your histamine levels tested (whole blood histamine)?  Low or high? and have you found results with the Pfeiffer protocol?

I have tested mine and have low histamine/histapenia and absolutely do benefit from the low histamine protocol.

Filed Under: Anxiety and panic, MTHFR, The Anxiety Summit 3 Tagged With: anxiety, Ben Lynch, Bill Walsh, Carl Pfeiffer, histadelia, histapenia, the anxiety summit, Trudy Scott

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