Tag Archives: B6

Methylation Cycle Defects – in me – genetic screening “for research purposes only”

I purchased an independent genetic analysis which clearly states that it is “For research purposes only. Not for use in diagnostic procedures.” The screening is for informational purposes as there isn’t a physician providing individual care. But that is okay since I enjoy research with an experimental group of N=1 (me).

The genetic screening panel, is self pay, not covered by insurance, and while the company provides free information it also sells nutritional supplements designed to support the special metabolic needs associated with defects in the methylation cycle, which can affect levels of B12 and folate in particular. The screening assessed my genes, (from a finger stick blood sample that I provided by mail), for thirty different gene mutations known to be involved in the methylation cycle, and found — drum roll — eleven mutations in my genes. Four of them are double mutations which I think means that the mutation is on both genes – no normal genes for that protein for me, means that my body has no recipe card to make four types of proteins.

And — drum roll — one of the single gene mutations is on my Vitamin D Receptor gene — specifically of the Fok1 type which has been associated with an increased risk for autoimmune disease.  With a single gene mutation I think roughly half of my Vitamin D Receptors might be normal and half might be three amino-acids longer than normal as described in the following excerpt from a research article about Type 1 Diabetes:

“Variants of the VDR gene have been associated with susceptibility to several autoimmune processes. The roles of the VDR gene polymorphisms depend on their locations (Slattery, 2007). FokI polymorphism is within the DNA binding domain, near the 5′ end, and the rest of the SNPs are in the 3′UTR region within the ligand binding domain. The FokI polymorphism creates an alternative ATG initiation codon in exon 2 leads to a 3 amino-acids longer VDR protein by directly introducing a start codon. A functional impact of this polymorphism on the immune response has been demonstrated (Colin et al., 2000; van Etten et al., 2007). However, VDR gene SNPs influence on VDR expression differ in different populations.” – Elham O. Hamed et. al., “Vitamin D Level and Fok-I Vitamin D Receptor Gene Polymorphism in Egyptian Patients with Type-1 Diabetes,” [http://app.egyptlearn.com/eji/pdf/june2013/1-Elham-Sohag.pdf]

I’m not sure if having an extra “start” codon on half of my Vitamin D Receptors makes them more “startable” / more over active, or whether it would make them less effective. The article suggests the mutation does leave patients more likely to become calcium and vitamin D deficient but it never mentions whether hormone D levels were ever measured or not.

Additional link 7/14/16, suggests that the Fokl polymorphism may have long and short versions and the long version may cause over activity of the vitamin D receptor and the short version may be under active. And it mentions that defects in the VDR gene may increase risk for hyperparathyroidism, osteoarthritis, cancer and infection risk. Increased intestinal absorption of calcium and increased bone turnover may be a factor in the increased risk for osteoarthritis. Excerpt:

“In a series of 20 fibroblast cell lines of different VDR genotype, the relative transcription efficiency was measured of the endogenous VDR protein which was differing by the genotype at the FokI RFLP (F and f alleles) and the poly(A) stretch with long (L) and short (S) alleles which is acting as a transcription factor for a 1,25-dihydroxyvitamin D3-responsive reporter gene. This study provided evidence for so-called high (of the “FL” genotype) and low (of the “fS” genotype) VDR activity.”

“Indeed, the VDR gene has been found associated with a number of different phenotypes of which, especially, the associations with osteoarthritis, hyperparathyroidism, cancer and infection-susceptibility, so far are supported by several independent and large studies reporting similar associations.” “For example, VDR gene variants can influence calcium metabolism through differential absorption in the intestine and, at the same time, influence bone turnover, while also the occurrence of osteophytosis (as a part of osteoarthritis) can be influenced, together resulting in a net effect on BMD measured at a certain site, at a certain age and in a subject with a certain diet.”

[Uitterlinden A., et. al., Vitamin D receptor gene polymorphisms in relation to Vitamin D related disease states. Journal of Steroid Biochemistry & Molecular Biology 89–90 (2004) 187–193http://web.udl.es/usuaris/e4650869/Morella06/BB/VDR%20related%20diseases.pdf] [via http://questioning-answers.blogspot.com/2015/07/vitamin-d-metabolic-gene-variants-and-risk-for-autism.html]

That is interesting as I’ve had osteoarthritis symptoms in two of my toes for years (there’s an increased risk for dancers and people in other sports to have osteoarthritis develop due to overuse or injury and I had broken two toes as a teen. The toes healed at the time but lost range of motion later in life. I’ve also experienced secondary hyperparathyroidism which was diagnosed more recently and the hormonal imbalance can cause significant mental health symptoms. Maintaining my calcium and magnesium intake in balance  while limiting intake of vitamin D and exposure to excessive sunlight seems to be adequate for helping me to be able to keep my parathyroid hormone level within normal limits without further medication or other treatment.

A different older post has a citation that clarified the roles of vitamin D and hormone D. Vitamin D is actually only associated with a carrier protein that seems to act as an “off” switch and prevents it from activating the Vitamin D Receptor. Any free D that is not carried by the special carrier protein, becomes activated to the hormone. And since there are typically many, many more open Vitamin D Receptors in the body than the supply of active hormone could ever fill, any free D, if there is a deficiency or lack of the carrier protein, is likely to become activated to hormone D and then proceed to activate a Vitamin D Receptor. My lab tests and symptoms have always been worse when I have excess D so I’ve been wondering if I might have a genetic mutation in my D carrier protein gene, but this methylation cycle panel didn’t check that gene.

The four double mutations are in the genes: MTHFRC677T (Call – T), MTRR/A66G (Call – G), BHMT/1 (Call – T), and MAO A/R297R (Call – T).

The seven single mutations are in the genes: SHMT/C1420T (Call – Hetero), MTR/A2756G (Call – Hetero), BHMT/8 (Call – Hetero), CBS/A360A (Call-Hetero), COMT/V158M (Call-Hetero), COMT/H62H (Call-Hetero), as well as the VDR/Fok1 (Call-Hetero) mutation.

Genetic defects in the methylation cycle of expectant mothers or in the expected infant have been associated with an increased risk for autism developing in the infant later in life. Children with a COMT mutation were at increased risk to develop autism, but I will have to dig through old posts, (1, 2), to find that citation: [4: Schmidt RJ1, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tancredi DJ, Tassone F, Hertz-Picciotto I., Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism., Epidemiology. 2011 Jul;22(4):476-85, [http://www.ncbi.nlm.nih.gov/pubmed/21610500] I didn’t include the specific genetic mutations in the old posts; the article mentioned two for mothers and one for the child. The COMT 427 AA gene in the child turns out to be a slightly different mutation than the COMT mutations reported in my genetic panel, however I do have the double T mutation in my MTHFR 677 gene mentioned in this article as placing expectant mothers at increased risk for having a child with autism. But my CBS mutation is single and also different than the one mentioned in the following excerpt:

Excerpt from the Abstract:

“Significant interaction effects were observed for maternal MTHFR 677 TT, CBS rs234715 GT + TT, and child COMT 472 AA genotypes, with greater risk for autism when mothers did not report taking prenatal vitamins periconceptionally (4.5 [1.4-14.6]; 2.6 [1.2-5.4]; and 7.2 [2.3-22.4], respectively). Greater risk was also observed for children whose mothers had other one-carbon metabolism pathway gene variants and reported no prenatal vitamin intake.”

Excerpt from the article:

“However, children with the COMT 472 AA genotype were at increased risk for autism if their mothers reported having taken periconceptional prenatal supplements (OR = 1.8 [CI = 0.99–3.5]), and were at substantially higher risk if their mothers did not (7.2 [2.3–22.4];”              [4, full text article available]

The four double mutations are in the genes:

  1. MTHFRC677T (Call – T), Methylene tetrahydrofolate reductase, This version of the gene may have less activity than the more typical version of the gene (the T stands for Thymine, the more effective version has a C, cytosine). https://en.wikipedia.org/wiki/Methylenetetrahydrofolate_reductase  It may cause hyperhomocysteinemia especially if levels of folate, B6 and B12 are deficient. [http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/81648] May make deficiency of methylated folate more of a risk and make folic acid supplements not useful.
  2. MTRR/A66G (Call – G), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase or methionine synthase reductase, This mutation may increase risk for elevated levels of homocysteine and may affect folate and vitamin B12 methylation. Levels of B12 might be normal but not functional due to the lack of methylation. [http://mtrra66g.com/] * this site is commercial and recommends a methyl form of B12 however one of my other mutations might be affected negatively by excess methyl donors, see the selfhacked.com link in the #4 “warrior gene” within this list.  [https://ghr.nlm.nih.gov/gene/MTRR] [http://www.ncbi.nlm.nih.gov/gene/4552]
  3. BHMT/1 (Call – T), Betaine-homocysteine methyltransferase (BHMT),  This enzyme helps produce  the amino acids methionine and Dimethylglycine (DMG). DMG has been found helpful in ADHD, autism, allergies, alcoholism drug addiction, and chronic fatigue syndrome among other chronic issues. Methionine has been found helpful in treating depression, allergies, alcoholism and schizophrenia among other chronic issues. Hypothyroidism may be associated with over expression of this gene: [http://www.wikigenes.org/e/gene/e/635.html] Choline deficiency disease and hyperhomocysteinemia (a heart disease risk factor) may be associated with this gene — (not necessarily with this specific mutation though). The protein that the gene normally produces is necessary in metabolism and in the CDK-mediated phosphorylation and removal of Cdc6 SuperPath: [http://www.genecards.org/cgi-bin/carddisp.pl?gene=BHMT] And the CDK-mediated phosphorylation and removal of Cdc6 SuperPath involves 97 other pathways which include a Calcium2+ pathway and a Parkinsons Disease pathway and creatine metabolism (important for muscles) and synthesis of DNA and many other metabolic paths/chains of chemical events  (so a double mutation in this gene may make it difficult for me to make phospholipids endogenously, but this information is out of my depth, organic chemistry wise): [http://pathcards.genecards.org/card/cdk-mediated_phosphorylation_and_removal_of_cdc6] This double mutation in combination with the single mutation (+/-) in (#3 below) BHMT/8 and (#4 below)CBS/A360A may exacerbate each other’s negative effects on my body, causing an up-regulation of the CBS pathway and also may make it more difficult for me to remove toxic heavy metals from my body – see #4 in the next list for the link.
  4. MAO A/R297R (Call – T). “Monoamine oxidase A (MAO-A) is an enzyme in the brain,” Nick-named “The Warrior Gene” because levels need to be just right because it causes the breakdown of neurotransmitters and too little or too much can cause different symptoms from increased violence to increased anxiety and less aggression. “The G or GG allele indicates higher levels of the enzyme, while the T allele indicates lower levels (T is the ‘risk’ allele). (R)   In females, the G allele was associated with higher outward anger (p = 0.002) and it seems like G allele also causes aggression in males. (R)” The T version of R297R mutation is associated with generalized anxiety disorder (which was one of my earlier “diagnoses” but it was from talk therapy with a MSW so it never really “counted” with psychiatrists that I saw more recently.) “Females with TT reported higher levels of ‘‘angry temperament’’.  Female suicide attempters with TT reported higher ‘‘self-aggression’’” “Women are less likely to have these genes.” “People with the low activity MAO-A gene (2R, 3R) are overall more prone to violence. Specifically, when these people feel very provoked or socially isolated their aggression will come out. People with low MAO-A are more likely to be risk takers.  They are are also more likely to take revenge and use greater force if they get screwed over, but not for small screw overs. Mice with low MAO-A are also more aggressive in general and are more likely to start turf wars. People and mice with low MAO-A are more impulsive and aggressive. People with low MAO-A who are abused as kids show more aggressive behaviour as an adult.” The herbal supplement Gingko biloba, riboflavin (vitamin B2), bio-identical progesterone, and keeping to my circadian rhythm, (keeping a regular day/night wake/sleep cycle instead of pulling all-nighters and then sleeping in), may help me if I have low levels of the enzyme (and excess aggression/anxiety): [http://selfhacked.com/2014/12/07/about-mao-a-and-what-to-do-if-you-have-the-warrior-gene/] Reserpine, a drug based on an herb called Rauwolfia serpentina, or Indian snakeroot or sarpagandha may also help: [http://www.warriorgene.info/] * a commercial site.

The seven single mutations/polymorphisms are in the genes:

  1. SHMT/C1420T (Call – Hetero), Serine hydroxymethyltransferase, This polymorphism was not found to have an increased risk of Down’s Syndrome (DS) (thought possible because it affects folate) and levels of metabolites of the folate pathway seemed similar between the experimental groups of mothers (had children with DS) and control groups of mothers (did not have children with DS).  A protective role was actually found for this polymorphism (which sounds nicer than mutation, allele is another word for variations of the same gene.) [http://www.ncbi.nlm.nih.gov/pubmed/21687976]
  2. MTR/A2756G (Call – Hetero), methionine synthase gene, This mutation may cause up-regulation of the conversion of homocysteine to methionine which requires and might use up stores of methylated B12. [http://mtra2756g.com/] * a commercial site.
  3. BHMT/8 (Call – Hetero), see #3 above for general information about this gene’s protein.
  4. CBS/A360A (Call-Hetero), “CBS (cystathionine beta synthase) is a gene that converts homocysteine into cystathionine. 
The CBS pathway is the gateway into a number of essential biochemical processes. 
The biochemical pathways that follow and are linked to CBS are Transsulfuration and Glutathionine Synthesis.

 It is essential to address that Glutathione (GSH) is among the most important endogenously-produced antioxidants in every cell of the body. Glutathione activity in cells is critical for normal detoxification and defense mechanisms in every cell.” (I’m suggested to eliminate eggs from my diet — too late, they are already gone, but also cruciferous vegetables, onions and garlic – sad face. but I’m also suggested to avoid excess methyl donors like choline — and coffee is a methyl donor – sad face – it is already gone too, very sad face): “Restriction of supplemental methyl groups is important. We all need methyl groups, but those with active CBS up-regulations 
need to be cautious with how much sulfur and how many methyl groups they are taking in daily.
 This includes common supplements such as: L-methionine, L-cysteine, L-taurine, MSM, Glucosamine,  L-Glycine, DMSO, SAMe, NAC, methylcobalamin, methyl-folate, Betaine HCL, Choline. Restricting Vitamin B6 may also be warranted in CBS up-regulations. P5P (pyridoxal 5 phosphate), however, does not appear to increase CBS activity.” [http://metabolichealing.com/metabolic-gateways-cbs-gene-mutations-glutathione/] *That link is to a clinic. (So when my B6 runs out, I should special order the P5P version — which a pharmaceutical company is trying to patent as a prescription medication, if it can gain the FDA’s approval to make the more biologically active form of an essential nutrient unavailable without a prescription because it would interfere with their potential profits: “How does Medicure think it can get away with this? Its petition states rather candidly: “Pharmaceutical companies developing new drugs must be protected from companies that may seek to market the ingredients in those drugs as dietary supplements. The marketing of such products has the potential to undermine the incentive for the development of new drugs because many people may choose to purchase the supplements rather than the drugs.”” An essential nutrient is not a drug — companies have to tack on a fluoride or bromide or something else that makes the new chemical slightly different in order to be able to patent a chemical within the normal process. Bio-identical nutrients are not usually able to be patent protected – because they are essential, especially for people with metabolic defects in their ability to convert less active forms to the more active form. In my state, the Michigan Consumer Protection Act of 1976 is supposed to protect people from having their disability used against them in business transactions such as buying a supplement or prescription medication. 445.903x: “(x) Taking advantage of the consumer’s inability reasonably to protect his or her interests by reason of disability, illiteracy, or inability to understand the language of an agreement presented by the other party to the transaction who knows or reasonably should know of the consumer’s inability.“, And products aren’t supposed to misrepresented such as calling an essential nutrient a prescription medication: 445.903e: “(e) Representing that goods or services are of a particular standard, quality, or grade, or that goods are of a particular style or model, if they are of another.”  [http://www.legislature.mi.gov/(S(45hcye5dzt3luno152p33nku))/mileg.aspx?page=getobject&objectname=mcl-445-903])
  5. COMT/V158M (Call-Hetero), Catechol-O-Methyltransferase, Variations of this gene may lead to swings in dopamine levels that can cause mood swings. Red and purple foods may not be processed well and also may cause problems in mood swings for some people (like purple berries and red food dye (?) just reading, aghast that I’ve survived this long. Red food dye was one of my earliest migraine triggers.) [http://resqua.com/702188759/what-does-the-comt-gene-mutation-mean] Defects in this gene are associated with ADD/ADHD. [http://www.snpedia.com/index.php/Yasko_Methylation] And with panic disorder. [http://www.genecards.org/cgi-bin/carddisp.pl?gene=COMT]
  6. COMT/H62H (Call-Hetero), see #5 above.
  7. VDR/Fok1 (Call-Hetero). – the gene for the Vitamin D Receptor, see the excerpts within the earlier text of this post. And: “VDR Fok is involved with Blood sugar regulation. VDR mutations oppose COMT mutations in the regulation of dopamine levels. A VDR mutation means that a person is less sensitive to methyl group supplement levels. (Mood swings.) A VDR mutation can result in behaviors opposite to a COMT mutation. See Dr. Roberts comments at http://www.heartfixer.com/AMRI-Nutrigenomics.htm#VDR%20Taq:%20%20Vitamin%20D%20Receptor%20Taq%20Abnormality ” [http://www.snpedia.com/index.php/Yasko_Methylation] Dr. Roberts comments suggest that my normal VDR Taq gene helps balance the COMT +/- genes so that I have reasonable dopamine production but might have increased risk for mood swings. hmmmm

So I went and bought some more wild yam progesterone cream because I had run out a while ago and forgot to buy more and it has helped my mood and other peri-meopausal symptoms in the past. I also bought some Gingko biloba because I have also used that in the past with no problems and mood swings and self-aggression are no fun.

/Disclaimer: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./

Methyl Donors and BPA

Methyl donors are chemicals that can donate a methyl group which is made up of one carbon atom and three hydrogen atoms. Methyl groups on DNA signal the genes to remain unactivated, to stay in an off position. Removing the methyl groups can signal the gene to become active. A gene that has few methyl groups atttached may be more easily activated than normally.

This excerpt includes methyl donors and at least one methyl remove-er (BPA).

“Nutritional components that may influence the methylation of epigenetically susceptible loci include folic acid, vitamin B6 and 12, selenium, choline and betaine, methionine, soy genistein, bisphenol A, tocopherols, diallyl disulfide in garlic, and tea polyphenols [28]” [1]                                               *tocopherols are the vitamin E group.

Bisphenol A is not a natural component of food as I understand nutrition but BPA may be part of the plastic lining of cans and other food packages such as plastic drink bottles. It is also found on the slick coating of some types of register receipts. BPA may cause hypomethylation of DNA, fewer methyl groups on the DNA may cause activation of genes.

Bisphenyl A can act similarly to the hormone estrogen. Soy genistein is a phytoestrogen that may help block harmful effects of the estrogen mimetics. Other methyl donors that may help block the effects of BPA are the B vitamins folic acid, vitamin B6 and B12 and choline and betaine.

Avoiding the supplement forms and eating more food sources of Folate and methyl B12 may be more beneficial for people with defects in the methylation cycle.(MTHFR is one example). Taking the unmethylated supplement forms may interfere with the smaller quantities of bioactive folate and B12 that might be found in natural sources.

Adequate B vitamins prenatally may also help protect against DNA changes in the infant.

Folate or Folic Acid:

Folate is the form of the vitamin found in food and it is more bioactive than Folic acid. Folic acid is the form that is commonly available as a supplement and in fortified foods however it requires adequate supplies of vitamin B12 to be available in order to be converted into a more usable form. A genetic difference may exist in some individuals that prevent the body from being able to convert the inactive Folic acid form into Folate, the methylated bioactive form of the vitamin.

Food Sources of Folate, the bioactive natural form, include: most beans and peanuts, black eyed peas, green peas, grains, asparagus, most dark green vegetables, orange juice, citrus fruits. Fortified cereal and rice are good sources of folic acid, the supplemental form.

Vitamin B12:

Food Sources of Vitamin B12 include: shellfish, fish, meat, poultry, eggs, milk, cheese, dairy products, Nutritional or Brewer’s yeast. Vegetarians who don’t eat dairy, eggs, fish or other meat products may need a supplement or nutritional yeast, a vegan food source of vitamin B12.

Injections of B12 may be needed for better absorption of the nutrient for some individuals with stomach problems. Adequate stomach acid and a cofactor are required for normal absorption of vitamin B12. A genetic difference may be a problem for some people causing them to need the methylated active form of B12 rather than being able to benefit from the more commonly available unmethylated supplement.

Vitamin B6:

Food Sources of Vitamin B6 include: fortified cereal, barley, buckwheat, avocados, baked potato with the skin, beef, poultry, salmon, bananas, green leafy vegetables, beans, nuts, sunflower seeds.

Choline and Betaine:

Choline is also a water soluble essential nutrient that is frequently grouped with the rest of the B vitamins. Choline is found throughout the body but is particularly important within the brain. Choline as a high dose supplement may cause mood symptoms in people at risk for unstable moods. It is a precursor for the brain neurotransmitter acetylcholine. Betaine is a metabolite of choline. Spinach and beets are rich in betaine. Good sources of choline include egg yolks, soy beans, beef, poultry, seafood, green leafy vegetables and cauliflower.

/Disclosure: This information is provided for educational purposes and is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./

  1. Kyung E. Rhee, et al., Early Determinants of Obesity: Genetic, Epigenetic, and In Utero Influences, International Journal of Pediatrics, Vol. 2012
  2. J. Higdon & V. Drake,  An Evidence-based Approach to Vitamins and Minerals:  Health Benefits and Intake Recommendations, 2nd Ed., (Thieme, Stuttgart / New York, 2012)
  3. “Choline” on whfoods.com: [whfoods.com]
  4. Betaine,” (Feb. 11, 2012) PubMed Health: [ncbi.nlm.nih.gov/]  *link not working, part of the information is available here: [med.nyu.edu]
  5. Rebecca J. Schmidt, et. al. , “Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism,” Epidemiology. 2011 Jul; 22(4): 476–485. [ncbi.nlm.nih.gov]
  6. MTHFR C677T Mutation: Basic Protocol,” 

Pyroluria, anxiety and deficiency of B6 and zinc

(originally posted on March 18, 2013, most recent update, 4/9/2017)

Research suggests that pyroluria is a condition caused by a genetic difference that prevents the normal breakdown of pyrroles which are side products of hemoglobin breakdown. [5 , 8] The excess pyrroles are not toxic but when they aren’t broken down to smaller chemicals they instead combine with vitamin B6 and zinc and form a compound that is excreted by the kidneys. In normal metabolism zinc and B6 molecules would be recovered for reuse instead of being excreted. The daily nutrient loss can lead to a chronic deficiency of vitamin B6 and zinc and a variety of symptoms.

Physical symptoms might include white spots on the fingernails from zinc deficiency. Zinc is important for wound healing so skin infections might be more common. Stunted growth and teeth that are crooked from overcrowding may result from zinc deficiency during childhood.

Poor dream recall is a symptom of B6 deficiency. Digestion problems and skin symptoms may occur. Dry peeling lips with poorly healing cracks at the corners of the mouth may be a problem with B6 deficiency.

Migraines, seizures and joint pain may be symptoms of pyroluria. Insomnia, exhaustion and sensitivity to light and sound may be problems. Anxiety can become severe over time and the person may isolate themselves to reduce stress. Depression, mood swings and temper outbursts are possible symptoms. [3, see link for more physical signs and symptoms.]

I learned of pyroluria as a possible cause of B6 and zinc deficiency in a book by Julia Ross, MA, called The Mood Cure, The Four Step Program to Take Charge of Your Emotions – Today. It included a self test and information from a book by Joan Mathews Larson, PhD, called Depression Free Naturally. Excerpts are available on her website which include more detail about pyroluria as a treatable cause of anxiety and depression: [7] Her work has helped patients at the Health Recovery Center for years. The center uses therapies designed to restore nutrient balance and correct deficiencies that may be underlying causes of anxiety, depression or addictions. [healthrecovery.com]

Zinc and B6 are needed for production of neurotransmitters that help prevent anxiety and depression. Mental health problems caused by nutrient deficiencies would not be helped much by typically prescribed antidepressants or anti-anxiety drugs. [1]

Ten percent of people may suffer from pyroluria but the condition is not yet widely recognized in the medical field. A research study found the condition to be more prevalent in people with mental health diagnoses and in groups of violent criminals. The pyrrole chemical was present in 71% of adults charged with sudden onset criminal behavior and in 33% of youth charged for a violent crime. Evidence of pyroluria was also more commonly found in patients with OCD, Multiple Sclerosis, Parkinson’s disease or Lyme Disease. It was found  in 40% or more of people with autism, ADHD, manic depression, schizophrenia, Down’s Syndrome, epilepsy, or porphyria. [35 ]

/Speculation/ This could explain why some studies have found B6 supplements helpful for autism but others weren’t able to replicate the results. If 40-50% of the autistic patients in a study had undiagnosed pyroluria then those participants might find high dose B6 supplements very helpful while the rest of the study group might not notice any change.

The good news is that, once identified, pyroluria is very treatable with use of well absorbed forms of vitamin B6 and zinc. The bad news — the supplements have to be taken everyday because the amounts needed are more than is really possible to be found in foods. The supplements are replacing the excessive nutrient loss caused by the daily excretion of the nutrient pyrrole compounds. Deficiency symptoms may start to return after only 48 hours without the high dose zinc and B6 supplements. [3]

A few other nutrient supplements may also be needed to restore nutrient balance. Magnesium may be helpful and niacin (B3), pantothenic acid (B5) and manganese may also be deficient. [1] The essential omega 6 fatty acid, arachidonic acid, may also become deficient. [2] The nutrients, zinc and vitamin B6, are essential for enzymes active throughout the body. Deficiency of B6 may lead to digestive problems and impaired absorption of B12 and other nutrients. Zinc deficiency can also lead to excessive levels of copper which can be neurotoxic and may require chelation therapy. [3] Avoiding foods rich in copper and red and yellow food dyes may be helpful. [2]

Evening primrose oil is recommended as an additional supplement by a medical doctor in the following post. Evening primrose oil would be a good source of essential omega 6 fatty acids. More detail is included in the article about the mental health and other physical symptoms common for patients with pyroluria to experience. It also states in the article that treatment with the supplements can quickly end the negative symptoms for patients when the condition is first diagnosed and treated. [8]

I have found personally that continuing the supplements daily is an ongoing necessity. Earliest symptoms of the B6 and zinc deficiency may be experienced after only missing a few days of the supplements. For me increased anxiety and headaches may occur after only a couple days of forgetting the supplements.

Before I had discovered the problem zinc deficiency was severe enough for me to have many white spots on my fingernails and for me it also seemed to be the cause of anorexia – extreme lack of appetite. Which is a symptom that was not mentioned in the article [8] that included a long list of symptoms. See excerpt:

Here is Dr. Walsh’s list of some of the symptoms correlated with pyroluria: Poor stress control, sensitivity to bright lights and loud noises, morning nausea, tendency to delay or skip breakfast, very dry skin, pale skin, inability to tan, high irritability and temper, history of underachievement, little or no dream recall, auto immune disorders, white spots on the finger nails, poor growth, coarse eyebrow hair, stretch marks on the skin, severe anxiety and/or depression, fearfulness, obsessions with negative thoughts, delayed puberty, dark or mauve colored urine, affinity for spicy and salty foods, abnormal fat distribution, delicate facial features, extreme mood swings, history of dyslexia, severe inner tension, frequent infections, premature graying of hair, poor muscle development, spleen area pain, joint pain, poor wound healing, psoriasis, tendency to stay up very late, abnormal or absent menstrual periods. [8]

Zinc deficiency has been associated with anorexia nervosa. [9]  For me at the time, swallowing just one or two bites of food at the time would seem like a lot of work. The food felt like dry sawdust when I would try to swallow and my mood when being encouraged to eat would tend towards feelings of “how can you ask such a difficult task of me,” (eating shouldn’t promote anxiety or feel like sawdust). Once I had been on the high dose supplements for a little while my appetite normalized and I don’t get many white spots on my fingernails (an opaque white spot instead of the pinkish color of the skin under the nailbed; white spots may appear in anyone’s fingernail after a bump or some sort of injury damaged it).

Caution: Taking high dose zinc supplements can be dangerous to copper balance in people who do not have pyroluria.

Gluten intolerance and excessive use of coffee or other diuretics may increase the severity of the condition. [3] Infections or other problems that cause increased destruction of red blood cells could also exacerbate the condition. The pyrroles can be a produced during hemoglobin synthesis and also during break down of red blood cells. [6]

If white spots on fingernails seems like a normal part of life then consider reading more about pyroluria. [7] Not all physicians are familiar with the condition and lab samples need to be treated carefully or the pyrrole compound will deteriorate. One lab protects samples from oxidizing by adding ascorbic acid (vitamin C) to the collection tube and the sample is then kept out of light and is frozen until testing. [4]

More information about vitamin B6 and food sources of B6 is available here: Vitamin B6

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

  1. By Julia Ross, MA, “The Mood Cure, The Four Step Program to Take Charge of Your Emotions – Today,” (Penguin Books, 2004 ed., New York) p314-315  *This book also addresses nutrients that can help during addiction recovery in addition to other mood disorders.
  2. J. Kaslow, MD, “Pyroluria,” DrKaslow.com: [drkaslow.com] This article suggests that avoiding red and yellow food coloring may be helpful.
  3. Pyroluria, A Hidden Disorder,” Naturalinsight.hubpages.com: [naturalinsight.hubpages.com]
  4. Do I Have Pyroluria,” A self test about the condition is available on this laboratory website under the Reference Tab: [kryptopyrrole.com/]
  5. McGinnis WR, et. al., “Discerning the Mauve Factor, Part 1,” Altern Ther Health Med. 2008 Mar-Apr;14(2):40-50.  [ncbi.nlm.nih.gov] *The abstract mentions that use of B6 and zinc or the use of antibiotics helped reduce urinary excretion of hydroxyhemopyrrolin-2-one (HPL). The chemical was originally nicknamed the Mauve Factor, due to its purplish color.  Prednisone has been known to increase urinary loss of HPL and it is theorized that increased stress would also cause increased excretion of HPL possibly due to changes in intestinal permeability that affect urinary concentrations.
  6. A patient forum, braintalkcommunities.org, has a post by member, Halsgluten, which suggests that SIBO, small intestine biofilm/bacterial overgrowth, may add to pyrrole production by causing an increase in red blood cell breakdown. The pyrrole compound, HPL, can be formed during synthesis of hemoglobin or during destruction of red blood cells. *The observation that antibiotics helped in reference #5 could be due to their helping fight an underlying intestinal infection or other chronic infection that is causing destruction of red blood cells.
  7. Joan Mathews Larson, PhD, “Soothing the Anxious Brain,” includes excerpts from her book, “Depression Free Naturally,” [joanmathewslarson.com]
  8. Pyroluria, Mental Health and the Immune System, JudyTsafirMD.com,
    http://www.judytsafrirmd.com/pyroluria-mental-health-and-the-immune-system/
  9. Humphries, L., et al., Zinc deficiency and eating disorders. J Clin Psychiatry. 1989 Dec;50(12):456-9.
    https://www.ncbi.nlm.nih.gov/pubmed/2600063