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. 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 4/9/17)

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.

Symptoms of Pyroluria:

Physical symptoms might include white spots on the fingernails from zinc deficiency. The spots can occur where a bruise to the fingernail occurred but they are more likely to form when zinc deficiency is present. Zinc is important for both wound healing and cell growth so skin infections may also be more common. Stunted growth and teeth that are crooked from overcrowding may result when zinc deficiency is a chronic problem throughout 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 (bipolar disorder), 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.

Pyroluria may also be associated with hypothyroidism and iodine deficiency according to lecture by Dr. Erica Peirson. And a lack of stomach acid may be involved and which would increase risk of nutrient deficiencies. If that is a chronic condition then having salsa or a dill pickle or something else acidic with larger meals can help improve digestion and absorption of B vitamins and other nutrients, especially as we get older in years. Watch this video, Dr Erica Peirson – Pyroluria: Links to Down syndrome and autism, for more information: [10] .

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 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
  10. Video: Dr Erica Peirson – Pyroluria: Links to Down syndrome and autism, https://www.youtube.com/watch?v=nOFU7q9EIyM

Good news about the deficit and about preeclampsia

With so many sad stories in the news it was nice to read an opinion piece with a positive tone. The deficit may seem huge but  it was encouraging to read that in relation to the national Gross Domestic Product (GDP), the national deficit has stabilized over the last few years. [1]

More jobs leads to more income which allows more people to buy more products and services which leads to more jobs to create more products and services  — which increases the GDP.

There was also good news in the prenatal health industry – an inexpensive diagnostic test has been discovered that can detect preeclampsia during early stages of the prenatal condition. Misshapen proteins similar to those found in Alzheimer’s disease were found to be present in the urine of women with preeclampsia. The beta-amyloid proteins have an unusual folded shape which can’t be broken down by enzymes and instead collect in the placenta and disrupt blood flow to the growing infant. [2]

Discovery of an accurate and inexpensive diagnostic test may add to the GDP through direct sales of the paper-based Congo Red Dot urine test and by helping prevent sick days during pregnancy. Preeclampsia can be life threatening for the woman and child but more typically the condition is associated with high blood pressure and increased protein losses in the urine. It is a leading cause of premature delivery which increases risk of low birth weight and other birth defects. [3] The discovery of the presence of beta-amyloid proteins in preeclampsia may also help researchers identify possible causes the condition, which are not known at this time.

Following the clue about the special type of protein found in common between Alzheimer’s and preeclampsia led me to a third condition that is associated with both conditions and with amyloidosis, which is a non-specific term referring to an excess of the misshapen proteins.

Cardiomyopathy can be a diagnosis  or symptom found with Alzheimer’s, preeclampsia, amyloidosis and it also may be associated with hypo- or hyperthyroidism or with infectious conditions such as sarcoidosis. Cardiomyopathy may also occur with starvation and with deficiencies of potassium and magnesium or taurine, carnitine, selenium and thiamine (vit. B1). [4] The amino acid taurine has also been found useful for preventing damage associated with Alzheimer’s disease. [5]

Starvation is certainly bad for pregnancy and so are nutrient deficiencies but at least those problems have known solutions – increase intake of healthy foods. A prenatal person with severe nausea and vomiting might not easily be able to increase their intake but use of targeted supplements or nutrient dense foods might help reduce the severity of symptoms or prevent worsening of an underlying condition.

Detecting who is at risk for preeclampsia before symptoms are severe could provide time to test and treat autoimmune thyroid disease which may not have been detected by standard thyroid lab tests. If sarcoidosis were present then excessive use of vitamin D and calcium might increase risk of there being a deficiency of magnesium and potassium.

Babies are made from nutrients not from medications. So discovering a medication that helps break down beta-amyloid protein might be helpful but finding out why the body is producing the folded malfunctioning protein and how to stop their production would be more helpful. – Addition 2/26/2017, a deficiency or defect in the cannabinoid system might be involved. THC and other chemicals found in marijuana helped cause the break down of beta-amyloid placques from Alzheimer’s disease.  [7 http://neurosciencenews.com/thc-amyloid-beta-alzheimers-4598/ ]

Interesting news from the pet food industry – It may be better not to feed cats raw fish more than three times per week because some species, when fresh and unheated, may be a source of an enzyme, thiaminase, which can  cause excessive break down of the B vitamin thiamine. And taurine is frequently added to processed foods for pet cats because heat processing causes destruction of the essential amino acid. [6]

/Disclaimer: This article is for educational or entertainment purposes and is not intended to be used in place of individual medical guidance for humans or cats./

DSC_0531
A catfish perhaps,
and raw, a source of thiaminase;
limit raw fish for cats to three times per week.

 

 

 

Vitamin B12 deficiency can cause long term nerve degeneration

Vitamin B12 (Cobalamin):

Neurological symptoms of B12 deficiency may include:

  • numbness and tingling of the arms and legs; problems walking; disorientation; memory loss; mood changes that may resemble schizophrenia; and dementia.  Damage may occur to the myelin sheath which surrounds and insulates nerves like the plastic coating around an extension cord.  Nerve damage and mental health symptoms may become permanent with long term deficiency of vitamin B12.

Digestive symptoms may include:

  • loss of appetite, a painful tongue, and constipation.  The reason for there to be digestive symptoms associated with B12 deficiency is not well understood.  One theory suggests that undiagnosed digestive problems might have been an initial cause of the  B12 deficiency.

Symptoms of vitamin B12 deficiency may also include:

  • pernicious anemia and megaloblastic anemia which are hemoglobin deficiencies that have symptoms of tiredness.  Folate deficiency symptoms are also possible because B12 is necessary in folate metabolism.  Increased heart disease risk from elevated homocysteine levels may result from B6,  B12, or folate deficiency.

People who may be more at risk for vitamin B12 deficiency include:

Those with malabsorption problems, or people with chronic use of antacids and those who are over age 60.  A specific protein cofactor called the intrinsic factor and normal stomach acidity levels are necessary for B12 absorption to be able to occur.  Some individuals receive monthly injections of B12 after reaching older age and some people need to receive them monthly throughout life due to having chronically low vitamin B12 for other reasons than normal aging such as a genetic issue with their production of the intrinsic factor protein.

Sublingual tablets of the supplement are also available which are absorbed in the mouth, bypassing any problems with the rest of the digestive system.

A genetic difference may exist that causes some individuals to require the methylated active form of B12 rather than being able to benefit from the more commonly available supplement which is an unmethylated and therefore inactive form.  [More about methylcobalamin.] A genetic screening test would need to be ordered to find out if there were any differences in the gene that might cause an inability to methylate vitamin B12 or folate/(folic acid is the commonly used supplement which is also in the unmethylated form, and therefore inactive for someone with a genetic inability to perform the methylation reaction – meaning an enzyme is malfunctioning somewhere in the complex chemical chain of events.)

A problem with lower digestive acidity in the stomach could also be managed simply by adding a side dish or condiment to meals that contains vinegar or acidic ingredients. Examples from around the world include chutneys, pickles, lime or lemon juice/fresh wedges, vinegary salad dressing, salsa or Tabasco Sauce, and Worcestershire sauce.

  • What is Worcestershire Sauce? (thespruce) (and how do you spell it?)- It is an interesting story – featuring the chemists Lea and Perrins. (Lea & Perrins is still the best selling brand of Worcestershire Sauce). Who knew chemistry could be so delicious?

Schizophrenia may also be associated with an increased risk for low levels of vitamin B12. Read more: (askdrgonzalez.com/deficiency-of-vitamin-b12-and-schizophrenia/)

Low stomach acid may be an underlying issue with symptoms of schizophrenia and in other mental health disorders. The balance and variety of microbes living within the gastrointestinal tract also may be involved in symptoms resembling mental illness. (Digestion & schizophrenia /PMC4437570/)

Pickles that are made fresh and need to be refrigerated  can be a source of healthy intestinal microbes, in a similar way to the healthy bacteria found in yogurt with active probiotics or Kefir drinks.  A variety of traditional products with live cultures are listed here – and a new one, probiotics are being added to chocolate in some products: (health.com/probiotics & chocolate) Scientists studying the microbiome tend to recommend the live culture foods rather than supplements of probiotics – based on my overview impression of multiple sources. An overview regarding the current recommendations about probiotic supplements is available here: (washingtonpost/people-love-probiotics-but-do-they-really-help/2017/05/19)

Probiotics refers to products that contain actual good guy bacteria, while prebiotics refers to foods that contain fiber or other nutrients which the good guy bacteria need to eat in order to survive and flourish – in competition with the more negative strains of bacteria or with yeasts or other microbes which might be found within our gastro-intestinal tract.

Eating vegetables and other foods that are good sources of some types of fiber also helps support healthier intestinal microbes, a few foods that provide the types of fiber that our intestinal microbes need to eat in order to flourish and protect us from more negative types of microbes, are listed here: (pcrm.org/seven-foods-to-supercharge-your-gut-bacteria)

It is a very good idea to get adequate fiber in the daily diet – because starving microbes will start breaking down and consuming edible portions of the intestinal cells for nourishment – if forced, and it may leave the body more at risk for infection (labblog.uofmhealth.org/gut-bacteria-eat-colon-lining-when-starved-for-fiber) – but why starve your good guy microbes? Our intestinal microbes may also help prevent anxiety. (neuroscienceresearch.wustl.edu.pdf)

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. (nutritional yeast/pubmed/11146329)
  • See the post on Vitamin B6 for more information about how the group of B vitamins work together in energy metabolism and cell growth.

Reference for more information:

An Evidence-based Approach to Vitamins and Minerals:  Health Benefits and Intake Recommendations, 2nd Ed., by J. Higdon & V. Drake, (Thieme, Stuttgart / New York, 2012)

  • A description and source for purchasing the text: (thieme.com)
  • A review of the text: (ajcn.nutrition.org/content/79/5/892.full)
  • The text is produced in cooperation with the Linus Pauling Institute. He is a researcher who used large doses of vitamin C to cure cancer tumors. His work was met with skepticism. More recently research supports his work in that a specific type of cancer cells is very susceptible to vitamin C – while to the rest of the body it is water soluble and non-toxic at the level that was toxic to the cancer cells. (sciencedirect.com/science/article/pii/S2213231716302634)

Last reviewed and revised on 9/30/2017.

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.

The Academy of Nutrition and Dietetics has a service for locating a nutrition counselor near you at the website eatright.org: (eatright.org/find-an-expert)