Newborn screening for autism – 3 sets of 5 potential biomarkers

I bought the research study regarding newborn screening for autism and it is exciting but was based on a small number of patients with a diagnosis of autism spectrum disorder (n=16, control group n=32).

  1. Newborn screening for autism: in search of candidate biomarkers. [http://www.ncbi.nlm.nih.gov/pubmed/23547820 ]

The research study evaluated the newborn umbilical cord blood for 90 biomarkers (various types of lab tests), 76 biomarkers were found to have consistant data available for all study subjects,  and three sets of five biomarkers were found to be consistently increased or decreased in the infants who were diagnosed with autism later in life compared to the infants in the control group (the research study only used patients with an autism diagnosis who had been screened and diagnosed by the same physician in order to reduce risk of inconsistent diagnostic standards in the experimental group (n=16).

The three sets of five biomarkers need to be tested with a larger group of children with autism diagnoses to see if the results can be repeated. Feasibly to save money on lab tests all newborns might be screened with the set of five most predictive lab tests and the infants who are positive for those five might then be screened for the second set of five tests or all ten of the other biomarkers. The fifteen biomarkers include calcitonin (increased) and Thyroid Stimulating Hormone (TSH, decreased). Low TSH levels can cause increased calcitonin levels which causes reduced blood calcium levels. Elevated blood levels of calcium may cause an increase in calcitonin and having adequate levels of hormone 1, 25 D may be necessary for keeping calcitonin levels within a normal range. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC442503/]

Vitamin D was not one of the 90 lab tests that were included in this research study, however the sibling study performed in Sweden suggested that low vitamin D at birth is involved but that other factors are also involved because all of the children born to Somalian refugees were found to have low vitamin D so that lab value would not be helpful as a screening test. 2) Swedish Study Suggests Low Vitamin D at Birth May Increase Autism Risk [https://www.autismspeaks.org/science/science-news/swedish-study-suggests-low-vitamin-d-birth-may-increase-autism-risk]

Alpha feto-protein (AFP) is one of the fifteen biomarkers found to be predictive for autism later in life. Levels of AFP have been found to be increased in both the mothers of infants who develop autism later in life and in the infants who develop autism later in life. Buy the research study to find out the other twelve – feasibly a concerned parent (with money and a cooperative physician) might be able to have their newborn’s blood screened for the fifteen biomarkers on their own initiative, right away, rather than waiting for the mainstream medical industry to do further research studies.

— The fact that autism was unknown in Somalia suggests that it is unlikely to be a naturally occurring condition and that it is unlikely to be caused by a lack of anti-autism medicine or by the lack of an anti-autism vaccination, so waiting for the for-profit medical industry to devise a for-profit strategy to prevent autism seems like it might take awhile. Concerned parents should have a right to seek effective care for their children and for themselves.

Autism seems to be a condition that occurs prenatally which leaves the newborn infant with metabolic differences but who otherwise appears normal and then, depending on nutritional and environmental conditions, at around age two to four the child’s development shifts towards symptoms of autism. The goal of newborn screening would be to identify which infants are most at risk for that later shift towards autism so that they might be able to be given additional care in order to prevent the damaging autoimmune like changes to the child’s brain. A few different genetic defects that affect nutrient needs may be involved so a newborn who is identified as high risk for developing autism symptoms later in life might then benefit from being screened for genetic defects in the methylation cycle, or with the vitamin D binding protein, or with hemoglobin metabolism. Infants identified as more at risk for autism later in life may also benefit from being screened for hypothyroidism, iodine deficiency, or an excess of bromide, chloride and fluoride.

In summary, for now, this is complicated but very exciting — we have the information we need in order to help women prevent autism before conception and to help identify which newborns may be more at risk for developing autism symptoms later in life so that we can help give the infants the additional nutritional and environmental support that might help them prevent the longterm autoimmune like brain damage from ever occurring.

Older individuals who already have autism diagnoses may also be helped by additional nutritional and environmental support (reduce their exposure to pollutants and foods or foods additives that their unique metabolism can’t digest as well as average) but a “cure” for the changes that already occurred in the brain may not be possible for children and adults who have already been diagnosed with an autism spectrum disorder. Individualized nutritional support might help reduce negative symptoms and improve quality of life for patients who already have an autism diagnosis.

/Disclosure: 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./

A few perinatal tips that may help reduce risk of autism for the expected infant

The term Perinatal generally refers to the one to three months prior to conception. A woman might be advised about healthy diet and exercise habits during perinatal health education and would likely be encouraged to take a prenatal vitamin supplement during a time when she is trying to conceive.

The summary of potential risks associated with autism in the last post suggest that there are two basic groups of health tips for reducing risk of autism perinatally or prenatally:

  • tips for avoiding toxins from the environment; or for reducing internal production of toxins that are a result of the stress response, or are due to undiagnosed metabolic defects;
  • and tips for increasing intake of healthy nutrients; or strategies for identifying and treating any undiagnosed metabolic defects or low-grade chronic infections that may be causing nutrient imbalances or deficiencies.

This first set of tips will focus more on avoiding toxins from the environment and includes primarily recommendations that are already standard for perinatal or prenatal health.

For a woman of reproductive age:

  1. Don’t have unprotected sex after drinking a Rum and Diet Cola that is sweetened with aspartame/Nutrasweet.
  2.  Don’t have unprotected sex after drinking a Rum and regular cola either or any other beverages that contain alcohol.
  3. After drinking a Diet beverage that is sweetened with aspartame/Nutrasweet, don’t have unprotected sex with a male partner who has been drinking alcohol in excess. (A male’s alcohol intake during the few days prior to sexual relations may increase a baby’s risk for Fetal Alcohol Syndrome so it may also be involved in the infant’s risk for autism – more research is needed but in the meantime we do know conclusively that alcohol and Nutrasweet isn’t good for fetuses. Males produce sperm throughout their lives while women develop a large number of eggs during the fetal stage which are then released one or a few at a time each month throughout her reproductive years, approximately from age 10-12 through age 45-55. A woman’s health habits during a pregnancy with a female fetus will be affecting the health of any potential grandchildren that the daughter may have later in her life.)
  4. A regular cola or root beer may be better choices for beverages to drink before having unprotected sex. Brominated vegetable oil may be a food additive in citrus flavored beverages such as Mountain Dew and the chemical is in the same group as the flame retardant polybrominated diphenyl ethers which have been associated with brain development problems in children, fertility problems, and increased risk for hypothyroidism and cancer.[http://www.webmd.com/food-recipes/20130129/brominated-vegetable-oil-qa?page=2]
  5. If you are a woman with leprosy being treated with thalidomide then do your best to not have unprotected sex, possibly invest in a longterm family planning method such as an IUD or Essure for use during the treatment with thalidomide.
  6. If you are a woman being treated with valproic acid for bipolar disorder, migraines or for some other reason then do your best to not have unprotected sex, possibly invest in a longterm family planning method such as an IUD or Essure for use during the treatment with valproic acid.
  7. If you are a woman being treated for autoimmune disease, hypothyroidism, obsessive-compulsive disorder, schizophrenia, or depression then it may be a good idea to not have unprotected sex at least while your disease is in a more severe stage. It might be a good idea to invest in a longterm family planning method such as an IUD or Essure for use while you’re being treated for a severe chronic disease or mental illness. Rubella, cytomegalovirus, stress, and allergic reactions have also been associated with increased risk for autism, so avoiding unprotected sex during acute sickness, stress, or allergy flair-ups might also be a good idea.
  8. In case you missed the theme – try to avoid having unprotected sex unless you are healthy and toxin free and your partner is also – it is not easy to grow a baby. And if you are in a relationship with someone who is not willing to discuss or plan for a safer pregnancy then it may be worth ending the relationship or seeking help. [http://www.reuters.com/article/us-health-sexassault-coercion-idUSKCN0R42CD20150904] (In the U.S. call the National Domestic Violence Hotline for support and referrals: 1-800-799-7233 | 1-800-787-3224 (TTY), http://www.thehotline.org/ )

The perinatal time period is a time to prepare a healthy and welcoming environment so the egg and sperm will be able to successfully implant as a healthy little zygote (the fetal stage where the egg and sperm have combined into a single cell). “One-half of all pregnancies in the U.S. are unintended.”Population Connection [From a handout: “Our Mission At Population Connection is Critical!,” 15AK-1l]

If we hope to reduce the rate of children born in the U.S. who later develop autism, and it is a problem that develops during the early weeks of pregnancy, then we really need to reduce the rate of unintended pregnancies. If autism is able to be prevented in the first week of pregnancy then women will need to either always be healthy and ready for an unexpected pregnancy (because rapists wouldn’t want their love power-and-domination-child to be autistic, surely?) or women will need to plan and prepare before trying to become pregnant so that their body will be as healthy and as ready to receive the implantation of the zygote as possible.

/Disclosure: 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. 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