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Vitamin B2 Deficiency in Autism

Nutritional Sufficiency of Children

The maternal decision to carry a child to term creates a beneficence-based fiduciary obligation on the part of the mother (and physician) to act in the best interest of the unborn child, and to sacrificially care for and nurture that child, There can be no doubt that this extends to ensuring nutritional sufficiency of the child in its early life. (Centre for Bioethics) Unfortunately the dietary guidelines for pregnant women vary from publication to publication and generally do not include recommendations for Iodine, Selenium and Molybdenum, which are essential minerals involved in the activation of the essential vitamin, riboflavin, vitamin B2. (Ortega, 2001). Further the majority of the health professionals do not understand the importance of these minerals. There are though guidelines on the National Health sites in the US, UK and Australia, particularly for Iodine and Selenium.

Vitamin B2 Deficiency in autism

Activation of dietary or supplemental vitamin B2 (riboflavin) requires a series of activation steps involving Thyroid Stimulating Hormone (TSH), thyroid hormone (T4), deiodinated T4 - triiodothyronine (T3), activation of riboflavin to FMN and finally modification of FMN to form FAD. During this activation, Iodine is required by the thyroid to make Thyroid Hormone, T4. The T4 is subsequently deiodinated by the Selenium dependent enzyme, Iodothyronine, deiodinase. A deficiency of Selenium can cause the reduced production of T3, with subsequent lack of conversion of Riboflavin to FMN by Riboflavin Kinase. The final step in activation of vitamin B2 involves the Molybdopterin-enzyme, FAD synthase, which converts FMN to FAD. FMN and FAD are required for over 100 enzymes in the body. Specifically FAD is used by each of the enzymes that metabolize fat for energy. Lack of FAD leads to  a reduced ability of the foetus, neonate or child with autism to metabolism fat for energy. FMN is involved in the activation of vitamin B6, and a deficiency in Iodine, or Selenium can cause reduced activity of over 100 B6-dependent enzymes. Deficiency in the activity of fat metabolizing enzymes can lead to many conditions including: failure to thrive, ketotoic hypoglycemia, metabolic acidosis, lethargy, developmental delay, hypotonia, seizures, dystonia, and myopathy (Wolfe etal, 2011)

FAD works together with activated vitamin B1 (TPP) and lipoate in the metabolism of various sugars. Hence deficiency in FAD also leads to a reduced ability of the child with autism to use glucose as the preferred energy system in the brain. The inability of the child to effectively utilize sugar or fat for energy, leads to the need for the child to use either dietary or skeletal muscle for energy, and in turn leads to significant elevation of oxalate in the urine (Russell-Jones 2022).

Dietary deficiency of riboflavin, Iodine, Selenium and Molybdenum in Autism

Reduced consumption of dairy products in many countries has lead to many mothers being deficient in intake of dietary riboflavin (vitamin B2). In the period 1970 to 2010 average milk consumption in the US dropped from 25 gals/person/year to only 8 gals/person/year. This is compounded by an decrease in the levels of functional vitamin B2, with functional B2 deficiency being found in up to 40% of women of reproductive age being deficient in Canada and nearly 75% of women in Malaysia (Aljaadi etal, 2019). Functional deficiency of B2 can occur due to low intake of any of vitamin B2, Iodine, Selenium and/or Molybdenum. Each of Iodine, Selenium and Molybdenum are required for the "cascade" of reactions that are involved in vitamin B2 activation.

Iodine is required by the thyroid to make thyroid hormone, which is the initiating factor for the activation of vitamin B2.

Iodine deficiency has been recognized by the WHO as the single most preventable cause of mental retardation in the world and has mandated Iodine supplementation in all countries. Current recommendations are for women who are pregnant to consume 225 ug/day Iodide. Despite this recommendation, few doctors notify the mothers about this, and few mothers know of it, this is despite clear recommendations by governments in the US, Canada, UK and Australia.

A recent review of iodine status in pregnant women has stated

" Iodine deficiency in pregnancy impairs the neurological development of the fetus... Iodine deficiency in the mother ... causes irreversible brain damage with mental retardation" (Panth etal, 2019). These findings, though, are not new and it has been known for nearly 40 years that Iodine deficiency in the mothers can have disastrous neurological consequences in the neonate (Pharoah, et al, 1971; Morreale de Escobar et al, 2004, 2007; Williams 2008; Pop etal, 1999; 2003; Kooistra etal, 2006; Zoeller, and Rovet, 2004;Skeaff, et al 2009; Rohner etal, 2014).Despite this insufficient iodine intake in mothers is common in many countries including the USA, Canada, UK, Australia (41% of child bearing age - Burns etal, 2018), New Zealand, Croatia (Vidransky etal, 2020) and the majority of European countries (Itterman etal, 2020) Iodine deficiency is more common in families that do not use Iodized salt, who have low dairy intake, or consume "gluten-free" products (Panth etal, 2019). Plant-based diets are low in Iodine, and as such vegans may be at risk of Iodine deficiency (Mangels etal, 2011: Leung etal, 2011).The incidence of "gluten-free" consumption now is very common with as much as 25% of persons in the US, UK, and Australia adopting a nutrient poor gluten-free diet. Women tend to be lower in Iodine, as estrogen inhibits the absorption of Iodide. In a recent study 80% of those on a vegan diet were Iodine deficient (Flechas, 2020). Many families do not use Iodized salt, but instead opt for salt alternatives such as Himalayan Pink Salt, which does NOT provide dietary Iodine. Fear of mercury in fish has also driven many families away from seafood, the other major source of Iodine. In Australia, babies are supposed to have a heel prick test to look for low thyroid hormone, despite this over 50% of children with autism were Iodine deficient by HMTA. The effect of moderate to severe iodine deficiency during pregnancy has long been known to cause cretinism in the offspring. According to the Australian Thyroid Foundation " More than 50% of children and pregnant or breastfeeding women living in Australia have been shown to be iodine deficient and are at risk of developing thyroid disease". Interestingly the foundation appeared to have little idea of the pathway of activation of vitamin B2 and its dependency on I/Se/Mo. This is despite being directly asked!! Iodine and your family: a guide | Raising Children Network

Iodine levels in the population in the US have halved in the US in the past thirty years (See) "Women who are pregnant and lactating require increased iodine intake. Unfortunately, median iodine levels in the United States have decreased by 50% in the past 3 decades, with recent studies demonstrating that pregnant women are mildly iodine deficient. Nevertheless, data from the NHANES 1999–2006 showed that only 22% of US pregnant women take an iodine-containing dietary supplement". Over the same period of time autism rates have increased from 1 in 1000 to 1 in 38 in the US. Iodine deficiency is now so common that in some areas the Pathology Labs have shifted the range of their "normal" data up from TSH of 0.05 to 3.0 to 1.8 to 3.0 mlU/L, which technically means that the "average" person in the population is now hypothyroidic. Iodine deficiency is more likely in those who have limited exposure to dairy, baked goods, table salt and seafood (Booms etal, 2016). A recent study in the UK found that the average female in many parts of the country was deficient in Iodine (Pearce etalm, 2016; WHO 2007).

Iodine is required for the formation of Thyroid Hormone (T4), initially in the pregnant mother, and later, by 16-18 weeks, the fetal thyroid has developed sufficiently for Iodine to be required by the foetus itself for foetal development. Deficiency of Iodine either in the mother or later in the foetus leads to lower metabolism and poor neurological development of the foetus. Comparison of children born to mothers with low Iodine showed a reduced IQ score in Wechshler Intelligence Scale Tests, and 19% children born to mothers with hypothyroidism had an IQ score of 85 or lower, compared to only 5% of control children. Knowledge of the importance of Iodine is generally poor, particularly in women below 40 in many countries including Croatia (Vidransky etal, 2020), Australia (Lucas etal 2014), Northern Ireland (McMullan etal, 2019), the UK (Combet etal, 2015), Norway (Henjum etal, 2018), Ukraine and India (Rai etal, 2016). The United Nations Convention on the Rights of a Child has stated that "Every mother has the right to adequate iodine nutrition to ensure that he unborn child experiences normal mental development" (2007), yet despite this Iodine deficiency is extremely common. Despite recommendations for Iodine supplementation by WHO in 1999, as recently as 2015 and 2020, studies in the UK were still considering whether supplementation was necessary, this despite the rapidly rising rate of autism in the UK (Dineva etal, 2020).

Selenium is required for the function of 25 enzymes, but importantly for vitamin B2 activation Selenium is required for the enzyme Iodothyronine deiodinase, which converts thyroid hormone (T4) to T3. Declining Selenium levels in the brain of the elderly have been associated with cognitive decline (Berr et al, 2012). Selenium levels in many soils in many countries has recently been identified as a nutrient deficiency of concern in the UK, Europe, New Zealand, many states in the USA, and in Canada. In the period 1975-1995 selenium intake in the UK dropped from 60-34 ug/day, or less the half the RDA (Rayman, 2000). The situation will be worse now (2022). Selenium deficiency is more common in those on a low dairy diet, or those who have adopted the nutrient poor gluten-free diet. Roughly 48% of children with autism have overt Selenium deficiency. Selenium deficiency is also common in large parts of south-west Western Australia and coastal Queensland, as well as parts of NSW, Victoria, South Australia and Tasmania. The body of a replete person contains 10-20 mg of Selenium, so if person is deficient, it may take many days of high dose supplementation (above the RDA) to become replete (Kim etal, 2012). In 2012 Selenium intake was relatively high in places like Canada (113-224 ug/day), Japan (129 ug/day) and USA (114 ug/day), but much lower in places such as Korea (57.6 ug/day). HMTA has shown that levels have dropped significantly from 2000 to 2023 (personal observations).

Molybdenum is required for several molybdopterin-containing enzymes, but most importantly it is required for the enzyme FAD-synthase, which converts FMN to FAD (Giancaspero etal, 2015; Miccolis etal, 2014; Leone et al, 2019; Kisker  etal, 1997; Tolomeo etal, 2020)  Molybdenum levels in many countries have been steadily declining and molybdenum deficiency is common in those with autism with approximately 50% of children with autism having less than the recommended levels. Molybdenum deficiency is common in children with sulphite sensitivity, a common preservative in many foods, as well as sensitivity to high sulphite-containing foods such as eggs, cabbage, onions, etc (see Sulfite Sensitivity FAQ - Australasian Society of Clinical Immunology and Allergy (ASCIA). Often the association between sulphite sensitivity, and food allergy, and Molybdenum deficiency goes undiagnosed/recognized. This is exemplified by the Sulphite allergy site (quoted before), where they have identified lack of activity of the enzyme sulphite oxidase in treating sulphite sensitivity, YET, have failed to mention the need for Molybdenum for the activity of the enzyme(?!)

Dual deficiencies of Iodine, Selenium and/or Molybdenum has been found in 50% of children with autism. Combined Selenium and Iodine deficiency is particularly bad for the child and in extreme cases has been shown to cause myxedematous cretinism (Zimmerman and Kohrle, 2002). Severe sulphite oxidase deficiency (which is associated with Molybdenum deficiency) has been associated with feeding difficulties, decreased activity, neonatal seizures, and movement disorders within a few days after birth (Lee etal, 2017; Hobson etal, 2005; Claerhout eta;. 2018). In such cases levels of urinary sulfite, thiosulfate, and S-sulfocysteine may be elevated (Bindu etal, 2017). Our studies have shown that around 50% of children with autism are molybdenum deficient, which may explain the high rate of seizures/epilepsy in this group. A study looking at elevated urinary sulfite in children with autism, found that 36% responded to addition of Molybdate, which is similar to our findings (Williams 2020;Waring and Klovrza, 2000; Russell-Jones, 2022 Personal observations). Treatment with Molybdate was associated with an improvement in clinical symptoms in these children (Waring and Klovrza, 2000).

Vitamin B2 deficiency and Altered glycolysis

Functional vitamin B2 is required for the metabolism of glucose, due to its role as a cofactor in the enzyme pyruvate dehydrogenase. Lack of activity of this enzyme is associated with congenital microcephaly, hypotonia, epilepsy, and ataxia. Developmental delay is universally associated with pyruvate dehyrogenase deficiency (Sofou et al, 2017). Lack of functional B2 in turn causes the accumulation of lactic acid, which alone can cause developmental delay. Elevated lactic acid is very common in ASD (Russell-Jones 2022). Lack of vitamin B1 (thiamine), in addition to lack of functional B2 leads to elevated pyruvate in OAT tests.

Urinary Markers of functional B2 deficiency

Functional B2 deficiency leads to elevations in urinary organic acids such as Oxalic Acid, Ethymalonic acid, lactic acid, succinic acid, glutaric acid and the short chain fatty acids, adipic acid, suberic acid, and sebacic acid. Elevated ethylmalonic acid has been associated with developmental delay/ mild-to-sever intellectual disability, hypotonia, spasticity, tonic-clonic seizures, loss of social interaction, speech delay, or absence and failure to thrive (Meo etal, 2017). Elevated oxalic acid has previously been reported in autism (Konstantynowicz et al, 2011).

Vitamin B2 deficiency and Altered GABA

Production of GABA requires the conversion of Glutamate to GABA via the B6-dependent enzyme, Glutamic Acid decarboxylase. In functional B2 deficiency, or specifically FMN deficiency (due to Iodine or Selenium deficiency), brain glutamate levels become highly elevated. Further, the ability of the Autistic child to control their behaviour becomes highly compromised (Gevi etal, 2020). Clearly in the study by Geva, his subjects were Iodine, and/or Selenium deficient. The high incidence of Epilepsy in Autism, is likely to be due to lower production of GABA (Trieman, 2001).

Vitamin B6 deficiency with the resultant block in production of GABA (Gevi etal, 2020)

Vitamin B2 deficiency and vitamin B12 deficiency

Maintenance of vitamin B12 activity is critically dependent upon functional vitamin B2 sufficiency. Hence the activity of two enzymes MTHFR and MTRR, which are both involved in the methylation cycle, are critically dependent upon active B2 (as FAD and FMN) for function. In addition, the activation of vitamin B6 is dependent upon the FMN (the first of the two active forms of B2), and so in functional B2 deficiency vitamin B6 is not activated and this then affects the formation of the methylation precursor 5,10-methylene-THF, and will result in further reduction in the rate of methylation and hence B12 deficiency.

"Rescue" of inactive Co(II)B12 by Methionine Synthase Reductase (MTRR).

Demand for Iodine in the Neonate

As soon as the child is born, it must take over the production of TSH and T4 from the mother. The demand for Iodine in the neonate is largely met by Iodine in colostrum (2744 ug/L) and milk (1295 ug/L, 4 weeks post partum), however, it is highly dependent upon the Iodine intake of mothers and hence dietary insufficiency in the mother will result in insufficiency in colostrum and milk (Moon and Kim 1999; Bertinato etal, 2020). Iodine content in milk varies enormously from country to country with levels highest in Korea (>200 ug/L), moderate in Morocco and China (100-200 ug/L) and lowest in countries such as Germany, Italy, USA and New Zealand (<50 ug/L), (Dror and Allen, 2018). The suggested optimal concentration is 150 ug/L (Dror and Allen 2018). "If iodine insufficiency leads to inadequate production of thyroid hormones and hypothyroidism during pregnancy, then irreversible fetal brain damage can result" (American Thyroid Association, 2006) Original recommendations were for 150 ug/day for pregnant women, this has now been increased to 250-300 ug/day, with 90 ug/day for newborns (Toloza etal, 2020). Despite these recommendations and position statements by the governments of Canada, USA, UK and Australia, few women know of them.  Iodine deficiency is much more prevalent than has previously been recognized and a recent study in Canada concluded that "that large proportions of pregnant (>50%) and lactating (>75%) women in Canada will not meet iodine requirements without iodine supplementation.. Studies from Austria, performed over different ages have shown that over 75% of the population had mild to moderate Iodine deficiency (Kapelari etal, 2008). One thing, though, is almost universal, the role of Iodine in the eventual activation of vitamin B2 is not generally known. The demand for Ioe production of thyroid hormone by the neonate is reflected in a huge surge in TSH in the neonate  (Jayasuriya etal, 2018 - see below). At this stage, if mother is deficient in Iodine, there will be a deficiency in milk and there will be a vast increase in TSH levels.

Demand for Selenium and Functional B2

Selenium is critical for the activation of vitamin B2 (riboflavin) to FMN, studies comparing Selenium in Hair (HMTA), have shown that in Selenium deficiency the levels of the tryptophan metabolite Quinolinic Acid can become very elevated, and that the ratio of QA:KA increases. This is presumably because conversion of Kynurenine to Kynurenic acid requires a PLP-dependent enzyme, which will have lower activity in FMN deficiency. Optimal levels of Selenium in hair appear to be above 1.0 ppm.

Iodine deficiency on the increase

Iodine deficiency was all but eliminated in many countries in the 1960-70s, however it has become apparent that Iodine deficiency is now on the increase in the UK. An increase in the rate of veganism, and avoidance of dairy and seafood has lead to a great increase in the rate of Iodine deficiency. This is further exacerbated by the shift in sterilization of the udders of milking cows from Iodine treatment to steam sterilization. In addition in the UK and many other countries there has been a shift away from the use of Iodized salt. Median Iodine intake in the US has declined by half since 1970 (Kerver etal, 2021). Iodine deficiency is particulalry prevalent in pregnant women, and consumers of non-dairy products."Pregnant and lactating women are particularly vulnerable to iodine deficiency disorders because of their increased iodine requirements. Severe maternal iodine deficiency has been associated with cretinism or impaired neurodevelopment in children as well as obstetric complications." (Rodriguez-Diaz and Pearce, 2020). In Australia, in an attempt to overcome Iodine deficiency, they have mandated Iodination of commercial bread. However, most commercial breads now have soy flour in them. Soy flour contains goitrogenic isoflavones, including genistein, daidzein, and glycitein. These compounds block the TPO enzyme that converts Iodine to Iodide, which is required in the early step in thyroid hormone production. If consumed in excess it can destroy thyroid function. Amazingly stupid, in that they are iodizing bread, but using soy flour in it.

Gluten Free Diets

Many children with ASD are placed on gluten-free diets, which is then accompanied by additional nutrient deficiencies, such as vitamin D, calcium, folates, vitamin E, iodine and iron. include goitrins from foods such as cabbage, brussel sprouts, rapeseed oils, primrose, kale, spinach, mustard greens, and thiocyanates from foods such as cassava, flaxseed, almond kernels, and Flavinoids, such as soy, over-consumption of such foods greatly inhibits thyroid function.

Goitrogens and vitamin B2

The activation of vitamin B2 begins with the production of thyroid hormone, T4, in the thyroid. A group of foods, called goitrogens, disrupt the production of thyroid hormones by interfering with the uptake of Iodine into the thyroid. These include goitrogens from foods such as cabbage, brussel sprouts, rapeseed oils, primrose, kale, spinach, mustard greens, millet (known to be a strong goitrogen, and to result in Iodine deficiency, it also has prussic acid, a cyanoglycoside) (millets include ragi, foxtail millets, quinoa, jawar, bajira}  and thiocyanates from foods such as cassava, flaxseed, almond kernels, and Flavinoids, such as soy, Overconsumption of such foods can lead to reduced thyroid function, and lack of activation of vitamin B2 results. Amazingly, soybeans are also used in infant formula. See List Examples of non-goitrogenic foods include Squash, tomato, bell peppers, green beans, peas, cucumber, asparagus, eggplant, carrots, and celery

Vaccines, infection, the Immune Response and vitamin B2

The generation of an effective immune response to vaccines, or to various infections, involves the usage of large amounts of active vitamin B2, as it is used in the activation of over 100 B2 dependent enzymes, 130 B6 dependent enzymes, and the cycling of methyl B12 which is used in over 200 B12-dependent methylation enzymes, the activation and processing of iron and also activation and processing of vitamin D. Further, the generation of this immune response to vaccines and to infections involves the activation of macrophages, which has been shown to be dependent upon vitamin B2 (Araki etal, 1995; Hevel etal, 1991; Steuhr and Ikda-Saito, 1991, Baek etal, 2991; Ghosh and Steuhr, 1995; Steuhr etal, 1990; 1991; . Part of this activation is turning on production of high levels of the enzyme NOS, an enzyme that requires FMN/FAD/BH4/NAD/and heme iron, and lots of energy, which requires folate and B12. Sequestration of folate and vitamin B12 is so high that sites of inflammation can actually be imaged with radioactively labelled folate and vitamin B12. In addition, low vitamin B2 is associated with a reduced ability to deal with infections (Schramm etal, 2014, Dey and Bishayi 2016; Mazur-Bialy etal, 2013; 2015). Thus, it is obvious that reserves of vitamin B2 may be drained as a response to vaccines, or chronic infections, and at such times, there is significant risk of post-vaccination or post infection stress on methylation, and in adults such stress can be an initiator in conditions such as Chronic Fatigue Syndrome, LONG COVID, and potentially in developmental delay in children. The longer the infection or the higher the response, the more likely that prolonged B2 deficiency, with accompanying vitamin B12 deficiency will result. As such, care must be taken to ensure sufficient vitamin B2, and I/Se/Mo at these times, in order to minimalize the effects of these conditions.

Resolving Vitamin B2 Deficiency in Pregnant mothers

Mothers should ensure vitamin B2 sufficiency before they are pregnant, however, if this is not possible, urinary Organic Acids Testing should be carried out to establish sufficiency, and cases of deficiency mothers should supplement not only with vitamin B12, but also with Iodine, Selenium, Molybdenum and vitamin B2 if there is reason to believe that these may also be deficient. Warning signs in the mothers can be fatigue, obesity, gestational diabetes, insufficient dietary intake such as occurs in vegetarian or vegan diets.

Signs of Vitamin B2 Deficiency in Pregnant mothers

There are many warning signs of potential vitamin B2 deficiency in the pregnant mothers, including

i) Gestational Diabetes - lower functional B2 leads to poorer processing of blood glucose, leading to elevated blood sugar

ii) Elevated TSH - Insufficient Iodine in the mothers leads to an increase in TSH levels during pregnancy, leading to hypothyroidism

iii) Low T3 - Insufficient Selenium in the mothers - either due to increased demand, or low intake, leads to lower T3 in the mother

iv) Difficulty in getting pregnant. Often this is due to inadequate nutrition which can also cause irregular cycling before pregnancy

v) PCOS - Insufficient vitamin B2, leads to lower conversion of testosterone to estrogen, with elevated testosterone and lower estrogen levels. PCOS has been associated with autism in the result child (Cherskov etal, 2018; Dubey etal, 2021; Abu-Zaid etal, 2022; Lee etal, 2017)

Detecting Vitamin B2 Deficiency in Pregnant mothers

Many mothers rely upon their General Practitioner for advice on nutrition during pregnancy. There seems to be a general lack of knowledge by the obstetricians about the biochemistry of vitamin B2 activation, particularly as it relates to nutrition. This is compounded by the Pathology labs, who report data in reference to the general population (ie within the normal range seen in the population), rather than to biochemical normality. In many pregnancies, there is no follow up on I/Se/Mo status, and the implications of functional deficiency in vitamin B2 is completely "lost" on the medical profession in general, and more specifically on the General practitioner who examines the mother early in pregnancy. Further the implications of functional B2 deficiency on functional B12 deficiency is lost on all but a very minor few. Few would argue that whilst the mother is unlikely to have suitable information or knowledge in the area, the medical professional who examines the mother should be qualified in this area.

Resolving Vitamin B2 Deficiency in Autism

Successful resolution of vitamin B2 deficiency requires supplementation with Iodine, Selenium and/or Molybdenum, depending upon deficiency as well as supplementation with sufficient riboflavin. Hence both Iodine and Selenium are involved in the initial activation of riboflavin (vitamin B2) to FMN, the first active B2 molecule. Molybdenum is then used by FAD-Synthase to convert FMN to FAD. Interestingly FMN is also used to activate vitamin B6 to the active molecule PLP (also known as P5P). This is an essential co-factor in the enzyme Serine-hydroxymethyltransferase, the source of 5,10-methylene-THF in the folate cycle see https://b12oils.com/methylation.htm

Associated Deficiencies in Autism

Vitamin B2 is ultimately involved in the uptake and processing of the heme molecule, and in uptake of iron from the intestine. A condition called porphyria results from functional vitamin B2, with porphyria being one of the classic symptoms of autism. Every child that we have data for who has autism is also deficient in active vitamin B2 (FMN and FAD) and is deficient in active vitamin B12 (Adenosyl and Methyl B12) (Russell-Jones 2022A), these deficiencies also have to be addressed or the child will not progress developmentally. Accompanying these deficiencies, deficiencies of Iodine, Selenium and/or Molybdenum are very common. Mutations in the fatty acid processing proteins or lack of active B2 also leads to poor processing of fat, with an increased rate of obesity in older chlidren with autism (Patel, etal, 2014; Denton, 2009; Vidal etal, 1996; Scouten etal, 1980).

Active vitamin B2, as FAD is required by the enzyme glutathione reductase (Parsons etal, 1985), and lower B2 is associated with lower GSH:GSSG ratios, which is extremely common in ASD.

Elevated porphyrins are common in B2 deficiency. The last step in closure of the porphyrin ring requires the FAD-dependent enzyme, protoporphyrin oxidase. In functional B2 deficiency, the efficacy of the enzyme drops and there is a loss of the various porphyrin precursors.

Neonatal Screening

See Newborn blood spot screening FAQs - NHS (www.nhs.uk)

Testing is offered for

  • Sickle cell disease

  • Cystic fibrosis

  • Congenital hypothyroidism

  • Phenylketonuria

  • Medium-chain acyl-CoA dehyrogenase deficiency (MCADD)

  • Maple syrup urine disease

  • Isovaleric acidaemia

  • Glutaric aciduria type 1

  • Homocystinuria

These tests should pick up Iodine deficiency (hypothyroidism) and functional B12 deficiency, BUT, apparently they are missing lots of children, OR, the parents are not taking up the offer.

More recently a position statement has been issued by Professor Cres Eastman "All GPs should test for thyroid function and prescribe iodine supplements as necessary, says University of Sydney clinician, endocrinologist and researcher Professor Cres Eastman.“The commonest cause of preventable neurodevelopmental defects or disability in our world is iodine deficiency,” says Professor Eastman, pointing to the 2008 World Health Organization assessment.

Pyruvate dehydrogenase

Pyruvate dehydrogenase is the enzyme that processes pyruvate, the end product of glycolysis. Deficiency in co-factors for the enzyme result in greatly increased lactic acid (in functional B2 deficiency) or pyruvate (in functional B1 deficiency).

Interestingly, riboflavin deficiency caused an up-regulation of Parkinson’s disease pathway, steroid catabolism, endoplasmic reticulum stress and apoptotic process, while the fatty acid metabolism, tricarboxylic citrate cycle, oxidative phosphorylation and iron metabolism were down-regulated (Xin etal, 2917).

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The descriptions and findings on vitamin B2 and autism, is the property of B12 Oils Pty Ltd. Reproduction in whole or in part constitutes an infringement in the Copyright law. Copyright infringement carries serious penalties.

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AAP Recommendations on Iodine Nutrition During Pregnancy and Lactation | American Academy of Pediatrics (aappublications.org)

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