RnB Treatment Protocol

This protocol has been developed to help to overcome functional B2 deficiency in conditions such as Chronic Fatigue Syndrome and Autism Spectrum Disorder, where it is commonly seen that the functional B2 deficiency is reducing the effectiveness of vitamin B12 supplementation. The protocol could equally well be used in Paradoxical B12 deficiency, as well as Diabetes, Obesity, Dementia, CVD, cachexia (muscle wasting) hypertension, or other conditions associated with either functional B2 deficiency or Paradoxical B12 deficiency (Paradoxical). The use of the protocol is a preparatory step before injection or transdermal application of vitamin B12.The protocol is the property of B12 Oils Pty Ltd.

Riboflavin and B12 treatment

It has been known for over 40 years, that active vitamin B2 (as FMN and FAD) are essential to maintain the activity of vitamin B12, and very commonly it has been found that functional vitamin B12 deficiency is caused by lack of functional vitamin B2 (as FMN and FAD), which has been caused by a lack of vitamin B2 per se, and a possible lack of Iodine, Selenium and/or Molybdenum, all of which are required for the activation of vitamin B2. Riboflavin (vitamin B2) is inactive unless it is first activated within the cell. This activation requires three specific steps, which require Iodine, Selenium and Molybdenum. The protocol revolves around a very gradual introduction of Iodine, Selenium and Molybdenum. Introduction is slow as in extreme deficiency simultaneous administration of all three can have strong side effects. Supplementation with vitamin B2 alone will not work, unless there is sufficient Iodine, Selenium and Molybdenum.

Caution

The protocol assumes that you are low on all of Iodine, Selenium and Molybdenum, which can be assessed by analysis of HMTA and/or thyroid markers. If you are already sufficient in Iodine, or Selenium or Molybdenum, as judged by these markers, then you do not need to necessarily supplement the mineral you are sufficient in. Everyone, regardless, does require at least the Recommended Daily Allowance (RDA) or Recommended Daily Intake (RDI) of Iodine, Selenium and Molybdenum. You need this each and every day of your life or you become deficient. This means everyday, for ever more, not just at the time of the protocol, but on-going, basically until you stop breathing. If you do not get the RDA for Iodine, Selenium and Molybdenum then the activation of vitamin B2 will be compromised. The ranges listed represent minimum and maximum ranges of daily intake for a person who is replete in Iodine, Selenium and Molybdenum. The protocol assumes that you remain on the same brand of supplement, and that you do not change mid-way, if you do, you may have to start titrating up again. If you go up a dose and you get a strong reaction, you should go back to the dose that you tolerated and make the incremental increase smaller.

First start by introducing Iodine

Iodine is at the top of the vitamin B2 activation cascade, as pictured below. (Iodine - I, Selenium - Se, Molybdenum - Mo)

Iodine build

Start with 50 ug/day for one week and increase to 100 ug/day, week 2. Week 3 and ongoing 150 ug/day. The iodine should be as either the Sodium or Potassium Iodide salt. Lugol's Iodine does not work in this protocol. A suitable topical product is available at https://b12oils.com/order.htm

Natural sources of Iodine are: Seafood, Dairy, Eggs, Grains, and fortified products such as Iodized bread and Iodized salt.

You should avoid goitrogens, such as soy, Cassava, Broccoli, Cauliflower, Cruciferous veggies, and Kale.

Symptoms of over-supplementing with Iodine are generally flu-like symptoms, drowsiness, brain fog following Iodine supplementation, and a drop in TSH below 0.5. RDA for Iodine is 150-300 ug/day (each and every day).

Care must be taken not to over-supplement with Iodine, as this can lead to autoimmune thyroiditis (AIT), in which thyroid autoantibodies are elevated.

Over-consumption of high iodine containing seaweed has lead to AIT, as has consumption of Iodine-containing multivitamins which have contained much higher levels of Iodide than stated on the label.

Our data suggests that a suitable target for Iodine can be assessed by monitoring TSH, where a target of between 0.5 and 1.5 should be aimed for. This is in agreement with suggestions made by Kelly (2018) and Cohen and co-workers (2018).

Selenium build

The RDA for Selenium is 55-200 ug/day, and the aim is to achieve this. In children under 10 aim for 55ug, for adults 200 ug. After 2 weeks of Iodide supplementation (week 3), continue with the Iodide and add 25 ug/day Selenium and slowly build to 200 ug/day. The selenium should be as the Selenite, or Selenate salt, but should not be Selenomethionine or Selenium chelates, or Selenium amino acids complex, each of which has been shown not to work. Start with 25 ug/day for one week and increase to 50 ug/day, week 2. Week 3, 100 ug/day, with week 4 and ongoing 200 ug/day. Adjust doses for children. Some persons may find some of the increases too much, in which case you would need to reduce the size of the increase. If you switch from Selenomethionine to Selenite, you would have to start at the lowest dose, as the efficacy of Selenomethionine is minimal. A suitable topical product is available at https://b12oils.com/order.htm

Natural sources of Selenium are: Eggs, Tuna, Shrimp, Beef, Turkey, and wheat from Selenium sufficient soils. Organic foods or gluten-free foods are often low in Selenium as too wheat from selenium depleted soils such as the UK, much of Europe, New Zealand, much of Australia and many States in the USA.

Avoid administering any product with diatomaceous earth, fulvic acid, large dose vitamin C, as they can reduce absorption of Selenite (Robinson etal, 1985; Ip, 1986). Further do not administer any product together with calcium or magnesium as they will bind to the Selenite and make it non-bioavailable.

Molybdenum build

The RDA for Molybdenum is 100-300 ug/day. This is addition to Iodine, and Selenium. At week 4, continue with the Iodine and Selenium. Start with 50 ug/day Molybdenum (as the Molybdate salt) and gradually increase to at least 200 ug/day. Some adults have been found to need as much as 300 ug/day. The Molybdenum should NOT be a Molybdenum chelate or Molybdenum or Molybdate chelate or Molybdenum amino acids complex. Half the doses for children under 10. A suitable topical product is available at https://b12oils.com/order.htm

Natural sources of Molybdenum are lentils, peas, beans, oats, barley, bread, pasta, but only if they are grown in Molybdenum sufficient soils that are basic.

Avoid administering any product with diatomaceous earth, fulvic acid, large dose vitamin C, as they can reduce absorption of Molybdate (Robinson etal, 1985; Ip, 1986). Further do not administer any product together with calcium or magnesium as they will bind to the Molybdate and make it non-bioavailable.

Vitamin B2 (riboflavin) build

>At week 4 you can slowly start to introduce vitamin B2. Start with 2 mg/day for week 4, 5 mg/day for week 5 and 10 mg/day ongoing (after week 6). You must keep going with the Iodine, Selenium and Molybdenum.

Vitamin B12 (Adenosyl/Methyl B12) build

Once the Iodine/Selenium and Molybdenum and B2 have been introduced (at around week 6), then you can start on the mixed Adenosyl/Methyl B12 oil mixture (see https://b12oils.com/order.htm ). Start with just a drop of oil from a dropper. Apply the oil into an area of clean dry skin and rub it in like a massage oil. If the child/adult can tolerate the drop, then on the following day increase to 2 drops and gradually increase to a whole squirt/dose. NB you cannot get enough vitamin B12 to restock the brain of a child or an adult from any oral supplement, whether it be lozenge, high dose oral or even nasal delivery. Further, the effect of doing so will take time to become apparent. Myelination is a slow process.

Depression and Anxiety

As the protocol starts to work, levels of serotonin and dopamine that have been over-produced due to the vitamin B12 deficiency may start to drop down to what should eventually be normal levels. For example a twenty-fold increase in serotonin is not uncommon in B12 deficiency, and levels at much as 200 times normal have also been noted. As the body starts to fix B12 deficiency, these levels can drop precipitously. The body can take a long time to adapt to these new "normal" levels and in some that can lead to feelings of depression and anxiety. This is indicative that you are starting to fix functional B2 and then B12 deficiency, and that your body is returning to normal levels. If at this time you feel you need help, you should make sure you have good emotional support. A brief description of what is going on is at https://b12oils.com/receptors.htm

Vitamin B1 Deficiency

Most children or adults on GFCF diets are vitamin B1 deficient (as too B2/I/Se/Mo and Calcium). Further B2 deficiency begats B1 deficiency. Vitamin B1 should be introduced at around week 6.

Folate Deficiency

Early on in the protocol, avoid folate until the B2 and B12 have been optimized. You can introduce folate (either as folic acid, folinic acid or 5MTHF - 400 ug/day). You can and should try to get folate naturally in the diet by eating leafy green veggies. This will also provide the essential mineral magnesium.

Biotin Deficiency

Many people with ASD or CFS believe that the condition is due to an allergy to eggs, and so avoid them. In this case they will more than likely be biotin deficient. Supplement with 150 ug/day - or introduce eggs once the protocol has been established.

Iron Deficiency

Iron deficiency is extremely common in ASD. For neurotypically normal development large quantities of iron are required for the process of myelination of the brain and peripheral nervous system. Estimates are 7 mg/day for children 1 to 8 years old. This estimate is of bioavailable iron, NOT of iron in the supplement. It is best to introduce iron containing meats, such as beef or chicken liver, clams, mollusks or mussels or oysters >> beef, lamb goat, deer, bison, sardines turkey, all of which have much higher iron contents than chicken or pork. Non-meat sources of iron are extremely poorly absorbed.

Alternative Protocol

Buy a multivitamin that has all of Iodine (as Iodide 150 ug), Selenium (as Selenite 55-200 ug) and Molybdenum (as Molybdate 100-300 ug). Start with a low dose (around 1/8th of the above) and slowly increase to a full dose over a period of about 4 weeks. It should be noted that you will also be slowly increasing the dose of vitamin B2, along with the I/Se/Mo. A mixed product is available at https://b12oils.com/order.htm

Potentially suitable supplements

It is quite hard to find a suitable multivitamin that has all of Iodine (as Iodide 150 ug), Selenium (as Selenite 55-200 ug) and Molybdenum (as Molybdate 100-300 ug) in the right forms, and many will require additional supplementation with Iodide, Selenite, or Molybdate.

Iodine Supplements

Iodine should be as the sodium or potassium Iodide salts.

https://shop.bodybio.com/collections/liquid-mineral/products/iodine-9-liquid-mineral-2oz

https://au.iherb.com/pr/Nature-s-Plus-Potassium-Iodide-150-mcg-100-Tablets/42445

https://au.iherb.com/pr/World-Organic-Liquid-Potassium-Iodide-2-fl-oz-59-ml/7775

Benevolent Iodine - potassium Iodide 100 ug/drop

Selenium Supplements

https://www.pureformulas.com/selenium-solution-8-fl-oz-236-ml-liquid-by-allergy-research-group.html

https://au.iherb.com/pr/nutricology-selenium-solution-8-fl-oz-236-ml/17257

https://www.chempro.com.au/NUTRITION-CARE-SODIUM-SELENITE-DROPS-50ML

http://www.iherb.com/Eidon-Mineral-Supplements-Selenium-Liquid-Concentrate-2-oz-60-ml/26013

https://www.amazon.com/dp/B0002UIRBM/ref=psdc_3774471_t1_B000IRJOZ2

https://www.amazon.com/gp/product/B00024D52Y/ref=oh_aui_search_detailpage?ie=UTF8&psc=1

https://shop.bodybio.com/collections/liquid-minerals/products/selenium-8-liquid-mineral-2oz

https://www.fair-pure.com/en/selen-50g-from-sodium-selenite-vegan

Molybdenum Supplements

NB only sodium and ammonium molybdate supplements work, as Molybdenum is internalized via a molybdate transporter, and so other forms of Molybdenum do not work (Mendel and Bittner, 2006)

https://www.metabolics.com/sodium-molybdate-pot-of-90-capsules.html

https://www.fair-pure.com/en/molybdenum-150g-120-tablets-molybdate-vegan

https://www.biocare.co.uk/nutrisorbr-liquid-molybdenum-15ml

https://www.epigenetics-international.com/product/molybdenum-100ml

https://www.b12oils.com/order.htm Molybdenum - NaMolybdate 300 ug Molybdate / 8 drops. Transdermal.

Multivitamin Supplements

Combined Iodide/Selenite/Molybdate

https://www.b12oils.com/order.htm ISeMo Iodine - NaIodide (150 ug), Selenium - NaSelenite (55 ug), Molybdenum - NaMolybdate (100 ug)

Multivitamin Supplements

https://www.naturesway.com/Product-Catalog/Alive-Once-Daily-Women-s-50-Ultra-60-Tabs KI(150 ug), NaSelenate (250 ug) NaMolybdate (75 ug).

https://www.biocare.co.uk/methyl-multinutrient KI (200ug), NaSelenite (200 ug), NaMolybdate (200 ug) MeCbl (400 ug)

Side Reactions

The start of methylation can sometimes induce a higher than normal production of Adenalin, which can cause some odd side-reactions, such as

Increased fatigue, joint or muscle pain, skin rashes, photosensitivity, irritability, paresthesia, dizziness, sleep disturbances, asthenia, muscle cramps, night sweats, hypertension, hypotension, headaches (especially migraines) and swollen glands. Also reported are heavy perspiration, metallic taste in mouth, chills, nausea, bloating, constipation or diarrhea, low grade fever, heart palpitations, tachycardia, facial palsy, tinnitus, mental confusion, uncoordinated movement, pruritus, bone pain, flu-like syndrome, conjunctivitis and throat swelling"

If the person attempting the protocol has these symptoms during the dose escalation stage of the protocol, go back to the previous dose for a few days before increasing the dose once more. Be aware that children with autism cannot tell you what these symptoms. Further they have no idea of what is causing the symptoms or how to tell you. The most likely symptom is a rise in blood pressure, which may cause them to experience head-aches.

Follow Up

Once the person or child has been on the vitamin B2/I/Se/Mo supplementation combined with the mixed Adenosyl/Methyl B12 oils for two months, the urinary Organic Acids test should be repeated in order to check that the regime is working. At this time Contact us and we can help determine if the protocol has been effective.

Natural food sources of Iodine, Selenium and Molybdenum

	Tolerable Upper limit
Iodine	Iodine deficiency >50% of population,
150-300 ug/day	more likely if no dairy.
	Hypothyroidism with <20 ug/day
	Seafood, Dairy, eggs, grains
	AVOID
	Goitrogens: Soy, cassava, cabbage, Chard,
	broccoli, cauliflower, cruciferous veggies.
`	Deficiency of iron or vitamin A
Selenium	Tolerable Upper limit - 200 ug
55 -200 ug/day	Tuna, Ham, Shrimp, Beef,
	Turkey, Chicken, eggs.
	Grains, depending upon where they come from.
	Brazil Nuts have selenomethionine,
	not selenocysteine.
Molybdenum	Tolerable Upper limit - 2 mg
100 -300 ug/day	Lentils, peas, beans, oats,
	Barley, Bread, Pasta, Rice

NB. Most gluten-free products are deficient in Iodine, Selenium and Molybdenum. Further they are not fortified with either folate or vitamin B1. Additionally they often contain high levels of arsenic, lead, and mercury, which is readily seen by increases in values in Hair Metals Test Analysis

Role of Vitamin B2

More about vitamin B2 and the effect of deficiency can be found at

https://lpi.oregonstate.edu/mic/vitamins/riboflavin#deficiency-risk-factors

Iron Supplements

The most readily absorbed form of iron is heme iron, from sources such beef, goat, lamb, squid, octopus, mussels, oysters and clams etc. Non-heme iron, such as the iron in quoted vegetables such as soy, lectins, spinach, etc are very poorly absorbed and have not been found to significantly raise serum ferritin levels.

Potential supplements

Ortho Iron (Iron-ferric pyrophasphate/lactoferrin (30 mg) lactoferrin (100 mg), Copper (0.9 mg) https://au.iherb.com/pr/advanced-orthomolecular-research-aor-ortho-iron-60-vegetarian-capsules/73593

ProFerrin ES90 10.5 mg Heme iron https://proferrin.com/international-distribution

General Supplements

Plain B group supplement

Klaire.com B comples plus https://klaire.com/v803-10-b-complex-plus

Supplements containing Iodide, Selenite, and Molybdate are rather hard to find. Some are listed below:

https://au.iherb.com/pr/Nature-s-Way-Alive-Once-Daily-Women-s-Ultra-Potency-Multi-Vitamin-60-Tablets/39614 KI 150 ug, NaSelenate 250 ug, NaMolybdate 75 ug.

https://www.seroyal.com/trace-mineral-comple-cws.html KI 50 ug, NaSelenate 50 ug, NaMolybdate 50 ug.

https://www.biocare.co.uk/methyl-multinutrient KI (200ug), NaSelenite (200 ug), NaMolybdate (200 ug) MeCbl (400 ug)

https://www.awakennutrition.com/supplement-facts/ KI(100 ug) NaSelenite (50 ug), NaMolybdate (100 ug) MeCbl (1000 ug).

NB, Oral MeCbl in high doses is inactivated in the stomach, so although it may be present in a supplement, its utility in any oral supplement is questionable.

Supplements that may not work due to Calcium and Magnesium content

https://au.iherb.com/pr/Nature-s-Way-Alive-Once-Daily-Women-s-Ultra-Potency-Multi-Vitamin-60-Tablets/39614 KI 150 ug, NaSelenate 250 ug, NaMolybdate 75 ug. Magnesium 100 mg, Cacium 195 mg

https://www.biocare.co.uk/methyl-multinutrient KI (200ug), NaSelenite (200 ug), NaMolybdate (200 ug) MeCbl (400 ug) Magnesium (60 mg)

https://www.naturesway.com/Product-Catalog/Alive-Once-Daily-Men-s-Ultra-60-Tabs KI 150 ug, NaSelenate 250 ug, NaMolybdate 75 ug. CN Cbl 100ug Calcium 130 mg

https://www.awakennutrition.com/supplement-facts/ KI(100 ug) NaSelenite (50 ug), NaMolybdate (100 ug) MeCbl (1000 ug). Magnesium (200 mg)

Supplements that have been shown NOT to work

https://www.bioticsresearch.com/node/1526

https://www.seekinghealth.com/products/molybdenum-90-capsules

https://www.allergyresearchgroup.com/liquid-molybdenum-1-fl.-oz.-30-ml

https://shop.bodybio.com/collections/liquid-minerals/products/molybdenum-7-liquid-mineral-2oz

https://www.biocare.co.uk/selenium - It is Selenomethionine, not Selenite

https://www.nutricology.com Nutricology Liquid Molybdenum - has sodium molybdate, BUT, also has citric acid in it, which reduces Molybdate.

Supplements with undesirable side-effects

Genestra Trace Minerals complex - contains Chromium, which has been shown to cause flushing reactions on the skin in many individuals.

References

Mendel and Bittner, 2005 https://www.sciencedirect.com/science/article/pii/S0167488906001017

Kelly, TM, 2018 The Art and Science of Thyroid Supplementation for The Treatment of Bipolar Depression (Book)

Robinson etal 1985 Effect of megadose of ascorbic acid, a meal and orange juice on the absorption of selenium as sodium selenite. NZ Med J. 98: 627-9 PMID 3861972.

Ip C. Interaction of vitamin C and selenium supplementation in the modification of mammary carcinogensis in rats. J. Natl. Cancer Intst 1986 77:299-303 PMID 3088312

Cohen et al.Antidepressant-Resistant Depression in Patients With Comorbid Subclinical Hypothyroidism or High-Normal TSH Levels.Am J Psychiatry. 2018 Jul 1;175(7):598-604. doi: 10.1176/appi.ajp.2017.17080949.