Vitamin B12 Forms - MTHFR Support Australia

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How to pick the right B12 for you!

Vitamin B12 Forms Methylcobalamin

Hydroxocobalamin

Adenosylcobalamin

Cyanocobalamin

• Essential for folate metabolism and the formation of choline containing phospholipids. It protects against NMDA glutamate receptor activity, regulates circadian rhythms, improves concentration, alertness and sleep quality. Ideal for SNP’s - MTR - MTRR - FUT2 - TCN2

• A potent nitric oxide scavenger. It detoxifies cyanide – so it is really good for smokers, cytoprotective and helps to recycle methionine.

• Required for the formation of succinyl CoA, which is involved in the formation of neural lipids. Cofactor for the methylmalonyl CoA mutase and methionine synthase enzymes. It is essential for energy metabolism, and required for normal myelin sheath production and nucleotide production. Deficiency gives rise to nerve and spinal cord degeneration. Ideal for SNP’s - MMAB - MUT

• Synthetic form of Vitamin B12 of low biological activity , and has to be converted in the liver to a more active form. It contains cyanide and over time may have toxic effects.

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So what can affect B12?

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Gastrointestinal disorders like Crohns disease, coeliac disease, chronic pancreatitis, ileal disease, parasitic infections

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Alcohol

•

Exposure to nitrous oxide – it irreversibly oxidises the cobalt atom of B12 making it inactive. Inhibits methionine synthetase

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Mercury – interferes with B12’s ability to cross the blood brain barrier

•

Genetic disorders – more later.

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Low dietary intake – veganism, lacto-ovo vegetarianism, low animal source food intake, low stores and intake by breastfed infants.

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Other medications – colchicine, histamine 2 receptor antagonists (H2RA) like Zantac, Tagamet, Pepcid, antacids – Mylanta, metformin


So who is more at risk?

Vegetarians and vegans

People over 60 years of age

Anyone who has had any form of gastric surgery

Anyone using proton pump inhibitors and drugs affecting B12

Anyone who uses nitrous oxide

People with eating disorders

People with Gastrointestinal disorders

Babies born to and breast fed by women who are deficient in B12


Deficiency Signs •

Dementia

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Ataxia, falls

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Paresthesia and weakness in peripheral nerves

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Weakness, dizziness

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Numbness

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Tingling, pins and needles

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Confusion

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Depression, psychosis

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Megaloblastic macrocytic anaemia

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Mild or moderate leucopoenia or thrombocytopenia

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High homocysteine, low methionine

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Multiple sclerosis like symptoms

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Chronic Fatigue

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Infertility

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Enlarged red blood cells (macrocytosis)

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Low platelets

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Megaloblastic anemia.

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Abnormal white cell (neutrophils)

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Vision loss

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Leg pains

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Sleep latency = trouble staying asleep


B12 Deficiency Signs and Symptoms Mental Changes

Neurological signs and symptoms

• • • • • •

•

• • • • •

Irritability Apathy Sleepiness Suspiciousness (paranoia) Personality changes Depression (including postpartum depression) Memory loss Dementia, intellectual deterioration Hallucinations Violent behaviour In children, developmental delay and/ or autistic behaviour

• • • • • • • • • • •

Abnormal sensations i.e.: pain, tingling, numbness of legs, arms, trunk Diminished sense of touch, pain and/or temperature Loss of position sense (awareness of body position) Weakness of limbs Clumsiness Tremor Symptoms mimicking Parkinsons disease or MS Spasticity of muscles incontinence (urine or stool) Paralysis Vision changes Damage to the optic nerve – neuritis, inflammation, atrophy

Sally M. Pacholok, Jeffrey Stuart. Could it be B12? An Epidemic of Misdiagnosis, Quill Driver Books, California, 2011



B12 Deficiency Signs and Symptoms Vascular Problems

Other

• • • • • • • • •

• • • • • • • • • • •

Transient ischemic attacks (TIA’s) Cerebral vascular accident Coronary artery disease Myocardial infarction Congestive heart failure Palpitations Orthostatic hypotension Deep vein thrombosis Pulmonary embolism

Shortness of breath Generalised weakness Chronic fatigue or tiredness Loss of appetite/weight loss Epigastric pain Osteoporosis Increased susceptibility to infection Failure to thrive in infants Vitiligo Premature greying of hair Burning feet

Sally M. Pacholok, Jeffrey Stuart. Could it be B12? An Epidemic of Misdiagnosis, Quill Driver Books, California, 2011



Current Reference Ranges: US and Australian ranges are too low ! You should be 500pmol/L. If you are not then you need to supplement

US REFERENCE RANGES • 200 - 900 picogram per milliliter (pg/mL)/ 150-650pmol/L

AUSTRALIA REFERENCE RANGES • > 250 picomole per litre (pmol/L)

JAPAN REFERENCE RANGES • 500 – 1300 picogram per milliliter (pg/mL)



Genetic disorders of cobalamin transport and metabolism Cbl-A

MMAA Gene (methylmalonic aciduria type A

 AdoCbl,  MMA, metabolic acidosis, Methionine ,  glycine, ammonia. No megaloblastic anemia

Cbl-B

MMAB gene (methylmalonic aciduria type B)

 AdoCbl,  MMA, metabolic acidosis, Methionine ,  glycine, ammonia, no megaloblastic anemia.

Cbl-C

MMACHC gene

 AdoCbl,  MMA,  MeCbl, megaloglastic anemia.

Cbl-D

Cbl-E

 AdoCbl,  MMA,  MeCbl MTRR- (methionine synthase reductase deficiency

MeCbl,  MMA, metabolic acidosis, increased ammonia, glycine,  methionine megaloblatic anaemia.

 AdoCbl,  MMA,  MeCbl, megaloglastic anemia.

Cbl-F Cbl-G

   

MTR

As per Cbl-E

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650358/ http://www.scribd.com/doc/230760936/Inborn-Errors-of-Folate-and-Cobalamin-Peds#scrib Gherasim C, et al. Navigating the B12 Road: Assimilation, delivery and disorders of cobalamin. J Biol Chem, 2013, 288:13186-13193; Whitehead VM, Acquired and inherited disorders of cobalmin and folate in children. BJH, 2006, 134, 125-136



Genetic disorders of cobalamin transport and metabolism TCN

Transcobalamin

 transcobalamin,  immunoglobulins,  MMA,

GIF (TCN 3)

Gastric Intrinsic Factor

 homocysteine, methylmalonic aciduria, homocystinuria, megaloblastic anemia.

MUT

L-methylmalonyl-CoA mutase

Methylmalonic aciduria, metabolic acidosis, methylmalonic acidemia, megaloblastic anemia, homocystinuria/hyperhomocysteinemia.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650358/ http://www.scribd.com/doc/230760936/Inborn-Errors-of-Folate-and-Cobalamin-Peds#scrib Gherasim C, et al. Navigating the B12 Road: Assimilation, delivery and disorders of cobalamin. J Biol Chem, 2013, 288:13186-13193; Whitehead VM, Acquired and inherited disorders of cobalmin and folate in children. BJH, 2006, 134, 125-136



B12 Genes: Nutraceutical Supports Hydroxocobalamin • When there is dizziness/low blood pressure (perhaps an indication of high nitric oxide/hydrogen sulphide levels – can’t test NO here yet (May cause acneiform dermatitis – small papules/ pustules on the face, upper parts of the back and chest. Go away within a week of stopping.)

Adenosylcobalamin • When You see increased MMA in bloods or have MMAA, MMAB, MMADHC, MUT mutations

Methylcobalamin

TCN mutations

• Especially when neurological symptoms. (Caution in homozygous COMT, or those people likely to get cranky easily. Great if sleep is bad, constipation predominates, increased oxidative stress

• Problem getting B12 into the cell so consider injections. May see increase in B12 in bloods.



Your options



Dose?

Pick your B12. As a chewable tablet they will be much better absorbed than a capsule. Great for kids:

Hydroxy and Methyl are 2mg. Start with ¼ dose (500mcg) and do this for 3-4 days. If the patient feels ok then increase to ½ tablet and so on until they are taking one per day or one every second day. Adenosylcobalamin Take 1 per day for the first week or as prescribed by your practitioner. You may wish to take 2 per day.

Links to products:

Australia and NZ Hydroxycobalamin Methylcobalamin (note adenosylcobalamin is not a registered product in Australia)

International Adenosylcobalamin Methylcobalamin Hydroxycobalamin


Further Comments

It is essential to have B12 in place before you introduce any methyl’s. this is because B12 helps to move the methylfolate into the methionine cycle. This is a key reason why many people react to methylfolate.

Hydroxocobalamin – this is the precursor to the active B12’s – methylcobalamin and adenosylcobalamin. People who have trouble with methyl’s may do better on this form. That way your body will convert to both of the above pathways. Methylcobalamin – this is your neurological B12. Important for brain function and neurological function. Adenosylcobalamin is our mitochondrial B12 and important for our energy pathways.

So we have our cofactors and then our B12 in place. You need to do this for at least 2 weeks before starting on any methyl folate

However if you have any of the following conditions you may need to address these with your practitioner first: 1. Gut dysfunction 2. Sleep disturbances 3. Liver issues like sensitivity to sulphur foods and products, severe brain fog or headaches, migraines etc.

The reason that we want you to address this first is because if you stimulate the pathway with methyl folate and you are increasing CBS (Cystathione Beta Synthase) activity then your symptoms may get worse. If you think you are ready to introduce methylfolate products then see how resource on what is the best methyl for you and what to do if you have a reaction.