Everything You Need To Know About Vitamin B12 Deficiency

Photo courtesy of www.freedigitalphotos.net

Do you suffer from any of the following symptoms?

• Weakness, tiredness, or light-headedness
• Rapid heartbeat or difficulty breathing
• Poor memory or difficulty concentrating
• Depression, anxiety, mania
• Numbness and tingling of hands or feet
• Difficulty with balance, poor coordination
• Pale skin
• Sore tongue
• Easy bruising or bleeding gums
• Upset stomach or weight loss
• Diarrhea or constipation
• Depression, irritability, paranoia, mania, hallucinations

If you answered “yes” to any of the above, it may be time to get tested for B12 deficiency.

Vitamin B12 (cobalamin) is a water-soluble vitamin that is crucial to normal neurologic function, red blood cell production, and DNA synthesis. Vitamin B12 is essential for three enzymatic processes: the conversion of homocysteine to methionine; the conversion of methylmalonic acid to succinyl coenzyme A; and the conversion of 5-methyltetrahydrofolate to tetrahydrofolate, a process necessary for DNA synthesis and red blood cell production. It cannot be manufactured by humans and must be regularly obtained from the ingestion of animal proteins or fortified food products. Gastric acid liberates vitamin B12 from animal proteins, after which it combines with intrinsic factor produced by gastric parietal cells and is absorbed in the terminal ileum.

How common is vitamin B12 deficiency?

B12 deficiency is common and reported to affect up to 25% of the U.S. population. Up to 20% of people over the age of 60 years old show marginal B12 status.  The CDC reports, one out of every 31 Americans over 50 are B12 deficient.  Sadly the current lab values of serum B12 grossly underestimate the incidence by using a cut-off range far too low. The current ranges for a common commercial laboratory, which I use are 211-946pg/ml. Many researchers propose that we raise the lower limit of normal to 550pg/ml, which is what I use for optimal levels. In my clinical practice, I have seen many patients who have significant symptoms of low intracellular B12 and they still show “within normal range” on serum lab values. Serum homocysteine and methylmalonic acid are much more sensitive markers as they may show a deficiency earlier than serum B12.

So what causes B12 deficiency?

The main causes of B12 deficiency include inadequate dietary intake and malabsorption issues. Vitamin B12 deficiency may occur if you have certain conditions, such as:

• Pernicious anemia, which makes it hard for your body to absorb vitamin B12 (characterized by a lack of intrinsic factor - individuals cannot properly absorb vitamin B12 in the gastrointestinal tract)
• Atrophic gastritis or inadequate production of stomach acid (occurs in 10-30% of older adults!)
• Helicobacter pylori infection in the stomach
• Surgery that removed part of your stomach or small intestine including bariatric surgery (Surgical procedures in the gastrointestinal tract, such as weight loss surgery often result in a loss of cells that secrete hydrochloric acid and intrinsic facto
• Alcoholism
• Autoimmune conditions, such as Grave’s disease or Lupus
• Malnutrition or eating disorders
• Long term use of medications
  • Proton Pump inhibitors
  • H2 blockers
  • Metformin
  • Certain antibiotics
• Conditions that affect the small bowel, such as:
  • Crohn’s disease
  • Celiac disease (up to 41% of patients with celiac disease will have B12 deficiency)
  • Small intestinal bacterial overgrowth (SIBO)
  • Parasite infections, such as giardia, tapeworm
  • Chronic pancreatitis

Who should be tested for B12 deficiency?

• Anyone over age 60 years old
• Anemia with elevated MCV (mean corpuscular volume)
• Neurological symptoms, such as numbness, tingling, difficulty with walking or balance issues
• Changes in mental status, confusion, or disorientation
• Early dementia or Alzheimer’s disease
• Bipolar, mania, or schizophrenia
• Gastrointestinal disorders with malabsorption, like pancreatic insufficieny
• Patients who have had gastrointestinal surgeries or gastric bypass
• Restricted diets: vegans, vegetarians, macrobiotic diets
• Autoimmune disorders
• Children with autism spectrum disorders or developmental delay
• Breast fed infants of mothers at risk
• Eating disorders
• Family history of pernicious anemia
• Chronic use of PPI medications (Nexium, Prilosec, prevacid, etc) or Metformin
• Occlusive vascular disorders (heart attack, stroke, blood clots)

Children may present differently from adults and should be tested if any of the following symptoms occur:

• Developmental delay or regression
• Apathy or irritability
• Weakness
• Tremor
• Seizures
• Lack of coordination
• Lack of appetite or failure to thrive
• Poor socialization or poor motor skills
• Speech problems or language delay
• Anemia

You can request following blood tests from your doctor to determine if you are deficient:

1. Serum B12
2. Methylmalonic acid
3. Homocysteine
4. Complete blood counts – anemia with elevated MCV may be due to B12 deficiency

So what if I do have a B12 deficiency?

B12 is nontoxic and water soluble so if you are deficient the good news is it is easy to replace! Traditionally B12 has been given in the form of intramuscular injections to ensure absorption but studies have shown that sublingual forms may be equally effective. B12 may come in the form of cyanocobalamin, methylcobalamin, hydroxycobalamin, and adenoxylcobalamin. You can discuss with your doctor which form is best for you. I typically start patients with sublingual methylcobalamin in lozengers or drops at 1000-5000mcg daily. Some patients require subcutaneous or intramuscular injections, which can be taught in the office and given by the patient at home. Depending on how severe the deficiency, I will typically prescribe 5000mcg anywhere from once per month to 2-3X per week initially. Liver stores of B12 are usually repleted with a half a dozen or so doses but full repletion may take up to 20 doses. Once a patient’s symptoms are improving, maintenance of B12 may occur with as little as one injection every 2-4 weeks. There are now forms of B12 available orally, sublingually, intranasally, transdermally and through injection.

Dietary Sources of B12

Vitamin B₁₂ can be found in large quantities in animal products, including meat, poultry, fish, seafood, eggs, and dairy products; and the consumption of these products is the most longstanding method by which human beings have taken vitamin B₁₂ into their systems.

Want more FREE content like this?  Sign up here.

Reference:

1. http://ajcn.nutrition.org/content/89/2/693S.full
2. http://www.ncbi.nlm.nih.gov/pubmed/8856015
3. http://www.aafp.org/afp/2011/0615/p1425.html

What's the Big Deal about Methylation?! Update of the popular MTHFR blog post...

UPDATE OF POPULAR MTHFR BLOG POST

Do you have a genetic defect in the MTHFR gene??

Maybe you've have a family history of heart attack or stroke... maybe you've suffered through multiple miscarriages.  Or maybe you struggle with chronic migraine headaches or irritible bowel syndrome or depression.  Perhaps your child or a sibling has autism.  What do all these things have in common?  Well, these are just some of the conditions liked to a faulty enzyme called MTHFR.

What's up with MTHFR?

MTHFR stands for methyl-tetrahydrofolate reductase, an enzyme that is responsible for the process of methylation in every cell in your body.  MTHFR is a common genetic variant that causes this key enzyme in the body to function at a lower than normal rate.  This can lead to a variety of medical problems.  Although there are over fifty known MTHFR variants, the two primary ones are called C677T and A1298.  Your doctor can order a blood test to determine if you have these genetic variants. Better yet, you can order a complete genetic profile yourself through 23andMe.

What's the big deal about methylation?

Methylation is a core process that occurs in all cells to help your body make biochemical conversions.  When people with genetic mutations is MTHFR are exposed to toxins, they have a harder time getting rid of them which can cause some very serious illnesses.  The methylation process is responsible for:

• Cellular Repair: synthesis of nucleic acids, production and repair of DNA and mRNA
• Detoxification and Neurotransmistter  Production:  interconversion of amino acids
• Healthy Immune System Function:  formation and maturation of red blood cells, white blood cells & platelet production

The 677T variant is most commonly associated  with early heart disease and stroke and the 1298C variant with a variety chronic illnesses, but either anomaly can cause a wide variety of health problems.  The MTHFR anomaly is reported out as heterozygous or homozygous.  If you are heterozygous that means you have one affected gene and one normal gene.  Your enzyme activity will run at about 60% efficiency compared to a normal.

If you are homozygous or have 2 abnormal copies, then enzyme efficiency drops down to 10% to 20% of normal, which can be very serious.   The worst combination is 677T/1298C in which you are heterozygous to both anomalies.  Many chronic illnesses are linked to this anomaly.   Fibromyalgia, irritable bowel syndrome, migraines, chemical sensitivity, frequent miscarriage and frequent blood clots are all conditions associated with MTHFR anomaly.  For a great diagram of more methylation related health problems, check this out:

MTHFR Related Health Problems 

Glutathione is the body's primary antioxidant and detoxifier.  One of the ways that MTHFR gene mutation can make you susceptible to illness is by lowering your ability to make glutathione.    People with MTHFR anomalies usually have low glutathione, which makes them more susceptible to stress and less tolerant to toxic exposures.  Accumulation of toxins in the body and increased oxidative stress, which also leads to premature aging.

Some conditions that may be associated with MTHFR gene mutations

• Autism
• Addictions: smoking, drugs, alcohol
• Down’s syndrome
• Frequent miscarriages
• Male and female infertility
• Pulmonary embolism and other blood clots
• Depression and anxiety
• Schizophrenia
• Bipolar disorder
• Fibromyalgia
• Chronic Fatigue Syndrome
• Chemical Sensitivity
• Parkinson’s disease
• Irritable Bowel Syndrome  
• Stroke
• Spina bifida
• Migraines
• Hyperhomocysteinemia
• Breast cancer
• Atherosclerosis
• Alzheimer’s
• Multiple Sclerosis
• Myocardial Infarction (Heart Attack)
• Methotrexate Toxicity
• Nitrous Oxide Toxicity

 

Treatment for MTHFR

Fortunately, you can easily be tested for the MTHFR mutation.  If you find out that you have one or more of the gene mutations, you can supplement with methyl-folate  and methyl B12, the active forms of these B vitamins.   You can also supplement with liposomal or acetyl-glutathione, the end product of the pathway.  Glutathione is poorly absorbed so either the liposomal form or a precursor, called n-acetylcysteine (NAC) may be used. Some of my favorites are Thorne Research Methyl Guard Plus and 5-MTHF 1mg and 5mg.

There are prescription medicines, that also contain methyl-folate: Deplin, MetanX, CerefolinNAC are a few.   Methyl B12 can also be given as shots, nasal sprays, and sublingually.  The intramuscular shots are by far the most effective method and must be prescribed by your physician.  The choice of nutrients will vary from patient to patient and should be done under a doctor's supervision.  There is a bell-shaped optimal curve so you may not feel well with too much or too little of the appropriate supplements.   Other B vitamins, such as riboflavin and vitamin B6 also play an important role.  As you may have surmised, this can be quite complex and I suggest you find a functional medicine trained physician to help you sort through your needs for the different nutrients if you have a chronic health condition related to the gene mutations.  It is not uncommon for patients with these genetic polymorphism's to be very sensitive to supplementation.

Patients who I recommend be screened for MTHFR mutations:

• Mood disorders: depression, anxiety, irritability, mood swings, bipolar
• Infants and children of parents with MTHFR mutations
• Family members related to someone with MTHFR mutations
• Infertility and Pre-conception care: test both man and woman
• Elevated folate (not processing to active 5-MTHF due to inability to methylate)
• Elevated homocysteine (due to low active 5-MTHF and methylcobalamin)
• Elevated s-adenosylhomocysteine (due to low active 5-MTHF and methylcobalamin)
• Elevated serum cobalamin (due to inability to methylate cyanocobalamin to methylcobalamin)
• Elevated methylmalonic acid (due to methylcobalamin deficiency)
• Patients with syndromes: IBS, multiple chemical sensitivity, fibromyalgia, Down syndrome, chronic fatigue syndrome
• Neurological disorders: Multiple sclerosis, Autism, Alzheimer’s, Epilepsy, Parkinson's
• Cancer: family history of cancer or undergoing cancer treatment
• Cervical dysplasia
• Cardiovascular risk: family history of strokes, embolisms, heart attacks, clots, hypertension
• Birth defects: cleft palate, tetralogy of Fallot, spinal bifida, midline defects
• Drug sensitivities: methotrexate, anti-seizure meds, nitrous oxide, anesthesia

If you are interested in knowing more about your genes, the 23andme gene test will be the best $99 investment you've ever spent !

Check out Health Tips for Dealing with MTHFR Gene mutations...

More reading

23andMe Gene Test
Holistic Primary Care 
Genetics Home Reference
Molecular Biology of MTHFR
Genetics of Homocysteine Metabolism
Homocysteine and MTHFR mutation
LiveWello Gene app