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Nutrient deficiencies are a common finding in chronic fatigue syndrome. Research has also shown that there is a relationship between nutrient deficiencies and symptom severity. This article focuses on Vitamin B12.

Before moving on I will mention a great book called ‘Could it be B12?’ which can be bought from Amazon here, and a great resource which is referenced below, which can also be accessed here. There is also a youtube video (55 minutes) called Diagnosing And Treating Vitamin B12 deficiency that can be watched here. Within a few minutes you will get an understanding of how important this nutrient is.

Dr. Sarah Myhill also has a great article which you can find here.

The Importance Of Gut Health In Vitamin B12 Status

I mentioned in my article ‘Digestive Health in Chronic Fatigue Syndrome‘ that en elevation in hydrogen sulphide, produced by various bacteria in the gut, can contribute to gut inflammation and symptoms such as fatigue.

What nutrient binds to hydrogen sulfide? Vitamin B12!

This, as mentioned by Alex Vasquez in an interview during the Abundant Energy Summit, may explain why so many people with CFS have a vitamin B12 deficiency – it is not because of a lack of dietary intake but because it is being bound to hydrogen sulphide being produced in the gut.

B12 has numerous roles to play, one of them particularly relevant to CFS is its role in as the most powerful scavenger of nitric oxide, this is particularly important in patients with CFS.

Diagnostic Tests

The most common test is serum vitamin B12 – There is a problem however with relying solely on this test –  it often misses deficient people.  The serum B12 test, records all B12 in the blood, active and inactive, it does not record what is happening at cellular level. This is similar to a lot of hormonal tests. The body cannot access inactive B12 and this can represent as much as 80% of the level showing in serum.

Serum MMA – (methylmalonic acid) is available on the NHS although not routinely used, but fortunately  is widely available through private labs.

Urinary MMA – This test is only available privately.

Active B12 (HoloTc or Holotranscobalamin) – This test can be carried out as a home test kit – click here for more information.

Homocysteine – This test is not routinely used but can be carried out at your GP practice or at your local hospital if requested by your doctor. This test is widely available through private labs. Homocysteine can rise to a toxic level if vitamin B12, B6, folate, B2 and magnesium are low. It has been thoroughly documented that even moderately elevated homocysteine levels are a strong risk factor for cardiovascular disease, stoke, and neuro-degenerative diseases including dementia and Alzheimer’s.


Folate and iron deficiency often go hand in hand with B12 deficiency. It is important to have folate and Ferritin (iron storage) levels checked alongside vitamin B12.

The following results from a blood chemistry test are also important when considering a B12 deficiency:

  • MCV
  • MCH
  • MCHC
  • RDW
  • WBC

Causes Of B12 Deficiency

According to Tracey Witty the six most commonly identified causes of B12 deficiency are;

  • An inability to absorb B12
  • A diet deficient in B12
  • An autoimmune disorder
  • A genetic defect (including MTHFR)
  • Medications that hinder the body’s ability to use B12
  • A secondary deficiency in a child, stemming from maternal deficiency prior to conception, during pregnancy or during nursing.

Chris Kresser states the most common causes as:

  • intestinal dysbiosis
  • leaky gut and/or gut inflammation
  • atrophic gastrits or hypochlorhydria (low stomach acid)
  • pernicious anemia (autoimmune condition)
  • medications (especially PPIs and other acid-suppressing drugs)
  • alcohol
  • exposure to nitrous oxide (during surgery or recreational use)

In general, the following groups are at greatest risk for B12 deficiency:

  • vegetarians and vegans
  • people aged 60 or over
  • people who regularly use PPIs or acid suppressing drugs
  • people on diabetes drugs like metformin
  • people with Crohn’s disease, ulcerative colitis, celiac or IBS
  • women with a history of infertility and miscarriage

Toxic exposure could also be a factor.

Other causes may include:

  • Decreased stomach acid
  • Atrophic gastritis
  • Autoimmune pernicious anaemia
  • Helicobacter pylori
  • Gastrectomy, partial or complete
  • Gastric bypass surgery (weight loss)
  • Malnutrition
  • Eating disorders – anorexia – bulimia
  • Inadequate diet
  • Vegetarianism / veganism
  • Malabsorption syndromes
  • Alcoholism
  • Crohn’s disease
  • Coeliac disease (gluten enteropathy)
  • Diverticulosis
  • Inflammatory bowel disease
  • Small intestine bacterial overgrowth
  • Gastric irradiation
  • Ileal irradiation (bladder,cervix, uterus,prostate)
  • Inborn errors of B12 metabolism
  • Pancreatic exocrine insufficiency & Chronic pancreatitis

Drug induced causes – Please note that this list is not exhaustive

  • Antacids
  • Colchicine (treatment of gout)
  • H2 Blockers (Zantac, Tagamet, Pepcid)
  • Metformin – Diabetes drug (Glucophage)
  • PPI’s – Proton pump inhibitors (Omeprazole, Nexium, Prevacid, Protonix)
  • Nitrous oxide anaesthesia
  • Nitrous oxide recreational abuse (Laughing gas / Whippets / Hippy crack)
  • Mycifradin sulphate (Neomycin) antibiotic
  • Para aminosalicylates antibiotic
  • Phenytoin (Dilantin) – anti-epileptic
  • Potassium chloride (K-Dur)
  • Cholestyramine (Questran)
  • Chemotherapy and radiation treatment

Signs & Symptoms Of A Vitamin B12 Deficiency

Taken from a fantastic resource, found here.


  • Tinnitus
  • Tremor
  • Paresthesia – numbness, tingling and pain
  • Confusion / disorientation
  • Weakness of legs, arms, trunk
  • Impaired vibration – position sense
  • Abnormal reflexes
  • Unsteady or abnormal gait / falls
  • Ataxia (Neurological disorder affecting balance, coordination and speech)
  • Balance problems
  • Difficulty walking
  • Dizziness
  • Restless legs
  • Visual disturbances / decreased-blurred vision / damage of optic nerve
  • Forgetfulness, memory loss
  • Dementia / intellectual deterioration
  • Impotence
  • Paralysis
  • Impaired fine motor coordination
  • Muscular spasticity
  • Bladder or bowel incontinence
  • Impaired pain perception
  • Nocturnal cramping
  • Disturbance in taste and smell
  • Optic atrophy


  • Confusion/disorientation
  • Psychosis
  • Post natal depression
  • Hallucinations
  • Memory loss
  • Delusion
  • Depression
  • Suicidal ideation
  • Mania
  • Anxiety
  • Paranoia
  • Irritability
  • Apathy
  • Personality changesInappropriate sexual behaviour
  • Violent/aggressive behaviour
  • Schizophrenic symptoms
  • Sleep disturbances
  • Insomnia
  • Changes in taste, smell, vision, and sensory/motor function which can be mistaken for psychiatric problems

Haematological signs and symptoms

  • Anaemia
  • Macrocytosis (large red blood cells)
  • Hyper segmented neutrophils
  • Generalised weakness, fatigue
  • Breathlessness
  • Pallor / jaundice
  • Chronic fatigue

Vascular Problems

  • Orthostatic hypotension/ Postural hypotension (low blood pressure when standing, which can cause fainting and falls)
  • Postural orthostatic tachycardia
  • Palpitations
  • Occlusive vascular disorder
  • Transient ischemic attacks (TIAs, or ‘mini stroke’)
  • Cerebral vascular accident (CVA or ‘stroke’)
  • Myocardial infarction (‘heart attack’)
  • DVT – Deep vein thrombosis (blood clot to the leg or arm)
  • PE – Pulmonary embolism


  • Infertility
  • Recurrent miscarriage
  • Abnormal PAP smears
  • Intrauterine growth retardation


  • Infertility
  • Impotence
  • Low sperm motility
  • Low sperm count

Gastrointestinal – signs and risk factors

  • Loss of appetite/weight loss or anorexia
  • Epigastric pain (poor digestion, bloated feeling after eating small or normal sized meals)
  • IBS – Irritable bowel syndrome
  • Constipation
  • GERD – Gastric reflux disease – ulcers / mouth ulcers
  • Giardiasis
  • Pancreatitis, pancreatic exorine insufficiency
  • Decreased stomach acid
  • Gastropareisis
  • Helicobactor pylori infection
  • SIBO Small intestinal bacterial overgrowth
  • Gastrectomy (partial or complete) – bariatric surgery
  • Illeal resection (partial or complete)
  • Malabsorption syndromes – Crohn’s disease, coeliac disease etc)
  • Liver disease
  • Diphyllobothrium latum (fish tapeworm)

Additional Signs and Symptoms

  • Dry cracked corners of the mouth
  • Premature greying
  • Glossitis – swollen / sore tongue, geographic tongue
  • Fainting/light headedness
  • Osteoporosis
  • Fractures
  • Suppressed activity of osteoblasts (cells that build bone)
  • Symptoms mimicking Parkinson’s and MS
  • Nominal aphasia – difficulty recalling names or words
  • Radiculopathy, spinal nerve pain – commonly in lower back and neck
  • Increased susceptibility to infections
  • Poor wound healing
  • Malnutrition
  • Enlarged spleen (splenomegaly)
  • Enlarged liver (hepatomegaly)
  • Skin hyper pigmentation or hypo pigmentation
  • Poor antibody production following vaccines
  • MTHFR Gene mutation

As you can see there are numerous causes of a B12 deficiency and the effects are staggering. It is crucial this is explored in detail when seeking resolution of chronic fatigue. It also is another great example of how we have to consider the role of the gut when considering nutrient status.