Vitamin B12 Deficiency Manifested as Mania.
“My brain hums with scraps of poetry and madness.” – Virginia woolf.
Case study.
Ms. Edith was a 29-year-old woman with no personal or family history of psychiatric disorders, who was admitted to the hospital in February of 2011 with a 4-week history of episodes of manic symptoms of several hours’ duration, including grandiosity, hyperactivity, sexual indiscretion, hyperphagia, irritable mood, reckless behavior, flight of ideas, and overbearing manner. These episodes had a sudden onset and conclusion, and the patient was able to remember them. No hallucinations were reported at any time.
At admission, she was oriented in all spheres, but was easily distractible. Full manic syndrome (DSM-IV criteria) was present and there was no coexisting delirium. All these psychiatric symptoms disappeared after 1 hour, without any medical intervention.
An examination revealed the presence of a left Babinski’s reflex and ataxia, as well as a bilateral loss of proprioception, vibration, and sensation of light touch and pain in the lower extremities. Strength and reflex in the lower extremities were diminished.
The results of general blood chemistries, a thyroid function test, and a comprehensive drug screen were within normal limits.
Although the results of electroencephalogram (EEG) and brain magnetic resonance imaging were normal, the duration, as well as the sudden onset and conclusion of episodes, suggested an epileptic cause for this patient’s mania. She was treated with valproic acid for 3 weeks with no improvement.
Serum vitamin B12 level was measured and was found to be markedly diminished––less than 60 pg/mL. Vitamin B12 (1000 µg/day) was administered intravenously for 1 week. After the third day of B12 replacement therapy, our patient did not experience new manic episodes. Therapy was continued with 1000 µg intramuscular injections weekly for 1 month and then with monthly intramuscular injections as maintenance treatment. Within 1 month, neurologic symptoms had improved. One year after B12 vitamin replacement started, her mental status was still normal.
Q. How prevalent is vitamin B12 deficiency in our society.?
B12 deficiency is far more common than most health care practitioners and the general public realize. Data from the Tufts University Framingham Offspring Study suggest that 40 percent of people between the ages of 26 and 83 have plasma B12 levels in the low normal range – a range at which many experience neurological symptoms. 9 percent had outright deficiency, and 16 percent exhibited “near deficiency”. Most surprising to the researchers was the fact that low B12 levels were as common in younger people as they were in the elderly.That said, B12 deficiency has been estimated to affect about 40% of people over 60 years of age. It’s entirely possible that at least some of the symptoms we attribute to “normal” aging – such as memory loss, cognitive decline, decreased mobility, etc. – are at least in part caused by B12 deficiency.
Q. Why is B12 deficiency so under-diagnosed?
B12 deficiency is often missed for two reasons. First, it’s not routinely tested by most physicians. Second, the low end of the laboratory reference range is too low. This is why most studies underestimate true levels of deficiency. Many B12 deficient people have so-called “normal” levels of B12. Yet it is well-established in the scientific literature that people with B12 levels between 200 pg/mL and 350 pg/mL – levels considered “normal” in the U.S. – have clear B12 deficiency symptoms.Experts who specialize in the diagnosis and treatment of B12 deficiency, suggest treating all patients that are symptomatic and have B12 levels less than 450 pg/mL. They also recommend treating patients with normal B12, but elevated urinary methylmalonic acid (MMA), homocysteine and/or holotranscobalamin (other markers of B12 deficiency).
In Japan and Europe, the lower limit for B12 is between 500-550 pg/mL, the level associated with psychological and behavioral manifestations such as cognitive decline, dementia and memory loss. Some experts have speculated that the acceptance of higher levels as normal in Japan and the willingness to treat levels considered “normal” in the U.S. explain the low rates of Alzheimer’s and dementia in that country.
Q. What are the signs and symptoms associated .?
Vitamin B12 deficiency is the medical condition of low blood levels of vitamin B12. A wide variety of signs and symptoms may occur including a decreased ability to think and behavioural and emotional changes such as depression, irritability, and psychosis. Abnormal sensations, changes in reflexes, and poor muscle function can also occur as may inflammation of the tongue, decreased taste, low red blood cells, reduced heart function, and decreased fertility. In young children symptoms include poor growth, poor development, and difficulties with movement. Without early treatment some of the changes may be permanent.
The presence of peripheral sensory-motor symptoms or subacute combined degeneration of spinal cord strongly suggests the presence of a B12 deficiency instead of folate deficiency. Methylmalonic acid, if not properly handled by B12, remains in the myelin sheath, causing fragility. Dementia and depression have been associated with this deficiency as well, possibly from the under-production of methionine because of the inability to convert homocysteine into this product. Methionine is a necessary cofactor in the production of several neurotransmitters.
Each of those symptoms can occur either alone or along with others. The neurological complex, defined as myelosis funicularis, consists of the following symptoms:
- Impaired perception of deep touch, pressure and vibration, loss of sense of touch, very annoying and persistent paresthesias
- Ataxia of dorsal chord type
- Decrease or loss of deep muscle-tendon reflexes
- Pathological reflexes — Babinski, Rossolimo and others, also severe paresis Q. Why is B12 deficiency so common? The absorption of B12 is complex and involves several steps – each of which can go wrong. Causes of B12 malabsorption include:
- 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
Note to vegetarians and vegans: B12 is found ONLY in animal products
B12 is the only vitamin that contains a trace element (cobalt), which is why it’s called cobalamin. Cobalamin is produced in the gut of animals. It’s the only vitamin we can’t obtain from plants or sunlight. Plants don’t need B12 so they don’t store it.
A common myth amongst vegetarians and vegans is that it’s possible to get B12 from plant sources like seaweed, fermented soy, spirulina and brewers yeast. But plant foods said to contain B12 actually contain B12 analogs called cobamides that block intake of and increase the need for true B12.
This explains why studies consistently demonstrate that up to 50% of long-term vegetarians and 80% of vegans are deficient in B12. This is why it’s absolutely crucial for those that abstain from animal products to understand that there are no plant sources of B12 and that all vegans and most vegetarians should supplement with B12.
Q. Treatment of B12 deficiency.?
One of the greatest tragedies of the B12 epidemic is that diagnosis and treatment is relatively easy and cheap – especially when compared to treatment of the diseases B12 deficiency can cause. A B12 test can be performed by any laboratory.
As always, adequate treatment depends on the underlying mechanism causing the problem. People with pernicious anemia or inflammatory gut disorders like Crohn’s disease are likely to have impaired absorption for their entire lives, and will likely require B12 injections indefinitely. This may also be true for those with severe B12 deficiency causing neurological symptoms.
If you suspect you have B12 deficiency, the first step is to get tested. You need an accurate baseline to work from. If you are B12 deficient, the next step is to identify the mechanism causing the deficiency. This is something you’ll probably need help with from a medical practitioner. Once the mechanism is identified, the appropriate form (injection, oral, sublingual or nasal) of supplementation, the dose and the length of treatment can be selected.
Q. What is the active form of vitamin B12.?
Cyanaocobalamin is the most frequently used form of B12 supplementation in the US. But recent evidence suggests that hydroxycobalamin (frequently used in Europe) is superior to cyanocobalamin, and methylcobalamin may be superior to both – especially for neurological disease.
Japanese studies indicate that methylcobalamin is even more effective in treating the neurological sequelae of B12 deficiency, and that it may be better absorbed because it bypasses several potential problems in the B12 absorption cycle. On top of that, methylcobalamin provides the body with methyl groups that play an role in various biological processes important to overall health.
Q. Is there any danger of overdose with Vitamin B12 which can result in toxicity.?
Treatment based on symptoms instead of blood values.
The recommended treatment in the Netherlands consists of a hydroxocobalamin injection of 1mg every two months, after an initial loading dose of 10 injections in 5 to 10 weeks.
No reference is made to the serum value or a danger of overdosing, unlike for instance in case of a vitamin D or A deficiency. The lack of danger of an overdose is further underlined by the advice to treat patients with neurological involvement with two injections a week for up to two years, if necessary. This also emphasizes that symptoms and not blood values should be used as a guideline. If serum values were decisive, even patients with neurological involvement could suffice with the maintenance dose of one injection every two months after the initial loading dose.
The treatment with high dose B12 injections is not only completely safe but fortunately also very effective. With the right treatment patients can recover completely. Starting straight away with treatment is essential, as is the continuing treatment in order to give the body enough B12 to fully recover. Therefore it is essential that patients are no longer exposed to the real danger of irreversible symptoms because of the imaginary fear of overdosing.
“What you are afraid to do is a clear indication of the next thing you need to do.” – Ralph Waldo Emerson.