What do we know about vitamin B12 deficiency?

Victoria, British Columbia by night. (Dr. Noorali Bharwani)
Victoria, British Columbia by night. (Dr. Noorali Bharwani)

Even after more than 100 years, vitamin B12 (cobalamin) is still the subject of intense research.

Vitamin B12 plays an important role in red blood cell formation, cell metabolism, nerve function and the production of DNA. As we know, the function of DNA is to store all of the genetic information that a person needs to develop, function, and reproduce.

Vitamin B12 is also necessary for normal bone marrow and central nervous system function. The vitamin is absorbed in the distal ileum (where the small bowel joins the large bowel). Its absorption in the distal ileum requires intrinsic factor.

Where can you find intrinsic factor?

Intrinsic factor is a natural substance normally found in the stomach. Lack of intrinsic factor leads to vitamin B12 deficiency and pernicious anemia, and can cause brain and nervous system problems. There may be cognitive decline. There may be peripheral neuropathy. Quite often the presentation can be very suttle and potentially serious.

Vitamin B-12 deficiency is associated with dementia and low cognitive function, but it’s not clear whether vitamin B-12 supplements might help prevent or treat dementia.

The discovery of vitamin B12

“The discovery of vitamin B12, the elucidation of its role in metabolism, and the effects and treatment of its deficiency occurred in distinct phases over more than 100 years, and it was the subject of two separate Nobel Prizes,” says an article in Ann Nutr Metab 2012 (The discovery of vitamin B12 – authors Scott and Molloy).

The next advance was made with the discovery that a gastric component, which was named intrinsic factor, was missing in pernicious anemia. Many years later, intrinsic factor was found to be a glycoprotein that formed a complex with vitamin B12, promoting its absorption through ileal receptors.

The article says vitamin B12 is still the subject of intense research and, in particular, its role in preventing some irreversible neurological lesions remains unclear.

The incidence of vitamin B12 deficiency increases with age. The condition affects five to 20 per cent of adults older than 60 years.

The main source of vitamin B12 is animal-based foods such as meat, fish, eggs, and dairy products. In addition, some vegetable-based foods have been fortified with vitamin B12.

Individuals who do not consume these foods are more susceptible to vitamin B12 deficiency.

Other common causes include autoimmune gastritis (which causes pernicious anemia), malabsorptive states (e.g., pos-gastrointestinal surgery), and certain medications like metformin, proton pump inhibitors and histamine-2 receptor antagonists.

Managing B12 deficiency

The recommended daily amount of vitamin B12 for adults is 2.4 micrograms. Most people get enough of it from a balanced diet.

But it is important to recognize that certain segment of the population is vulnerable to be B12 deficient. If left untreated, vitamin B12 deficiency can lead to anemia, fatigue, muscle weakness, intestinal problems, nerve damage and mood disturbances.

All people over 65 years of age who are malnourished, all people in institutions or psychiatric hospitals, and all people with hematological or neuropsychiatric symptom should have their serum B12 levels measured.

Older adults, vegetarians, vegans and people who have conditions that affect their ability to absorb vitamin B12 from foods might benefit from the use of oral supplements.

Vitamin B12 supplements also are recommended for women who are pregnant or breastfeeding. Vitamin B12 is transferred through the placenta to the fetus during pregnancy and through breast milk after birth. Infants who drink breast milk from a mother who consumes adequate amounts of vitamin B12 or infants who drink infant formula, will receive enough vitamin B12.

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Why is PSA test so controversial?

Echo Dale Regional Park in Medicine Hat, AB. (Dr. Noorali Bharwani)
Echo Dale Regional Park in Medicine Hat, AB. (Dr. Noorali Bharwani)

Prostate cancer remains the most commonly diagnosed non-skin cancer among Canadian men and is the third leading cause of cancer-related death.

The natural history of prostate cancer ranges from a potentially inconsequential course to a fatal disease. Doctors continue to grapple with the question of how to identify those with clinically important disease while avoiding overdiagnosis and overtreatment, says an article in the Canadian Medical Association Journal (CMAJ October 24, 2022 194) written by Kikachukwu et al.

History of PSA (prostate-specific antigen) test

T. Ming Chu, PhD, DSc, Chair Emeritus of Diagnostic Immunology Research and Professor Emeritus of Urologic Oncology, led the research in the 1970s that resulted in the discovery of PSA and the development of the PSA test.

PSA test was originally approved by the FDA (Food and Drug Administration in U.S.) in 1986 to monitor the progression of prostate cancer in men who had already been diagnosed with the disease. FDA approved PSA as a screening test seven years later.

Even after 30-years, why is PSA screening test controversial?

Using the PSA test to screen men for prostate cancer is controversial because it is not yet known for certain whether this test actually saves lives. Moreover, it is not clear that the benefits of PSA screening outweighs the risks of follow-up diagnostic tests and cancer treatments.

The Canadian Task Force on Preventive Health Care (CTFPHC) recommends against routine PSA screening for men of all ages, but states that the greatest benefit from screening is likely in those aged 55–69 years.

The guideline identifies and reports the increased risk of prostate cancer among Black people, but does not provide specific guidance on managing this increased risk. The new guideline was published online on October 27, 2022 in the Canadian Medical Association Journal (CMAJ).

Research from the United States and Europe has shown the incidence and lifetime risk of developing prostate cancer among Black people are more than double than among their white counterparts (CMAJ October 24, 2022 194).

There is no doubt prostate cancer screening can help identify cancer early on, when treatment is most effective. But some prostate cancers are slow growing and never spread beyond the prostate gland. This is where the dilemma is.

Some other points about PSA test

  1. False positive results and overdiagnosis. This happens quite often with PSA testing and only about 1 in 4 abnormal results is due to cancer. A false-positive result can lead to unnecessary testing that is more invasive, such as repeated biopsies. It can cause unnecessary anxiety and distress. (CCS – Canadian Cancer Society website).
  2. A false-negative result means that the test shows the PSA level is normal even though prostate cancer is present. Not all prostate cancers cause a high PSA level. PSA testing misses about 15 per cent of prostate cancers (CCS).
  3. Most medical organizations encourage men in their 50s, men age 45 who have family history of prostate cancer or are Black individuals to discuss the pros and cons of prostate cancer screening with their doctors.
  4. Most organizations recommend stopping PSA tests around age 70. Men at age 70 and over have the highest incidence of prostate cancer over-diagnosis and several studies have suggested that screening in this age group is likely not beneficial.
  5. In most men with prostate cancer, the tumour grows slowly, and they’re likely to die of another cause before the prostate tumour causes any symptoms. The prognosis for most prostate cancers is good, with a 10-year survival rate of 95 per cent.

Questions remain – Who should get PSA test, at what age to start (45, 50 or 55) and how to manage patients with elevated PSA test results?

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Photo Quiz: Scalp Lumps

Dermatofibrosarcoma Protuberans (Dr. Noorali Bharwani)

This is a 34-yr-old male with a history of scalp lumps. Is this a case of…
Lipoma?
Dermatofibrosarcoma? or
Sebaceous Cyst?

Correct Answer
Dermatofibrosarcoma Protuberans. This is a rare neoplasm of the dermis layer of the skin, and is classified as a sarcoma. It usually occurs in the trunk or extremities but can involve the head and neck particularly the scalp. In many respects, the disease behaves as a benign tumour, but in 2%-to-5% of cases it can metastasize, so it should be considered to have malignant potential.

This photo quiz was published on the Canadian Healthcare Network website.

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Justin Bieber and Ramsay Hunt Syndrome

Maui, Hawaii. (Dr. Noorali Bharwani)
Maui, Hawaii. (Dr. Noorali Bharwani)

Canadian singer, Justin Bieber, recently announced he has taken time off from his tour to recover from Ramsay Hunt syndrome. We hope his recovery is quick and complete.

What is Ramsay Hunt syndrome?

Ramsay Hunt syndrome was first described in 1907 by James Ramsay Hunt in a patient who had ear pain associated with skin and mucosal rashes. Ramsay Hunt (1872 – 1937), was an American neurologist.

Ramsay Hunt syndrome is a viral infection. The varicella zoster virus, which also causes shingles and chicken pox, typically infects facial nerve near the inner ear, causing weakness, inflammation and sometimes pain in the surrounding areas.

After chickenpox clears up, the virus still lives in the nerves. Years later, it may reactivate. When it does, it can affect the facial nerve causing one-sided facial paralysis and hearing loss.

According to a report published in the Canadian Medical Association Journal (cmaj.ca/content/189/8/e320), Ramsay Hunt syndrome has an annual incidence rate of 3.2 to 4.2 cases per 1,000 people.

Ramsay Hunt syndrome can occur in anyone who has had chickenpox. It’s more common in older adults, typically affecting people older than 60. It is rare in children.

What is Bell’s palsy?

Ramsay Hunt syndrome can be confused with Bell’s palsy. A famous example of Bell’s palsy sufferer who experienced permanent effects is former Prime Minister of Canada, Jean Chretien, who had Bell’s palsy as a child.

Bell’s palsy is named after Sir Charles Bell, a Scottish doctor and surgeon in the 19th century. In 1821, Bell described the anatomy of the facial nerve and its association with the unilateral facial paralysis. Historically, the descriptions of the facial distortion were first told by early Greek and Roman physicians.

The cause of Bell’s palsy is unknown. Swelling and inflammation of the cranial nerve VII is seen. Most scientists believe that reactivation of an existing (dormant) viral infection may cause the disorder.

Bell’s palsy can strike at any time, and although most symptoms can improve within a few weeks and a complete recovery is usually anticipated, some people have lingering effects, and others may be burdened with symptoms for life.

What is the difference between Bell’s palsy and Ramsay Hunt syndrome?

Compared with Bell’s palsy (facial paralysis), patients with Ramsay Hunt syndrome often have more severe paralysis at onset and are less likely to recover completely. Overall, the chances of recovery are better if the treatment is started within three days.

Prevention and Management of Ramsay Hunt syndrome:

Shingles vaccination is the only way to protect against shingles and postherpetic neuralgia, the most common complication from shingles.

Shingrix, the shingles vaccine, can provide protection against both shingles and Ramsay Hunt syndrome. It’s available for adults age 50 and older, given in two doses two to six months apart, and is more than 90 per cent effective in preventing shingles.

Children are now routinely vaccinated against chickenpox, which greatly reduces the chances of becoming infected with the chickenpox virus. A shingles vaccine for people age 50 or older also is recommended.

Time is of the essence when it comes to treatment of Ramsay Hunt syndrome. If treatment begins within three days of the diagnosis, partial paralysis of the face resolves itself by 75 per cent. If treatment starts four to seven days after diagnosis, or more than eight days, paresis is resolved by 48 and 30 per cent, respectively.

Medical treatment may include: antiviral drugs, corticosteroids, and anti-anxiety medications. Drugs such as diazepam (Valium) can help relieve vertigo. The pain associated with Ramsay Hunt syndrome can be severe. Prescription pain medications may be needed.

Complications:

Complications of Ramsay Hunt syndrome may include permanent hearing loss and facial weakness.  Usually, it is temporary but can be permanent. There may be eye damage because of the weakness of eye-lids. There may be postherpetic neuralgia.

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