Perhaps the most insidious distraction that throws a doctor off the diagnosis of vitamin B12 deficiency is the medical teaching that B12 is stored in the adult human liver in an amount sufficient for 5 to 10 years of total deprivation. Obviously not so. I have seen cases in which B12 reserves ran out in less than half that time. This is more likely nowadays when so many people have been avoiding red meat and liver in their diet for years on end. Vegetarian and, of course, fruitarian diets can induce severe B12 deficiency in susceptible people, i.e. those who may have a defect in B12 absorption. Such people are at severe risk of B12 deficiency if they go along with the crowd. Luckily, almost half of all Americans are taking multivitamin and B complex supplements containing B12 at least some of the time. On the other hand, there are still lots of folks who cling to the idealistic notion that they can get all their vitamins and minerals from a "balanced" diet.
I will never forget Caroline, an 18 year old college student, who had the lowest B12 level I have ever seen. She had been on a macrobiotic diet for two years and then for six months followed a fruitarian diet before mental confusion, delusion and agitation closed in on her. The diagnosis of B12 deficiency was considered after her dietary lifestyle became known. Her blood test was almost devoid of the vitamin, only 10 pg/ml. Fruits and vegetables contain no B12. The fermented soy (miso and tempeh) and nutritional yeasts at the ashram would have provided only small amounts; and then as a fruitarian she ran out of reserves.
Once a brilliant student, Caroline has never fulfilled herself since, has not been self-supporting, and has required almost continuous psychiatric care and frequent hospitalizations due to psychotic relapses in the 20 years since her period of acute B12 deficiency. The only good news is that she survived, and that she did not develop spinal cord damage with paralysis and end up in a wheel chair.
Most doctors are taught that B12 deficiency is a hereditary illness, which it is in many cases. However the medical students are not well taught about the many non-genetic hazards that cause depletion of this vitamin. For one thing there are so few dietary sources of B12 other than vitamin pills and injections! As mentioned already, fruits and vegetables contain none. Milk and cheese contain little, and in company with fish, fowl, eggs and even beef, the usual dietary intake is too low to satisfy optimal requirements.
Only organ meats, especially liver, kidney and, yes, calves brains, provide a reliable and adequate source. But people are avoiding these foods because they all contain cholesterol along with the B12. This is a downside result of the "war on cholesterol and fat" that is the official current dietary policy of the health establishment of--the world! As a result of cholesterol fetishism in our Washington bureaucropolis and cholesterol phobia everywhere else, dietary B12 deficiency is more common than ever.
In my book Meganutrition, I described Joe, a 35 year old 7th Day Adventist janitor, who had followed a strict vegetarian diet for over 15 years. He gradually changed, becoming dangerously hostile, and suspicious, especially towards his wife and children. Due to increasing pressure of his delusions, overtly suspicious and unreasonable behaviors, he eventually lost his job, and his wife and children left him. His parents brought him to consult with me; and even after the diagnosis of B12 deficiency he refused treatment. He had to be hospitalized finally before he would accept vitamin B12 injections; but when treated, he quickly recovered his personality--but not his family.
Vegetarians are often quite militant in defense of the B12 content of vegetables and about the fact that B12 is present in spirulina and seaweed. However in a study of 110 adults and 42 children living in a macrobiotic community in New England1half of the adults had low B12 levels and over half of them had abnormal amounts of methyl-malonic acid in the urine, indicating impairment of amino acid and fatty acid utilization. More than half the children were likewise abnormal in Methyl-malonic acid, and most were also short in stature and underweight. Dairy products were protective to some and so were home-made fermented soy products, such as tempeh. Commercial fermented products were not adequate however, and sea vegetables were also found to be unreliable sources of B12. Even spirulina and blue green algae seem to produce mostly false forms of B12, that may actually interfere with the active vitamin.2
These inactive vitamin B12 look-alikes in food are released by intestinal digestion and bind to the transport proteins that otherwise would carry vitamin B12 into the blood and liver, and thence to the rest of the body tissues and cells where it is used. Pseudo-B12 look-alikes give false normal readings in the conventional blood tests for B12. Luckily there is a protozoal assay which measures only the active B12; but it is offered by only one laboratory in the world3 and is not as well known as it deserves to be even though the accuracy is higher and cost lower than any other method. A lymphocyte B12 assay has recently become available also4. This is a test-tube test of growth of the patient’s lymphocytes after adding B12. Above normal growth means that the cells need more B12 than they have been getting.
Anyone who has had stomach surgery should be alert for B12 deficiency--in fact anyone who has had stomach surgery should take regular B12 injections as a precaution because the B12 transport proteins are manufactured and secreted by the stomach. If the stomach lining is damaged by heredity, aging, wear and tear, auto-immune disease, or ulcer surgery, which removes the acid-secreting cells, vitamin B12 replacement should be maintained for life.
Antacids and histamine blockers (Tagamet and Zantac) and Prilosec (omeprazole) interfere with absorption of B12 sufficiently to cause deficiency.5 Ten healthy volunteers were studied before and 2 weeks after measured vitamin B12 doses. Absorption of the vitamin was reduced by 75% in those taking 20 mg of omeprazole; and by 80% in those taking a 40 mg dose. Ordinary antacid doses interfere with B12 big time. So does intestinal malabsorption, especially Crohn’s disease, and a variety of liver diseases. Anemias of all types use up B12 to generate new blood. Blood donations lower B12 levels the same way. So do chronic infections, major trauma and extensive burns--all deplete the vitamin stores.
Folic acid deficiency can complicate and aggravate B12 deficiency. In most cases, B12 deficiency is associated with deficiency of stomach acid. This interferes with folic acid digestion because stomach acid is essential to trigger release of pancreatic digestive enzymes, without which folic acid cannot be digested and absorbed. Hence low stomach acid can lower folic acid despite a high vegetable diet rich in folic acid. This is a vicious circle, for without folic acid, vitamin B12 activity is impaired and the vitamin can accumulate, unused in the body. This is another cause of false normal or high B12 levels in laboratory testing.
A number of chemicals inactivate vitamin B12. Nitrous oxide, (also called laughing gas) destroys the vitamin and so do the common anesthetic agents, halothane and enflurane.6 A combination of nitrous oxide and halothane is a favorite in surgeries that do not require deep anesthesia. Post-operative delirium, psychosis and neuropathy, any of these is a warning to check and treat possible B12 deficiency. Antibiotics, particularly Flagyl (metronidazole) and chloramphenicol, can lower B12 levels. The anti-protozoal drug, chloroquine, can do the same. Chlorinated and brominated chemicals, such as pesticides, herbicides and fungicides destroy vitamin B12. This includes lindane, which is still in use for treating lice, even in children. Fluoride-containing refrigerants and propellants, such as freon and fluorohalomethanes, are another class of chemicals that destroy B12; but they are seldom appreciated because doctors are not taught to consider this possibility. I made the diagnosis in a bank executive who suffered neuropathy and cardiac irregularity after repeated exposure to chloro-fluoro-methanes from the insulating materials of his desert home. The 110-degree heat vaporized these toxics, which were sucked into his home office through the air-conditioner.
Female hormones can cause low blood levels of B12 and folic acid. There was a 40 percent reduction in serum B12 in 20 healthy women on oral contraceptives compared to a control group. Serum folic acid was also reduced.7Diabetes drugs such as metformin and phenformin interfere with B12 absorption; so does the anti-gout drug, colchicine. Likewise for neomycin, often used as a pre-operative bowel-sterilizing antibiotic. This list is incomplete and new anti-B12 drugs will be recognized in time, but it is obvious that there are a lot of conditions other than heredity that cause B12 deficiency. But if there is a family history of pernicious anemia, then the patient is likely to be more vulnerable to these environmental hazards.
One reason that B12 deficiency is not diagnosed more often is that researchers and laboratories have set the normal range too low. The normal range is usually given as 115 to 800g/L (billionths of a gram). The numbers should be revised upwards to 500 to 1500 pg/L out of respect for optimal rather than minimal benefits of the vitamin. In the past, patients might go without B12 treatment even in the face of macrocytic anemia typical of B12 deficiency because their doctors were misled by the laboratory range.
Lindenbaum broke through this widespread error about vitamin B12 diagnosis in his 1988 report of increased nerve and brain damage associated with B12 blood levels from 190 to 250 pg, levels that used to be regarded as normal. No more. Now the mainstream standard of care is to treat anyone with serum under 300 pg.8 Those more impressed with the complexity and pitfalls associated with B12 favor 500 pg as an indication for a trial of treatment, even if symptoms are not yet evident--in order to prevent irreversible damage.
Therefore, I prefer to treat with injectable B12 in any case of persistent fatigue, depression, psychosis, nerve pain or numbness, memory loss, headache, premature aging, arthritis, delayed healing, regardless of the results of the B12 test. Urine testing for homocysteine and methyl-malonic acid are also indications for B12 treatment, even when serum B12 levels are "normal." While the injections are almost painless, there are some patients who balk. Luckily the sub-lingual forms of B12 are effective if taken regularly at a minimum dose of 1 mg (1000 mcg) daily. Nasal gel B12 is even more readily absorbed though a bit messy.
In Dr. Lindenbaum’s series of 141 neuro-psychiatric patients whose symptoms were attributed to B12 deficiency, 40 (28%) had no anemia. Symptoms of sensory loss, ataxia and dementia were prominent and elevated methylmalonic acid and homocysteine were observed. Serum B12 was over 200 pg/ml in 2 patients; between 100 and 200 pg in 16 others. In an editorial comment on this research, Dr. William Beck of Massachusetts General Hospital concluded: "It would appear that measurement of serum levels of the nutrient may not always be the answer." Indeed, testing for methylmalonic acid and homocysteine may be more useful than the direct blood level of B12. For best results it is wise to test both ways if there is any suspicion of vitamin deficiency."
Dr. Beck also considered the increased costs of such testing: "but if real benefits await these patients, the costs are justified." And he concluded with the following classic line: "Could it be that the many cobalamin (B12) injections given over the years for vague symptoms were in fact justified?" That is progress! Doctors are finally waking up.
However sometimes patients are their own worst enemies, for to refuse B12 treatment is to risk Alzheimer’s and quadriplegia, paralysis of the legs and loss of control of the bladder. I am thinking of Lora, a 50 year old woman who consulted me because of chronic depression and then tested very low for B12. I had a complete laboratory work-up and gave her a typewritten nutrition prescription, including regular injections of B12. But she refused my advice and was rather chill when I followed up my report with a personal telephone call--three times. She was obviously suspicious and paranoid, already at the early stages of irreversible brain damage and dementia. There was nothing more I could do. The medical fates can be extremely unforgiving.
That was the same story with Petra, but her case was particularly galling because her husband and family doctor had all the information from me and should have known better. Instead they placed her in a nursing home within 6 months after partial but inadequate treatment, using B12 by mouth rather than returning for a series of B12 shots as recommended. Once she was given a diagnosis of Alzheimer’s by the family doctor, everyone got the erroneous idea that nothing further could be done! I called and wrote the family but her husband was in a state of disbelief. It was beyond my power. Neglected and deteriorated, it is almost certain that she was already beyond repair. Now she really does have "Alzheimer’s"-- one of the approximately 30 percent of the millions of Alzheimer’s cases each year that are caused by vitamin B12 deficiency.
While writing this review I had occasion to do a laboratory update for one of my patients, a 40 year old woman, who has her blood tested for vitamin and mineral levels every two years, even though she is in excellent health and already on a nutrient support regimen. Therefore I was surprised to find a low B12 in this follow-up panel. There it was, only 250 ng/L. Her 13 year old son was even lower, only 210 ng/L. Review of her family history brought forth that her father had ulcers at age 30 and underwent surgery to remove the acid-secreting cells of his stomach. He was never well again after that because he was never told about the need for vitamin B12 replacement. Over the next few years he became irritable, paranoid and an irascible alcoholic.
Alcohol dependency is sometimes the poor man’s answer to chronic biological depression. The alcohol by-passes carbohydrate metabolism, yields rapid energy, douses the fires of regret, and powers an almost irresistible uplift of mood. Unfortunately it also turned him to violence against his family and caused repeated conflicts requiring police intervention. No one ever thought to replace his lost B12 and he died in his 60s, a young-old, and miserable man. How sad it is to be able to clarify the diagnosis from thousands of miles away and years after his untimely demise when no one thought of it in the 30 years before!
It helps a little to be thankful that his sad experience prepared Jane and her son to accept B12 therapy. Both were amazingly responsive, he to sublingual tablets, his mother to B12 injections. The first few weekly shots quelled her depression and made her appear visibly younger. Her son regained his mental concentration ability and began doing household chores that he used to shirk. It helps to have a healthy level of physical and mental energy. Vitamin B12 has given this family a lot more cheer as they greet the New Year.
©2000 Richard A. Kunin, M.D.