Dr. Richard Kunin

Vitamin B12: Under Appreciated

I have recently treated over half a dozen patients whose lives have been ruined by vitamin B12 deficiency--a preventable disorder. In every case there was medical error and/or patient ignorance and skepticism leading to permanent harm. It is easy to miss the diagnosis of vitamin B12 deficiency. In the first place, it is a vitamin and our medical education is not only weak on vitamin diagnosis, it often reviles those doctors who treat with vitamins.

For example, B 12 injections are generally considered unnecessary, just one step short of quackery, by peer review committees and health insurance claims reviewers. Even if the patient feels better, the powers that be still condemn the practice as a form of suggestibility and placebo effect. No question about it: doctors are discouraged from treating with vitamin B12 unless there is documentary evidence, such as macrocytic anemia, with large sized red cells, over 100 microns in volume, or a B12 blood test less than 115 pg/ml (billionths of a gram per milliliter). Unfortunately the laboratory signs are not always that clear. Then the doctor’s experience must take over.

Vitamin B12 is an essential co-factor for two vital enzymes.
1. MMA (methylmalonyl CoA mutase). If B12 is deficient, methylmalonic acid cannot be converted to succinate, a necessary step in the utilization of odd-numbered fatty acids, those ending with a 3 carbon propionic acid group, rather than the usual 2 carbon acetic acid group. As a result methylmalonic piles up in the blood, blocked from its normal metabolism into succinate, which can be oxidized in the citric acid cycle, thus producing energy in the form of ATP.

In other words, without adequate B12 fats do not enter the carbohydrate cycle. As a result, there is a drop in energy level and a tendency to hypoglycemia, low blood sugar.

2. Methionine synthetase: necessary for recycling the essential amino acid, methionine, by transferring a carbon atom to homocysteine. There is no other mechanism to make this methyl carbon transfer except by means of B12; hence B12 deficiency causes two chemical problems here: homocysteine accumulates in the blood, and methionine becomes scarce at the same time.

Homocysteine is bad because it binds copper, literally attracting it out of its reaction sites in collagen, and thus unraveling collagen, the bio-glue that holds tissues together, especially the intimal lining of blood vessels. This internal damage can cause blood vessel leaks, clots and deposits. If the coronary arteries are affected it can cause heart attack; in the cerebral arteries it causes strokes, and any damaged artery is liable to enlarge, forming an aneurysm, which can rupture. In a large vessel, such as the aorta, this can cause sudden death.

A shortage of methionine causes deficiency of a vital enzyme, SAM, that
is S-Adenosyl-Methionine, which becomes homocysteine by giving up its active methyl carbon in the manufacture of several essential body chemicals (see below). The re-cycling of methionine from homocysteine by means of capturing a methyl from methyl-THF is an equally key step in order to conserve methionine, which otherwise comes only from the diet. B12 is required to transfer the methyl carbon from methyl-folate (mTHF) and in the process serves also to activate folic acid for several other vital functions, such as nucleic acid synthesis. By giving up a methyl group, methyl THF becomes THF, which is interconvertable with four other sub-types of folic acid.

Deficient B12 status therefore blocks the utilization of methyl-THF, which can rise to above normal levels of folic acid blood tests. That is a tip-off to B12 deficiency.

Low THF is a serious deficiency, associated with birth defects and increased incidence of cancer. The connection is obvious once you know that THF is required for synthesis of nucleic acid components, the purine and pyrimidine bases, from which DNA and RNA are formed.

SAM is also vital for the production of adrenalin (a neurohormone); creatine (a muscle energy source); choline, an acetyl-choline component (neuro-transmitter); phosphatidyl-choline, a lecithin (cell membrane repair); and polyamines spermine and spermidine (stimulate cell growth and repair).

If these relationships seem complicated they are; but the practical effects of B12 activity are straight-forward:
1. Nucleic acid synthesis (healing, manufacture of all body cells, especially red blood cells, DNA, and antibodies;
2. Activation of the vitamin, folic acid, (redoubles anti-cancer effect and together they support synthesis of myelin, the insulating covering of nerves;
3. Synthesis of SAM (most powerful natural anti-depressant-via epinephrine);
4. Recycling of methionine (conserves this scarce amino acid, permits lower protein intake);
5. Removal of toxic homocysteine (thus protecting against collagen damage in blood vessel lining, hence protects against atherosclerosis and aneurysm (damage), and hypertension (spasm);
6. Protection from copper deficiency otherwise caused by homocysteine (thus protects against heart damage and arrhythmia, diabetes, chronic fatigue);
7. Efficient oxidation of fats, so that methylmalonic acid and propionic acid do not accumulate. These organic acids deplete the vitamin Carnitine, and this causes fatigue, loss of muscle tone and simulates depression.
8. Production of myelin, the insulation of nerves. Repair of nerves prevents damage to the spinal cord and brain, so-called subacute combined degeneration. This involves pain (early) and loss of muscle perception and vibration sense (late) in the hands and feet. It also causes mental impairment, typically with paranoia and depression, is similar to Alzheimer’s. In fact, about 30 percent of patients with Alzheimer’s actually have B12 deficiency.

If B12 is so important, why is there such medical skepticism and resistance to its use? As recently as 1989, the Journal of the American Medical Association saw fit to publish a featured article devoted to persuading patients to stop taking B12 injections--even though the patients claimed good results . The setting of the study was a clinic serving over 1200 patients and recently taken over by new owners. A records audit showed120 patients had been receiving B12 injections regularly; however only 4 of the 120 met the medical criteria for receiving vitamin B12 therapy. The authors accepted only four indications for prescribing this vitamin: 1) pernicious anemia; 2) deficiency documented by laboratory test; 3) a history of gastric surgery; 4) intestinal disease with malabsorption.

The authors real motivation for performing the study is that the health insurance companies were refusing payment for B12 injections. The authors did not seem opposed to the practice, saying only "The use of cyanocobalamin (B12) injections for patients without documented deficiency has been a common practice both ridiculed and indulged by the medical profession." On the other hand, they referred to an insurance review agency that rejected more than 75% of almost 3000 cyanocobalamin injection claims for payment. There lies the problem. Insurance companies do not "indulge." Lawyers and accountants do not think like doctors. Money comes before comfort in the bureaucratic mind, and the doctor-patient relationship gets little credence when it comes to substantiating benefits. That’s just the way it is.

Historically vitamin B12 was first recognized in relation to pernicious anemia; however in this study, 80 percent of the patients were motivated by weakness and fatigue, not anemia, and the average benefit was rated as "good". In fact, these patients reported a high level of effectiveness for most of the 25 indications listed in the study. They authors concluded: "It is likely that this injection-seeking behavior was reinforced and perpetuated by the perception of benefit. Past recipients of cyanocobalamin who perceived little or no benefit would be less likely to return for repeated injections and, thus, would be less likely to be included in the study."

If that paragraph seems obtuse, it is a classic of medical obtuseness. The point is that the patients who came back for repeat injections were the responders to B12. That is understandable. What is not is the cynicism of the authors--who reflect a majority of the medical-political establishment, a bureaucratic dragon, dead-set against giving an admittedly harmless treatment that the patients consider helpful, because it doesn’t fit current medical dogma, e.g. the four indications considered "acceptable." In fact, the bottom line of this clinical study is: "Despite the generally high perceived value of the injections, a majority of those approached (25 of 48) were willing to consider discontinuing them, at least temporarily."

The implication of this report is that patients do not know what is good for them and that clinic administrators do. This report ignores the inherent bias involved when those with a financial interest in a medical business write and publish a report that justifies terminating a treatment for 116 of 120 patients, not because the patients rejected the treatment as ineffective, but because the laboratory test results didn’t support the benefits the patients claimed to get!

This violates a fundamental tenet of medical teaching: "never diagnose a patient on the basis of laboratory evidence alone." Diagnosis must be in the context of the history, examination (including laboratory testing), clinical trials and follow-up that are part and parcel of rational and scientific medical practice.

The hidden tragedy of this report is that it pits the doctor against his own patients. In fact the authors admitted that 41 of these 120 patients dropped out of the clinic and sought medical help elsewhere. That is a 33% drop-out rate, about the same drop-out rate that medical practices are seeing across America as patients switch to alternative and non-medical health practitioners, mainly chiropractors, acupuncturists and nutritionists.

Patients rightfully want to be helped and they want to be respected. We all do. Especially when we are sick and feeling bad. It is the arrogance and inflexibility of medical orthodoxy that threatens to topple the entire medical profession and turn it into a mindless public health system, run by text-book bureaucrats and computerized robots. I don’t think the American people will buy it; but that doesn’t seem to have gotten across to the medical-political-bureaucratic people who have just designed the Kennedy Kassebaum bill, which reflects the psychology of this study by defining "unnecessary services" as medical fraud. This is the criminalization of medicine.

Prove it, you say! The bill increases penalties from $2000 (already high) to $10,000 per infraction; and potential jail time has been increased from 2 years to 10. If B12 and other nutrient therapies are "unnecessary," the hottest game in town may soon be: "Cops and Docs." If you wonder why doctors seem uninterested in nutrition, perhaps this gives you an idea why. Not until our legislators wake up and give back our medical rights, such as the right to have a treatment when we find that it is beneficial, even though the regulations deny it, are you really the master of your own medical care. Who is the ultimate master of your body? You or a politician, bureaucrat or lobbyist, whose rules satisfy their interests, not necessarily yours.

Vitamin B12 does not fit the mold of the deficiency diseases theory, or the one-disease-one-drug model of medicine that is taught in medical schools. The most important medical fact about vitamin B12 is that deficiency does not show up only as anemia. In fact, in many cases there is no anemia, only neurological symptoms, such as numbness in the extremities, inability to walk and stay in balance, especially at night or in the dark, and serious personality changes, such as depression and paranoia. Unlike the anemia, which always responds to B12 replacement, if the nerve and brain symptoms are not treated promptly the damage is likely to be permanent.

Pernicious anemia is a serious disease. The bone marrow produces large numbers of defective cells, called megaloblasts, along with a reduced number of normal and more durable ones. As the disease progresses, the normal cells are increasingly replaced by large cells, macrocytes, so the average size of the circulating red cells increases by 25 to 50 percent. Doctors recognize pernicious anemia by these large sized cells in a blood smear.

Unfortunately, doctors are taught to diagnose and treat the anemia and it is all too common that physicians, even experienced psychiatrists, overlook the nerve symptoms and treat the paranoia as depression or schizophrenia, with drugs rather than a vitamin. Two cases were published in 1984. in which EEG brain waves and mental symptoms were reversible with B12 therapy This convinced the authors that all patients with dementia should be checked for B12. That message has not gotten through.

One reason is that most doctors expect to find B12 problems in patients past age 60; and therefore may fail to consider it in younger folks. One of my patients was only 28 when B12 deficiency reached a critical state. Patricia had been able to cover-up her mental fuzziness and depression for years but the pain in her extremities finally drove her to seek medical help. Somehow the diagnosis was missed at two medical centers. Only after she had a severe progression of spinal cord damage following anesthesia for laparoscopic surgery did the diagnosis become obvious.

Anesthetic agents, such as nitrous oxide (laughing gas) and halothane and enflurane, destroy vitamin B12. This pushed her into severe deficiency and within a few weeks she lost muscle sense in her extremities, became unable to walk and unable to control her bladder. Despite ongoing treatment for over ten years now, she remains confined to a wheel-chair, evidently for life.

Some recovery is possible. Mary, a school-teacher, was placed on a hospital psychiatric ward when she became depressed and paranoid. When she complained of leg pains, the medical team were led astray by the fact that she is diabetic, since this condition also can present as nerve symptoms. It was only after several months, as her mental condition deteriorated into severe confusion and dementia the diagnosis of B12 deficiency was obvious. By that time she too was in a wheel-chair. By the time she consulted me she was better but on crutches, barely able to get along on her own. Happily, she has responded very well to nutrient support, especially the use of Carnitine, Coenzyme Q, Ginkgo, glutamine and, of course B12 injections. Her mental acuity has improved, she is not depressed or paranoid--and she is able to walk with a cane.

Another unhappy fate was that of a 72 year old real-estate sales woman, whose son I had treated after adverse reaction to PCP 20 years earlier. He had improved from the paranoia and confusion that had disabled and hospitalized him, but he never regained his full intellect and was never able to be fully self-supporting as a result. I didn’t make the connection to his mothers galloping senility, forgetfulness, depression, inability to cope with her business that quickly became disabling until her laboratory tests came back showing low B12 under 100 ng/L. and the co-dependent vitamin folic acid, was also very low. Her deterioration came on after she underwent surgery for pain in her feet and toes. Naturally the laminectomy didn’t help, the pain was undoubtedly due to neuropathy, which was obvious at my physical exam a year later.
She also had panic attacks after the surgery, made much worse by pneumonia. A 60 year smoker, she was treated with Prednisone for emphysema until she consulted me. The combination of low B12 and high smoke exposure probably accounted for her considerable loss of vision, a concentric field defect. That year was so full of sickness they remembered a viral illness, Herpes zoster, only as an afterthought!.

She seemed better after large oral doses of B12 (2500 mcg) and folic acid (10 mg). Repeat blood testing showed B12 581 mcg, mid-range normal, and folic acid 39 ng, above normal. She was able to absorb these vitamins. But she refused injections and failed to follow-up with me, choosing instead her family doctor. Four years later I heard from her son that she was placed in a long-term-care facility due to Alzheimer’s dementia and anemia, a combination typical of B12 deficiency. Here is the way her son wrote of his view of her condition: "She had some problem metabolizing foods to get the nutrients from them. Possibly a lot of her condition could be from nutritional deficiencies--and lack of exercise and worry.

While I don’t agree that exercise and freedom from worry would cure her dementia, my heart aches for this family: a woman too confused to treat herself; a son too discredited by his own chronic disability to gain the ear of his father and the family physician after 4 years of trying, even though he had a rough idea of the problem; and a husband who has lose his wife. Most of this could have been avoided.