| | 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.
©2000 Richard A. Kunin, M.D.
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