Vitamin B12 Research Excerpts

"Depression seems characteristic of most vitamin B deficiencies." British Journal
of Psychiatry. June 1990.

"Pernicious anemia results from a deficiency of cobalamin, or vitamin B12. The
neurological symptoms associated with cobalamin deficiency were identified more
than 100 years ago. Today, cobalamin deficiency is more likely to be recognized in
its earlier stages, and the associated neurological symptoms are more easily
reversed by vitamin B12 treatment." Neurologic aspects of cobalamin deficiency,
Medicine, July 1991, research by: Heaton, Savage, Brust, Garrett, Lindenbaum.

"Of 369 patients with documented cobalamin deficiency seen over a 17-year
period, 189 developed neurological symptoms. In 114 cases, the neurological
symptoms were the first indications of the vitamin deficiency. The most common
initial complaint was paresthesia, or abnormal sensation, which affected more than
70 percent of the patients with neurological symptoms. These abnormal sensations
took the form of a 'pins and needles' feeling, numbness, or tingling. In 10 cases,
these feelings were strong enough to be considered disabling by the patient. In
122 episodes of deficiency, neurological abnormalities were found at the time of
initial diagnosis. The most common was reduced sensitivity to vibration, which was
observed in 107 episodes. Proprioception, the awareness of position and
movements of the body, was impaired or absent in the toes or ankles in 72
episodes." Ibid.

"The majority of cases improved with treatment; moderate or severe neurologic
disability was known to persist in only 6.3 percent of the patients who received
adequate follow-up. Eleven of the 18 patients with mental impairment had a
complete response to vitamin B12 therapy." Ibid.

"The extent of nervous system dysfunction was clearly related to the duration of
neurologic symptoms before treatment." Ibid.

"In the 10 episodes in which the pretreatment severity score was 20 or greater a
complete response was seen in only 2 and residual neurologic dysfunction was
observed in all of the 8 episodes in which the severity score was more than 23
before therapy." Ibid.

"Duration of symptoms correlated quantitatively with post-treatment severity."
Ibid.

"When mental impairment occurred, however, it was frequently the most disabling
and dominant neurologic abnormality." Ibid.

"A striking feature of our patients was the high degree of responsiveness to Cbl
[cobalamin] therapy." Ibid.

"The severity score was reduced by 50% or greater after treatment in 91% of
the episodes. Residual long-term moderate or severe neurologic disability was
noted following only 7 (6.3%) episodes." Ibid.

"Vitamin B12 deficiency causes abnormalities in both the blood and in neurological
function. In many patients, the neurological abnormalities resulting from vitamin
B12 deficiency become apparent before any blood abnormalities develop. These
neurological abnormalities may cover a wide spectrum, ranging from abnormal
sensations and impairment of vibration sensitivity to conditions as severe as
abnormal gait and even dementia." Cerebrospinal fluid methylmalonic acid levels in
normal subjects and patients with cobalamin deficiency, by Stabler, Allen,
Barrett, Savage, Lindenbaum. Neurology. Oct. 1991.

"Among patients with cobalamin deficiency, the blood level of methylmalonic acid
was about eight times greater than among controls. However, in the cerebrospinal
fluid, the level of methylmalonic acid was, on the average, 600 times greater than
among control patients." Ibid.

"Cobalamin deficiency worsens with increasing age and has been implicated in
declining cognitive functions in elderly persons. Early diagnosis and treatment of
cobalamin deficiency are thus important in preventing or slowing down
neuropsychiatric disorders in the elderly." Review: cobalamin deficiency and
mental impairment in elderly people, Age and Ageing, Nov. 1995.

"Cobalamin deficiency increases with advancing age and is found in 3% to 42% of
persons aged 65 and over." Ibid.

"It has been shown that nearly 50% of patients with low serum cobalamin and a
normal Schilling test are unable to absorb protein-bound cobalamin as opposed to
the free cobalamin used in the Schilling test." Ibid.

"Another manifestation of cobalamin deficiency is altered mental status, which
consists of impairment of attention span, memory abstraction, or other intellectual
functions with or without abnormalities of behaviour, mood, affect, or logical
thought. Neuropsychiatric symptoms may be the initial, or the only, manifestations
of cobalamin deficiency." Ibid.

"Cobalamin deficiency may result in a variety of mental symptoms, such as organic
psychosis, dementia paranoia, memory impairment, mania, slow mentation,
hallucinations, and depression." Ibid.

"A finding of low serum cobalamin levels in Alzheimer's disease and multi-infarct
dementia, but not in other forms of dementia or cognitive impairment, would
suggest that cobalamin deficiency may cause specific types of dementia and is not
the result of dementia with consequently insufficient dietary intake of
cobalamin." Ibid.

"In a recent study 18 subjects with low serum cobalamin and evidence of cognitive
dysfunction were investigated. Only patients who had symptoms for less than 1
year showed improvement after therapy. The best clinical responders had been
symptomatic for less than 6 months." Ibid.

"These investigations indicate that the duration of the cobalamin deficiency plays
an essential role in the degree of improvement of neuropsychiatric symptoms after
treatment." Ibid.

"This is important, because cobalamin deficiency may have to be acknowledged as
a significant cause of neuropsychiatric disorders in elderly people. Early
treatment may prevent irreversibility of the neuropsychological features and
organic lesions of the brain related to the deficiency." Ibid.

"Classical disorders such as pernicious anemia are the cause of this deficiency in
only a small proportion of the elderly. A more frequent problem is food-cobalamin
malabsorption which usually arises from atrophic gastritis and hypochlorhydria
but other mechanisms seem to be involved in some patients." Cobalamin, the
stomach, and ageing. American Journal of Clinial Nutrition. Oct. 1997.

"The partial nature of this form of malabsorption produces a more slowly
progressive depletion of cobalamin than does the more complete malabsorption
engendered by disruption of intrinsic factor-mediated absorption. The slower
progression of depletion probably explains why mild, preclinical deficiency is
associated with food-cobalamin malabsorption more often than with pernicious
anemia." Ibid.

"Attention has shifted recently to the challenge of milder cobalamin deficiency
states in which signs such as megaloblastic anemia are not apparent. This is a much
more common problem than classical deficiency. This entity has emerged largely
because of the application of sensitive metabolic tests to patients." Mild
cobalamin deficiency. The Western Journal of Medicine. June 1998.

"An examination of the relationship of plasma cobalamin (vitmin B(12)) level to
overall psychological distress, specific mood states, and major depressive disorder
was conducted in 159 bereaved men... findings suggest that cobalamin level may be
physiologically related to depressed and anxious mood level, as well as to
syndromal depression." Cobalamin level is related to self-reported and clinically
rated mood and to syndromal..." Health Source - Consumer Edition, 2000.

"In community-dwelling older women, metabolically significant vitamin B(sub 12)
deficiency is associated with a twofold risk of severe depression." Vitamin B12
deficiency and depression in physically disabled older women: epidemiologic
evidence from the Women's Health and Aging Study. American Journal of
Psychiatry. May 2000. (Authors include Stabler)

"Evidence for vitamin [B.sub. 12] deficiency usually involves combinations of low
serum vitamin [B.sub.12] levels, clinical and metabolic abnormalities, and
therapeutic response. Identification of the underlying cause is important in the
diagnosis of vitamin [B.sub. 12] deficiency that is usually attributed to
malabsorption. Helicobacter pylori is one of the most common causes of peptic
ulcer disease worldwide and a major cause of chronic superficial gastritis leading
to atrophy of gastric glands. It is suggested that there maybe a causal
relationship between H pylori and food cobalamin malabsorption." Helicobacter
pylori--Is It a Novel Causative Agent in Vitamin [B.sub.12] Deficiency? Archives
of Internal Medicine. May 2000.

"Food cobalamin is released as a stable complex with gastric R binder and its
absorption depends on the initial release from the binders in food. Food-cobalamin
malabsorption is marked by the inability to release cobalamin from food.
Therefore, cobalamin cannot be taken up by intrinsic factor for absorption.
Release of cobalamin from food requires acid and pepsin, and most food-cobalamin
malabsorptive states can be traced to gastric defects. However, other mechanisms
may also play a role." Ibid.

"It has been proposed that pernicious anemia may represent the final phase of a
process that begins with H pylori--associated gastritis and evolves through
progressive levels of atrophy until parietal cell mass is entirely lost." Ibid.

"In a retrospective study that was conducted in 1994 and 1995, we demonstrated
that a majority (55%) of cases of cyanocobalamin (vitamin [B.sub.12]) deficiency
were related to the inability to release cobalamin from food and that pernicious
anemia was a rare condition (17%). In a second retrospective study that was
conducted between 1995 and 1998, we confirmed that food cobalamin
malabsorption was emerging as a major cause of vitamin [B.sub.12] deficiency. We
found that 68 patients (60%) had a vitamin [B.sub.12] deficiency caused by food
cobalamin malabsorption and 7 subjects (6%) had pernicious anemia." Food
Cobalamin Malabsorption: A Usual Cause of Vitamin [B.sub.12] Deficiency.
Archives of Internal Medicine. July 2000.

"There is little reason to treat food cobalamin malabsorption differently than
pernicious anemia." Ibid.

"The objective of this study was to investigate whether cognitive functioning is
affected in adolescents (aged 10-16 y) with marginal cobalamin status as a result
of being fed a macrobiotic diet up to an average age of 6 y... Conclusion: Our data
suggest that cobalamin deficiency, in the absence of hematologic signs, may lead to
impaired cognitive performance in adolescents." American Journal of Clinical
Nutrition. Sept. 2000.

"Patients with mild-moderate dementia and elevated plasma homocysteine levels
improved clinically with increased test scores after vitamin substitution."
Improvement of cognitive functions after cobalamin/folate supplementation in
elderly patients with dementia and elevated plasma homocysteine. Alternative
Medicine Review. Oct. 2001.

"Mild cobalamin (Cbl) deficiency is frequently found in older persons and is
associated with cognitive and cerebral abnormalities... Conclusion. Electrographic
signs of improved cerebral function and improved cognitive function were found
after Cbl supplementation in older subjects with low plasma Cbl concentrations
who were free of significant cognitive impairment. These improvements were
related to a reduction of plasma tHcy concentration." Cobalamin supplementation
improves cognitive and cerebral function in older, cobalamin-deficient persons.
The Journals of Gerontology, Series A. Dec. 2001.

"Megalin has previously been shown to bind and mediate endocytosis of
transcobalamin (TC)-[B.sub.12]. However, the physiological significance of this has
not been established, and other TC-[B.sub.12] binding proteins have been
suggested to mediate renal uptake of this vitamin complex. The present study
demonstrates by the use of megalin-deficient mice that megalin is, in fact,
essential for the normal renal reabsorption of TC-vitamin [B.sub.12] and for renal
accumulation of this highly conserved vitamin." Megalin is essential for renal
proximal tubule reabsoption and accumulation of transcobalamin-[B.sub.12]. The
American Journal of Physiology. March 2002.

"Elevated metabolites of the enzyme cofactor cobalamin in elderly patients may
predict the future development of cognitive dysfunction, especially in men,
according to a study presented at the annual meeting of the American Geriatrics
Society. High levels of methylcitric acid and, to a lesser degree, other cobalamin
(vitamin [B.sub.12] metabolites correlated significantly with lower scores on many
sections of the California Verbal Learning Test (CVLT), reported Dr. Angela
Garcia of Queen's University, Kingston, Ont." Cobalamin markers could signal
cognitive decline. (Nondemented Elderly Patients). Family Practice News. Oct.
2002.