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LIBRARY OF CONGRESS CATALOGING-IN-PUBLICATION DATA
Vitamin B : new research / Charlyn M. Elliot, editor.
Includes bibliographical references and index.
1. Vitamin B in human nutrition. I. Elliot, Charlyn M.
[DNLM: 1. Vitamin B Complex--pharmacology. 2. Vitamin B 12--therapeutic use. 3. Vitamin B
Complex--therapeutic use. QU 187 V837 2007]
Published by Nova Science Publishers, Inc. New York
Commentary Cobalamin Communication Current State
of Oral Vitamin B12 Treatment 1
Chapter I Inhibitory Effect of Vitamin B6 Compounds on DNA Polymerase,
DNA Topoisomerase and Human Cancer Cell Proliferation 5
Hiromi Yoshida and Kiminori Matsubara
Chapter II The Causes and Consequences of Vitamin B-3 Deficiency:
Insights from Five Thousand Cases 21
Harold D. Foster and Abram Hoffer
Chapter III Folic Acid and Health: An Overview 39
Chapter IV Nutritional Issues in Inflammatory Bowel Disease: Focus on
the Vitamin B Complex Deficiencies and their Clinical Impact 57
Petros Zezos and Georgios Kouklakis
Chapter V New Bacterial Cobalamin-Dependent CoA-Carbonyl
Mutases Involved in Degradation Pathways 81
Thore Rohwerder and Roland H. Müller
Chapter VI Cystalysin: An Example of the Catalytic Versatility
of Pyridoxal 5’-Phosphate Dependent Enzymes 99
Barbara Cellini, Riccardo Montioli
Chapter VII Vitamin B Treatment and Cardiovascular Events in
Hyperhomocysteinemic Patients 121
Chapter VIII Vitamin B12, Folate Depletion and Homocysteine:
What Do They Mean for Cognition ? 139
Rita Moretti, Paola Torre and Rodolfo M. Antonello
Chapter IX Vitamin B6 as Liver-targeting Group in Drug Delivery 153
Guo-Ping Yan, Xiao-Yan Wang and Li-Li Mei
Chapter X The Role and Status of Vitamin B12:
Need for Clinical Reevaluation and Change 175
Ilia Volkov, Inna Rudoy and Yan Press
The B vitamins are eight water-soluble vitamins that play important roles in cell
metabolism. Historically, the B vitamins were once thought to be a single vitamin, referred to
as Vitamin B (much like how people refer to Vitamin C or Vitamin D). Later research
showed that they are chemically distinct vitamins that often coexist in the same foods.
Supplements containing all eight B vitamins are generally referred to as a vitamin B complex.
Individual B vitamin supplements are referred to by the specific name of each vitamin (e.g.
B1, B2, B3). The B vitamins often work together to deliver a number of health benefits to the
body. B vitamins have been shown to:Support and increase the rate of metabolism; Maintain
healthy skin and muscle tone; Enhance immune and nervous system function; Promote cell
growth and division — including that of the red blood cells that help prevent anemia;
Together, they also help combat the symptoms and causes of stress, depression, and
All B vitamins are water soluble, and are dispersed throughout the body. They must be
replenished daily with any excess excreted in the urine.Vitamin B deficiency can lead to an
enormous group of health problems.
This book presents new and important research in the field.
Expert Commentary - Background: In contrast to global traditions, most patients in
Sweden with vitamin B12 deficiency are treated with oral vitamin B12, 1 mg daily.
Objective: Analysis of current state of oral therapy with vitamin B12 in clinical research
Material and Methods: Review of basic documentation of oral vitamin B12 therapy in
Results: In the period 1950-1960, various doses of vitamin B12 below 1 mg daily were
tested and mainly rejected. During the period 1960-1968, the leading research groups agreed
that oral cyanocobalamin, 1 mg daily, is the optimal dose for oral vitamin B12 prophylaxis
and treatment of deficiency states. The efficacy of such regimens varies between 80-100% in
different studies. The regimen has gained widespread clinical use in Sweden, comprising 2.5
million patient years in the period 1964-2005. Lower doses of oral vitamin B12 still lack
documentation of clinical efficacy and long-term clinical safety and reliability.
Conclusions: Oral cyanocobalamin, 1 mg daily, is a safe and reliable therapy for most
patients with vitamin B12 deficiency. It is suggested that this regimen is compared with a
generally accepted parenteral regimen in a prospective, randomized, open-labeled study of
adequate size in conclusive patients.
Chapter I - Vitamin B6 compounds such as pyridoxal 5'-phosphate (PLP), pyridoxal
(PL), pyridoxine (PN) and pyridoxamine (PM), which reportedly have anti-angiogenic and
anti-cancer effects, were thought to be selective inhibitors of some types of eukaryotic DNA
polymerases (pols) and human DNA topoisomerases (topos). PL moderately inhibited only
the activities of calf pol α, while PN and PM had no inhibitory effects on any of the pols
tested. On the other hand, PLP, a phosphated form of PL, was potentially a strong inhibitor of
pols α and ε from phylogenetic-wide organisms including mammals, fish, insects, plants and
protists. PLP also inhibited the activities of human topos I and II. PLP did not suppress the
activities of prokaryotic pols such as E. coli pol I, T4 pol and Taq pol, or DNA metabolic
enzymes such as HIV reverse transcriptase, RNA polymerase and deoxyribonuclease I. For
pols α and ε, PLP acted non-competitively with the DNA template-primer, and competitively
with the nucleotide substrate. To clarify how vitamin B6 inhibits angiogenesis, this review
was performed to examine the effect on human umbilical vein endothelial cell (HUVEC)
proliferation and HUVEC tube formation. Consistent with the result of an ex vivo
angiogenesis assay, PLP and PL markedly suppressed the proliferation of HUVEC, while PN
and PM were inactive. Suppression of HUVEC proliferation by PLP and PL was evident in a
dose-dependent manner with LD50 values of 112 and 53.9 μM, respectively; however,
HUVEC tube formation was unaffected by PLP and PL. On the other hand, PL inhibited the
growth of human epitheloid carcinoma of the cervix (HeLa), but PLP, PN and PM had no
influence. Since PL was converted to PLP in vivo after being incorporated into human cancer
cells, the anti-angiogenic and anti-cancer effects leading to PL must have been caused by the
inhibition of pol and topo activities after conversion to PLP. These results suggest that
vitamin B6 suppresses cell proliferation and angiogenesis at least in part by inhibiting pols α
Chapter II - Inadequacies of vitamin B-3 (niacin) can occur in at least six distinct, but
overlapping ways. Even when diet contains adequate niacin and there are no absorption or
storage problems, intake may be inadequate. This is because some individuals, for genetic
reasons, have abnormally high vitamin B-3 requirements that cannot be met by the typical
diet. As many as one-third of gene mutations result in the corresponding enzyme having a
decreased binding affinity for its coenzyme, producing a lower rate of reaction. About fifty
human genetic illnesses, caused by such defective enzymes, therefore, can best be treated by
very high doses of their corresponding coenzyme. Several such genetic disorders have been
linked to enzymes that have vitamin B-3 as their coenzyme. These include elevated
alcoholism and cancer risk, caused by defective binding in aldehyde dehydrogenase and
phenylketonuria II and hyperpharylalaninemia that are associated with inadequate binding in
There are two recently discovered types of niacin-responsive receptors, HM74A and
HM74B. HM74A is a high affinity receptor that mediates the stimulation of the synthesis of
prostaglandin by niacin. In parts of schizophrenics' brains, the protein for HM74A is
significantly decreased, confirming a niacin-related abnormality that results in very elevated
vitamin B-3 requirements. The simplest cases of niacin deficiency is caused by diets that
contain little or no vitamin B-3. Pellagra, for example, has traditionally been diagnosed in
patients who have been eating excessive quantities of maize, a food that lacks easily available
niacin. Vitamin B-3 deficiencies are also present in patients with absorption and storage
problems. Excessive consumption of sugars and starches, for example, will deplete the body's
supply of this vitamin, as will some antibiotics.
Addiction typically leads to niacin deficiency and can often be treated by taking high
doses of this vitamin. The breakdown of alcohol, for example, is vitamin B-3 dependent
because niacin is required as a coenzyme for one of the main enzymes involved, aldehyde
dehydrogenase. Since niacin is chemically similar to nicotine, the latter may occupy niacin
receptor sites. Certainly, high dose vitamin B-3 has helped many people shed their addiction
Niacin deficiency also may be the result of excess oxidative stress, which causes an
abnormally high biochemical demand for this nutrient. It appears that multiple sclerosis,
amyotrophic lateral sclerosis, and Parkinson's disease involve the excessive breakdown of
dopamine, generating neurotoxins such as dopachrome. Vitamin B-3 can mitigate this
process but body stores are typically depleted by it. Similarly schizophrenics overproduce
adrenaline and its neurotoxic byproduct adrenochrome and other chrome indoles. As a
consequence, they become niacin depleted, a characteristic that is now being used as a
diagnostic symptom of this illness.
The ability to absorb nutrients typically declines with age. As a result, many vitamin
deficiencies, including niacin, are commonest in the elderly. These inadequacies are reflected
in cholesterol imbalances, cardiovascular disorders, stroke and arthritis, all of which respond
While optimum dosages vary, the literature, and Dr. Abram Hoffer's experience with
over 5,000 patients, suggest that required daily therapeutic intervention range from 10 mg in
newly diagnosed cases of pellagra to 6 to 10 grams for cholesterol normalization, and the
treatment of cardiovascular disease and stroke.
Chapter III - The review summarizes current thinking on the relationship between folate
and health with an emphasis on the potential benefits and risks associated with folic acid
supplements and fortification of food.
For decades, folate has been known to produce a form of anemia called “megaloblastica”,
there is now evidence that it is also essential to the development of the central nervous
system and that insufficient folate activity, at the time of conception and early pregnancy, can
result in congenital neural tube defects. More recently, degrees of folate inadequacy have
been found to be associated with high blood levels of the amino-acid homocysteine (Hcy).
Hcy is a well known risk factor for cardiovascular and neurodegerative diseases, dementia
and Alzheimer’s disease, osteoporotic fractures and complications during pregnancy.
Moreover, folate has been implicated in modulating the risk of several cancers. For instance,
recent epidemiological studies support an inverse association between folate status and the
rate of colorectal adenomas and carcinomas, suggesting that maintaining adequate folate
levels may be important in reducing this risk.
On the other hand, several studies suggest that a high intake, generally attributable to
supplemental folic acid, may increase the risk of breast cancer in postmenopausal women,
particularly those with moderate alcohol consumption.
There is also the risk that widespread folate fortification, may mask B12 deficiency,
which in turn may lead to neurological damage. Vitamin B12 deficiency produces an anemia
that is identical to that of folate deficiency and also causes irreversible damage to the central
and peripheral nervous systems. Folate fortification may also affect antiepileptic drug seizure
control, and influence the genetic selection of a potentially deleterious genotype, albeit over a
As folic acid is now under consideration worldwide as an important functional food
component, there is great interest in finding whether dietary supplements and food
fortification with folic acid can improve health or be harmful. These and other aspects of this
matter will be explored in this review.
Chapter IV - Inflammatory bowel disease (IBD) is a chronic relapsing and remitting
inflammatory condition of unknown cause, which manifests with two major forms: as
Crohn’s disease (CD), affecting any part of the gastrointestinal tract and as ulcerative colitis
(UC), affecting the colon. Medical management with aminosalicylates (5-ASA), steroids, and
immunomodulating or immunosuppressive agents is the mainstay of therapy for most IBD
patients. Surgery is reserved for patients with severe disease refractory to medical
management or for patients with complications.
Nutrition plays an important role in pathogenesis, management and treatment of IBD.
Malnutrition is a common problem in patients with IBD, especially in those suffering from
Crohn’s disease (CD). A wide array of vitamin and mineral deficiencies has been described
in patients with IBD. Nutritional abnormalities are often overlooked in the management of
IBD patients, despite their pathogenic role in clinical manifestations and complications of
IBD. The causes of malnutrition in IBD are multiple, including decreased oral nutrient intake,
malabsorption, excessive nutrient losses, increased nutrient requirements, and iatrogenic due
Thiamin (B1), riboflavin (B2), niacin, pyridoxine (B6), pantothenic acid, biotin, folic acid
(B9) and vitamin B12 are referred to as members of the “vitamin B complex”. These are
water-soluble factors, playing an essential role in the metabolic processes of living cells,
functioning as coenzymes or as prosthetic groups bound to apoenzymes. These vitamins are
closely interrelated and impaired intake of one may impair the utilization of others.
Folate and vitamin B12 deficiencies are frequently described in IBD patients and are
implicated in anemia, thrombophilia and carcinogenesis associated with IBD. Low serum
concentrations of other members of the “vitamin B complex” have also been described in
IBD patients, producing the syndromes due to their deficiency.
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