Volkov Review-The Critical Role of Vit B12

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THE PHYSICIAN AND SPORTSMEDICINE ISSN 0091-3847, December 2008, No. 1, Volume 36 1

CLINICAL FOCUS: NUTRITION

IntroductionVitamin B12 plays a functional role in a growing list of various organs and body systems. Vitamin B12 deficiency is a common problem. Early detection of vitamin B12 deficiency is essential in order to prescribe opportune treatment, and there is evidence that such deficiency occurs more frequently than expected. Vitamin B12 deficiency can occur in individuals with dietary patterns that exclude animal food products and patients who are unable to absorb vitamin B12. Vitamin B12 deficiency has many causes, and pernicious anemia has been described as a widespread cause of vitamin B12 deficiency. Current studies on vitamin B12 deficiency, including more precise definitions and the description of new etiologies of vitamin B12 deficiency, such as insufficient dietary intake,1 food-vitamin B12 malabsorption syndrome,27 and hereditary vitamin B12 metabolism diseases, such as Imerslund-Grasbeck syndrome,8 show that hematological abnormalities are generally incomplete, as compared with historical descriptions.

Persons with B12 deficiency may be asymptomatic, but in patients presenting with myelopathy, cognitive decline, neuropathy, psychiatric disturbances, or specific hematological signs and symptoms, vitamin B12 deficiency should be suspected.

The author will demonstrate the critical roles of vitamin B12 by surveying and analyzing available reports, as well as reporting personal clinical experience.

Vitamin B12 and DevelopmentMany research studies emphasize the health complications of nutritional vitamin B12 deficiency and a necessity of clinical, biochemical, and metabolic monitoring in infants born to mothers with a vita-min B12 deficiency. Dietary deficiencies of vitamin B12 during pregnancy and lactation may result in health problems in exclusively breastfed infants. Physical examinations of these children often reveal psychomotor retardation, apathy, muscular hypotonia, irritability, anorexia, abnormal movements, and failure to thrive. Laboratory analyses show hematological abnormalities, such as a megaloblastic anemia, low levels of vitamin B12, high levels of homocysteine and methylmalonic acid, and methylmalonic aciduria. Magnetic resonance imaging (MRI) of the brain reveals diffuse frontotemporoparietal

The Critical Role of Vitamin B12

Ilia Volkov, MD

Abstract: Vitamin B12 affects the peripheral and central nervous systems, bone marrow, skin and mucous membranes, bones, and vessels, as well as the normal development of children. Although there is undoubtedly an association between vitamin B12 and homo-cysteinemia, their relative influence on cardiovascular events is controversial.

Some large studies confirm that a supplementation with group B vitamins did not reduce the risk of major cardiovascular events

or all-cause mortality in patients with vascular disease. The outcomes of these and similar trials could have been different had the

researchers considered the following points: Using vitamin B12 or B-complex as secondary prevention of cardiovascular events for

patients with irreversible changes of blood vessels is probably in error. Rather, vitamin B12 or B-complex should be used as primary

prevention. Also, using high doses of vitamin B12 will probably be more effective than using low doses of group B vitamins.

The effect of vitamin B12 on the proliferation of malignant cells has been examined in vivo and in vitro in numerous studies. Their

results indicate that methylcobalamin inhibits the proliferation of malignant cells and propose the possibility of methylcobalamin as

a candidate of potentially useful agents for the treatment for some malignant tumors.

There are many articles indicating the increasing prevalence of low vitamin B12 level in different segments of general population.

In order to prevent serious health problems, vitamin B12 routine fortification should be seriously considered and discussed.

Keywords: vitamin B12; homocysteine; malignancy; vitamin B12 routine fortification; recurrent aphthous stomatitis

Ilia Volkov, MD1

1Department of Family Medicine, Faculty of Health Sciences,

Ben-Gurion University of the Negev, Beer-Sheva, Israel

Correspondence: Ilia Volkov, MD Hogla Street 6,

Lehavim, 85338, Israel Tel: 972-8-6431530 Fax: 972-8-6413135

E-mail: [email protected]

Conflict of Interest Statement: Ilia Volkov, MD

discloses no conflicts of interest.

Ilia Volkov


2 THE PHYSICIAN AND SPORTSMEDICINE ISSN 0091-3847, December 2008, No. 1, Volume 36

atrophy and retardation of myelination.9 Some studies have shown a relationship between maternal vitamin B12 status and birth weight. One extends those findings directly in terms of neonatal vitamin B12 status and birth weight. Vitamin B12 status in the mother was related to neonatal vitamin B12 status as measured by cord serum vitamin B12 concentra-tion. In addition, low neonatal vitamin B12 concentrations were adversely associated with low birth weights.10 Marginal maternal vitamin B12 status increases the risk of an offspring with spina bifida.11

Children have specific and increased nutritional require-ments in comparison with adults. Rapid growth and enhanced energy expenditure explain these differences. Any diet devia-tion will increase exposure to the risk of nutritional deficiency along with corresponding health consequences. Whenever a diet restriction for children is required for medical reasons, particular attention must be paid to the food regimen in order to avoid any health problems, especially growth retardation.12

Vitamin B12-Responsive Neuropsychological ConditionsThe only function that has been indicated as unique for vitamin B12 is the synthesis of myelin, a component of the sheaths that protect nerve fibers. Vitamin B12 deficiency can cause peripheral neuropathy and combined system diseases involving demyelination of the dorsal columns and the corticospinal tract. A wide variety of neuropsychological symptoms and signs have been encountered, such as ataxia, loss of cutaneous sensation, muscle weakness, diminished or hyperactive reflexes, spasticity, urinary or fecal incontinence, orthostatic hypotension, loss of vision, dementia, psychoses, and disturbances of mood. Multiple neurological syndromes were often seen in a single patient. Severity of neurological dysfunction before treatment is clearly related to the duration of symptoms prior to diagnosis.13

Multiple sclerosis (MS) and vitamin B12 deficiency share common inflammatory and neurodegenerative pathophysi-ological characteristics. Due to similarities in the clinical presentations and MRI findings, the differential diagnosis between vitamin B12 deficiency and MS may be difficult. Additionally, low or decreased levels of vitamin B12 have been demonstrated in MS patients. Moreover, recent studies sug-gest that vitamin B12, in addition to its known role as a cofac-tor in myelin formation, has important immunomodulatory and neurotrophic effects. These observations raise questions

of possible causal relationship between the two disorders, and suggest further studies of the need to closely monitor vitamin B12 levels in MS patients, as well as possibly requiring supplementation of vitamin B12 alone or in combination with the immunotherapies.14 Interferon-beta is a mainstay therapy of demyelinating diseases, but it has only a partial effect on MS in humans and in several animal models of the disease. In a recent report, the author demonstrated a dramatic improve-ment in the clinical, histological, and laboratory parameters of disease in in vivo mouse models of demyelinating disease. This was seen following combination therapy with inter-feron (IFN)-beta and vitamin B12 cyanocobalamin (B12CN) in nonautoimmune primary demyelinating ND4 (DM20) transgenic mice and in acute and chronic experimental auto-immune encephalomyelitis in mice. Clinical improvement, manifested as near normal motor function, was associated with reduced astrocytosis and demyelination. Interferon-beta-B12CN combination therapy may be promising for the treatment of MS.15

The association of vitamin B12 deficiency with psychiatric illness has been studied and debated since the vitamin was first discovered in the 1940s. The clinical relevance of this deficiency remains the subject of investigation and academic discussion. Vitamin B12 has fundamental roles in brain function. Intracel-lular vitamin B12 is converted to adenosylcobalamin, coenzyme for methylmalonyl-CoA mutase and to methylcobalamin, coenzyme for methionine synthase, which mediates conver-sion of homocysteine to methionine. Consequently, there is an increase in the level of homocysteine (Hcy) in B12 deficiency. Homocysteine has been implicated as a risk factor for vascular disease, as well as brain atrophy. There is evidence to implicate Hcy in increased oxidative stress, DNA damage, and the triggering of apoptosis and excitotoxicity, all of which are important mechanisms in neurodegeneration. Homocysteine is also prothrombotic and proatherogenic, causes damage to the vessel wall, and is related to brain atrophy and possibly to white matter hyperintensities in the brain. Epidemiological evidence and longitudinal data support the finding that Hcy is a risk factor for cognitive impairment and Alzheimers dis-ease. 1618 This may be due to cerebrovascular as well as direct neurotoxic mechanisms.

As well as cognitive impairment, the common psychiatric symptoms of vitamin B12 deficiency are continuous depression,19 psychotic symptoms,20 mania, and obsessive compulsive disorder. The neuropsychiatric severity of vitamin B12 deficiency

Critical Role of Vitamin B12



and the therapeutic efficacy depends on the duration of signs and symptoms. Therefore, the consideration of vitamin B12 deficiency and testing for serum B12 levels is recommended in all patients with organic brain syndrome, atypical psychiatric symptoms, and fluctuation of symptomatology.

Relationship of Vitamin B12 and Homocysteine: Is Their Function in Cardiovascular Events Obvious?Vitamin B12 deficiency and homocysteinemia are undoubt-edly related,21,22 but their synergistic or separate role in the development of atherosclerosis and influence on cardiovas-cular events is nevertheless controversial. In observational studies, elevated plasma total homocysteine levels have been positively associated with ischemic stroke risk.2325 Numer-ous retrospective and prospective studies have revealed a consistent, independent relationship between mild hyper-homocysteinemia and cardiovascular disease or all-cause mortality. Starting at a plasma homocysteine concentration of approximately 10 mmol/L, the risk increase follows a linear dose-response relationship with no specific threshold level. Hyperhomocysteinemia, as an independent risk fac-tor for cardiovascular disease, is thought to be responsible for approximately 10% of the total risk. Elevated plasma homocysteine levels ( 12 mmol/L; moderate hyperhomo-cysteinemia) are considered cytotoxic and are found in 5% to 10% of the general population and in up to 40% of patients with vascular disease. Based on various calculation models, reduction of elevated plasma homocysteine concentrations may theoretically prevent up to 25% of cardiovascular events. Treatment of hyperhomocysteinemia is recommended for the apparently healthy general population.26 Some large studies confirm that a supplementation with group B vitamins did not reduce the risk of major cardiovascular events or all-cause mortality in patients with vascular disease.27,28 The outcomes of these and similar trials could have been different if the researches had used vitamin B12 or B-complex for primary prevention of cardiovascular events for patients with high risk of developing atherosclerosis. Also, using high doses of vitamin B12 will probably be more effective than using group B vitamins as a rule presented by a set of various vitamins of this group in low doses. For example, using folic acid alone for prevention of cardiovascular diseases has been proven to be ineffective,29 while very high doses of vitamin B12 (60 mg

every day for 6 months) has been used effectively without any toxic side effects for the treatment of other diseases.30

What about Hematological Abnormalities?Hemopoesis is the process in which new blood cells are produced and in which vitamin B12, folate, and iron have funda-mental roles. New erythrocytes replace the oldest erythrocytes (normally about 1%) that are phagocytosed and destroyed each day. Erythroblasts require folate and vitamin B12 for proliferation during their differentiation. Deficiency of folate or vitamin B12 inhibits purine and thymidylate syntheses, impairs DNA synthesis, and causes erythroblast apoptosis, resulting in megaloblastic anemia from ineffective eryth-ropoiesis. The presence of macro-ovalocytes having a high mean corpuscular value (MCV), anisocytosis, poikilocytosis and hypersegmented neutrophils, anemia, leukopenia, and thrombocytopenia or pancytopenia suggests a megaloblastic disorder associated with a nutritional deficiency, ie, vitamin B12. The usual presentation accompanies symptoms of anemia. Asymptomatic patients can be identified by routine hema-tologic investigations. Vitamin B12 deficiency produces the classic picture of macrocytic anemia, with a MCV 100 fL. The MCV correlates with estimated vitamin B12 level: MCV of 80 to 100 fL indicates 25% probability of vitamin B12 defi-ciency; MCV of 115 to 129 fL indicates a 50% probability; MCV 130 indicates 100% probability.31 It is a classic textbook picture of vitamin B12 deficiency, but usually the clinical picture looks different. Hematological abnormalities, such as anemia or macrocytosis, may be absent at the time of neurological presentation.32 It is well known that vitamin B12 deficiency may be accompanied by iron deficiency, and this associa-tion can mask the macrocytosis.33,34 There are no generally accepted guidelines for the definition, diagnosis, treatment, and follow-up of patients with vitamin B12 deficiency. Total serum vitamin B12 may not reliably indicate vitamin B12 status. Probability of functional vitamin B12 deficiency decreases upon increasing the blood level of vitamin B12. To increase specificity and sensitivity in diagnosing vitamin B12 deficiency, the concept of measuring Hcy, methylmalonic acid (MMA) is intended. Lately, for the solution of this problem, an evaluation of holotranscobalamin II has aroused great interest.35

Vitamin B12 deficiency may also influence the granulocyte and platelet lines and may be mistaken for leukemia.36 In all cases, the important practical indicator is positive response to vitamin B12 treatment.

Ilia Volkov



Known Cutaneous and Mucous Manifestations of Vitamin B12 Deficiency and the Novel Use of Vitamin B12 in DermatologyThe characteristic dermatological sign of vitamin B12 deficiency is cutaneous pigmentation,3740 which can be reversed by admin-istration of vitamin B12. Increased cutaneous pigmentation is especially accentuated in palmar creases, on the dorsa of hands and feet, in intertriginous areas, on oral mucosa, and in recent scars. The mechanism of hyperpigmentation is unexplained. Histology shows an increase of melanin in the basal layer. In an electron microscopic study, many melanosomes were observed in melanocytes and surrounding keratinocytes. There is supposition that the dominant mechanism of hyperpigmen-tation due to vitamin B12 deficiency is not a defect in melanin transport, but is rather an increase in melanin synthesis.

The author investigated and reported a case of the paradoxical disappearance of chronic erythema nodosum,41 which had persisted for more than 6 months in spite of a prolonged treatment with nonsteroidal anti-inflammatory drugs. When the patient complained of paresthesias, a blood test for vitamin B12 was performed and a prominent vitamin B12 deficiency was discovered. Since treatment was initiated with intramuscular vitamin B12 injections, not only did the par-esthesias disappear, but the erythema nodosum did as well. The patient continued to receive maintenance therapy with vitamin B12 without recurrence of erythema nodosum.

Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosa lesions seen in primary care. Most treatments given to patients suffering from RAS achieve short-term therapeutic goals, such as alleviation of pain, reduction of ulcer duration, and recovery of normal oral function. Just a few reported treatments have achieved long-term therapeutic goals, such as reduction of the frequency and severity of RAS and maintenance of remission. Although the precise role of vitamin B12 deficiency in the pathogenesis of RAS is unclear, suppression of cell-mediated immunity and changes in the cells of the tongue and buccal mucosa have been reported.42,43 We have reported previously the successful treatment with vitamin B12 of RAS patients (Figure 1).44,45 According to the authors 6 years of clinical experience, vitamin B12 treatment achieves long-term therapeutic goals and can be effective for patients suffering from RAS, regardless of their serum vitamin B12 level. The author and his colleagues have finished a randomized, double-placebo, controlled clinical trial, and received results to confirm their previous clinical observations.

Potential Role and Uses of Vitamin B12 in Previously Uncommon AreasA possible correlation between vitamin B12 and fertility problems, which indicates vitamin B12 deficiency as one of cause of recurrent abortions and the use of vitamin B12 in initial treatments in order to prevent these conditions, has been debated for a long time.4648 In a statistical meta-analysis

Figure 1. Frequency of recurrent aphthous stomatitis (RAS) episodes prior to and during vitamin B12 treatment (episodes per month).

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performed on 5 studies in which serum B12 was assayed in women suffering from early recurrent abortions (ERA), a significant relationship was found between ERA and vitamin B12 deficiency.49 No difference was noticed between cases and controls for folate. Vitamin B12 evaluation should be considered in women with ERA regardless of whether or not hematological or neurological abnormalities are present.

Osteoporosis is a widespread problem, which frequently has devastating health consequences because of its association with fragility fractures. The total number of fractures, and hence the cost to society, will increase dramatically over the next 50 years as a result of demographic changes in the number of elderly people. Thus, prevention of osteoporosis by identifying risk factors or risk indicators, as well as developing new treatment strategies, is a major health issue. Recent data suggest that vitamin B12 affects bone metabolism, bone quality, and fracture risk in humans.50 Strokes increase the risk of subsequent hip fracture by 2 to 4 times. Hyperhomocysteinemia is a risk factor for both ischemic stroke and osteoporotic fractures in elderly men and women. In a population with a high baseline fracture risk, combined treatment with folate and vitamin B12 has been shown to be safe and effective in reducing the risk of a hip fracture in elderly patients following stroke.51 The relationship of Hcy and vitamin B12 with bone turnover mark-ers, broadband ultrasound attenuation (BUA), and fracture incidence in healthy elderly people was studied by researchers who found that high homocysteine and low vitamin B12 con-centrations were significantly associated with low BUA, high markers of bone turnover, and increased fracture risk.52 A preventive vitamin B12 supplementation for healthy people with mandatory risk factors for osteoporosis and a treatment with vitamin B12 of patients suffering from osteoporosis could be a promising treatment for this serious problem. Controlled clinical trials should be conducted to confirm the safety and effectiveness of vitamin B12 therapy for osteoporosis.

Vitamin B12 carrier proteins, the transcobalamins (TC), are elevated during trauma, infections, and chronic inflammatory conditions. This remains unexplained. It is proposed that such TC elevations signal a need for vitamin B12 central to the resolution of inflammation.53 Vitamin B12 is an effective scavenger of nitric oxide (NO).54 Septic shock has an extremely high mortality rate, with approximately 200 000 people dying from sepsis annually in the US. The high mortality results partially from severe hypotension secondary to high serum NO concentrations. Reducing NO levels should be beneficial

in sepsis; a possible approach in reducing NO levels in sepsis is the use of an NO scavenger, which would leave sufficient free NO for normal physiological functions. Animal and human clinical data suggest that high-dose vitamin B12 may prove a promising approach to systemic inflammatory response syn-drome (SIRS), sepsis, and septic and traumatic shock.

Drugs which directly counteract NO, such as endothelial receptor blockers, NO-synthase inhibitors, and NO-scavengers, not only may be effective in the acute treatment of migraine, but also are likely to be effective in migraine prophylaxis. The first prospective, open study indicated that intrana-sal hydroxocobalamin may have a prophylactic effect in migraine.55

A number of studies have demonstrated that vitamin B12 is important in maintaining differentiation, proliferation, and metabolic status of cells. Nitric oxide can cause both apoptosis and necrosis, making it a good candidate for anti-tumor therapy. Initially, vitamin B12 was proposed for use as a scavenger and cytoprotective agent to bind and inactivate NO. The use of vitamin B12 as a carrier to deliver NO into tumor cells is novel. One investigational study showed that complex NO-vitamin B12 inhibited tumor growth in vivo and in vitro by activating the extrinsic apoptotic pathway.

Researchers have attempted to correlate vitamin B12 with malignancy ever since the multifunctional role of vitamin B12 has begun to be understood. There are many hypotheses about the role of vitamin B12 in growth of malignancy. What is the explanation for elevation of vitamin B12 level in oncological patients? Is it a marker of malignancy? Elevated levels of serum vitamin B12 may be a sign of a serious, even life-threatening, disease. Hematologic disorders, like chronic myelogeneous leukemia, promyelocytic leukemia, polycythemia vera, and hypereosinophilic syndrome can result in elevated levels of vitamin B12. Not surprisingly, a rise of the vitamin B12 concentration in serum is one of the diagnostic criteria for the latter two diseases. Several liver diseases, like acute hepatitis, cirrhosis, hepatocellular carcinoma, and meta-static liver disease, can also be accompanied by an increase in circulating vitamin B12. This phenomenon is caused predominantly by vitamin B12 release during hepatic cytolysis and/or decreased vitamin B12 clearance by the affected liver. Altogether, it can be concluded that an observed elevation of vitamin B12 in blood merits a full diagnostic examination to assess the presence of disease.56

Ilia Volkov



Maybe an elevated level of vitamin B12 is a sign that the body is fighting disease and that, as result of this battle, there is a mobilization of resources and an attempt to compensate by activating biologically active substances for repair of defects.

Carmel et al (1977) studied 139 patients with non-hematologic malignancy in order to define the incidence of vitamin B12-related abnormalities and correlate them with clinical findings. A high serum vitamin B12 level usually implied a poor prognosis in a patient with cancer. However, while most such patients had hepatic and other metastases, hepatic involvement was not universal nor did most of the patients with hepatic disease have high vitamin B12 levels.57

The relationship between vitamin B12 levels and survival was studied in a group of 161 terminally ill cancer patients. Their average age was 74.7 years. The length of survival decreased with the increase in serum vitamin B12 levels. In multivariate analyses, C-reactive protein (CRP) was the most important prognostic factor in this population, and vitamin B12 provided information independent of CRP in predicting survival. These data indicate that an elevated serum vitamin B12 level is a predictive factor for mortality in patients with cancer, independent of CRP or other factors.58

The effect of vitamin B12 on the proliferation of malignant cells has been examined in vivo and in vitro in numerous studies.5961 Methylcobalamin inhibited the proliferation of androgen-sensitive SC-3 cells (a cloned cell line from Shionogi mouse mammary tumor, SC115) in culture at the concentration of 100 to 300 g/mL. An inhibitory activity of methylcobalamin on the proliferation was also observed in other cell lines (estrogen-sensitive B-1F cells from mouse Leydig cell tumor and MCF-7 cells from human mammary tumor) at the concentration of 500 g/mL. Moreover, large doses of methylcobalamin injected intraperitoneally (100 mg/kg body weight/day) were nontoxic and suppressed the tumor growth of SC115 and B-1F cells in mice fed a vitamin B12-deficient diet. These results indicate that methylcobalamin inhibits the proliferation of malignant cells in culture and in vivo and propose the possibility of methylcobalamin as a candidate of potentially useful agents for the treatment for some malignant tumors.59

Every system in mechanics and nature seeks some sort of balance. The human body is no exception. Upon an imbalance or disease, the organism tries to compensate by the mobilization of its inner resources. There is an ongoing process of accumulation of biologically active substances

to fight disease. Unfortunately, this battle for balance is not always successful. Being stressed, the organism shows us signs of distress and calls for help.

The author proposes that a high level of vitamin B12 in oncological diseases is such a sign.62 The basis for such a proposal can be summarized as follows:

1. The well-known fact that a high level of vitamin B12 is present in different kinds of malignancy.

2. There is a positive correlation between level of vitamin B12 and the severity of the disease; the more severe the disease, the higher the level of vitamin B12.

3. A number of the experimental laboratory studies indi-cate an inhibition in the growth of malignant cells upon use of vitamin B12.

4. There are no experimental results indicating that vitamin B12 stimulates growth of malignant cells.

5. There is no data about toxic effect of vitamin B12 in the treatment of various diseases. Sometimes it is necessary to use very high doses to achieve therapeutic effect.30 Vitamin B12 is the only known vitamin that does not have any toxic effect.

The author has not yet been able to find another explanation for high levels of vitamin B12 in oncology patients other than that it is a compensatory mechanism.

Necessity of New Approach to the Problem of Vitamin B12We know that not only can individuals with special prob-lems and vegetarians suffer from vitamin B12 deficiency, but also patients with low meat intake. There are many articles indicating the increasing prevalence of low vitamin B12 levels in different segments of general population.6368 In the past decade, it has become evident that vitamin B12 deficiency occurs commonly in industrial countries at different levels of economic and social status. A high prevalence of symptomatic vitamin B12 deficiency was discovered in a pre-urban Bedouin area in Southern Israel due to low intake of animal products.63 Dietary vitamin B12 deficiency is a severe problem in India, Mexico, Central and South America,64 and selected areas in Africa.65 For example, at least 40% of the population in Central and South America has deficient or marginal plasma vitamin B12 concentrations in almost all areas and in all age groups.66 As a rule, it appears to be prevalent in 30% to 40% of those in the lower socioeconomic levels. The authors clinic serves middle to upper-middle class populations, and,




according to data received in that clinics study,69 frequency of deficient or marginal vitamin B12 level ( 250 pg/mL) was about 35%. The author cannot extrapolate the finding to general population in this area, because the study population is a selected sample, but a prevalence of low level of vita-min B12 in the overall population may be similar. Today there is a tendency in modern society to change habits, for example cessation of smoking, fighting with obesity, accen-tuating physical exercise, and adopting correct eating habits. The author concludes that as a result of media information disseminating the relationship between meat and cholesterol/cardiovascular diseases, consumption of meatparticularly beefhas decreased. The author hypothesizes that the decrease of level of vitamin B12 in the population with higher educational level is caused by a premeditated decrease in consumption of animal products. Also, in modern society, there is a tendency for ideological motives, particularly among the younger generation, to be vegans. Changes in lifestyle among segments of the population with high socioeconomic level on one hand, and the existence of poverty on the other, are two main factors in the decreasing consumption of animal products (particularly red meat). This causes a decrease in the level of vitamin B12 in general population; as a consequence, this will increase pathology due to vitamin B12 deficiency (such as neurological and hematological disorders). As mentioned, vitamin B12 defi-ciency has various and serious health effects. In lieu of these possible developments and in order to prevent serious health problems, vitamin B12 routine fortification should be seriously considered and discussed.

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Ilia Volkov



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Volkov Review-The Critical Role of Vit B12