Studies into vitamin B12 deficiency and vegetarianism .
Vitamin B12 is only synthesized by microorganisms in nature and thus, is obtained by human beings through their diet. Since the most important source of vitamin B12 is animal proteins, vegetarians may lack sufficient quantities of this vitamin in their diets. Vitamin B12 deficiency may stem from a lower dietary intake, an autoimmune issue related to intrinsic factors or gastrointestinal system diseases resulting in vitamin B12 malabsorption. The most important symptoms and findings of severe vitamin B12 deficiency are anemia and neurological problems. If it is not treated, anemia symptoms and neurological disturbances resulting in spinal cord and cerebral cortex demyelination may emerge. Vitamin B12 deficiency is one of the most frequent vitamin deficiencies worldwide. This deficiency is a highly important public health issue because of its serious complications if it is not detected and treated appropriately, although its treatment is very simple. Epidemiological studies in this field are, therefore, of great value. Most of the studies on this subject have been examined vitamin status of the general population. The research generally contains to the national or provincial populations data. Nevertheless, the few data are not fully representative in the general population. Determining risk factors and at‐risk groups, and educating them about vitamin B12 deficiency and proper diet would prevent the irreversible complications of this type of deficiency. The goal of this study is to review epidemiological studies related to vitamin B12 deficiency and to point out the importance of identifying and treating it.
- vitamin B12
Vitamin B12 is only synthesized by microorganisms in nature and thus, is obtained by human beings through their diet . Since the most important source of vitamin B12 is animal proteins, vegetarians may lack sufficient quantities of this vitamin in their diets.
Vitamin B12 deficiency may be caused by a lower dietary intake (impaired absorption or decreased intake), an autoimmune issue related to intrinsic factors or gastrointestinal system diseases resulting in vitamin B12 malabsorption . The most important symptoms and findings of severe vitamin B12 deficiency are anemia and neurological problems. Vitamin B12 deficiency is one of the most common causes of macrocytic anemia [3, 4]. If it is not treated, anemia symptoms and neurological disturbances resulting in spinal cord and cerebral cortex demyelination may emerge .
Epidemiology concerns health and disorders, etiological agents, the symptoms of disorders, diagnoses and the benefits of clinical care, and its discontinuation. Determining risk factors and at‐risk groups as well as educating them about vitamin B12 deficiency, proper diet, and replacement would prevent any irreversible complications of this type of deficiency. The goal of this study is to review epidemiological studies related to vitamin B12 deficiency and to point out the importance of identifying and treating it.
2. The metabolism of vitamin B12
The major metabolic pathway of vitamin B12 formation is shown in Figure 1.
Vitamin B12 is essential for DNA synthesis in cells. It has two different forms in cells.
Deoxyadenosyl B12 converts methylmalonyl CoA to succinyl CoA. It also transfers methyl groups from methyltetrafolate to synthesized methionine. Transferring a methyl group from methyltetrafolate forms tetrahydrofolate. If there is a lack of vitamin B12, there is no receptor to transfer a methyl group from methyltetrafolate. Then the methylfolate is trapped and tetrahydrofolate that is needed to support DNA synthesis is decreased .
3. The absorption and distribution of vitamin B12
The absorption of vitamin B12 is a multiple staged process. Vitamin B12 intake through dietary sources initially combines with binding proteins (R‐protein) in the saliva. Then it reaches the intestine where pancreatic protease is extracted and it combines with intrinsic factors which contain glycoprotein. Vitamin B12 is absorbed efficiently when it combines with such intrinsic factors. In fact, very little uncombined free vitamin B12 is absorbed. The vitamin B12 and intrinsic factor binds with a specific receptor on the mucosa cells of the terminal ileum and is extracted to the circulation system from the intestine wall. Vitamin B12 is bound with transcobalamin proteins in circulation. The most important transcobalamin protein is transcobalamin II that is the main transporter protein in distributing vitamin B12 to the tissues and liver .
Tissues rich in vitamin B12 include parenchymal tissues (above 100 mcg/100 g), fish, muscular organs, dairy products, and egg yolks (1‒10 mcg/100 g) . In the West, daily vitamin B12 intake by nonvegetarians is approximately 5‒7 mcg/day, which is sufficient for normal homeostasis of body functions . However, vegetarians are at risk of vitamin B12 deficiency because they only consume 0.25‒0.5 mcg/day vitamin B12 from their diet . Vitamin B12 is stored well in tissues; for adults, vitamin B12 levels are 2‒5 mg and this is mostly located in the liver (approximately 1 mg). Daily loss of vitamin B12 level is 0.1%. When someone no longer obtains vitamin B12 through their diet, depletion of the stored vitamin may take as long as 3‒4 years .
4. The clinical spectrum of vitamin B12 deficiency
Both vitamin B12 deficiency and folate deficiency cause megaloblastic anemia. In fact, only vitamin B12 deficiency causes neuorological change. Additionally, the difference between these two anemia types is the duration between the start of deficiency and symptoms being apparent. The symptoms of B12 deficiency appear within years after the removal of vitamin B12 from the diet whereas the symptoms of folate deficiency are seen within 4‒6 weeks.
Vitamin B12 deficiency is one of the most frequent vitamin deficiencies worldwide . So, this deficiency is an extremely important public health issue owing to its serious complications if it is not detected and treated appropriately. Epidemiological studies in this field are, therefore, of great value. There are many epidemiological studies related to vitamin B12 deficiency, which have used different methods and evaluated different disorders accompanying it [8, 9].
5. The epidemiology of vitamin B12 deficiency
Although vitamin B12 deficiency is considered to be a public health problem, its incidence and prevalence are not exactly known. The reasons for this condition are the ethnic and sociocultural differences between societies and their varying dietary habits. The most comprehensive knowledge about vitamin B12 deficiency has been extracted from a review, which was conducted through studies in Africa, America, South‐East Asia, Europe, Eastern Mediterranean, and Western Pacific in 2008 . Another review evaluated 41 studies in Latin America and the Caribbean and found that the prevalence of vitamin B12 deficiency was 61% .
The data extracted from this study have shown that vitamin B12 deficiency is still a public health problem in these regions. The main reasons for vitamin B12 deficiency are nutritional deficiencies that affect large sectors of the population including vegetarians and their children who are affected during and after pregnancy, the elderly, frequent drug users as well as nutritional deficiency linked to low socioeconomic level .
Although it is thought that vitamin B12 deficiency is rarely seen except in strict vegetarians, it is, in fact, commonly seen in all vegetarian groups (lacto‐vegetarians, ovo‐vegetarians, lacto‐ovo‐vegetarians, and vegans), as well as among the elderly and for reasons related to medicine and drug use [12‒15]. Particularly, vegetarians should take care of protective measures for vitamin B12 deficiency that involve to identify the inadequate vitamin level and to receive supplements containing B12 in necessary condition .
|Reference||Country||Participants||Rate of deficiency|
et al. 
|Netherlands||N = 73, age range|
: 9‒15 years
|Donaldson ||USA||N = 49, mean age|
: 55 years
|Geisel et al. ||Germany||N = 71, mean age|
: 53‒51 years
|Gibson et al. ||Ethiopia||N = 99, mean age|
: 27.8 years
|Gilsing et al. ||UK||N = 65, mean age|
: 42.8 years
|Hermann et al. ||Germany and|
|N = 111, mean age|
: 46 years
|Hermann et al. ||Oman (German and Asian‐|
|N = 96, mean age|
: 50 years
|66% of German and 69%|
|Hermann et al. ||Germany||N = 34, mean age|
: 22 years
|Hermann et al. ||Germany and|
|N = 66, mean age|
: 48 years
|Hermann et al. ||Germany||N = 114, mean age|
: 50 years
|Kwok et al. ||China||N = 119, mean age|
: >55 years
|Kwok et al. ||Hong Kong||N = 113, mean age|
: >55 years
|Miller et al. ||USA||N = 110, adults|
N = 42, children
|Obeid et al. ||Germany and|
|N = 111||Unclear. Figure shows 58%|
but text reports 85%
|Refsum et al. ||India||N = 78|
|Rush et al. ||New Zealand||N = 6|
|Schneede et al. ||Norway||N = 41, infants|
|van Dusseldorp et al.|
|Netherlands||N = 73, adolescents|
The effects of vitamin B12 on the central nervous system are well known. Lifelong optimal vitamin B12 levels are very important for cognitive function. Vitamin B12 deficiency that is caused by suboptimal vitamin B12 intake and/or changes in absorption due to aging, directly causes neurocognitive deficiencies by neurotoxic effect [34, 35]. Several epidemiological studies about vitamin B12 and the effects of aging on cognitive function have found a correlation between vitamin B12 and cognitive function among middle‐aged and elderly cases in Central and Eastern Europe .
Vitamin B12 deficiency resulting from drug use has been shown in several previous studies and indeed is still being discussed. Especially, metformin, which is used to treat diabetes mellitus type‐2 (DM), influences vitamin B12 absorption by affecting the calcium‐dependent ileal absorption of intrinsic factor‐vitamin B12 complex [40, 41].
However, there are studies which defend the contrary [41, 42]. Neither intestinal motility changes nor bacterial over reproduction could be shown in these studies. The relationship between vitamin B12 absorption and metformin was first observed in 30% of type‐2 diabetic patients in 1971, and Ting et al. also found a relationship between vitamin B12 and the use of metformin in treatment doses in 2006 [15, 43].
Vitamin B12 deficiency related with the use of metformin was observed among 30 patients, 90% of whom had minor hematological abnormalities, 30% had mild peripheral neuropathy, and two patients had symptomatic anemia and pancythopenia .
A meta‐analysis, which evaluated six randomized controlled trials, found that using metformin in different doses caused vitamin B12 deficiency and there was a correlation between the metformin dosage and level of vitamin B12 deficiency .
Levodopa is another drug which is used for parkinsonism and believed to cause vitamin B12 deficiency. Levodopa has an effect on vitamin B12 levels by affecting the catechol‐O‐methyl transferase pathway and carbidopa metabolism [46‒48]. According to these studies, vitamin B12 levels should be checked before planning to use metformin and levodopa for a long‐term period.
Consequently, vitamin B12 deficiency has been found to be very common in specific groups of the population, and there is a high risk of vitamin B12 deficiency as far as vegetarians, infants, pregnant and breastfeeding mothers, and the elderly are concerned. There is clearly a need to establish both national and prophylaxis programs in order to prevent vitamin B12 deficiency among such cases.