A study of the prevalence of vitamin B12 deficiency in Turlock, California

Corinne Lee-Guzman, OMS III, Midwestern University AZCOM, 26911 Caddy Ct, El Macero, CA 95618.

E-mail address: Corinne.LeeGuzman@azwebmail.midwestern.edu.

Vitamin B12 (cobalamin) is necessary to maintain proper neurologic functioning. Cobalamin can be found in high amounts in red meat and seafood and in lesser amounts in chicken, eggs, and dairy products.1,2 The body can store vitamin B12 in the liver and delay symptoms of deficiency from three to ten years in persons with inadequate intake of cobalamin.2,3 Patients with vitamin B12 deficiency can have fatigue, neurologic disease, paresthesia, and megaloblastic anemia. Patients may also develop Hunter’s glossitis, a condition in which the tongue takes on a smooth and shiny appearance caused by atrophy of the surface papillae.1-5

In developed countries, it is estimated that approximately 20% of the population is cobalamin-deficient, although studies vary between 5% and 60% owing to the lack of a standard definition of B12 deficiency.6 Some people may fall within a normal laboratory diagnostic range of vitamin B12 and still have symptoms of deficiency, whereas other people might be diagnostically vitamin B12– deficient according to laboratory results but not have any symp- toms.5,7-9 This makes standardizing diagnostic criteria very difficult. Proof that symptoms of vitamin B12 deficiency are indeed caused by deficiency of the vitamin is exemplified through administration of vitamin B12 and the reversal of symptoms.7 In the past, this type of therapeutic testing was the primary method to confirm diagnosis of cobalamin de- ficiency. Today, therapeutic testing is used as an adjunct to the current diagnostic method of measuring vitamin B12 blood serum levels.8

‌Causes of B12 deficiency

Inadequate intake of cobalamin is a major cause of vitamin B12 deficiency.1-4 The recommended intake varies with body size and type because some people require more vi- tamin B12 than others to prevent neurological symptoms. Therefore, an exact adequate value is unknown to prevent all symptoms of B12 deficiency, although diets that contain at least 0.5 µg/day prevent megaloblastic anemia.1,2,4 In addition, babies born to or breast-fed by mothers who are vitamin B12– deficient will also receive inadequate intake of the vitamin.1,2,10

Vitamin B12 deficiency can be caused by malabsorp- tion due to conditions such as pernicious anemia, certain enzyme deficiencies, and damage or resection of the terminal ileum.1-4 Pernicious anemia is an autoimmune disorder caused by antibodies reacting against intrinsic factor (a factor needed to bind and absorb cobalamin) and/or autoimmune destruction of gastric mucosa.1-3,7 Several pancreatic enzymes are needed to help transport cobalamin through the stomach to the small intestine. People with certain enzyme deficiencies thus have difficulty with vitamin B12 absorption. Furthermore, the ileum is needed to convert cobalamin into a form that can be deliv- ered through the body. Diseases such as Crohn’s disease, amyloidosis, scleroderma, tuberculosis, and certain lympho- mas can cause damage to the terminal ileum.1-3

Food-cobalamin malabsorption syndrome commonly caused by gastric atrophy is a frequent reason for deficiency in the elderly but occurs in other populations as well.5,11-13 This condition results from by the inability of the body to sepa- rate cobalamin from food or transport proteins throughout the body.1,5 Helicobacter pylori infection contributes to gastric atrophy, as does chronic alcoholism and the use of certain medications such as antibiotics, biguanides, and

infestation of the aforementioned tapeworm or chronic in- fection with Giardia is needed to cause significant malab- sorption of vitamin B12.1-4

‌Contributing factors to B12 deficiency

‌Age

Research has long shown that elderly populations in the United States and Europe have a higher prevalence of cobalamin deficiency compared with younger popula- tions,1-9,11-13,15 with a minority of studies in dispute.16 As an example, Mollin and Ross noted in their 1952 study that people older than 70 years had lower serum cobal- amin than both 15 to 40 years-old and 50 to 70 years-old groups.15 The high prevalence of cobalamin deficiency among the elderly is likely caused by the higher inci- dence of pernicious anemia in this group, although this is currently thought to be a small contributor overall com- pared with absorption problems such as food-cobalamin malabsorption syndrome.4,7,17 Elderly Latinos in the United States especially were shown to have a high prevalence of low B12 serum levels when compared with elderly Caucasians, African Americans, and Asian Amer- icans.4

‌Diet

Although many people follow a vegetarian or vegan diet because of religious, cultural, or health reasons, they are putting themselves at risk for vitamin B12 deficiency, be- cause meat is a primary source for the vitamin.1-4,18,19 In Hong Kong, a study showed that 75% of elderly vegetarians had vitamin B12 deficiency.4 In India, the majority of the population is lacto-vegetarian (consumption of dairy prod- ucts in addition to a plant-based diet), making megaloblastic anemia and neurologic symptoms highly prevalent among the Indian community.18 One study showed that 11% of young infants in India suffered from tremor because of inadequate vitamin B12 levels.20 Populations in the Middle East and rural Central Mexico also consume less meat in their diets and consequently show an increased prevalence of B12 deficiency.4

‌Gender

The contribution of gender to cobalamin deficiency ap- pears to be controversial. A study of 88 male and 89 female multi-ethnic college students found no overall difference in cobalamin intake or serum levels,21 whereas another study of 159 healthy subjects found higher serum levels in fe- males compared with males.22 Females have a higher prev- alence of pernicious anemia– based cobalamin deficiency compared with males, particularly in Northern Europe and the United States.1,4 In a study of seniors in California, there were 8300 females per 100,000 with pernicious anemia and only 4100 males per 100,000 with pernicious anemia; and in Minnesota there was an incidence of 49.2 females and 25.1 males with pernicious anemia.4

‌Prevalence of B12 deficiency in Turlock, California

‌Methods

Demographic reports on Turlock, California were stud- ied using information from the US Census Bureau. Data were collected from three primary care offices in Turlock, California, with diverse patient populations that reflect the population of that city. Reports were developed using a computer-based medical record search for patients with vitamin B12 deficiency as a diagnosis in each of the three primary care offices. All three offices used the following diagnostic criteria for vitamin B12 deficiency: (1) serum cobalamin level <200 pg/mL with or without additional findings or (2) serum cobalamin level 200 to 400 pg/mL with additional findings such as clinical symptoms, hema- tologic changes, and/or high suspicion based on risk factors (e.g., age, diet, race). Cases meeting the second criterion were often confirmed by resolution of symptoms/hemato- logic changes upon replacement therapy of B12. The num- ber of vitamin B12– deficient patients found in each practice was then compared with the total number of patients with- out B12 deficiency as a diagnosis within that same practice. Data were then combined from the three practices to obtain an overall picture of the prevalence of vitamin B12 defi- ciency in Turlock, California. Furthermore, data were sep- arated to develop a better idea of which (1) age range and (2) gender is most affected by vitamin B12 deficiency. This study reflects a community-based case-control study where cases of vitamin B12 deficiency patients were compared with the control group of non–vitamin B12– deficient pa- tients in the community of Turlock.

Percentage of Patients Percentage of Patients Percentage of Patients Percentage of Patients

‌21-40 yo who are B12 Deficient

41-60 yo who are B12 Deficient

61-80 yo who are B12 Deficient

>80 yo who are B12 Deficient

Figure 2 Office 1: Percentage of B12-deficient patients per age group relative to amount of patients per age group. Data were calculated by dividing the total number of B12-deficient patients in each age group by the total number of patients of the same age group.

Table 2 Office 2: Patient comparison between vitamin B12– deficient patients and non–vitamin B12– deficient patients

Male Female Total

the 61 to 80 years-old range (Figure 3). When comparing the amount of B12-deficient patients in an age range with the total amount of patients in the same age range, data show an upward trend in percentage of B12-deficient patients with increasing age, also similar to Office 1 (Figure 4). Only 13

‌Results

‌Office 1

Table 1 shows there are 291 (18.7%) B12-deficient pa- tients of 1556 total patients in the practice. The greatest absolute number of B12-deficient patients is in the 61 to 80 years-old range (Figure 1). However, when comparing the amount of B12-deficient patients in an age range to the total amount of patients in the same age range, data show an upward trend in percentage of B12-deficient patients with increasing age (Figure 2). Although only 54 of the total 291 B12-deficient patients were in the >80 years-old category, data show that these patients accounted for 24% of total patients >80 years-old in Office 1. When comparing the absolute number of B12-deficient men and women sepa- rately, there are more women in each age range than men (Figure 1). In total, there are approximately twice as many female patients than male patients who are seen in Office 1, but there are more than twice as many female B12-deficient patients than male B12-deficient patients in every age cat- egory (Figure 1). Furthermore, Table 1 illustrates that there are 66 (13.04%) male cobalamin-deficient patients of 506 total males and 225 (21.43%) female cobalamin-deficient patients of 1050 total females.

‌Office 2

Table 2 shows there are 73 (4.79%) B12-deficient pa- tients of 1525 total patients in the practice. As in Office 1, the greatest absolute number of B12-deficient patients is in old categories, more B12-deficient men than women in the

41 to 60 years-old categories, and more B12-deficient women than men in the 61 to 80 years-old and >80 years- old categories (Figure 3). There were approximately 140 more female patients than male patients seen in Office 2 and more female B12-deficient patients than male B12-deficient patients. Table 2 illustrates that there are 32 (4.63%) male B12-deficient patients of 691 total males and 41 (4.92%) female B12-deficient patients of 834 total females.

‌Office 3

Table 3 shows there are 11 (0.93%) B12-deficient pa- tients of 1188 total patients in the practice. The greatest absolute number of B12-deficient patients is in the 61 to 80 years-old range (Figure 5), as in Offices 1 and 2. Also similar to Offices 1 and 2, when comparing the amount of B12-deficient patients in an age range with the total amount of patients in the same age range, data show an upward trend in percentage of B12-deficient patients with increasing age (Figure 6). In contrast to Offices 1 and 2, Office 3 had no B12-deficient patients under the age of 40. Although three of the total 11 cobalamin-deficient patients were in the

>80 years-old range, data show that these patients account for 2.70% of total patients >80 years-old in Office 3, slightly more compared with other age ranges (Figure 6). When comparing the absolute number of B12-deficient men and women separately, there were more B12-deficient women than men in the 41 to 60 years-old and 61 to 80 years-old categories, and equal amounts of men and women in the >80 years-old category (Figure 5). There were ap- proximately 70 more female than male patients seen in Office 3 and more female than male B12-deficient patients. Table 3 shows that there were three (0.54%) male cobala- min-deficient patients of 552 total males and eight (1.26%) female cobalamin-deficient patients of 636 total females.

‌Combined data

There are 375 (8.78%) B12-deficient patients of 4269 patients in this study. The greatest absolute number of B12-deficient patients were in the 61 to 80 years-old range, but the greatest percentage of B12-deficient patients per age group was in the >80 years-old category. There are also 274 (10.87%) B12-deficient women of 2520 female patients and 101 (5.77%) B12-deficient men of 1749 male patients, giv- ing an approximate ratio of 2:1 female-to-male B12-defi- cient patients.

‌Discussion

Table 3 Office 3: Patient comparison between vitamin

The population size of Turlock, California is 67,866, with 17,432 people who are foreign-born; approximately 50.2% of the population is female and 49.8% is male.23 The pop- ulation breakdown is White (72.3%), and a mix of different ethnicities (27.7%). The Asian population makes up 4.5% with more than half comprising Asian Indians.24 The Lati- no/Hispanic demographic, which includes any race (Whites and Non-White) declaring themselves as such, makes up 34.4% of the Turlock population, which is more than double the US average of 15.1%.23

Because Turlock has a significant percentage of people who are from Latin, Asian, and Indian backgrounds, it is expected that there should be a high prevalence of vitamin B12– deficient individuals. As noted earlier, elderly Latinos have a high prevalence of low vitamin B12 levels, as do certain Asian and Indian groups, who primarily consume diets low in meat.4,18 However, only 8.78% of the studied Turlock population is cobalamin-deficient, which is lower than the 20% average in developed countries.17 Possible factors to explain this discrepancy are detailed next.

Results of vitamin B12 deficiency by age group are consistent with previous studies.1-9,11-13,15 A greater per- centage of elderly patients in this study are vitamin B12– deficient compared with the younger population. When con- sidering gender, the results of this study showed a 2:1 ratio of female to male B12-deficient patients. The higher prev- alence of pernicious anemia in women might partially ex- plain why there are more women in Turlock that are vitamin B12– deficient, but more research needs to be done to eval- uate the prevalence of pernicious anemia and determine whether it is a true contributing factor.1,4 Further studies also need to investigate other confounding factors, such as the possibility that more women than men in Turlock are vegetarians or vegans.1-4,18-20

As described earlier, major problems with investigating

B12 deficiency is the lack of standardized diagnosis guide- lines, and the fact that patients display symptoms at differ- ing levels of serum cobalamin.5,7-9 The latter issue was exemplified by a patient seen in Office 1. An 81-year-old female patient with serum cobalamin <50 pmol/L (below the detectable amount) presented with classic Hunter’s glos- sitis and macrocytosis, but no overt neurological symptoms or fatigue. Inadequate dietary intake of cobalamin and malabsorption caused by alcoholism were ruled out through

This study may be skewed by information bias owing to misclassification of which patients are truly deemed vitamin B12– deficient. A current problem with cobalamin defi- ciency diagnosis and treatment is the lack of a gold standard for defining vitamin B12 deficiency among different patient populations.25 As a result, doctors may draw the cutoff for vitamin B12 deficiency differently from office to office or even from patient to patient, making accurate classifications difficult. In addition, doctors may screen for vitamin B12 levels at different frequencies. For instance, the offices in this study used similar diagnostic criteria, but through ob- servation, Office 1 frequently ordered vitamin B12 levels when ordering laboratory work, regardless of whether pa- tients had symptoms of B12 deficiency, whereas Office 3 only ordered vitamin B12 levels when patients demon- strated symptoms suggestive of B12 deficiency. Therefore, more B12-deficient patients may have been discovered in Office 1 compared with Office 3 based on screening fre- quency, despite both offices using similar criteria for mak- ing the final diagnosis.

Confounding bias may also be present in this study. Although groups were studied separately by age and gender, confounding factors of race, socioeconomic status, and health insurance coverage were unable to be studied indi- vidually. Some groups of people may not receive health screening as frequently because of some or all of these factors. Thus, it is unclear how strongly race, socioeco- nomic status, and health insurance coverage contributed to the results. More detailed research and analysis is needed to rule out such confounding factors.

‌Conclusion

This study assessed the prevalence of vitamin B12 defi- ciency in Turlock, California and found that elderly patients had a higher prevalence of B12 deficiency than younger patients, and women also had a higher prevalence of B12 deficiency than men. The increased prevalence of B12 de- ficiency found among elderly patients is consistent with previous studies and is likely attributed to atrophic gastritis and food-cobalamin malabsorption syndrome.5,11-13 The higher prevalence of cobalamin deficiency found in female patients in Turlock, California is not consistently docu- mented across vitamin B12 studies21,22; however, this find- ing could be attributed to females having a higher incidence of pernicious anemia when compared with males.1,4 Further evaluation is needed to study this relationship. In addition, other confounding factors such as race, diet, and culture were not independently assessed in this study and may be worth investigating in future studies.

This study aimed to further expand current knowledge of B12 deficiency in the areas of epidemiology, risk factors such as age and gender, and diagnostic issues and aware- ness. Hopefully, clinicians continue to effectively recognize and treat this curable disorder despite the current lack of standard diagnostic guidelines.17 Recognizing and treating vitamin B12 deficiency can have a positive impact, because therapy is simple, cost effective, and removes potential symptom overlap with other disorders, thereby improving overall patient care and quality of life.1-4

2.68%

2.70%

0.90%

3.00%

2.50%

2.00%

1.50%

1.00%

0.50%

0.00%

‌Percentage of Patients 41-60 yo who are B12 Deficient

Percentage of Patients 61-80 yo who are B12 Deficient

Percentage of Patients >80 yo who are B12 Deficient

Figure 6 Office 3: Percentage of B12-deficient patients per age group relative to amount of patients per age group. Data were calculated by dividing the total number of B12-deficient patients in each age group by the total number of patients of the same age group.

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