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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 57:M583-M587 (2002)
© 2002 The Gerontological Society of America

Vitamin B12 Deficiency and Incontinence

Is There an Association?

Justin O. Endoa, Shijie Chenc, Jane F. Pottera, Anthony E. Rannob, Saira Asadullahd and Parthasarathi Lahiric

a Section of Geriatrics and Gerontology, Department of Internal Medicine
b Department of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha
c Department of Math and Statistics, University of Nebraska–Lincoln
d Mason District Hospital, Havana, Illinois

Jane F. Potter, Section of Geriatrics and Gerontology, 981320 Nebraska Medical Center, Omaha, NE 68198–1320 E-mail: jpotter{at}unmc.edu.


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
Background. This study investigated the relationship between B12 (cobalamin) levels and incontinence in older outpatients using secondary data analysis.

Methods. Between 1991 and 1999, there were 929 patients (258 men and 671 women) for whom urinary incontinence (UI), fecal incontinence (FI), and B12 were prospectively recorded. Covariates included race, gender, age, medications, Mini-Mental State Examination, modified illness rating, and instrumental activities of daily living (IADLs).

Results. Some form of incontinence (UI or FI or both) was found in 41% of subjects, isolated UI in 34%, double incontinence (DI) in 12%, and isolated FI in 4%. Having UI increased the risk of also having FI (p < .0001). Serum B12 levels of 300 pg/ml or less were not predictive of isolated UI or isolated FI. However, in logistic regression, DI was predicted by B12 (odds ratio [OR] = 2.113, p = .0094), IADLs (OR = 0.810, p < .0001), cathartics/laxative use (OR = 1.902, p = .126), and diuretic use (OR = 2.226, p = .006). Considering isolated UI in women, higher IADLs reduced risk of UI (OR = 0.956, p = .002), while diuretics (OR = 1.481, p = .041) and antihistamines (OR = 1.909, p = .046) both increased risk of UI. In men, only use of anticonvulsant medications (OR = 4.529, p = .023) increased risk of isolated UI. Greater physical illness in both genders increased risk of isolated FI (OR = 1.204, p = .006).

Conclusions. These findings suggest that serum B12 at levels of 300 pg/ml or less are not associated with isolated UI or isolated FI but may play a role in DI. A possible association of low B12 levels with DI is intriguing because of the implications for treatment and prevention. More immediately, medication side effects should be considered when evaluating this problem.

INCONTINENCE is a common problem among older people and one that burdens patients as well as society (1)(2)(3). Urinary incontinence (UI) affects 11–30% of community-based elders (3)(4)(5), 33% of those in acute care facilities (1), and 39–50% of nursing home residents (6) at an annual cost in the United States of $26.3 billion (7). The prevalence of fecal incontinence (FI) varies from 0.75–2.2% in the adult population, increases to 2.8–9% at age 65 years and older, and affects at least 17% of persons aged 85 years and older who live in homes for aged people (6)(8)(9)(10). The financial burden of FI is as yet unknown (11).

Both FI and UI are age-related problems, and the two conditions are not independent. Studies of combined or double incontinence (DI) show a consistent association between FI and UI, such that 50–75% of persons with FI also have UI (11)(12). DI may affect 5.3% of noninstitutionalized people older than 65 years (13) or 5.6% of men and 9.6% of older women (11). However, people with DI tend to be cognitively impaired, reside in nursing homes for longer periods, and have mobility limitations (14). In women, one of the links between UI and FI is likely pelvic relaxation (12), while in men it is less well understood (11).

Cobalamin deficiency is also an age-related problem (15). Cobalamin deficiency produces neurological syndromes that may involve the peripheral nerves, spinal nerves, or mental status (16). Symptoms of B12 deficiency include autonomic dysfunction such as postural hypotension, UI, FI, and impotence, due to myelopathy and/or neuropathy (16). Whether cobalamin deficiency is important in UI and/or FI among older people remains little studied, and evidence that B12 replacement restores continence is isolated to case reports (17)(18)(19). Even so, major references on geriatric incontinence list B12 deficiency in the differential diagnosis of UI (20).

This study explores a possible association between low serum B12 and the occurrence of UI, FI, and DI in a group of frail, older persons. We also describe the prevalence of various forms of incontinence and their association with function, medications, and medical illness.


   Methods
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 Abstract
 Methods
Results
 Discussion
 References
 
This is a retrospective analysis of data from a geriatric assessment clinic. Detailed methods, including sources of referral and detailed information on this population, are described elsewhere (21). Between September 25, 1991, and December 31, 1999, geriatricians evaluated 981 patients for UI and FI as elements for the clinic database.

Following the Agency for Health Care Policy and Research guideline (22), UI was defined as involuntary loss of urine that was sufficient to be a problem. While there is no similarly accepted definition for FI, we defined FI as involuntary loss of stool of sufficient severity to be a problem. For all analyses, continence was defined as having neither FI nor UI. Various combinations of UI and FI are considered in these analyses. Isolated UI was defined as only UI without FI, while isolated FI was FI without UI. Any UI was defined as UI with or without FI, and any FI was defined as FI with or without UI. Any incontinence was defined as FI or UI or both. Double incontinence was defined as both FI and UI.

Serum B12 was measured using the Biorad competitive protein-binding assay. In this analysis, deficiency was defined as a B12 level of 300 pg/ml or less, which has been recommended as a level meriting further evaluation (17)(23)(24).

Several variables that might influence continence were routinely collected and considered as covariates in the analyses. These included functional status, cognition, age, gender, race, and medical illness (13)(25). Instruments and tests used to measure these variables are briefly described here. The Cumulative Illness Rating Scale (CIRS) is a measure of the degree of impairment for each of 13 organ systems on a five-point scale from 0 (no impairment) to 4 (extremely severe impairment) (26). The maximum possible score is 13 x 4 = 52. In the analyses, we omitted the "Genitourinary Problems" and "Lower Gastrointestinal Problems" where UI and FI would be scored. For example, the presence of UI would add two points to the CIRS score. To avoid weighting the independent variable (CIRS) in prediction of the dependent variable (UI), the genitourinary component of CIRS was deleted. Similarly, the gastrointestinal component of CIRS was also deleted. The Lawton-Brody instrumental activities of daily living (IADLs) scale (27) describes competence in IADLs, with higher scores indicating greater independence. Mini-Mental State Examination (MMSE) measures cognitive function (28). In this analysis, MMSE, IADLs and CIRS are all treated as continuous variables.

Medications were coded by a pharmacist using a version of the American Hospital Formulary Service Pharmacologic Therapeutic classification for drugs (29). Several medications that are potential causes or contributors to UI (22) or FI were considered as covariates. For UI, these are antihistamines; anticholinergic agents; sympathomimetic agents; skeletal muscle relaxants; calcium channel blockers; sympatholytics; opiate agonists; anticonvulsants; tricyclic and related antidepressants; antipsychotic agents; anxiolytics, sedatives, and hypnotics; antimanic agents; diuretics; narcotic antitussives; and antiemetics. For FI, we examined any class of drugs associated with constipation, diarrhea, or changes in gut motility: calcium channel blockers; antacids; cathartics and laxatives; antiemetics; metoclopramide; sucralfate; misoprostol; miscellaneous antidiabetic agents (acarbose); and amantadine. In preliminary analysis, each drug category was examined separately for its effect on continence (UI, FI, and DI). Only those drug categories that reached a p < .1 level were used as covariates in multivariate analysis. Drugs meeting p < .1 for any of the dependent variables are given in Table 1 along with the proportion of subjects taking them.


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  		Table 1. Characteristics of the Study Population

 
Chi-square analysis was used to examine associations between various types of incontinence and gender. Stepwise logistic regression was used to develop models to predict incontinence (0 = absent, 1 = present). Covariates entered into the model were B12 status (1 = greater than 300 pg/ml or 0 = less than or equal to 300 pg/ml), gender, age, IADLs, illness (CIRS), MMSE, and select medications (as described above).

Separate logistic regression models were used: two for UI (men and women separately due to significant differences in pathophysiology), one for FI (men and women together), and one for DI (men and women together). We also performed logistic analysis of any incontinence (i.e., either FI, UI, or both) versus three B12 cutoffs. The objective of the latter was to replicate a study by Rana and colleagues, which used B12 cutoffs of less than 250, 300, and 350 pg/ml (17). We accounted for their case control characteristics (age, gender, race, cognitive status, ambulation), except genitourinary tract problems, as covariates. Ambulation was derived from the physical ambulation subscale of the Lawton-Brody self-maintaining ADL as a categorized variable (1 = independent; 0 = dependent). Dependent persons were those who required any assistance for mobility within their residence. All analyses were done with STATA for Windows version 7.0 (STATA Corp, College Station, TX).


   Results
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 Abstract
 Methods
 Results
Discussion
 References
 
Of the 981 patients evaluated between 1991–1999, one patient was younger than 60 years of age, one patient was missing assessment of FI, and 50 were missing B12 levels. The remaining 929 patients were predominantly white women with mild cognitive impairment (mean MMSE = 20.4), an average of five to six treated medical illnesses (mean CIRS = 11.3), and moderate IADL impairment (11.5 points out of a possible 24) (Table 1 ). B12 levels of 300 pg/ml or less were found in 23% of all subjects, in 23% of those with isolated UI, in 23% of continent subjects, in 33% of subjects with isolated FI, and in 33% with DI. However, only DI was associated with B12 levels less than 300 pg/ml in bivariate analysis (p = .03).

Table 2 shows the prevalence of incontinence types by gender. All combinations of incontinence except isolated FI or any FI were significantly more prevalent among women than men. Using chi-square, there was a strong association between FI and UI, with three quarters of subjects with FI also experiencing UI (p < .0001). This association between UI and FI was comparable for men (66.8%) and women (80.6%) (p = .20).


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  		Table 2. Prevalence Rates of Incontinence Types by Gender

 
Results of the logistic analyses are shown in Table 3 . In stepwise logistic analysis of isolated UI in men, the following covariates were entered: medications (as described above), age, MMSE, IADL, CIRS, race, and serum B12; only anticonvulsant medications predicted UI. The same covariates were entered in logistic regression analysis for isolated UI in women; IADL, antihistamines, and diuretics were predictive. For isolated FI, medications, age, MMSE, IADL, CIRS, race, gender, and serum B12 were entered in logistic regression; only CIRS was predictive. For DI, bladder- and bowel-active medications, age, MMSE, IADL, CIRS, race, gender, and serum B12 were entered; only B12 level, IADL, cathartic/laxatives, and diuretics predicted DI.


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  		Table 3. Predictors of Incontinence in Logistic Regression

 
Having any incontinence was not associated with B12 cutoffs of 250 (OR = 1.190, CI = 0.788–1.799), 300 (OR = 1.273, CI = 0.914–1.772), or 350 pg/ml (OR = 1.039, CI = 0.774–1.396) after controlling for age, gender, race, cognition, and ambulation. The number of people with B12 deficiency using the 250, 300, and 350 cutoffs were 125 (14%), 216 (24%), and 317 (35%).


   Discussion
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 Abstract
 Methods
 Results
 Discussion
References
 
The incontinent older people in our study share characteristics with those in other studies. UI, isolated or in combination with FI, was 1.6 times more common in women than in men, which is in the range of 1.3–2.0 previously reported (3). The 11.0% prevalence of FI, alone or in combination with UI, in our study population is comparable to the 3–17% prevalence in community-dwelling older people (13)(25)(30) and the 10–17% reported in nursing home residents (11). Similar to a previous study, we report the prevalence of DI to be higher in women (13.3%) than in men (10.6%), although our rates were higher than the 9.4% (women) and 5.9% (men) previously reported (11).

Drug side effects are common in older people, and several drug categories previously associated with incontinence (22) were predictors in this population. While laxative use was not associated with isolated FI, laxatives and diuretics each increased the risk of DI twofold. Among women, diuretic use increased risk of isolated UI by 50%, while antihistamine use nearly doubled the risk. Among men, these relationships were not seen, yet anticonvulsant use increased risk of isolated UI fourfold. This association led us to examine these male patients more closely. Thirteen men in all, seven with isolated UI, were consuming anticonvulsants. UI in these patients was chronic and was not limited to ictal episodes. Three men with UI were taking two anticonvulsants, one had toxic levels of phenytoin, and another took gabapentin along with clonazepam. At least in case reports, gabapentin has been associated with incontinence, which reverses when the drug is stopped (31). One of the other men who took nontoxic doses of phenobarbital was also taking other drugs with potential central nervous system (CNS) toxicity. His UI reversed when medications were stopped, and his CNS cleared. The other three men with UI were taking either phenytoin (n = 2) or carbamazepine (n = 1) and had nontoxic levels.

Other factors also influence continence. Among women, every one-point decline in IADLs increased the risk of UI by 5%. Whether IADL impairment is a cause or a consequence of the incontinence cannot be determined from this study. The impact of IADLs on risk of DI was greater, with each point of IADL decline increasing risk of DI by 18%. In our study, isolated FI was associated only with greater illness (i.e., higher CIRS score), a finding paralleled in Wisconsin (25) and Japan (13) where greater illness predicted FI.

The 22% prevalence of low B12 levels reported here is in the range of 19–37% (32) seen in other studies. Whether cobalamin plays any role in incontinence in older people has not been extensively examined. This report employs a relatively large sample to examine the relationship between B12 deficiency and various forms of incontinence and finds that B12 levels of 300 pg/ml or less increase the risk of DI more than twofold, an effect equal to that of laxatives and diuretics.

One of the few other studies to examine the relationship between low B12 levels and continence in older people showed an increasing risk of incontinence ("any involuntary loss of urine or stool or both") with decreasing B12 levels (17). That case control study did not report results for DI and is not directly comparable with ours. We did, however, attempt to approximate their analysis. In our sample, B12 deficiency was not associated with our definition of "any incontinence" (involuntary loss of urine or stool, sufficient to be a problem) at any of the three B12 cutoffs (250, 300, 350) that they examined. This discrepancy might be explained by the differences in definition of "any incontinence" or the difference in study populations. Ours is a frail and disabled population as would be served in a geriatric assessment clinic, while theirs is a general geriatric clinic with a greater number of higher functioning older people. We also were not able to control for genitourinary conditions as they had done. Another study by Garcia and colleagues employed methylmalonic acid and homocysteine levels with serum B12 (<165 pmol/l) to detect B12 deficiency (33). That study used a sample of community-dwelling older people and did not find a relationship between B12 deficiency and UI. Despite the differences in methodology, we also found no relationship between B12 deficiency and UI.

Serum cobalamin level is a screening test for deficiency. The B12 level associated with tissue deficiency varies among patients, and some of this variation is explained by gender and race (23)(34). Lindenbaum and colleagues reviewed the records of 419 patients with clinically significant cobalamin deficiency and concluded that the serum cobalamin assay has decreased sensitivity for borderline levels (200–300 pg/ml) (35). They suggested measuring serum metabolites (methylmalonic acid or homocysteine) to improve accuracy in borderline cases. In our population, metabolic markers were not routinely obtained as a follow-up to borderline levels. Therefore, we can expect both false positives and a small number of false negatives using only B12 levels.

UI and FI are not completely independent phenomena. In our population, 75% of persons with FI also had UI. Three other studies also suggest that the presence of one increases risk of the other (6)(12)(36). However, those studies focused on stress UI, institutionalized individuals, and women with a mean age of 53.5 years, respectively. Roberts and colleagues (11) studied a community-based population and found a higher prevalence of DI in women but noted the association between UI and FI was stronger in men than women. Roberts also suggested that the FI and UI in men with DI might be linked by a common etiology. B12 deficiency remained in our multivariate logistic model after adjusting for covariates, including gender. In considering these studies, our report suggests that in some cases, the link between UI and FI in both genders may be B12 deficiency.

Several limitations to our findings must be noted. Our failure to show a relationship between low B12 and isolated UI may relate to our inability to separate subjects by type of UI (neurogenic vs stress). We also did not score the severity and frequency of the incontinence, as some have done (13). Other variables that were not accounted for include diabetes, previous stroke, prostate disorders or cancer, and multiple or extreme vaginal deliveries. These data may have improved our models (3)(11)(12)(13)(17)(37)(38). We must also interpret the results of FI with caution because of the small number of individuals with isolated FI. Finally, these results at best are representative of a geriatric assessment clinic and cannot necessarily be extrapolated to the general older population.

We report the type and prevalence of incontinence in a large population of frail older patients. The strengths of the study lie in the sample size and our ability to classify various combinations of UI and FI. We describe factors associated with each type of incontinence, and, not surprisingly, medication side effects are prominent findings. Should these findings be replicated in more sophisticated studies, the association of low B12 levels with DI is intriguing because of the potential implications for treatment and prevention.


   Acknowledgments
 
This research project would not have been possible without the support of the National Kidney Foundation of Nebraska and UNMC's Department of Research and Development. Many thanks to the entire GAC staff and to the patients and their families who participated in this study. Thanks also to M. Kallin Carter at UCLA's Division of Geriatrics and Thomas Reardon of UNMC for significant assistance with analysis.

Received December 3, 2001

Accepted March 11, 2002


   References
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 Abstract
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 Results
 Discussion
 References
 

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