Abstract
Objective:
To determine if vitamin D intake is associated with reduced progression of urgency UI in women.
Methods:
We used the Nurses‟ Health Study (NHS) I and NHSII cohorts to evaluate the association of vitamin D intake with progression of urgency UI and mixed UI, from mild-moderate to severe symptoms, from 2004–2012 (NHS) and 2005–2013 (NHSII). Intake of vitamin D at study baseline was categorized and updated at the start of each 2–4 year follow-up period. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (95%CI) of progression to severe UI were estimated using Cox proportional hazard models.
Results:
At baseline, of the 20,560 older women (age range 58–73 years) in NHS I with mild/moderate urgency or mixed UI, 21% reported oral vitamin D intake of at least 800 IU per day. Among 12,573 middle-aged women (age range 42–59) in NHS II with mild/moderate urgency or mixed UI, 17% reported oral vitamin D intake of at least 800 IU daily. From 2004–2012, 4,853 incident cases of urgency/mixed UI progression were identified among older women. From 2005–2013, 1,378 incident cases of urgency/mixed UI progression were identified among middle-aged women. After multivariable adjustment, no significant associations between vitamin D intake and incidence of urgency/mixed UI progression were observed in either cohort (RR=1.10, 95% CI 0.99–1.23 in older women, RR=0.88, 95% CI 0.71, 1.10 in middle-aged women).
Conclusion:
Despite interest in vitamin D as a low-cost strategy to prevent or reduce UI, our findings indicate oral vitamin D may not reduce urgency/mixed UI progression.
INTRODUCTION:
Urgency urinary incontinence (UI) and mixed UI increase with aging and are the most common and bothersome types of UI in middle aged and older women.1,2 Although effective behavioral treatment strategies for urgency and mixed UI are available, not all older women are willing or able to learn these behavioral techniques or practice them consistently.3–5 As a result, many women are interested in other, low-cost, easy-to-implement prevention strategies for UI that may have even greater opportunity for broad uptake.
Vitamin D has garnered significant interest as a nutritional supplement to treat or prevent urinary symptoms because of its anti-inflammatory properties and potential to influence muscle function of both the detrusor smooth muscle and striated pelvic floor muscle.6–8 While recent studies show conflicting evidence regarding the potential association of low vitamin D intake or low serum 25-hydroxyvitamin D status (marker of vitamin D status) and incident urgency UI,9,10 no previous, large studies have examined the relationship between vitamin D intake and progression of urgency UI and mixed UI in middle-aged and older women.
Two longitudinal studies, Nurses‟ Health Study (NHS) I and NHS II, provide a unique opportunity to evaluate the association between dietary and supplemental vitamin D intake and progression of urgency UI and mixed UI in adult women followed over many years with detailed collection of diet and supplements.11 While initial results from NHS and NHS II have suggested no relationship between vitamin D intake and incident UI among women who are continent at baseline,10 it is possible that vitamin D may be more effective when used in a targeted population who already have UI symptoms. Thus, we sought to determine the association between vitamin D intake and progression from mild-moderate urgency or mixed UI to the development of severe UI symptoms.
SUBJECTS AND METHODS:
Study Population
NHS I was initiated in 1976 when female registered nurses ages 30–55 years responded to a mailed questionnaire about their medical history and lifestyle. Using similar methodology, NHS II was initiated in 1989, among women between 25 and 42 years old; the upper age of NHS II was selected to correspond with the lowest age in NHS I in that year. Both cohorts utilize identical methods for data collection and follow-up, including biennial mailed questionnaires to update health and lifestyle information. During each questionnaire cycle, full-length questionnaires are sent in initial mailings, followed by abbreviated questionnaires to maximize participation. To date, the follow-up in both cohorts is approximately 90%. The Institutional Review Board of Brigham and Women‟s Hospital approved both NHS I and NHS II.
Vitamin D Assessment
The NHS questionnaires administered every two years request details of multivitamin supplements (including brand/type of multivitamin, to facilitate extraction of doses of specific vitamins), and specific vitamin D supplements and dose. In addition, starting in 1980 for NHS and 1991 for NHS II, and approximately every four years thereafter, the Willett food frequency questionnaire (FFQ) was administered to collect information on intake of 130 foods. For each food, for specified portion sizes (e.g., 1 cup skim milk) women were asked to report frequency of intake over the previous year (never/almost never, 1–3 times a month, once a week, 2–4 times a week, 5–6 times a week, once a day, 2–3 times a day, 4–6 times a day, or >6 times a day). Dietary vitamin D intake was computed by multiplying the frequency of consumption of each unit of food and the vitamin D content of the specified portion. Nutrient values in foods are obtained from the USDA and other sources, using year-specific information to capture changes in fortification and nutrient content over time.
We calculated vitamin D intake by combining amounts from multivitamins, specific supplements, and foods (for years when the FFQ was not administered, food data were carried forward from the previous questionnaire – regardless, supplements provide substantially more vitamin D than foods for most participants). We previously documented the validity of this approach to measuring vitamin D intake in our cohorts. In a subset of participants, we compared the FFQ to 7-day diet diaries completed 4 times throughout a year; we found correlations of 0.81 for milk and 0.66 for fish, the two largest contributors to dietary vitamin D. For supplements, the sensitivity and specificity of the FFQ was 78 and 93%, respectively. Thus, vitamin D intake sources are well-reported by participants.
Urinary Incontinence
In 2004 (NHS I) and 2005 (NHS II), women were asked, “During the past 12 months, how often have you leaked or lost control of your urine?” Response choices were never, < 1/month, 1/month, 2–3/month, approximately 1/week, and almost every day. Women reporting UI were further asked about the amount of leakage, with response options of: a few drops, enough to wet underwear, enough to wet clothing, enough to wet the floor. A reliability study among a subgroup of these nurses demonstrated high reproducibility of responses;12 further, our previous work has demonstrated that these nurses have similar UI rates, including progression, as the general population of women in the US.13,14 The Sandvik Severity Score was calculated by multiplying responses on frequency and amount (with frequency categories as 1–4 after combining <1/month with 1/month; and quantity categories as 1–2, for a few drops or enough to wet underwear or more); thus the score ranged from 1 to 8. 15 Mild UI or moderate UI was defined as a score from 1 to 5, and severe UI as 6 or greater.
UI subtype was also ascertained from all women reporting UI. UI classifications were based on the participants‟ reports of their dominant symptoms. Urine loss with a sudden feeling of bladder fullness or when a toilet was inaccessible was defined as „urgency UI‟. Women who reported that stress and urgency symptoms occurred equally were defined as cases of „mixed UI‟. All UI questions were repeated in 2006, 2008, 2010 and 2012 in NHS, and in 2009 and 2013 in NHS II.13 For this report, analyses focused on women with urgency or mixed UI at baseline or the start of each reporting period. Incident cases of UI progression were defined as those progressing from mild or moderate urgency or mixed UI to severe UI.
Measurement of Demographic and Health Characteristics/Covariates
We used data from the cohort questionnaires in 2004 (NHS I, older women) and 2005 (NHS II, middle-aged women), as well as subsequent questionnaires, to obtain and update information on covariates. We used their questionnaire report to assess demographic, health, and lifestyle covariates, including age, race, height and weight, parity, smoking, postmenopausal hormone use, thiazide diuretic use, hysterectomy, and reported diagnosis of depression. In addition, women reported the number of hours spent on various leisure activities (e.g., walking, running) during the past year, and total energy expenditure was calculated in metabolic-equivalent task hours per week, which has been previously described in detail.20 Finally, women reported diagnoses of stroke, myocardial infarction, and type 2 diabetes on every questionnaire.
Population for Analysis
At baseline in each cohort, we excluded women with a history of stroke or Parkinson‟s Disease, as well as women who died during the first follow-up period. We then identified women with mild or moderate urgency or mixed UI (ie, women who were eligible for subsequent progression of UI from mild/moderate to severe). Of the 22,066 NHS I participants with mild or moderate, mixed or urgency UI at our analytic baseline in 2004, we excluded 1506 women missing information on vitamin D intake; thus, 20,560 women were included in analyses at baseline. Of the 15,989 NHS II participants with mild or moderate mixed or urgency UI at our analytic baseline in 2005, we excluded 3,416 missing information on vitamin D intake; thus, 12,573 women were included in analyses at baseline. Subsequent to the first time-period, at the start of each follow-up, we added any women who had newly developed mild or moderate urgency or mixed UI since the previous time period, and further excluded those missing information on vitamin D intake during that period. At the end of each follow-up period, women were censored who developed incident severe UI, at loss-to-follow up, or at death, whichever came first. Overall, 21,072 women with mild or moderate urgency or mixed UI were included in analyses in NHS from 2004–2012, and 13,469 in NHS II from 2005–2013 (Figure 1).
Figure 1:
Population for Analysis
Statistical Analysis
Analyses were conducted separately for NHS and NHS II. We identified participants‟ intake of vitamin D at study baseline (ie, 2004 in NHS I and 2005 in NHS II), and updated information at the start of each follow-up period. Vitamin D intake was categorized as <200IU, 200–399, 400–599, 600–799, 800–999, and 1000+. Multivariable-adjusted relative risks of progression to severe UI, estimated by hazard ratios, were calculated using Cox proportional hazard models across categories of vitamin D intake. We calculated 95% confidence intervals for all relative risk estimates, and conducted tests of linear trend using an ordinal variable representing the median value of each vitamin D category. To control for potential confounding, models were stratified by age (in months) and time period, and in models we included covariates that were identified from the existing literature as potential risk factors for UI, or were related to vitamin D: parity (none, 1–2, 3+ children), body-mass index (continuous), cigarette smoking (never, current, past), type 2 diabetes (yes, no), postmenopausal hormone therapy (never, current, and past use, and a further dummy variable for premenopausal women), and physical activity (quintiles). All analyses were conducted using SAS version 9.3 (SAS Institute, Cary, NC).
RESULTS:
Among the 20,560 older women (age range 58–73 years) in NHS I with mild/moderate urgency or mixed UI at baseline, 21% of women reported a daily vitamin D intake of at least 800 IU per day (Table 1a). Among the 12,573 middle-aged women (age range 42–59 years at baseline) in NHS II with mild/moderate urgency or mixed UI at baseline, 17% of women reported a daily vitamin D intake of at least 800 IU or more per day (Table 1b). Key similarities between the older and middle-aged women at baseline included similar race/ethnicity (97–99% Non-Hispanic White) across vitamin D categories, and greater self-reported physical activity among women with higher vitamin D intake levels. Current cigarette smoking was lower with greater vitamin D intake among older women and middle-aged women. In the older women, type 2 diabetes was also somewhat lower with higher vitamin D intake. Postmenopausal hormone use was slightly more common for higher vitamin D intake categories compared to low intake categories for older women and middle-aged women (Tables 1a and 1b).
Table 1a.
Nurses’ Health Study: Age-Standardized Baseline Characteristics of Women with Mild or Moderate, Urgency or Mixed UI, According to Vitamin D Intake from Supplements and Food
| Total vitamin D intake (IU) | ||||||
|---|---|---|---|---|---|---|
| 0–<200 (n=3063) |
200–<400 (n=3185) |
400–<600 (n=5214) |
600–<800 (n=4664) |
800–<1000 (n=2221) |
>=1000 (n=2213) |
|
| Age* | 70.72 (7.00) |
69.88 (6.89) |
70.65 (6.89) |
71.47 (6.77) |
71.33 (6.65) |
71.60 (6.78) |
| Race/Ethnicity | ||||||
| White, % | 97 | 98 | 98 | 99 | 97 | 98 |
| Black, % | 1 | 1 | 1 | 0 | 1 | 1 |
| Asian, % | 1 | 0 | 0 | 1 | 1 | 1 |
| Other, % | 0 | 0 | 0 | 0 | 0 | 0 |
| BMI | 27.11 (5.38) |
26.98 (5.15) |
26.53 (5.03) |
26.36 (4.91) |
26.10 (4.75) |
25.75 (4.79) |
| Physical activity | 16.75 (23.22) |
18.88 (21.71) |
20.29 (23.34) |
21.11 (23.63) |
22.97 (27.57) |
22.59 (24.37) |
| Cigarette smoking | ||||||
| never, % | 45 | 46 | 45 | 47 | 47 | 46 |
| past, % | 47 | 48 | 49 | 48 | 49 | 51 |
| current, % | 8 | 6 | 5 | 5 | 4 | 3 |
| Thiazide Diuretic use, % | 19 | 19 | 18 | 19 | 19 | 18 |
| Type 2 diabetes, % | 10 | 10 | 7 | 8 | 7 | 7 |
| Depression, % | 6 | 7 | 7 | 7 | 6 | 8 |
| Parity | ||||||
| 0, % | 6 | 6 | 6 | 6 | 6 | 7 |
| 1–2, % | 32 | 32 | 32 | 32 | 34 | 34 |
| 3+, % | 62 | 62 | 61 | 62 | 60 | 60 |
| Hysterectomy, % | 45 | 46 | 47 | 46 | 45 | 45 |
| Postmenopausal hormone use | ||||||
| never, % | 32 | 29 | 25 | 25 | 25 | 23 |
| past, % | 54 | 56 | 59 | 58 | 59 | 61 |
| current, % | 15 | 15 | 16 | 17 | 16 | 16 |
Values are means (SD) or medians (Q25, Q75) for continuous variables; percentages for categorical variables, and are standardized to the age distribution of the study population. Values of polytomous variables may not sum to 100% due to rounding.
Value is not age adjusted.
Table 1b.
Nurses’ Health Study II: Age-Standardized Baseline Characteristics of Women with Mild or Moderate, Urgency or Mixed UI, According to Vitamin D Intake from Supplements and Food
| Total vitamin D intake (IU) | ||||||
|---|---|---|---|---|---|---|
| 0–<200 (n=2669) |
200–<400 (n=2687) |
400–<600 (n=2805) |
600–<800 (n=2235) |
800–<1000 (n=1095) |
>=1000 (n=1082) |
|
| Age* | 50.53 (4.53) |
50.83 (4.59) |
51.54 (4.52) |
52.17 (4.47) |
52.67 (4.16) |
52.97 (4.09) |
| Race/Ethnicity | ||||||
| White, % | 97 | 98 | 98 | 97 | 97 | 98 |
| Black, % | 1 | 1 | 1 | 1 | 1 | 1 |
| Asian, % | 1 | 1 | 1 | 1 | 2 | 1 |
| Other, % | 1 | 0 | 0 | 1 | 0 | 1 |
| BMI | 28.48 (6.86) |
27.77 (6.48) |
28.04 (6.63) |
27.66 (6.54) |
27.21 (6.27) |
27.88 (6.42) |
| Physical activity | 18.64 (25.99) |
21.10 (24.36) |
22.35 (26.73) |
23.23 (26.40) |
23.24 (27.45) |
23.64 (26.83) |
| Cigarette smoking | ||||||
| never, % | 63 | 64 | 66 | 65 | 67 | 66 |
| past, % | 26 | 30 | 27 | 29 | 28 | 29 |
| current, % | 11 | 7 | 7 | 6 | 5 | 5 |
| Thiazide Diuretic use, % | 10 | 9 | 11 | 10 | 10 | 11 |
| Type 2 diabetes, % | 4 | 4 | 4 | 4 | 4 | 5 |
| Vascular disease, % | 0 | 0 | 0 | 1 | 1 | 0 |
| Depression, % | 16 | 14 | 15 | 16 | 16 | 19 |
| Parity | ||||||
| 0, % | 15 | 17 | 19 | 17 | 21 | 26 |
| 1–2, % | 54 | 53 | 53 | 57 | 58 | 53 |
| 3+, % | 31 | 29 | 28 | 26 | 21 | 21 |
| Hysterectomy, % | 26 | 23 | 25 | 26 | 27 | 28 |
| Postmenopausal hormone use | ||||||
| never, % | 69 | 70 | 67 | 66 | 64 | 63 |
| past, % | 17 | 17 | 18 | 18 | 19 | 19 |
| current, % | 14 | 13 | 15 | 15 | 17 | 18 |
Values are means (SD) or medians (Q25, Q75) for continuous variables; percentages for categorical variables, and are standardized to the age distribution of the study population.
Values of polytomous variables may not sum to 100% due to rounding.
Value is not age adjusted.
Between 2004 and 2012, a total of 4,853 incident cases of urgency/mixed UI progression were identified among older women (Table 3a). Between 2005 and 2013, a total of 1,378 incident cases of urgency/mixed UI progression were identified among middle-aged women (Table 3b). In age-adjusted analyses of older women, no significant associations between vitamin D intake levels and incidence of urgency/mixed UI progression were observed (Table 2). Results were similar in multivariable models that further adjusted for body mass index, physical activity, cigarette smoking, history of type 2 diabetes, and use of postmenopausal hormone therapy. For example, the relative risk of UI progression comparing women with 1000+ IU of vitamin D compared to <200IU was 1.02 (95% CI 0.91,1.14) after adjustment for age, and was 1.10 (95% CI 0.99,1.23) with multivariable adjustment.
Table 3.
Nurses’ health studies: relative risk of UI progression from mild/moderate to severe UI, according to vitamin D intake from food and supplements
| (a) Nurses’ Health Study I | ||||
|---|---|---|---|---|
| Vitamin D Intake (IU) | Cases | Person-years | Age adjusted RR (95% CI) | Multivariable-adjusted RR‡ |
| 0–<200 | 627 | 12,189 | 1.0 (ref) | 1.0 (ref) |
| 200–<400 | 672 | 12,120 | 1.08(0.97, 1.21) | 1.10 (0.99, 1.23) |
| 400–<600 | 1163 | 21,805 | 1.05 (0.95, 1.16) | 1.09 (0.99, 1.21) |
| 600–<800 | 1031 | 19,964 | 1.00 (0.91, 1.11) | 1.05 (0.95, 1.16) |
| 800–<1000 | 558 | 10,635 | 1.03 (0.92, 1.16) | 1.10 (0.98, 1.24) |
| 1000+ | 802 | 15,731 | 1.02 (0.91, 1.14) | 1.10 (0.99, 1.23) |
| P trend = 0.3 | ||||
| (b) Nurses’ Health Study II | ||||
| Vitamin D Intake (IU) | Cases | Person-years | Age adjusted RR (95% CI) | Multivariable-adjusted RR‡ |
| 0–<200 | 296 | 16,375 | 1.0 (ref) | 1.0 (ref) |
| 200–<400 | 265 | 16,275 | 0.87 (0.74, 1.03) | 0.93 (0.79, 1.11) |
| 400–<600 | 301 | 16,916 | 0.95 (0.81, 1.12) | 1.00 (0.85, 1.18) |
| 600–<800 | 265 | 14,018 | 1.00 (0.85, 1.19) | 1.08 (0.91, 1.28) |
| 800–<1000 | 125 | 7283 | 0.89 (0.72, 1.10) | 0.98 (0.79, 1.22) |
| 1000+ | 126 | 8318 | 0.80(0.65, 0.99) | 0.88 (0.71, 1.10) |
| P trend = 0.7 | ||||
Multivariable models adjusted for age, body mass index, cigarette smoking, parity, use of postmenopausal hormone therapy, physical activity.
Table 2.
Nurses’ Health Studies: Relative Risk of UI Progression from Mild/Moderate to Severe UI, According to Vitamin D Intake from Food and Supplements
| NURSES’ HEALTH STUDY | ||||
|---|---|---|---|---|
| Vitamin D intake (IU) |
Cases | Person-years | Age-adjusted RR (95% CI) | Multi-variable adjusted RR‡ |
| 0–<200 | 627 | 12,189 | 1.0 (ref) | 1.0 (ref) |
| 200–<400 | 672 | 12,120 | 1.08 (0.97, 1.21) | 1.10 (0.99, 1.23) |
| 400–<600 | 1163 | 21,805 | 1.05 (0.95, 1.16) | 1.09 (0.99, 1.21) |
| 600–<800 | 1031 | 19,964 | 1.00 (0.91, 1.11) | 1.05 (0.95, 1.16) |
| 800–<1000 | 558 | 10,635 | 1.03 (0.92, 1.16) | 1.10 (0.98, 1.24) |
| 1000+ | 802 | 15,731 | 1.02 (0.91, 1.14) | 1.10 (0.99, 1.23) |
| p-trend=0.3 | ||||
| NURSES’ HEALTH STUDY II | ||||
| Vitamin D intake (IU) | Cases | Person-years | Age-adjusted RR (95% CI) | Multi-variable adjusted RR‡ |
| 0–<200 | 296 | 16,375 | 1.0 (ref) | 1.0 (ref) |
| 200–<400 | 265 | 16,275 | 0.87 (0.74, 1.03) | 0.93 (0.79, 1.11) |
| 400–<600 | 301 | 16,916 | 0.95 (0.81, 1.12) | 1.00 (0.85, 1.18) |
| 600–<800 | 265 | 14,018 | 1.00 (0.85, 1.19) | 1.08 (0.91, 1.28) |
| 800–<1000 | 125 | 7,283 | 0.89 (0.72, 1.10) | 0.98 (0.79, 1.22) |
| 1000+ | 126 | 8,318 | 0.80 (0.65, 0.99) | 0.88 (0.71, 1.10) |
| p-trend=0.7 | ||||
Multivariable models adjusted for age, body mass index, cigarette smoking, parity, use of postmenopausal hormone therapy, physical activity.
In age-adjusted analyses of middle-aged women (Table 2), women with vitamin D intake levels of ≥1,000 IU/day had an estimated 20% lower rate of incident urgency/mixed UI progression, relative to those with vitamin D intake levels <200 IU/day (RR=0.80, 95% CI 0.65,0.99). In multivariable analyses, this relative risk was attenuated and was no longer statistically significant (RR=0.88, 95%CI 0.71, 1.10).
We conducted secondary analyses to examine the effects of vitamin D intake ≥2000IU; these were conducted only among the older women, since few younger women reported these higher levels of vitamin D intake. When we examined relative risk of urgency/mixed UI progression among the older women, comparing those with ≥2000 IU of vitamin D/day to <200 IU/day (data not shown in table), in multivariable models, we found no suggestion of any decrease in risk of urgency/mixed UI progression (RR=1.35, 95% CI 1.06, 1.73).
Since vitamin D bioavailability is lower in obese women, and thus higher vitamin D intake may be especially relevant in this population, we also conducted secondary analyses specifically in women with BMI≥30kg/m2 (data not shown in table). In general, findings in obese women were consistent with those in all women. For example, in the older women with BMI≥30kg/m2, the multivariable-adjusted relative risk of urgency/mixed UI progression among those with vitamin D intake ≥1000 IU/day versus <200 IU/day was 0.95 (95% CI 0.76, 1.19). In the middle-aged women with BMI≥30kg/m2, the multivariable-adjusted relative risk among those with vitamin D intake ≥1000 IU/day versus <200 IU/day was 0.85 (95% CI 0.61, 1.19).
DISCUSSION:
Our analyses of data from two large, well-characterized, prospective cohort studies suggest that routine intake of vitamin D is not associated with decreased progression of mild or moderate urgency and mixed UI among middle-aged and older women. NHS I and NHS II provide longitudinal follow-up data during a time period before vitamin D supplementation was more widespread in the U.S population, thus there is a good distribution of vitamin D intake, from <200 through 1000IU or more (although few women used very high levels of supplementation).
Subgroup analyses included specifically considering UI progression among women with obesity, who would be expected to have a lower bioavailable vitamin D and may benefit more from supplementation;16 however, this did not reveal an association with higher vitamin D intake either. Similarly, among older women with the highest reported intake of vitamin D (≥ 2000 IU daily), there was no evidence of benefit either. Overall, the NHS I and NHS II cohorts provide a unique opportunity to assess dose response relations across moderate levels of vitamin D intake.
Given the conflicting evidence from population-based observational studies and one small pilot intervention study linking vitamin D and urgency UI, 9,17–20 future studies may focus on identifying optimal target populations for whom vitamin D improves UI symptoms, or whether a higher optimal dose improves UI. Many existing observational studies have focused on associations in older women, 9,20 with relatively few studies among younger women, 18,19 and even less data regarding the type of UI that may benefit from vitamin D supplementation.9,17,20 In addition, the timing of vitamin D supplementation to prevent or improve existing UI may be an important consideration, as well as targeting those women with serum 25-hydroxyvitamin D deficiency. Indeed, in the one small pilot intervention study of high dose vitamin D supplementation compared to placebo, only older, black women with low serum 25-hydroxyvitamin D levels reported improvement in urgency UI symptoms.21 Better understanding of high-risk groups of women with low serum vitamin D levels and UI may help guide understanding of the appropriate target population for recommending vitamin D supplementation.
Limitations of NHS I and NHS II include a lack of racial/ethnic diversity. We were unable to determine if vitamin D intake has differential impact on UI progression in women of non-white backgrounds. Because synthesis of vitamin D3 is reduced by melanin‟s absorption of ultraviolet B radiation, those with darker skin pigmentation particularly benefit from vitamin D supplementation.22 A second limitation is the lack of data on serum 25-hydroxyvitamin D levels in NHS I and NHS II participants. However, the availability of detailed FFQ data provides robust information about vitamin D intake that has not been available in other cohorts. Further, in public health terms, better understanding the possible impact of vitamin D intake is important even in the absence of measured serum levels, as many individuals may initiate higher intake or supplementation regardless of their serum levels. Another limitation is the possible misclassification of vitamin D intake, since data were self-reported. However, we have conducted careful validation studies, comparing women‟s self-reports to detailed 7-day diet diaries completed four times during one year, and found high correlation between self-reports and the diet diaries for vitamin D from diet and supplements. Thus, any misclassification is likely small and would not meaningfully impact findings. In this observational sample, we are not able to completely eliminate the possibility that women who consumed the most vitamin D were the ones who perceived themselves to be at greatest risk for UI or other similar overlapping conditions. If so, this could partially mask a protective association between vitamin D intake and UI progression, despite the attempt to limit the effects of confounding through multivariable adjustment. Finally, we did not consider other treatment strategies, such as pelvic muscle exercises. However, we have previously found that medical care for UI is low in NHS participants,1,23 despite being nurses; thus, treatment would not likely impact our findings substantially.
These data contribute to a growing body of research suggesting vitamin D intake does not impact urinary symptoms in generally healthy middle-aged and older women.10 Because certain subgroups could be affected differently further assessment of non-white populations or women and men with documented vitamin D deficiency may provide additional opportunities to evaluate vitamin D as a potential adjunctive treatment for urgency UI. However, findings from this study do not support broad recommendations for vitamin D intake to prevent urgency or mixed UI progression in community-dwelling women.
Acknowledgements:
The study team would like to acknowledge the support of Ashley Gilmore, MSW on this project.
Disclosures: This work was supported by 1R01DK115473 from the National Institute of Diabetes and Digestive and Kidney Diseases and Nurses Health Study I is supported by UM1 CA186107 and Nurses Health Study II is supported by U01 CA 176726 from the National Institutes of Health, Bethesda, MD, USA. Dr. Tangpricha receives support from National Center for Advancing Translational Sciences of the National Institutes of Health, Award Number UL1TR002378.
Footnotes
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