Low cardiorespiratory fitness and low serum 25-hydroxy vitamin D (25[OH]D) levels are associated with increased cardiovascular and all-cause mortality, but whether low 25(OH)D is independently associated with cardiorespiratory fitness in healthy adults is not known. We examined 25(OH)D levels and fitness in 200 healthy adults participating in a double-blind clinical trial investigating statins and muscle performance (STOMP study). Maximal aerobic exercise capacity (V o 2max ) was measured using metabolic gas analysis during graded treadmill exercise to exhaustion. 25(OH)D was measured using an enzyme-linked immunosorbent assay. Daily physical activity was assessed using the Paffenbarger Physical Activity Questionnaire. Serum 25(OH)D concentration was positively related to V o 2max (r = 0.29, p = 0.0001), even after adjusting for relevant predictors (e.g., age, gender, and body mass index). There was also a significant interaction between 25(OH)D level and self-reported hours of moderate to vigorous physical activity (MVPA; p <0.02). With each SD increase in 25(OH)D, V o 2max increased by 2.6 ml/kg/min (p = 0.0001) when MVPA was low (16 hours/week) and 1.6 ml/kg/min (p <0.0004) when MVPA was moderate (35 hours/week) but only 0.01 ml/kg/min (p = 0.9) when MVPA was high (64 hours/week). In conclusion, serum 25(OH)D levels predict V o 2max in adults; the effect is greatest in those with low levels of physical activity.
Vitamin D (25[OH]D) deficiency is present in approximately 50% of adults in the United States and is associated with increased cardiovascular (CV) events and overall mortality. Vitamin D deficiency may affect CV morbidity and mortality by its effect on CV risk factors such as increased blood pressure and incidence of type 2 diabetes. Poor cardiorespiratory fitness is an additional independent risk factor for CV morbidity and mortality, and cardiorespiratory fitness, measured as maximal oxygen consumption (V o 2max ), has recently been shown to be directly related to serum vitamin D in 59 healthy young women. The present study examined the relation of 25-hydroxy vitamin D (25[OH]D) levels to cardiorespiratory fitness in a larger cohort of men and women.
Methods
Baseline data were collected on 200 adults free of overt CV and metabolic disease who were participating in a double-blind clinical trial investigating the effect of STatin Medications On skeletal Muscle Performance (STOMP study). Subjects were not taking medications known to affect serum lipids, blood pressure, or muscle metabolism. Before statin or placebo treatment, subjects completed 3 study visits over a period of 2 weeks. Participants underwent a modified Balke treadmill test to determine V o 2max . V o 2max and ventilatory threshold were determined using breath-by-breath analysis of expired gases with a Parvomedics TrueOne 2400 metabolic cart (ParvoMedics Corporation, Sandy, Utah). Subjects fasted for 8 to 12 hours before the test. Attainment of V o 2max was affirmed when subjects met 3 of 4 criteria: plateau of oxygen uptake (defined as <50 ml/min increase with 1% increase in treadmill grade), attainment ±10 beats/min of age-predicted maximal heart rate, volitional exhaustion (defined as a rating of perceived exertion ≥18), and a calculated respiratory exchange ratio >1.10.
Subjects’ daily physical activity levels at baseline were documented using the Paffenbarger Physical Activity Questionnaire. Subjects reported their average hours of physical activity over the course of the week to identify hours of sedentary, light, moderate, and vigorous activities (question 8, Paffenbarger Physical Activity Questionnaire). Vigorous activities were defined as any strenuous sports, jogging, aerobic exercise, bicycling on hills, and similar activities. Moderate activities were defined as lighter sports, regular walking, golf, and house and yard work. Total hours of moderate to vigorous physical activity (MVPA) per week were used to examine the relation among 25(OH)D, cardiorespiratory fitness, and daily physical activity. Body weight was measured using a calibrated balance beam scale. Height was determined using a wall-mounted tape measure. Serum 25(OH)D, which measures combined serum vitamin D2 and D3 levels, was determined using blood collected at the first study visit using a standard enzyme-linked immunosorbent assay protocol (Clinical Laboratory Partners, Newington, Connecticut). The seasons in which the 25(OH)D level was measured were recorded to account for potential seasonal variation in 25(OH)D levels. The seasons were defined as winter (December to February), spring (March to May), summer (June to August), and fall (September to November).
The response variable of interest was cardiorespiratory fitness (V o 2max ). Independent variables included age, MVPA, 25(OH)D, body mass index (BMI), gender, cigarette smoking, and season. Means ± SDs were calculated for all continuous variables; frequencies and percentages were reported for all categorical variables. Bivariable associations were assessed using simple linear regression and t tests. Analysis of covariance was used to evaluate the relation between V o 2max and serum 25(OH)D level after controlling for clinically and statistically significant predictors. Two-way interactions between predictors were considered in our analysis of covariance models. All analyses were performed using SAS 9.1.3 (SAS Institute, Cary, North Carolina).
Results
Data from 200 healthy adults were analyzed, of whom 108 (54%) were women and 22 (11%) were long-term smokers ( Table 1 ). 25(OH)D levels were directly related to V o 2max (r = 0.29, p <0.0001; Figure 1 ). V o 2max was also significantly correlated with age (r = −0.58, p <0.0001) and BMI (r = -0.24, p = 0.0005). We also compared mean V o 2max levels among 25(OH)D-deficient (≤20 ng/ml, n = 29, 15%), 25(OH)D-insufficient (20 to 30 ng/ml, n = 52, 26%), and 25(OH)D-sufficient (>30 ng/ml, n = 119, 59%) groups and documented higher V o 2max values in the 25(OH)D-sufficient group ( Figure 2 ). The relation between 25(OH)D level and V o 2max remained statistically significant even after adjusting for gender (p = 0.001), age (p = 0.0001), BMI (p = 0.0001), and MVPA (p = 0.05). Seasonal variation (p = 0.7) and tobacco use (p = 0.2) were not significantly associated with V o 2max . There was also a statistically significant interaction between 25(OH)D level and MVPA (p <0.02), indicating that the effect of 25(OH)D level on V o 2max is modified by hours of MVPA. Consequently, we reanalyzed the effect of 25(OH)D on V o 2max by percentiles of physical activity. Mean hours of MVPA at the 25th (<23 hours/week, n = 49), 25th to 75th (23 to 48 hours/week, n = 103), and 75th (>48 hours/week, n = 48) percentiles were 16, 35, and 64 hours/week, respectively. Including these mean values in the model showed that for each SD (13 U) increase in 25(OH)D, V o 2max increased by 2.6 ml/kg/min (p <0.0001) when MVPA was low, 1.6 ml/kg/min (p <0.0004) when MVPA was moderate, and only 0.01 ml/kg/min (p = 0.9) when MVPA was high ( Figure 3 ).
| Variable | Total | Men (n = 92) | Women (n = 108) | p Value ⁎ |
|---|---|---|---|---|
| Maximal oxygen uptake (ml/kg/min) | 34 ± 10.3 | 40 ± 9.1 | 30 ± 8.5 | <0.01 |
| Age (years) | 40 ± 14.4 | 39 ± 15.2 | 42 ± 13.9 | 0.12 |
| Serum 25-hydroxy vitamin D (ng/ml) | 34 ± 13.3 | 33 ± 11.3 | 35 ± 14.6 | 0.44 |
| Waist circumference (cm) | 85 ± 13.7 | 92 ± 12.2 | 80 ± 11.9 | <0.01 |
| Body mass index (kg/m 2 ) | 26 ± 5.1 | 27 ± 4.5 | 26 ± 5.3 | 0.01 |
| Moderate to vigorous physical activity (hours/week) | 37 ± 19 | 36 ± 17.0 | 38 ± 20.0 | 0.56 |
| Season (serum 25-hydroxy vitamin D measurement) | 0.7 | |||
| Spring | 71 (35%) | 31 (34%) | 40 (37%) | |
| Summer | 53 (26%) | 27 (29%) | 26 (24%) | |
| Fall | 30 (15%) | 15 (16%) | 15 (14%) | |
| Winter | 46 (23%) | 19 (21%) | 27 (25%) |
