Abstract
Insulin-like growth factor-I (IGF-1) is a hormone associated with multiple physiologic outcomes including increased muscle growth and repair as well as uncontrolled cell growth, i.e. cancer. Both exercise and nutritional status (in particular protein intake) have been observed to influence circulating IGF-1 concentration but the magnitude and direction of effects have been inconsistent. In addition, it was previously unknown if exercise modulated the effect of dietary protein on IGF-1 concentration or vice-versa. This PhD research consisted of four studies designed to: 1) summarise past literature on exercise and IGF-1 concentration, 2) summarise previous research on dietary protein and IGF-1 concentration, 3) assess the acute response of exercise and/or dietary protein on IGF-1 concentration, and 4) investigate cross-sectional associations between physical activity, diet, and IGF-1 concentration.
To summarise previous literature, two systematic reviews and meta-analyses were performed. The first focused on the association between total IGF-1 concentration and dietary protein in healthy adults. The intervention studies revealed increasing protein intake results in elevated total IGF-1 concentration (Cohen’s d=0.62; 95% CI -0.10 to 1.33). The cross-sectional studies demonstrated that, on average, total IGF-1 concentrations were 0.03 nmol/L higher for every 1 g/day increment in dietary protein (95% CI -0.01 to 0.07 nmol/L). Despite high levels of heterogeneity (intervention I2=87.3%, cross-sectional I2=83.4%), consistency in the direction of effect suggests dietary protein is likely to increase total IGF-1.
The second systematic review and meta-analysis focused on the association between total IGF-1 concentration and exercise in healthy adults. Based upon the acute total IGF-1 concentration response, the results indicated that endurance exercise tends to decrease total IGF-1 concentration (studies that compared pre- and post-exercise total IGF-1 concentration Cohen’s d= -0.55, 95% CI -0.86 to -0.23, I2 = 74%; studies that compared to a non-exercise control Cohen’s d= -0.37, 95% CI -0.94 to 0.20, I2= 80.4%). Results of this meta-analysis also indicated that resistance exercise increases total IGF-1 concentration (studies that compared pre- and post-exercise total IGF-1 concentration Cohen’s d= 0.21, 95% CI 0.09 to 0.34, I2= 53.6%; studies that compared to a non-exercise control Cohen’s d= 0.65, 95% CI 0.23 to 1.06, I2= 87.3%).
The acute effects of dietary protein and/or exercise on plasma free IGF-1 and the time-course thereof was investigated by conducting a three-way crossover intervention with 24 healthy participants (13 male). The three conditions consisted of: 1) exercise (four 30 s sprints interspersed with 4 min 30 s of recovery- totalling 20 min), 2) a high protein (42 g) meal and, 3) exercise immediately followed by a high protein meal. In the non-exercising condition participants sat quietly for 20 min after consuming the high protein meal. In every condition, participants provided 8 blood samples over the 5 h following the initial fasted, resting baseline blood draw. Additionally, a blood sample was taken 24 h after the initial baseline measure. While there was no difference in the area under the free IGF-1 response curve between conditions, the shape of the response differed between conditions. Specifically, free IGF-1 concentration was higher at 30 min (immediately after exercise) in the exercise condition without protein (p= 0.04) and in the protein condition without exercise, the 24 h IGF-1 concentration was 17.5% higher (p= 0.02) than at baseline. Free IGF-1 concentration did not change over time, with respect to baseline, in response to exercise with protein.
The cross-sectional relationships between dietary protein and total IGF-1 concentration as well as physical activity and total IGF-1 concentration were investigated in 60,677 healthy adults enrolled in UK Biobank. Every 1.0 g of dietary protein was associated with a 0.030 nmol/L increase in total IGF-1 concentration (95% CI 0.027 to 0.033; p< 0.001). Individuals undertaking a moderate amount of physical activity (10-50 excess MET h/week) had 0.129 nmol/L greater total IGF-1 concentration than participants completing a low amount of physical activity (less than 10 excess MET h/week) (95% CI 0.028 to 0.230). Individuals in the high category of physical activity (>50 excess MET h/week) had a total IGF-1 concentration that was not significantly different from individuals in the low category of physical activity (<10 excess MET h/week) (-0.055 nmol/L; 95% CI -0.185 to 0.076). When dietary protein and physical activity were included in the same model, physical activity did not change the relationship between dietary protein and total IGF-1 concentration, nor vice versa.
The evidence presented in this PhD thesis is an overview of the associations between physical activity, dietary protein, and/or IGF-1 concentration, as opposed to a mechanistic analysis. This overview can inform individuals seeking increased IGF-1 concentration for the purpose of increased muscle mass, or for those wanting to lower IGF-1 concentration due to increased cancer risk. The strength of the association between dietary protein and circulating total IGF-I concentration is stronger than that of physical activity and circulating total IGF-I concentration. Thus, while our research has shown that dietary protein and resistance exercise increase both total and free IGF-1 concentration and endurance exercise decreases total IGF-1 concentration, the timeframe and dose(s) that exerts the most benefit has yet to be elucidated. Future research may provide insight into measuring outcomes to determine how modifying dietary protein and/or physical activity, and thus IGF-1 concentration, influence incident rates of certain types of cancer or mortality.