Nutritional Determinants of IGF-1 Ligand Expression
As demonstrated in vitro, and given the theoretical propensity of the IGF-1 ligand to circumvent selective blockade in vivo, it becomes important to study potential determinants of elevated IGF-1 expression.
In prospective animal studies, caloric restriction has been shown to prolong overall survival. Largely as a result of these trials, Caloric Restriction Societies have been created in many major cities. Geared towards eating exactly 1800 calories per day, members religiously measure, weigh and monitor nutritional intake to ensure that they meet the recommended daily allowances of all important macro and micro nutrients (which is what distinguishes calorie restriction from anorexia). As a general rule, calorie restrictors avoid refined and processed foods, given the low nutrient/calorie ratios present.
In calorie restricted mice, levels of serum inflammatory markers and IGF-1 levels are uniformly low, with an almost 50% reduction from normal seen in IGF-1 expression1. Similarly, calorie restrictors show low levels of systemic inflammatory markers, as well as reduced body mass index measurements. Paradoxically though, in contrast to their animal counterparts, their serum IGF-1 and IGF-1/IGFBP-3 ratios are markedly elevated2.
The same researchers then studied long term raw food vegans, who were age and sex matched to their calorie restricted counterparts. Raw food vegans also avoid refined and processed foods, in addition to all forms of animal sourced foods (red meat, poultry, fish, and dairy). Though they ate an average of 600-700 more calories per day than their calorie restricted counterparts, this group had low levels of BMI, serum inflammatory markers, as well as systemic IGF-1 levels.
When looking more closely at the total macronutrient intake consumed by both groups, researchers found that the calorie restrictors consumed approximately 25% of their calories from protein2,3 while the vegan protein intake was only 10-12% of calories2. As a result of this finding, calorie restrictors who then lowered their protein intake to 10% (for a total of 3 weeks, and not by completely vegan or vegetarian means) also saw normalization of their serum IGF-1 levels2.
Both groups described represent extremes in dietary adherence, and may not reflect the general population consuming the standard american diet. In normal weight patients without cancer, who consume a regular western diet, IGF-1 as well as IGF-1/IGFBP-3 ratio are elevated at baseline2,3. In both normal and overweight/obese patients, weight loss by itself does not reduce these levels3-5.
In an analysis of data from the National Health and Nutrition Examination Survey III (NHANES III), which studied a representative sample of healthy patients in the United States, total dietary protein intake was positive correlated with serum IGF-1 concentrations, and animal protein intake was more correlated with IGF-1 concentrations than vegetable protein, though this correlation was described as weak 6.
1. Dunn SE, Kari FW, French J, et al. Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-deficient mice. Cancer Res. 1997 Nov 1;57(21):4667-72.
2. Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell. 2008 Oct;7(5):681-7.
3. Racette SB, Weiss EP, Villareal DT, et al. One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue. J Gerontol A Biol Sci Med Sci. 2006 Sep;61(9):943-50.
4. Kaaks R, Bellati C, Venturelli E, et al. Effects of dietary intervention on IGF-I and IGF-binding proteins, and related alterations in sex steroid metabolism: the Diet and Androgens (DIANA) Randomised Trial. Eur J Clin Nutr. 2003 Sep;57(9):1079-88.
5. Irwin ML, McTiernan A, Bernstein L, et al. Relationship of obesity and physical activity with C-peptide, leptin, and insulin-like growth factors in breast cancer survivors. Cancer Epidemiol Biomarkers Prev. 2005 Dec;14(12):2881-8.
6. Sankey MR, LDN. IGF-1 AND IGFBP-3 LEVELS IN INDIVIDUALS WITH VARIED KIDNEY FUNCTION AND THE RELATION TO DIETARY PROTEIN INTAKE: Bowling Green State University, 2009. 73 p.