“As in our 1-year CR study, we found that there were no differences in serum IGF-1 and IGFBP-3 concentrations, and IGF-1 : IGFBP-3 ratio between the CR and Western diet groups.... These data provide evidence that, in contrast to the decrease in IGF-1 in rodents, a reduction of IGF-1 expression is not a component of the adaptive response to long-term CR in humans.”
Wednesday, October 5, 2011
Dietary Protein, IGF-1, and Hyperinsulinemic Diseases of Civilization
In their paper, “Hyperinsulinemic diseases of civilization: more than just Syndrome X,” Loren Cordain, Michael Eades, and Mary Dan Eades argue that dietary carbohydrate intake, particularly of refined sugars, promotes hyperinsulinemia, which in turn raises levels of insulin-like growth factor-1 (IGF-1) and androgens, while reducing levels of insulin-like growth factor-binding protein-3 (IGFBP-3) and sex hormone-binding globulin (SHBG).
These endocrine system changes create an environment that promotes cell proliferation and growth, acne, early menarche, epithelial cell cancers (breast, prostate, and colon), increased stature, myopia, cutaneous papillomas (skin tags), acanthosis nigricans, polycystic ovary syndrome (PCOS) and male vertex balding.
Effect of Protein Intake on IGF-1: Experimental Results
In “Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans,” Fontana et al report on their studies of the effect of either caloric restriction or protein restriction on these endocrine markers in humans. 
In one study, they compared the effects of three interventions:
1) 20% caloric restriction with no change in energy expenditure (CR)
2) 20% increase in energy expenditure with no change in caloric intake (EX)
3) healthy lifestyle control group with no specific manipulation of energy balance (HL)
All three groups consumed diets supplying about 16% of energy as protein.
After one year, although both the CR and the EX interventions produced substantial and similar changes in body mass (~ 6 kg lost) and body fat percentage (~ 23% decrease), neither intervention reduced levels of IGF-1 or increased IGFBP-3. This contrasts with rodent studies, wherein caloric restriction does reduce IGF-1 and increase IGFBP-3.
In the second study, they compared the IGF-1 and IGFBP-3 levels in members of the Caloric Restriction Society (CR) who had been practicing caloric restriction for an average of 6 years, with those of age-matched controls consuming a typical Western diet (WD). The CR group averaged only 1800 kcal per day with 24% of energy from protein and 28% from fat, while the WD group averaged 2500 kcal per day with 16% from protein and 34% from fat.
Thus, the CR group averaged 108 g of protein daily, and the WD group 100 g of protein daily, both at least twice the required amount for a 150 pound male.
In contrast to these findings, Fontana et al note that fasting for 10 days markedly reduces IGF-1 into the range found in growth hormone deficient patients, and this correlates closely with the excretion rate for urea, a marker for nitrogen balance and thus protein intake.
Consequently, Fontana et al did a third study “comparing the serum IGF-1 and IGFBP-3 concentrations, and IGF-1 : IGFBP-3 ratio in 28 vegans who had been consuming a moderately protein-restricted (PR) diet (0.76 g kg−1 per day; ~10% of intake from protein) for ~5 years age-matched with 28 members of the Calorie Restriction Society who consume a high-protein diet (1.73 g kg−1 per day; ~24% of energy intake from protein).”
The vegan/PR group had an average protein intake of 50 g per day, while the CR group averaged twice as much, 106 g per day.
Fontana et al found that “Both serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio were significantly lower in the moderately PR diet group than in the severe CR diet group, whereas fasting insulin and C-reactive protein were similarly low in the moderately low-protein vegan and CR groups.’
In other words, the vegan/PR group had the most favorable IGF-1 and IGFBP-3 levels, while also having low serum insulin and C-reactive protein comparable to the CR group, without enduring caloric restriction.
This table compares the values of the PR group to the CR group:
The low protein group had an IGF-1 level 21% lower than the low calorie group
Of interest, the “serum total and free IGF-1 concentrations were lower in the moderately PR group than in the severe CR high-protein diet group, despite the PR groups’ higher body weight, BMI and body fat content.”
This raised the possibility that the higher protein intake of the CR group prevented desired declines in IGF-1, so Fontana et al performed a fourth study. They had 6 CR volunteers to reduce their protein intake from 1.67 g/kg per day to 0.95 g/kg per day, a 43% reduction, while maintaining caloric intake constant. The 0.95 g/kg/d level of intake still exceeds the reference daily intake of 0.83 g/kg/d, which covers the needs of 98% of the population.
As a result of this reduction of protein intake, the CR volunteers had an average 25% reduction in IGF-1 levels, confirming the hypothesis that high protein intake prevents reduction of IGF-1 levels even in the context of caloric restriction.
This then suggests that high protein intake may raise IGF-1 levels and thus promote all the diseases that Cordain, Eades, and Eade linked to elevated IGF-1 and androgens and reduced IGFBP-3 and SHBG: acne, early menarche, epithelial cell cancers (breast, prostate, and colon), increased stature, myopia, cutaneous papillomas (skin tags), acanthosis nigricans, polycystic ovary syndrome (PCOS) and male vertex balding.
Another question arises from this research: Since the vegans had lower IGF-1 levels than the omnivorous CR group, and plant proteins have different amino acid profiles than animal proteins, I wonder if plant protein has a different effect on IGF-1 than animal protein?
Who eats a high protein diet?
Most people do not understand that the reference daily intake (RDI) is not a minimum requirement. In fact, the RDI for protein, 0.83 g/ kg of body weight per day, is calculated to cover the needs of the people in the 98th percentile of requirements.
Many people require substantially less protein than the RDI. The median requirement for the general population actually only amounts to 0.65 g/kg per day, about 20% less than the RDI. [ 4 ]
For a 150 pound (68 kg) male with 10% body fat, this translates to a requirement of 40 to 50 g of protein daily. NHANES data suggests that half of U.S. males consume 40% more than the RDI level of protein, which means that many consume more than twice as much protein as they actually require.
When I ate a meat-based paleo diet, my protein intake ranged from 130 -190 g per day, two to four times the maximum requirement of someone with my bodyweight; which according to human protein requirements research  amounts to an excessive protein intake.
According to this research, I probably had an elevated IGF-1 level and ratio to IGFBP-3.