Protein is a Stimulator of Free IGF-1

It seems that protein (in meat or dairy) is a stimulator of free-IGF-1


Aging Cell. 2008 Oct;7(5):681-7.
Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans.

Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO.

Division of Geriatrics & Nutritional Sciences, Washington University School of Medicine, St Louis, MO 63110, USA.


Reduced function mutations in the insulin/IGF-I signaling pathway increase maximal lifespan and health span in many species. Calorie restriction (CR) decreases serum IGF-1 concentration by ~40%, protects against cancer and slows aging in rodents. However, the long-term effects of CR with adequate nutrition on circulating IGF-1 levels in humans are unknown.

Here we report data from two long-term CR studies (1 and 6 years) showing that severe CR without malnutrition did not change IGF-1 and IGF-1 : IGFBP-3 ratio levels in humans. In contrast, total and free IGF-1 concentrations were significantly lower in moderately protein-restricted individuals. Reducing protein intake from an average of 1.67 g kg(-1) of body weight per day to 0.95 g kg(-1) of body weight per day for 3 weeks in six volunteers practicing CR resulted in a reduction in serum IGF-1 from 194 ng mL(-1) to 152 ng mL(-1).

These findings demonstrate that, unlike in rodents, long-term severe CR does not reduce serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio in humans. In addition, our data provide evidence that protein intake is a key determinant of circulating IGF-1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti-aging dietary interventions.



Dietary correlates of plasma insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations.
Cancer Epidemiol Biomarkers Prev. 2002 Sep;11(9):852-61.
Dietary correlates of plasma insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations.

Holmes MD, Pollak MN, Willett WC, Hankinson SE.

Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts 02115, USA.

Plasma levels of insulin-like growth factor I (IGF-I) have been associated with risk of several cancers. Although protein-calorie malnutrition is known to decrease IGF-I levels, few published studies have related diet to IGF-I levels in well-nourished humans.

We examined the cross-sectional association of plasma IGF-I and IGF-binding protein 3 (IGFBP-3) levels with intakes of alcohol, energy, macronutrients, micronutrients, and specific foods in 1037 healthy women. Adjusted mean hormone levels across categories of dietary variables were calculated by linear regression. Results were adjusted for non-dietary factors found to be associated with IGF levels.

Total energy intake was positively associated with IGF-I levels when adjusted for covariates. Adjusted mean levels of IGF-I (ng/ml) across increasing quintiles of energy intake were 181, 185, 191, 199, and 195 (P for the linear trend = 0.006). In other multivariate analyses, energy-adjusted fat and carbohydrate intake had no association with IGF-I levels. The most consistent finding was a positive association between protein intake with circulating IGF-I concentration (174, 188, 201, 192, and 196 ng/ml across quintiles of protein intake; P = 0.002), which was largely attributable to milk intake. Adjusted mean levels of IGF-I (ng/ml) across increasing quartiles of milk intake were 183, 189, 188, and 200 (P = 0.01).

Higher fat intake, in particular saturated fat, was associated with lower levels of IGFBP-3. We conclude that higher energy, protein, and milk intakes were associated with higher levels of IGF-I. These associations raise the possibility that diet could affect cancer risk through influencing IGF-I level.

PMID: 12223429 [PubMed - indexed for MEDLINE]


Dietary Correlates of Plasma Insulin-like Growth Factor I and-852.full.pdf


Cancer Epidemiol Biomarkers Prev. 2003 Aug;12(8):739-46.
Determinants of circulating insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations in a cohort of Singapore men and women.

Probst-Hensch NM, Wang H, Goh VH, Seow A, Lee HP, Yu MC.

University Hospital Zürich, Cancer Registry Zürich, Zürich, Switzerland.


Variation in the circulating concentrations of the insulin-like growth factor (IGF) system has been implicated in the etiology of chronic diseases including cancer (prostate, breast, colon, and lung), heart disease, type 2 diabetes, and osteoporosis.

We searched for sociodemographic, anthropometric, reproductive, lifestyle, and dietary determinants of IGF-I and insulin-like growth factor binding protein (IGFBP) -3 serum concentrations. Serum samples were collected in a Singapore Chinese cohort with a mean age of 61 years. Subject information was assessed during an in-person interview. Radioimmunometrically measured IGF-I and IGFBP-3 concentrations were available for 312 men and 326 postmenopausal women ages 50 years or older. Mean IGF-I concentrations were 144 ng/ml and 121 ng/ml for men and women, respectively (gender difference, P < 0.0001), and mean IGFBP-3 concentrations were 3710 ng/ml and 4147 ng/ml for men and women, respectively (gender difference, P < 0.0001). IGF-I and IGFBP-3 decreased with age (P for trend <0.0001); the age-related decrease in the IGF-I:IGFBP-3 molar ratio was stronger in women than men.

IGF-I concentrations were higher among physically inactive subjects and among women with an early age at menarche. Consumption of saturated fat was found to decrease, and intake of omega-3 polyunsaturated fatty acids and of dietary fiber was found to increase circulating IGFBP-3 concentrations.

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Intake of calcium from food and supplement was associated positively with circulating IGF-I, IGFBP-3, and molar ratio. Intake of soy was associated positively with IGF-I and molar ratio concentrations, but only in men.

The results of this study lend additional support to the hypothesis that circulating IGF-I concentrations increase the risk of prostate, bladder, colorectal, and breast cancer.

PMID: 12917205 [PubMed - indexed for MEDLINE]


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Public Health Nutr.  2003 Apr;6(2):175-80.

The influence of dietary intake on the insulin-like growth factor (IGF) system across three ethnic groups: a population-based study.

Heald AH, Cade JE, Cruickshank JK, Anderson S, White A, Gibson JM.

Department of Diabetes, University of Manchester, Salford Royal Hospitals University Trust, Hope Hospital, Stott Lane, Greater Manchester M6 8HD.


OBJECTIVE: The insulin-like growth factor (IGF) system has been implicated in the aetiopathogenesis of cancer, cardiovascular disease and diabetes. Since dietary factors and ethnicity are considered contributory to the development of these diseases, we examined the IGF system in relation to nutritional intake by ethnic group. DESIGN,

SUBJECTS AND SETTING: Dietary intake in 257 subjects of White European, African-Caribbean and Pakistani ethnic origin living in Manchester, UK was assessed using ethnic-group-specific food-frequency questionnaires to assess habitual nutrient intake over the previous 12 months. Fasting IGF-I, IGF-II and IGF-binding protein-1 (IGFBP-1) concentrations were determined and their relationship to specific dietary constituents was analysed.

RESULTS: Analysis by quintiles of nutrient intake showed a significant increase in circulating IGF-I concentration with increasing dietary fat intake (F for trend=3.9, ), saturated fat intake and for protein intake There was also a significant increase in IGF-II by quintiles of dietary protein intake There was a trend for increasing IGF-I with increasing energy intake.

The relationships between circulating concentration of IGFBP-1, an acute regulator of IGF action, and fat/protein intake were opposite to those for IGF-I and IGF-II.

Multiple linear regression modelling showed that people of Pakistani origin and older subjects had lower levels of IGF-I (Pakistani origin vs. others, ) (age, for both). There was an independent inverse relationship between IGF-I and dietary carbohydrate intake

CONCLUSIONS: This study provides evidence for a dietary contribution to regulation of the IGF system, although the effects of ethnicity on circulating IGF levels remain dominant. We propose that the IGF system’s influences on cancer risk in specific ethnic groups are potentially modifiable by dietary intervention.

PMID: 12675960 [PubMed - indexed for MEDLINE]


The associations of diet with serum insulin–like growth factor I and its main binding proteins in 292 women meat–eaters, vegetarians, and vegans.

Cancer Research United Kingdom Epidemiology Unit, University of Oxford, Oxford OX2 6HE, United Kingdom.


The lower rates of some cancers in Asian countries than in Western countries may be partly because of diet, although the mechanisms are unknown. The aim of this cross-sectional study was to determine whether a plant-based (vegan) diet is associated with a lower circulating level of insulin-like growth factor I (IGF-I) compared with a meat-eating or lacto-ovo-vegetarian diet among 292 British women, ages 20-70 years.

The mean serum IGF-I concentration was 13% lower in 92 vegan women compared with 99 meat-eaters and 101 vegetarians (P = 0.0006). The mean concentrations of both serum IGF-binding protein (IGFBP)-1 and IGFBP-2 were 20-40% higher in vegan women compared with meat-eaters and vegetarians (P = 0.005 and P = 0.0008 for IGFBP-1 and IGFBP-2, respectively). There were no significant differences in IGFBP-3, C-peptide, or sex hormone-binding globulin concentrations between the diet groups.

Intake of protein rich in essential amino acids was positively associated with serum IGF-I (Pearson partial correlation coefficient; r = 0.27; P < 0.0001) and explained most of the differences in IGF-I concentration between the diet groups.

These data suggest that a plant-based diet is associated with lower circulating levels of total IGF-I and higher levels of IGFBP-1 and IGFBP-2.

PMID: 12433724 [PubMed - indexed for MEDLINE]

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2 Responses to “Protein is a Stimulator of Free IGF-1”

  1. Free-IGF-1 lowers SHBG | Acne, Polycystic Ovarian Syndrome, Hyperinsulinemia and Diet | World Hair Research Says:

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