The Safety of Insulin-Like Growth Factor-I (IGF-I)

Dr. Normand St-Pierre, Dairy Management Specialist, The Ohio State University

Summary

  • The IGF-I in human plasma is found at concentrations that are 10.5 to 77 times greater than that in bovine milk.
  • The IGF-I concentration in bovine milk is quite variable regardless of whether the animals are supplemented with rbST or not. Many factors such as herd, stage of lactation, parity, and diet affect IGF-I concentrations to a greater extent than rbST supplementation.
  • Compared to gastrointestinal secretions in adults, bovine milk has in fact a very low IGF-I concentration. Daily ingestion from saliva and other digestive secretions in a normal adult equals the amount of IGF-I found in 95 quarts of milk.
  • Endogenous daily IGF-I secretions (i.e., body production) equal the IGF-I found in 3000 quarts of milk.
  • There has been some reports documenting an association between serum IGF-I and the risk of certain cancers. It is generally thought that the cancer cells are responsible for the elevated serum IGF-I and not the other way around. Regardless, the total daily IGF-I intake from milk is so low compared to endogenous secretions (less than 1% assuming that all IGF-I consumed is absorbed) that it seems highly unlikely that cancer would be directly related to IGF-I intake.

Details

One area of concern regarding the safety of rbST is that IGF-I in milk results in elevated IGF-I levels in humans after they consume milk from cows supplemented with rbST. The Food and Drug Administration (FDA) maintained and continues to maintain that "levels of IGF-I in milk whether or not from rbGH supplemented cows are not significant when evaluated against the levels of IGF-I endogenously produced and present in humans".

  • The IGF-I is normally found in human plasma at concentrations much higher than those found in bovine milk (Schaff-Blass et al., 1984). The levels in human plasma range from a low in neonates of 14 ng/mL to a high of 686 ng/mL in late pubertal females. The mean values of IGF-I concentrations in human plasma are between 42 and 308 ng/mL.
  • The mean serum IGF-I concentration in cows not supplemented with rbST is approximately 4 ng/mL at mid lactation (Collier et al., 1991). In this survey of 100 bulk tanks from farms not utilizing exogenous somatotropin supplementation, the mean IGF-I concentration was found at 4.3 1.1 ng/mL, with a range of 1.3 to 8.1 ng/mL. In another study (Juskevich and Guyer, 1990), milk samples from 5 commercial dairy herds not supplemented with rbST had a mean IGF-I concentration of 2.54 ng/mL.
  • Reported percentage increases in IGF-I concentrations in milk of rbST supplemented cows are deceiving and misleading because the levels of IGF-I in milk are so low prior to any increase. The IGF-I concentration in milk of rbST supplemented cows is increased by 2 to 3 ng/mL (Juskevich and Guyer, 1990; Torkelson et al., 1988), thus leading to the 50 to 100% increase often stated. Nowhere can one find in the scientific literature a 10- fold increase (1000 %) in serum IGF-I concentration from rbST supplementation as has been stated in public comments and various internet sites. In addition, the effect of farm, parity, and stage of lactation have a greater effect on serum IGF-I concentrations than rbST supplementation (Collier et al., 1991).
  • The total daily production of IGF-I (the endogenous production) in an adult is approximately 10,000,000 ng/day (Guler et al., 1989). Gastrointestinal secretions in adults are estimated at 357,400 ng/day (Chaurasia et al. 1994; Vander, Sheman and Luciano (ed.), 1990). Thus, the daily IGF-I from saliva and other digestive secretions equal the IGF-I in 95 quarts of milk. The IGF-I from whole body production equal to the IGF-I in 3,000 quarts of milk. Milk is just a very low source of oral IGF-I. In fact, the IGF-I concentration in saliva is more than 50% greater than that of milk.
     

Table 1. Volume and IGF-I concentrations in gastrointestinal secretions of human adults.

Secretion
Volume
(mL/day)
Concentration (ng/mL)
Range
Average
Saliva
1500
2.8 - 9.1
6.3
Gastric juice
2000
11.2 - 73.5
24.5
Intestinal secretions
1500
22.4 - 294.7
172.2
Pancreatic juice
1500
3.5 - 56.7
25.2
Bile
500
4.2 - 7.7
6.3

 

  • The IGF-I comprise one-tenth of one millionth of total milk proteins. It is digested in the gastrointestinal tract like other dietary protein. There is little to no direct absorption of IGF-I (NIH, 1990; Houle et al, 1995; Phillips et al., 1995). In fact, a massive dose of IGF-I administered orally (8.45 µg/day) resulted in an increase of less than 5 nmol/L in serum IGF-I in training athletes (Mero et al. 1997). Interestingly, a one hour training session has a greater impact on serum IGF-I than the oral supplement.
  • The IGF-I is normally found in human breast milk in concentrations higher than those found in bovine milk. The IGF-I concentrations in human milk ranged between 13 and 40 ng/mL (Corps et al., 1988; FDA, 2000). These levels are 3.25 to 15.7 times greater than those of bovine milk.
  • There has been some reports of increased IGF-I serum concentrations after humans consume milk (e.g., Heaney et al. 1999). The IGF-I increased observed in this study must be viewed in light of the total daily adult endogenous production of IGF-I, which is in the milligram range while the daily levels of IGF-I consumed in milk are in the microgram range - this is a thousand fold difference (FDA, 2000). Even if all the IGF-I in 1.5 liters of milk was directly absorbed - which it is not - the plasma IGF-I would be altered by a maximum of 1%. Well-controlled studies have reported no significant change in serum IGF-I levels over a 2 year period for women supplemented with four 8-ounce glass of milk for the duration of the trial (Storm et al., 1998).
  • Some have asserted a connection between increases in levels of IGF-I and breast, prostate, and lung cancer (Chan et al., 1998; Hankinson et al., 1998; Yu et al., 1999). These papers note a possible relationship between increased risks for these cancers and elevated levels of IGF-I, but none of them showed a causal relationship. In fact, one paper states "that the increased IGF-I plasma levels may be part of the phenotype [i.e., expression] of certain types of cancer." Thus, the cancerous cells themselves may promote IGF-I to maintain accelerated cell cycle (FDA, 2000). The presence of oxygen (air) is essential to start and maintain a fire, but it does not cause the fire. In addition, these cancers generally appear much later in life than peak IGF-I which occurs in late puberty. Also, strenuous exercise increases IGF-I concentrations without having any positive association with these cancers.

(References are available on request.)