IGF-1, Milk and Cancer

U.S. Food and Drug Administration
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Excerpts of IGF-1 and milk related statements and documents

The Canadian report indicates that milk from rbGH-treated cows contains significantly elevated levels of insulin-like growth factor I (IGF-I) in milk, and presents human health safety concerns. IGF-I is a protein normally found in all humans, and is not intrinsically harmful. IGF-I is necessary for normal growth, development, and health maintenance. Circulating plasma levels of the hormone increase from birth to late puberty and subsequently decline in adults to approximately 100 ng (10-9 grams)/ml (range = 42 - 308 ng/ml for men and women >23 yrs). IGF-1 is structurally similar to insulin and, like insulin, is not biological effective following oral administration.

The safety of IGF-I in milk was thoroughly considered by FDA in its review of the Posilac application. Some early studies suggested that treatment of dairy cows with rbGH produced a slight, but statistically significant, increase in the average milk IGF-I concentration. FDA determined that this modest increase in milk IGF-I concentration was not a human food safety concern because it was less than the natural variation in milk IGF-I levels observed during lactation and was less than the fluctuation observed in milk from treated and control cows prior to rbGH administration.

Since making that analysis, however, FDA has received and reviewed several more comprehensive studies designed to ascertain the effect of rbGH treatment on milk IGF-I levels. These studies have demonstrated that the levels of IGF-I found in milk from treated cows are within the range of those normally found in milk from untreated cows. In 1993, the JECFA Committee concluded, “the most definitive and comprehensive studies demonstrate that IGF-I concentrations [in milk] are not altered after rbGH treatment”. The 1998 JECFA Committee report summarized a study showing no significant difference in commercially available milk labeled as coming from non-rbGH treated cows and milk from cows presumed to be treated with rbGH but not labeled as to treatment.

A recent study(6) has been published on the association between prostate cancer and IGF-I. This study showed a positive correlation between the level of IGF-I in plasma and the increased risk of prostate cancer. Although the mechanism responsible for induction of cancer has not been characterized fully, it is clear that IGF-I is not the causative agent.

FDA has examined the literature and finds no definitive evidence of any direct link between IGF-I and breast cancer. Some authors have hypothesized a link, whereas others have expressed that while IGF-I is one of several growth factors and hormones that can contribute to an increase in cell numbers of many cell types invitro, no one factor is responsible for changing normal cells into cancerous cells. Furthermore, FDA has been advised that there is no substantive evidence that IGF-I causes normal breast cells to become cancerous.(7)

In evaluating the potential for human health risk from a natural component of the body, one can examine the effect of an increased exposure to IGF-I by employing several assumptions (i.e., IGF-I levels in milk from rbGH-treated cows are increased from 4 ng/ml to 6 ng/ml, all of the IGF-I in milk is absorbed into the body, and absorbed IGF-I is confined to the vascular compartment). Assuming 5000 ml blood plasma volume in a 60 kg person and assuming this person consumes 1.5 liters of milk containing 9000 ng IGF-I from rbGH-treated cows (as opposed to 6000 ng IGF-I in milk from untreated cows), the maximum increase in blood IGF-I would be less than 2 ng/ml of which only one-third could be attributed to the use of rbGH. This minute increase would dilute into the endogenous pool of circulating IGF-I. IGF-I entering the circulation is rapidly bound to serum binding proteins which attenuate the biological activity.(8)

It bears repeating that the assumptions that milk levels of IGF-I are increased following treatment with rbGH and that biologically active IGF-I is absorbed into the body are not supported by the main body of science. Careful analysis of the published literature fails to provide compelling evidence that milk from rbGH-treated cows contains increased levels of IGF-1 compared to milk from untreated cows. Despite recent studies that demonstrate that milk proteins protect IGF-I from digestion, the vast majority of the published work indicates that very little IGF-I is absorbed following ingestion. The most recent 1998 review by the JECFA concluded that, “the concentration of IGF-I in milk from rbGH-treated cows is orders of magnitude lower than the physiological amounts produced in the gastrointestinal tract and other parts of the body. Thus, the concentration of IGF-I would not increase either locally in the gastrointestinal tract or systemically, and the potential for IGF-I to promote tumor growth would not increase when milk from rbGH-treated cows was consumed; there is thus no appreciable risk for consumers.”

What about the possibility that insulin-like growth factor 1 in milk from treated cows will lead to increased rates of breast cancer and other human health problems?

FDA and other scientific and regulatory bodies have thoroughly examined the safety of milk produced by rbST-treated cows and have concluded that it is safe. There is absolutely no possibility that the consumption of milk from rbST-treated cows could increase the risk of breast cancer. Insulin-like growth factor 1 (lGF-1) is a natural protein which mediates many of somatotropin’s actions. It is required for normal growth and possibly health maintenance. IGF-1 is structurally and chemically similar to insulin and is normally present in most body tissues and fluids including human breast milk and saliva.

The consumption of dietary IGF-1 plays no role in either inducing or promoting any human disease, nor does it cause malignant transformations of normal human breast cells. Abnormally low levels of IGF-1 are associated with several disease conditions including dwarfism, malnutrition, osteoporosis and infertility. It has also been suggested that a decline in IGF-1 levels in human tissue causes many of the degenerative changes associated with aging.

Levels of IGF-1 in cow’s milk and meat are very much lower than the levels found naturally in human blood and other body tissues. The IGF-1 occurs naturally in human breast milk at about the same concentration as that found in cow’s milk. FDA has reviewed several comprehensive studies to determine if administering rbST in cows affects the IGF-1 content of their milk. These studies have demonstrated that rbST does not increase the IGF-1 content above levels normally found in milk of non-treated animals.

IGF-1 in milk and meat is not absorbed intact. Dietary IGF-1 in milk and meat is broken down in the gastrointestinal tract by digestion. Undigested IGF-1 is excreted in the feces.

The suggestion that IGF-1 in milk can induce or promote breast cancer in humans or premature growth stimulation in infants is scientifically unfounded. Milk from rbST-treated cows is safe for human consumption.