Insulin-like growth factor 1 (IGF-1)
Insulin-like growth factor 1 (IGF-1) is a hormone produced in the liver and body tissues of mammals. One important role for IGF-1 is to promote cell growth and division, this is important for normal growth and development. It plays an important role in childhood growth and continues to have anabolic effects (the building up of organs and tissues) in adults.
IGF-1 from cows is identical to human IGF-1 in that the amino acid sequence of both molecules is the same (Honegger and Humbel, 1986). Amino acids are the building blocks of proteins and there are 20 different amino acids. All proteins consist of amino acids joined together like beads on a string and the nature of the protein (how it behaves) is determined by the order in which the amino acids occur along the string. In both human and bovine IGF-1 the same 70 amino acids occur in exactly the same order, which may or may not have a significant impact on human health (see below). As previously stated, the use of recombinant bovine somatotrophin (rBST) in cows increases levels of IGF-1 in their milk, however, it should be noted that cow’s milk from cows that are not treated with rBST also contains IGF-1. Again, the significance of this is discussed below.
It has been suggested that IGF-1 is not destroyed during pasteurisation. Furthermore it has also been suggested that it is not completely broken down in the gut and that it may cross the intestinal wall in the same way that another hormone, epidermal growth factor (EGF), has been shown to do. EGF is protected from being broken down when food proteins (such as the milk protein casein) block the active sites of the digestive enzymes (Playford et al., 1993). This allows the molecule to stay intact and cross the intestinal wall and enter the blood. This raises a theoretical concern that IGF-1 from cow’s milk could increase normal blood IGF-1 levels and so increase the risk of certain cancers linked to IGF-1.
However, Professor Jeffrey Holly, Professor of Clinical Sciences at the University of Bristol says that although bovine IGF-1 is identical to human IGF-1 and in theory some of the IGF-1 that is present in ingested milk may be absorbed undegraded, it is implausible that this would affect the systemic levels of IGF-1 in humans. Holly states that the dynamics of the IGF-1 system (with a huge circulating reservoir and a large flux primarily due to production from the liver) means that even assuming the extreme estimates of what could be absorbed and not metabolised it would still require consumption of something like 60 litres of milk a day to increase serum levels by the least amount that could be measurable. However, he goes on to say that there are many small peptides and amino acids that are present in milk that potently stimulate hepatic IGF-1 expression and pituitary growth hormone release (Holly, 2013). In other words, drinking milk increases IGF-1 production from the liver which in turn leads to an increase in the levels present in the blood.
Milk is designed as the only food between birth and weaning and is designed to sustain the rapid growth that occurs at this stage of life. Holly states that his studies and those of others have consistently found that, of all the components of human diet, milk and dairy products have the greatest effects on IGF-1 levels. So it is not the presence of IGF-1 in milk that matters but rather the impact of milk on stimulating human IGF-1 production within individuals who consume milk and dairy products. He also points out that there is similar confusion over dairy cows treated with rBST (in the US), the milk from such cows has higher levels of bovine growth hormone and bovine IGF-1 but neither are likely to alter the effects on humans consuming such milk.
Whether cow’s milk ingestion increases IGF-1 levels in humans by bovine IGF-1 crossing the gut wall, or (as seems more likely) other components in milk initiating a rapid rise in human IGF-1 production from the liver, the net effect is the same; if you drink cow’s milk, you end up with higher levels of IGF-1 in your blood (see below).
As stated, IGF-1 regulates cell growth, development and division; it can stimulate growth in both normal and cancerous cells. Even small increases in serum levels of IGF-1 in humans are associated with increased risk for several common cancers including cancers of the breast, prostate, lung and colon (Wu et al., 2002). The link between IGF-1 and cancer is becoming increasingly apparent in the scientific literature.
In the first prospective study to investigate the relationship between the risk of breast cancer and circulating IGF-1 levels, researchers at Harvard Medical School analysed blood samples originally collected from 32,826 women aged between 43 and 69 years during 1989 and 1990. From this group, 397 women were later diagnosed with breast cancer. Analysis of IGF-1 levels in samples collected from these women compared to samples from 620 controls (without breast cancer) revealed a positive relationship between circulating IGF-1 levels and the risk of breast cancer among premenopausal (but not postmenopausal) women. It was concluded that plasma IGF-1 concentrations may be useful in the identification of premenopausal women at high risk of breast cancer (Hankinson et al., 1998a).
To investigate the link between prostate cancer risk and plasma IGF-1 levels, a study was conducted on 152 men with prostate cancer and 152 men without the disease. Analysis revealed a strong positive association between IGF-1 levels and prostate cancer risk (Chan et al., 1998). In agreement, a Swedish study compared IGF-1 levels in 210 prostate cancer patients with those in 224 men without the disease and found that there was a strong positive correlation between the risk of prostate cancer and raised serum levels of IGF-1. It was concluded that high levels of IGF-1 may be an important predictor for risk of prostate cancer (Wolk et al., 1998).
In a study into the link between the risk of lung cancer and IGF-1, serum IGF-1 levels were measured in 204 lung cancer patients registered at the University of Texas M.D. Anderson Cancer Centre and compared to those in 218 people without lung cancer. Results showed that high levels of IGF-1 were associated with an increased risk of lung cancer (Yu et al., 1999).
In order to assess colorectal cancer risk in relation to IGF-1, a research group at Harvard Medical School analysed blood plasma samples originally collected from a pool of 14,916 men. In a 14-year follow-up of these men, 193 had been diagnosed with colorectal cancer. Analysis of IGF-1 levels in samples taken from these men and 318 controls revealed an increased risk for colorectal cancer among the men who had the highest levels of circulating IGF-1 and it was concluded that circulating IGF-1 is related to future risk of colorectal cancer (Ma et al., 1999).
In summary, the literature strongly supports a link between high circulating IGF-1 levels and cancer, but what has this to do with the consumption of cow’s milk and dairy products? The answer is a lot: circulating IGF-1 levels are higher in people who consume milk and dairy products. Researchers at Bristol University investigating the association of diet with IGF-1 in 344 disease-free men found that raised levels of IGF-1 were associated with higher intakes of milk, dairy products and calcium while lower levels of IGF-1 were associated with high vegetable consumption, particularly tomatoes. In their study, published in the British Journal of Cancer, it was concluded that IGF-1 may mediate some diet-cancer associations (Gunnell et al., 2003).
US researchers from Harvard Medical School and Bringham and Women’s Hospital in Boston also investigated the link between IGF-1 levels and diet. They examined circulating IGF-1 levels in 1,037 healthy women. The most consistent finding was a positive association between circulating IGF-1 and protein intake; this was largely attributable to cow’s milk intake (Holmes et al., 2002). In another study, researchers at the Fred Hutchinson Cancer Research Centre in Washington investigated the link between plasma levels of IGF-1 and lifestyle factors in 333 people thought to be representative of the general population. They too found that milk consumption was linked to IGF-1 levels (Morimoto et al., 2005). One study actually quantified the effect of cow’s milk on circulating IGF-1 levels in 54 Danish boys aged 2.5 years. In this study an increase in cow’s milk intake from 200 to 600ml per day corresponded to a massive 30 per cent increase in circulating IGF-1. In agreement with Holly’s research, it was concluded that milk contains certain compounds that stimulate IGF-1 concentrations (Hoppe et al., 2004). An even earlier study concurred that cow’s milk contains many bioactive compounds such as hormones and cytokines, growth factors, and many bioactive peptides (Playford et al., 2000), which may also affect IGF-1 levels.
In conclusion, the research shows that nutrition has an important role in determining serum IGF-1 levels (Yaker et al., 2005). Whether the increase in IGF-1 caused by cow’s milk occurs directly (by IGF-1 crossing the gut wall), or indirectly (as a result of the action of other factors), the research is clear. The consumption of cow’s milk and milk products is linked to increased levels of IGF-1, which in turn are linked to various cancers. In time, the molecular mechanisms underlying these links will inevitably be teased out.