On 3/27/14 I sent the following letter to Shirley Wang pointing out the significant error she made in reporting the results of a new study that looked at the relationship between protein intake and mortality from cardiovascular disease and cancer. The main point of the article was that a recent study showed an increased risk of dying from cancer with high versus low levels of IGF-1 in normal aging adults. She then drew the conclusion that taking HGH for “anti-aging” could have the opposite effect. The problem with this is that the article said no such thing! It showed that people with higher protein intake, not IGF-1 level, who are 50-65 had a higher risk of dying than those with relatively lower protein intake. In the letter below I simply ask her to make this correction.
I read your WSJ article on growth hormone and aging with interest. I am curious to know the citations supporting your comment “Studies show that lowering IGF-1 by 50% decreases cancer risk significantly and that increased levels of IGF-1 are linked with higher cancer risk.”
While I am aware there are observational studies correlating higher IGF-1 levels with increases in common cancers in humans, the increase is almost completely nullified by controlling for the pro-apoptotic molecule IGFBP-3 which is increased in parallel with IGF-1 when GHRT is given. I am not aware of human studies that show a decreased incidence of cancer in humans in whom IGF-1 levels have been experimentally lowered. If you are talking about animal models, then that should be made clearer to your readers. These transgenic rodent models generally have extremely low or high IGF-1 levels from birth so that body size is considerably lower or higher than normal aging rodents. The only studies that give GH to normal aging rodents show no deleterious effects and rejuvenation of aging gene expression for metabolism (Tollet-Egnell 2004)
I have read the March 2014 Cell Metabolism paper from Dr. Longo’s group you appear to be quoting, and cannot find support for your statement, “They found that in those aged 65 and older, people with higher IGF-1 levels showed a fourfold increased risk for cancer and 75% increase in overall mortality compared with those with lower levels.”
On page 408 they do state the following: ” Among those ages 50–65, higher protein levels were linked to significantly increased risks of all-cause and cancer mortality (Table 1). In this age range, subjects in the high protein group had a 74% increase in their relative risk of all-cause mortality (HR: 1.74; 95% CI: 1.02–2.97) and were more than four times as likely to die of cancer (HR: 4.33; 95% CI: 1.96–9.56) when compared to those in the low protein group.” But this statement is about protein intake, NOT IGF-1 levels. They did look to see IGF-1 level interacted with protein intake to increase or decrease all-cause mortality or cancer mortality and only found an interaction in the 50-65 year old group.
While Dr. Barzilai’s group did report some interesting findings about lower IGF-1 levels predicting incremental survival in exceptionally aged females (but not males), it seems to me that this is hardly strong enough evidence to support the statement that growth hormone replacement studies in older adults would not be ethical.
Joseph M. Raffaele, MD
I didn’t get a response and sent the following email when a half-correction was made.
I see that you have corrected that age group in the statement about IGF-1 and mortality risk, but you have not corrected the substitution of IGF-1 for protein. This is an egregious error that really should be fixed. I see that it is probably the supplemental table 4 that you are referring to but the study did not show any increased risk of all-cause, cancer, or cardiovascular mortality by IGF-1 level alone and that should be retracted. What it showed was that within the younger age group, those with higher protein levels had their cancer mortality risk further increased as IGF-1 level increased.
The authors overstate their conclusions that IGF-1 is causal as they have no data to support this. The mouse data they offer is interesting, but mice have much higher cancer incidence/mortality than humans and the cardio-protective effect of GH through IGF-1 is likely to outweigh any potential increase in cancer risk.
Joseph M. Raffaele, MD
It is a shame that we cannot get a response or have this corrected! 3/31 update. Ms. Wang responds and I comment on her response. See comment #3 below.