Thursday, January 24, 2013

Soy, cancer, and thyroids

A friend messaged me this morning asking whether unfermented soy is truly linked with thyroid problems and breast cancer. I had never heard such a thing, so I decided to take a look around the internet.

Unfortunately, because some foods are political, info on the internet was filled with bias. The first article I came across I ended up closing before I even got to the parts about unfermented soy, because it started with,
For greater clarity, soy products are classified into two main groups: fermented and unfermented. There are also another two sub-groups: organic and Genetically Modified (GM). The GM soy is to be avoided at all costs, as the hazards of GM are some of the worst innovations of modern day bio-technology. Not only are all GM products unhealthy to humans and animals but also to the normal plants that grow in the surrounding area, due to the natural process of winds causing cross-pollination, resulting in mutated species of what were once natural variations of plants.
In fact there is a strong scientific consensus that GM foods are perfectly safe to humans and animals. (Wikipedia is good on this and you should follow the links to the many sources if you're interested.) Some will tell you that the scientific establishment is lying to line their own pockets, so you should buy their natural supplements and foods instead. I'll leave you to judge the quality of that argument. Furthermore cross-pollination can be beneficial to plants by increasing their genetic diversity or improving their defense mechanisms against herbivores. "Mutated" is a scare word--many mutations are beneficial. It strongly depends on what mutation is being passed around. Most of the other articles I stumbled across were similarly poor--many were of the "Ha ha take that vegetarians!" variety. Some accused dairy and meat lobbies of spreading a panic about the healthiness of soy to discourage use of alternatives. I did eventually end up reading the rest of the article above, and it did indeed make claims about thyroid problems and breast cancer, but I wanted some proper citations and a medical consensus.

So I had to dig into peer-reviewed articles through Google Scholar, and I thought it would be useful to share the results of my search. I am not a nutritionist and what follows is a non-expert's mini-summary of some peer-reviewed literature.

(Disclaimer: I am a vegan and eat lots of soy, but not for health reasons. In fact my understanding is that vegans have shorter lifespans than vegetarians and moderate meat eaters, so it would not have surprised me or discouraged me to find that soy is unhealthy.)

In question are a class of organic compounds called isoflavones, found in soy products. (That's all soy products, by the way; fermented soy products have a smaller amount of isoflavones, but they are still present.) In humans, these compounds act as phytoestrogens (also known as "dietary estrogens"). There's some confusion on this issue due to naming. My wife related a story that, when she was an undergrad buying some soy milk, someone walked up and told her not to eat soy because it would make her cry. Besides the fact that a little extra estrogen in your system probably won't make you more emotional, phytoestrogens are only named such because they resemble estrogen on a molecular level. They don't necessarily act in the same way as estrogen in your body. Estrogen supplements can increase your risk of breast cancer, so it's definitely important to figure out how phytoestrogens actually behave.

Thankfully some people have done this thing called "science" to find this out!

Short story: phytoestrogens do not act much like estrogen. One study1 found that phytoestrogens bind to the ERĪ² receptor in a manner very similar to Selective Estrogen Receptor Modulators (SERMs). Another2 used x-ray crystallography to show that isoflavone genistein (found in soy) acts more like raloxifene (a SERM) than estradiol (an estrogen).

Understand what that means? Neither do I, completely, except this: the phytoestrogens found in soy are chemicals that are molecularly similar to estrogen but do not act like estrogen in your body. Instead, they act like SERMs. Thus, worries about phytoestrogens causing breast cancer or any of the other health risks associated with estrogen supplements, just because they are chemically similar to estrogen, are unfounded. What are the health risks of SERMs? Well. . . they help prevent osteoporosis and breast cancer3. They have been indicated in lowering the incidence of prostate cancer as well4. The incidence of breast cancer is lower in areas (like Japan, China, and Indonesia) where soy intake is higher. (Link is to a graph; source is 5 in the bibliography. And yes, they do eat sufficiently more soy than westerners for it to make a biological difference9.)

None of this evidence is conclusive, but for now the tentative takeaway is that soy reduces the risk of breast and prostate cancer.

What about thyroid issues? This is one of those tricky things where what's indicated on a molecular level may not play out on a population level. Nutritional science is difficult and such results are common; this is why you may hear conflicting advice from different nutritionists.

Genistein, an isoflavone and phytoestrogen found in soy, has been shown through in vitro studies to inhibit thyroid peroxidase, an enzyme used to produce thyroid hormones. Thus, from a chemical level, it looks like soy could be capable of reducing thyroid hormones in your body. As a refresher, thyroid hormones regulate metabolism rates. People with hypothyroidism, or underproduction of thyroid hormones, frequently have abnormal weight gain low energy levels, infertility, and growth retardation in children. A common cause of hypothyroidism is iodine deficiency; this is one reason people raised in third world countries are frequently shorter.

The population studies I found on this front mostly regarded soy infant formula. One article found no statistically significant differences, in the short-term, between infants fed soy milk and infants fed breast milk* on factors of weight, height, or head circumference6. Another7 found no significant differences in weight, height, head circumference, blood albumin levels, and hemoglobin. Many of these are factors we should expect to be different if soy is causing mild hypothyroidism. One other8 looked for more long-term trends and found no significant differences across 30 different measures, including cancer, BMI, infertility, pubertal maturation, etc., though it did find that soy-fed babies later had slightly longer menstrual bleeding and slightly more discomfort during menstruation. Note, however, that at the 95% confidence level, for 30 different measures, at least one measure should give a false positive. While there is a decent prior for phytoestrogen having some effect on menstrual cycles, personally I would look for a higher confidence level to put any stock into this finding. It appears that the scale of pain was from 1 to 3 (I don't have access to the full study so I could be mistaken). The confidence interval is from 1.04 to 3. Not a striking result to my eyes.

So, it doesn't much look like soy's molecular effect on thyroid production translates into any population effects at all, even in the long-term, at least if one is fed soy during important early development periods.

Again, none of this is conclusive and nutritional science is dang hard, but the takeaway conclusion seems to be that, while soy could have some effects on thyroid production on a molecular level, it's not significant enough to express at the population level. It's probably just fine.

There are many other claims regarding the health effects of soy. Wikipedia once again appears to be good, and this overview article from which I source-hopped also seems to be quite good. I will leave it in the bibliography as citation 9 in case this link ever dies.

 Edit 01/27: Here is a blog entry from a real doctor and good skeptic on the link between genistein and breast cancer. His conclusions are less positive than what I came up with but the final conclusion is still basically "it's probably not dangerous." He adds that he would advise women currently under breast cancer treatment to reduce soy consumption, just in case.

*This should not be taken as medical advice regarding breastfeeding. I am not a doctor; the issue of breastfeeding is actually quite complicated and while I could do a literature search, this blog entry isn't concerned with that issue generally.

1. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA: Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139: 4252–4263, 1998.

2.Pike AC, Brzozowski AM, Hubbard RE, Bonn T, Thorsell AG, Engstrom O, Ljunggren J, Gustafsson JA, Carlquist M: Structure of the ligand-binding domain of oestrogen receptor beta in the presence of a partial agonist and a full antagonist. The EMBO Journal 18: 4608–4618, 1999.

3.Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, Norton L, Nickelsen T, Bjarnason NH, Morrow M, Lippman ME, Black D, Glusman JE, Costa A, Jordan VC: The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. Journal of the American Medical Association 281: 2189–2197, 1999. 
 
4. Steiner SS, Raghow S: Antiestrogens and selective estrogen receptor modulators reduce prostate cancer risk. World Journal of Urology 21: 31-36, 2003.
5. Jemal A, Center MM, DeSantis C, Ward EM:Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiology, Biomarkers & Prevention 19: 2010. Published online First July 2010: http://cebp.aacrjournals.org/content/19/8/1893.full

6. Churella HR, Borschel MW, Thomas MR, Breen M, Jacobs J: Growth and protein status of term infants fed soy protein formulas differing in protein content. Journal of the American College of Nutrition 13: 262-267, 1994. 

7.  Lasekan JB, Ostrom KM, Jacobs JR, Blatter MM, Ndife LI, Gooch WM, 3rd, Cho S: Growth of newborn, term infants fed soy formulas for 1 year. Clin Pediatr (Phila) 38: 563–571, 1999.

8. Strom BL, Schinnar R, Zeigler EE, Bamhart KT, Sammel MD, Macones GA, Stalings VA, Drulis JM, Nelson SE, Hanson SA: Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA 286: 807–814, 2001.
 
9. Setchell KDR: Soy Isoflavones—Benefits and Risks from Nature’s Selective Estrogen Receptor Modulators (SERMs). Journal of the American College of Nutrition 20: 3545-3625, 2001.