Eating Crow: That c/16 Estrogen Ratio Surfaces Again

By Jacob Schor, ND, FABNO

Thanks.

BLOCK QUOTE

Eating crow is a colloquial idiom, used in some English-speaking countries, that means humiliation by admitting having been proven wrong after taking a strong position. Crow is presumably foul-tasting in the same way that being proven wrong might be emotionally hard to swallow. The exact origin of the idiom is unknown, but it probably began with an American story published around 1850 about a dim-witted New York farmer. Eating crow is of a family of idioms having to do with eating and being proven incorrect, such as to “eat dirt” and to “eat your hat” (or shoe), all probably originating from “to eat one’s words,” which first appears in print in 1571 in one of John Calvin’s tracts, on Psalm 62: “God eateth not his words when he hath once spoken.” (Wikipedia, April 8, 2019)

The January 2013 issue of the Townsend Letter contained an article I wrote arguing that the science we relied on to categorize certain estrogen breakdown products as good or bad no longer held true and that it was time to abandon our reliance on measurement of these metabolic byproducts as predictive tools for assessing risk of breast cancer.

This set off a lively debate in subsequent issues of the magazine with Jonathan Wright, MD, and others advancing the argument that testing for these chemicals remained a useful practice. These letters only led me to dig in deeper.

Multiple large trials had been conducted without proving that this good vs. bad estrogen theory was valid. As far as I was concerned at that time, the debate was over.

I wrote, in hindsight rather smugly:

As naturopathic physicians, we are often ahead of the curve in translating new theories published in the scientific literature into clinical protocols for use with our patients.  This ‘early adopter’ tendency has its merits.  We will sometimes find ways to help our patients when ‘regular’ medicine has yet to develop a treatment.  Because we limit our interventions to relatively non-toxic, low-risk therapies, we set the bar relatively low in regard our requirement of proof before experimenting with new ideas. We can justify our experimentation with a ‘might help and won’t hurt’ summation of risk analysis.  If we were using more dangerous therapies, we would surely raise the bar, asking for stronger evidence before trying a new idea. 

Thus, adopting this estrogen metabolite theory early on before it was well proven did not threaten to hurt anyone if it eventually turned out to be wrong.  Except that many people, patients in particular and also some practitioners, forgot that it was theory and considered it proven fact.  

Being an early adopter does come with responsibility; if a new idea, doesn’t pan out, we need to abandon it and we need to let others know.  It is easier for us to take on new ideas than it is to let go of them. In the case of estrogen metabolites, the theory that the 2-hydroxy form is good for women and that 16α-hydroxyestrone is bad, is not holding up.  Growing evidence suggests that there is little correlation between these hormones and cancer risk; the situation is more complex than we first thought. There may be other theories that will make sense of this.  My colleagues after reading the results of these studies, quickly scramble to find alternate theories, ‘… perhaps there’s another metabolite that’s the key, maybe the 4 hydroxy?’  Maybe, but maybe not.

Sometimes you’ve just got to admit when you were wrong and move on. It is past time that we let this idea go.¹

That’s what I wrote nearly five years ago.

Now, I may have to eat my words. A Science Daily article from this April Fools’ Day has me reconsidering my position. It described a study presented at the American Association for Cancer Research Annual Meeting by Tengteng Wang, a doctoral student at the University of North Carolina. Wang and fellow researchers conducted a study in which they measured levels of estrogen byproducts in urine from a group of women with breast cancer. Relative levels of “good” versus “bad” estrogen byproducts were linked to survival. These good and bad estrogen byproducts are the same good 2-hydroxyestrone, and bad 16-alpha-hydroxyestrone, we argued about five years ago.²

According to Wang, “’A lot of research has been done to link these two metabolites with the probability of developing breast cancer. So far, we believe we are the first to look at the association of metabolites in relation to mortality after 18 years of breast cancer diagnosis.’”²

This idea was echoed by Marilie Gammon, PhD, professor in the UNC Gillings School of Global Public Health and supervising author of the study. “’This ratio may therefore represent an individual’s inherent estrogen metabolism profile. Our study reported here is the first to focus on the association between urinary estrogen metabolites and survival after breast cancer.’”²

The researchers examined the balance of these two metabolites in relation to mortality: “Specifically, they found that if the level of 2-OHE was more than, or equal to, 1.8 times the level of 16-alpha-OHE in urine, there was an associated 26% reduction in any cause of death in women with breast cancer. They also saw that there was a lower risk of breast cancer death, or cardiovascular death, for women who had higher levels of the ‘good’ metabolite.”²

The researchers had examined these associations in a group of 687 women who were diagnosed with breast cancer between 1996 and 1997, and who participated in the Long Island Breast Study Project. Levels of estrogen byproducts were measured in urine within three months after diagnosis.

They found that a higher urinary concentration of the ‘good’ versus the ‘bad’ metabolite was associated with a 24 to 27% reduced risk of dying from breast cancer, cardiovascular diseases, and any cause of death among breast cancer survivors. This association held even when other factors, such as lifestyle, diet, medical history, and menopausal status were factored in. Bottom line, as Dr. Gammon said: “’…regardless of the assumed levels of estrogen in a woman’s body, the relative balance of the estrogen metabolites appear [sic] to predict prognosis after breast cancer.’”²

The details of this study have yet to be published, but they certainly are intriguing. If these findings hold true, we have another tool to add to the predicting long-term outcome. While these results do not tell us whether shifting this estrogen ratio through diet or supplements will change a woman’s prognosis, the idea that it might is certainly compelling.

As Richard Lord, Bradley Bongiovani, and Alexander Bralley from Metamatrix Labs pointed out in an article in Alternative Medicine Review back in 2002:

The CYP1A1 enzyme that catalyzes 2-hydroxyestrone (2-OHE1) formation is inducible by dietary modification and supplementation with the active components of cruciferous vegetables, indole-3-carbinol (I-3-C), or diindolylmethane (DIM). Other dietary components, especially omega-3 polyunsaturated fatty acids and lignans in foods like flax seed, also exert favorable effects on estrogen metabolism. Thus, there appear to be effective dietary means for reducing reducing cancer risk by improving estrogen metabolism.³

To this list of foods that induce a shift in estrogen metabolite metabolism, we may have to add crow. I’ve heard it tastes like chicken.

References

1. Schor J. Estrogen Metabolite Ratios: Time for Us to Let Go. Townsend Letter. January 2013.

2. UNC Lineberger comprehensive Cancer Center. Estrogen byproducts linked to survival in breast cancer patients. ScienceDaily. April 1, 2019.

3. Lord RS, Bongiovanni B, Bralley JA. Estrogen metabolism and the diet-cancer connection: rationale for assessing the ratio of urinary hydroxylated estrogen metabolites. Altern Med Rev. April 2002;7(2):112-29.