Title: From bok choy to Hippocrates: ruminations on goitrogens, thyroid and the role of the physician
Jacob Schor, ND, FABNO
June 12, 2011
Abstract: We encourage patients to consume raw cruciferous vegetables to obtain optimal amounts of sulforaphane but this may be putting them at risk of hypothyroidism. This might not be such a bad side effect. Hyperthyroid function increases risk of a number of cancers. Interestingly, hypothyroid function is more common than expected in breast cancer patients. Could reduction in thyroid function be part of the body’s natural response to breast cancer? Could reducing thyroid activity actually help the ‘vis Medicatrix naturae’? Ruminating on the effects of bok choy leads to fundamental philosophical questions on the role of the physician.
Let us start with a case report published this past May that has potential implications to our clinical practices.
In the May 20, 2011 issue of the New England Journal of Medicine, Michael Chu and Terry Seltzer reported a case of myxedema coma caused by eating an excess of raw bok choy.
They describe an 88 year-old woman who was so lethargic when brought to the emergency room that she was intubated and admitted to the intensive care unit. She was diagnosed with severe hypothyroidism leading to myxedema coma. The cause was bok choy; she had been eating two to three pounds of raw bok choy daily for several months in the belief that it would control her diabetes. Four months earlier her TSH was 0.65 mIU, but at the admittance, it was 74.4 mIU. Her Free T-4 was undetectable.
Bok choy, the common name for Brassica rapa chinensis, is a cruciferous vegetable and contain glucosinolates, the chemicals credited with the anti-cancer effect possessed by this entire family of vegetables. These same, or at least similar, chemicals have long been known to inhibit thyroid function. The authors of this report referenced a study from 1924 that links cabbage consumption to goiter in rabbits and a report from 1949 that brassica seeds contain goitrogenic compounds. They explain, “When eaten raw, brassica vegetables release the enzyme myrosinase, which accelerates the hydrolysis of glucosinolates; the cooking process largely deactivates the myrosinase in these vegetables.”
If these chemical pathways sound familiar it is because this is how sulforaphane is made. Myrosinase released when raw brassica vegetables are eaten, converts glucophoranin into sulforaphane. Cooked brassica vegetables do not have goitrogenic effect. They also have minimal anti-cancer benefit.
The patient in this report was eating a huge amount of bok choy. Chinese women living in Shanghai typically eat about 3 ounces (75 grams) of bok choy each day, and in their case it is cooked. Although the amount eaten in this case study is excessive, it is not unreasonable to imagine that some patients could out do this woman, perhaps by juicing broccoli each day. Broccoli could possibly have a stronger goitrogenic effect. In a study that compared the isothiocyanate concentration of 9 different cruciferous vegetables, bok choy had the lowest concentrations, about 6% of the amount found in watercress. Broccoli when tested for chemical content, generally comes out with the highest levels. For example, in one study broccoli had two to five times as much sulforaphane as purple cabbage, which in turn had more than ten times the amount of green cabbage.
Some patients seeking even stronger effect will juice broccoli sprouts; broccoli sprouts are the most concentrated source of sulforaphane and contain 10-100 times the amount of glucoraphanin as in mature broccoli. Thus 4 ounces of sprouts may contain the equivalent of 25 pounds of broccoli.
I’ve been diligently encouraging my patients to eat raw cruciferous [read Brassica ] vegetables as a source of sulforaphane, assuming that this was both beneficial and safe to do. Could this have suppressed their thyroid function?
Cooking cruciferous vegetables neutralizes the risk of thyroid suppression but it also reduces anti-cancer benefit. If the vegetables are cooked, the myrosinase is destroyed and sulforaphane yield is low. For example, Brussels sprouts act as goitrogens if eaten raw, but few people ever do. When cooked they are safe to eat. Raw broccoli consumption lowers risk of bladder cancer occurrence or reoccurrence while cooked broccoli offers little if any protection.
A phase 1 clinical trial of broccoli sprouts published in 2006 found no toxicities after a week-long double blinded placebo controlled trial. Broccoli sprout extracts were given orally three times a day. Daily doses ranged from 25 micromol to 100 micromol of glucosinolate.  These doses are equivalent to 11.4 mg to 45.6 mg sulforaphane per day. No ill effects on thyroid function were reported. One might question whether a week was too short a time period and whether the equivalent of a few ounces of sprouts was too low a dose for negative effects to be significant.
The patient in this case report might not be representative of the general population. Her age and possible co-morbid conditions may have changed the way her body metabolized the goitrogens released from the bok choy leaving her more susceptible to their impact.
Are our patients suppressing their thyroid function by consuming broccoli sprout extracts or large amounts of raw cruciferous vegetables? Until now I’ve not even thought to wonder.
This case report should serve as a warning. It’s time to pay attention. I have begun testing thyroid function in ‘brassica naive’ patients, before they increase their intake of cruciferous vegetables and then will repeat the tests a few months later.
Now that the subject of thyroid function in cancer patients has been broached, I am obliged to mention that thyroid function changes risk for many types of cancer. According to several papers, thyroid hormones may stimulate tumor growth and development and hypothyroid function may reduce risk.
According to the results of a prospective study published in 2009, low TSH (<0.50 mU/L), suggesting hyperthyroid function, increases cancer risk by about a third compared to control groups (95% confidence interval (CI), 1.06-1.69). Lung and prostate cancer stand out for the greatest risk increases. The hazard ratio for lung cancer was 2.34 (95% CI, 1.24-4.40) and prostate cancer 1.97 (95% CI, 1.04-3.76).
Hyperthyroid function increases risk of breast cancer. A June 2010 publication reviewed data collected from another prospective study that followed 2,696 women for almost 20 years. T3 and/or TSH levels were measured at baseline. During follow-up, 173 breast cancer cases were reported. There was a statistically significant association between T3 and breast cancer risk. In postmenopausal women the relative risks for the women in the second, third and fourth quartiles of T3 level, as compared to the first, were 3.26 (0.96 to 11.1), 5.53 (1.65 to 18.6) and 6.87 (2.09 to 22.6), (P-trend: < 0.001). Women who have had really high T-3 levels are nearly seven times more likely to get breast cancer as women with normal T-3 levels.
On the flip side, Christofaneli et al reported in 2005 that hypothyroidism lowers risk of breast cancer. Yet despite what these studies tell us, women who actually have breast cancer are more likely to be hypothyroid than control groups.
The increased occurrence of hypothyroid disease in breast cancer patients was once thought to be the result of their cancer treatments; either chemotherapy, radiation or the stress of surgery were considered the cause of the low thyroid function. The data haven’t supported this idea.
We can no longer blame radiation. A 2008 study conducted by MD Anderson compared data on 38,225 women with breast cancer against 111,944 controls and found the five year incidence of hypothyroidism was identical (14%) whether patients received radiation or not, even supraclavicular radiation that touched the thyroid gland did not change risk of being hypothyroid. While radiation treatments did not increase risk of hypothyroidism, breast cancer did. The women who had breast cancer were at 21% higher risk of hypothyroidism compared to the control group.
A 2009 Norwegian paper compared the prevalence of thyroid disease in women who had underwent two types of radiation treatment, standardized field vs. computed tomography [CT]-based dose planning. All of the breast cancer patients had higher rates of hypothyroidism, triple the rate compared to the control group (18% vs. 6%, p < 0.001).
Breast surgery is not what causes the increase in hypothyroidism. In an Italian study that tested thyroid function even before diagnosis or surgery, a third of women eventually diagnosed with breast cancer had elevated thyroid antibody levels.
Perhaps, and this may be too philosophical a digression, part of the body’s response to breast cancer is to trigger a decrease in thyroid function. Hypothyroid cancer cells may grow more slowly and this may be a good thing. This would support a time-honored assumption that there is some natural intelligence in the body directing the healing response.
There are three different ways we can view the hypothyroid cancer breast cancer patient:
- She is hypothyroid, feeling fatigued. We should either stimulate thyroid function with iodine or herbs and if not successful, prescribe thyroid hormone.
- She is hypothyroid because part of her body’s protective response against the cancer is to suppress thyroid function and slow cancer growth. We should aid this reaction by encouraging consumption of goitrogenic cruciferous vegetables because these will lower her thyroid function further.
- We should simply observe the vis medicatrix naturae and avoid interfering with it.
Which approach is correct is not clear. It depends on what you believe is the role of the physician. This remains one of the fundamental questions asked by medical thinkers since the time of Hippocrates. Do we simply observe disease progression, gently helping the ‘vis medicatrix naturae’ takes its course, the classic ‘minister natrum’ of the ancients? Should we intervene to encourage and assist nature, serving as ‘magister naturae’ and actively suppress thyroid function? Or perhaps, knowing that hypothyroid patients are often fatigued and unhappy, should we act as the ‘domino naturae’ and prescribe thyroid hormones?
Two things are clear. First, large amounts of brassica vegetables can interfere with thyroid function in at least some patients. Second, thyroid function may be a more complex issue in cancer patients than many of us have appreciated. We need to pay more attention.
How we treat low thyroid in breast cancer patients may remain a matter of debate.
Sulforaphane and Myrosinase:
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Broccoli and COPD the Doctrine of Signatures revisited.
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July 1, 2010
Li Tang's recent paper tells us that eating raw broccoli once a month may cut the risk of dying from bladder cancer by more than half.
May 2001 Sprout update: http://denvernaturopathic.com/news/broccoli.html
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