Say the word "iodine" and most physicians automatically think, "thyroid."
While the thyroid gland is an unquestionable iodine sponge, and iodine is a key constituent of thyroid hormone, it has other important physiologic effects, among them maintenance of healthy breast and ovarian tissue in women, and fostering optimal neurocognitive development in babies.
Less than 30% of the body's total iodine load goes to the thyroid. Between 60–80% of total iodine is non-hormonal and concentrated in extrathyroidal tissues (Venturi S. The Breast. 2001; 5: 379–382). This fact is sadly overlooked by most clinicians, to the detriment of their patients, says Sherri Tenpenny, DO, a Strongsville, OH, holistic physician with a primary focus on women's and children's health.
"If you look at Braverman's The Thyroid, one of the bibles of endocrinology, it says in the very first chapter that iodine is important for the eyes, prostate, breast, ovaries. But medicine has largely ignored these tissues for decades. The FDA never even bothered to give a total body RDA for iodine beyond the anti-goiter recommendation of 150 mcg per day (in lactating women it's 220–290 mcg) established in the 1920s," Dr. Tenpenny told Holistic Primary Care.
"Since the early 1960s, we've known iodine deficiency was related to breast disease, including breast cancers. Carcinomas are most likely to develop in the ductal tissues that normally should be concentrating iodine [Russo J. Medicina. 1997; 57(Suppl 2): 81–89]. When these tissues are iodine-deficient, they are actually more sensitive to the stimulatory and proliferative effects of estrogen."
Though there's no way to prove a causal relationship, it is interesting that the growing prevalence of iodine deficiency in the US over the last few decades tracks strongly with the rise in breast cancer, said Dr. Tenpenny.
Breasts, Babies & Iodine
It is clear why iodine is important for the thyroid; T4, the principal output of this gland, is a tyrosine molecule bonded to 4 iodine ions. Cells throughout the body are capable of clipping off one of the iodines, creating T3, the hormonally active form. But what does iodine have to do with breasts?
The answer is simple: babies need lots of this halide for neuroendocrine development, and they're supposed to get it from breast milk. Milk ducts are designed to draw iodine from the bloodstream, concentrate it, and transmit it to the baby via the milk.
The importance of iodine for child development should not be underestimated, said Dr. Tenpenny. The International Council for the Control of Iodine Deficiency Disorders (www.iccidd.org) produces a quarterly newsletter packed with science on this topic. Researchers have shown that iodine-deficient children have mean IQ scores 10–15 points lower than iodine-replete kids. It is disturbing, then, that roughly one-third of all lactating women in the US are iodine-deficient.
Lactating milk duct cells are covered with sodium iodide symporters—special glycoproteins akin to those in the thyroid—that move iodine. They also have enzymes called lactoperoxidases that bind iodine to casein and other milk proteins. Together with free Iodine, these iodolactones are secreted into milk.
During lactation, breast tissue actually outpaces the thyroid in iodine capture, showing a particular preference for the molecular (I2) form. Until recently, many researchers believed non-lactating breast tissue did not absorb much because it does not express iodide symporters. But non-lactating tissue does express another iodide transporter protein called pendrin, and iodine is clearly important beyond lactation.
Like nearly all tissues of the body, breast tissues can cleave iodide ions from T4, to make active T3, and in euthyroid women, this forms a distinct iodine "pool" that has a primarily antioxidant function.
Does Iodine Protect Against Cancer?
Carmen Aceves, MD, of the Instituto de Neurobiolog?a, Universidad Nacional Autonoma de Mexico, Juriquilla, is among a number of international researchers studying iodine for breast cancer. She and others point out that iodine in its various forms has antiproliferative, anti-inflammatory and antioxidant effects in breast tissue.
Hormonal stimulation during lactation markedly increases iodide absorption into the breasts; it also increases production of free iodide molecules. The increased presence of iodine regulates mitosis, reduces free-radical induced DNA damage, and markedly reduces tissue fibrosis, all of which suggest a protective effect.
Dr. Aceves contends that the increased rates of breast cancer over the last century may, in part, reflect the fact that women now spend much more of their lives in non-lactating states during which breast tissue has a higher mitotic rate: tissue that has never differentiated to produce milk divides 20 times more often than tissue that has undergone the lactation transformation.
The notion that iodine may prevent breast cancer emerged from epidemiologic studies of Japanese versus Western women. The typical Japanese diet is rich in shellfish and seaweeds, like wakame, nori or mekabu. These contain high quantities of iodine in multiple forms. On average, Japanese women get 25 times more dietary iodine as American women, and on a population basis, this is associated with much lower incidence of breast cancer.
There's reason to believe that supplemental iodine may be protective or even therapeutic for breast cancer. A number of rodent studies show that supplemental iodine can shrink chemically-induced mammary gland tumors. And there's preliminary evidence that it can do the same in non-malignant human tumors.
In an excellent 2005 review paper on the role of iodine in breast health, Dr. Aceves stated that one of the primary effects of iodine is that it reduces breast tissue density and fibrosis, which are big risk factors for breast cancer [Aceves C, et al. J Mammary Gland Biol & Neoplasia. 2005; 10(2): 189–196]. She advocates iodine as a potential preventive and therapeutic option.
"I2 supplement[ation] is not accompanied by any harmful secondary effects on the health of women or animals (body weight, thyroid economy, reproductive cycle). Thus, we propose that I2 supplementation should be considered for use in clinical trials of breast cancer therapies," she wrote.
Bernard Eskin, MD, a gynecologist at Drexel University, has been at the forefront of research on iodine and women's health for decades. At the 2005 meeting of the American Association for Cancer Research, he reported that women with breast cancer (14 with invasive cancer; 6 with DCIS) had consistently lower urinary iodine excretion than similarly aged women without cancer. Low urinary iodine suggests deficiency, and the findings "imply potential diagnostic and therapeutic capabilities in the iodine pathway."
Resolving Fibrocystic Disease
Regulation of breast tissue proliferation is complex. The precise role of iodine and its potential as a breast cancer treatment remains to be determined. What seems clear, though, is that supplemental iodine reduces fibrocystic breast disease (FBD) and cyclic mastalgia.
In 1993, Dr. Eskin, working with Dr. William Ghent at Queens University, Ontario, showed that daily dosing with molecular iodine (I2) markedly reduced breast pain, tenderness, and tissue density in a cohort of more than 1,300 women with severe FBD. Fifty-one percent had complete resolution of symptoms after a median treatment time of 13 months (Ghent WR, et al. Can J Surg. 1993; 36: 453–460).
More recently, Dr. Lucius Hill, at the Swedish Medical Center, Seattle, studied a cohort of 106 women with chronic FBD, randomized to treatment with daily oral doses of aqueous I2, 10–25 mL, or placebo solution, for 7 months. The iodine doses corresponded to between 1.95 and 4.88 mg per day. Of the 92 evaluable patients, those on active iodine had substantially lower pain, tenderness, and overall symptom scores, as well as reduced breast nodularity and fibrosis.
However, Dr. Hill's study was compromised by the fact that 40% of those on iodine experienced interruptions owing to a shortage of the study preparation. I2 is inherently unstable, and difficult to formulate in supplemental forms. In fact, it was largely unavailable until recently, when Symbollon Pharmaceuticals (www.symbollon.com) introduced IoGen, a patented I2 formulation specifically for treatment of FBD and mastalgia.
In a Symbollon-funded study, 111 otherwise healthy women with history of cyclic mastalgia, were randomized to 6 months' treatment with placebo or IoGen at daily doses of 1.5 mg, 3.0 mg or 6.0 mg. Those on the 3 and 6 mg doses showed significant improvements in self-assessed symptom severity and physician-rated severity; women taking the 1.5 mg dose or those on placebo showed no significant changes (Kessler JH. Breast J. 2004; 10(4): 328–336).
These findings echo a much earlier Russian study in which iodine supplementation reduced mastalgia severity in 72% of treated women (Vishniakova VV, Muravievna NI. Vestn Akad Med Nauk SSSR. 1966; 21: 19–22).
Clinically, iodine can make a profound difference in the lives of women with chronic breast pain, said Dr. Tenpenny. Over the years, she has used a number of different iodine preparations to help women with mastalgia and FBD. She described a case involving a 45-year-old woman with very dense, hard breasts, intense cyclic pain, and frequent nipple discharges. She'd been suffering for 18 years, and was even considering prophylactic mastectomy.
"I was using Iodoral at the time, and I had her take 2 per day. Within one week, the nipple discharge stopped, and the pain began to abate. Within three weeks, she was largely symptom free, and no longer had to take pain medications."
That was a dramatic response. In other patients, the effect is subtler and takes longer. But most patients will show significant symptom resolution within 4–6 weeks. "If this is going to work, you'll certainly know within three months."
Given the widespread prevalence of iodine deficiency—according to the most recent World Health Organization data, 19.4% of the US population has low urinary iodine excretion (under 100 μg/mL)—supplementation makes sense, especially in women at risk of breast cancer.
How Much Is Too Much?
In recent years, there's been a surge of enthusiasm for iodine, due in part to greater awareness of "subclinical" hypothyroidism, and the wide availability of Iodoral, a product that essentially concentrates Lugol's solution (5% molecular iodine; 10% iodide) in tablet form. The increased awareness is due in large part to the work of Guy Abraham, MD, former professor of Obstetrics, Gynecology & Endocrinology at UCLA, who has championed iodine supplementation for decades. (Visit www.holisticprimarycare.net, and read Iodine Therapy Gains Favor for Thyroid Problems, Chronic Fatigue, from our Winter 2005 edition.)
Iodoral advocates often recommend that patients take 30–50 mg per day. Dr. Tenpenny and others have begun to question the wisdom of going that high. The issue, particularly when treating non-lactating women, is how to get optimal iodine supply to the breast tissue without overloading the thyroid.
There's a built-in mechanism within the thyroid that shuts down T4 production when the gland is confronted with a big iodine load; this is to prevent over-production of T4 and avert thyrotoxicity. Normally, the T4 production kicks back on within 24–48 hours, once the iodine levels drop back down. The process, known as the Wolff-Chaikoff effect, was first documented in the late 1940s.
In most people, a large iodine dose won't cause problems, but in some this mechanism doesn't work properly. The thyroid may shut down and then fail to re-start, ultimately leading to a severely hypothyroid state, explained Elizabeth Pearce, MD, an endocrinologist at Boston University.
In others, the thyroid does not shut down after an iodine load and starts cranking out excess T4, leading to a hyperthyroid state. Part of the problem is that unless there's overt thyroid disease, it can be difficult to determine in advance who will have problems. For this reason, Dr. Pearce takes a dim view of high-dose iodine therapy.
"If you're considering iodine supplementation for any reason, it's a good idea to do a thyroid workup. This is not something that patients should be doing on their own, without physician guidance, especially high-dose iodine protocols. They really need careful monitoring." The good news is that outside of the thyroid, there are no other tissues known to be adversely affected by high iodine levels.
Dr. Tenpenny said she's become a fan of the new IoGen product. It provides iodine in the molecular form, which is preferentially absorbed by the breast and less thyrotoxic than iodide. Patients with FBD or mastalgia need only take 3 mg per day. That's still "supraphysiologic" in that it is above the 1,100 μg range that conventional endocrinologists consider the "upper limit," but it is far less than what's delivered in other supplemental forms.
Good for the Gander
Supplementation, though important, is only part of the picture. Dr. Tenpenny said she often recommends turmeric, in doses of 300–900 mg/day. "It's anti-angiogenic, and anti-inflammatory. It cools the hotspots in the breast."
She's also a big fan of di-indolyl methane (DIM), a compound derived from cruciferous vegetables that produces strong and favorable shifts in the ratio between anti-inflammatory and pro-inflammatory subtypes of estrogen. (Visit www.holisticprimarycare.net, and read Cruciferous Indole at the Crossroad of Estrogen Metabolism, from our April 2002 edition.)
Generally speaking what is good for breast health in women tends to be good for prostate health in men. Iodine is no exception. Dr. Tenpenny said she's treated three men with highly elevated PSAs, all of whom showed marked PSA reductions after a few months on daily iodine.
"I had one gentleman, who was about 76 years old, and had PSA's in the 22–23 range. His urologist wanted to implant radioactive iodine pellets. I reasoned that we should just try iodine itself. After 6 months, his PSA was down to 0.6."