Does iodine deficiency contribute to plaque growth?
TRACK YOUR PLAQUE SITE
Background and interview with Dr. Stephen Hoption Cann
Thyroid status is proving to be a crucial facet of the Track Your Plaque program.
In this Special Report we review iodine's neglected role in thyroid health, and thereby heart health. This is supplemented by an interview with epidemiologist, trace mineral
and iodine expert, Dr. Stephen Hoption Cann.
Dr. Hoption Cann is author of the 2004 paper, Hypothesis: Dietary Iodine Intake in the Etiology of Cardiovascular Disease
In this important paper, Dr. Hoption Cann reviews the several decades of obscure - and much forgotten - clinical and scientific literature that makes a compelling argument for the critical connection between iodine and heart health.
Before we turn to Dr. Hoption Cann's important observations, let's discuss some background on iodine.
Iodine: Disinfectant, antioxidant, essential nutrient . . . coronary preventive agent?
Iodine: Yes, the same peculiar purple-brown liquid your mother applied to a scraped knee. Mom knew of iodine's anti-infective properties. But perhaps she was unaware of its potent anti-oxidative properties, its ability to sterilize drinking water, its radio-opaque quality (making it suitable for use as a contrast agent for x-ray), its necessity for thyroid function.
Paleontologists believe that iodine was the first protective anti-oxidant employed by primitive organisms exposed to the developing oxygenated world. Iodine became concentrated in the oceans, providing iodine to coastal regions. Areas away from the coasts, or never covered with oceans, contain little or no iodine. There is even a fascinating theory that Neanderthals were an iodine-deficient inland form of primate that resemble modern iodine-deficient humans, or "cretins"; the survival disadvantage of iodine deficiency permitted iodine-replete (due to better access and a theorized genetic alteration that made iodine retention more efficient) coastal primates (now called "early modern humans," formerly "Cro-Magnon") to replace Neanderthals. The ability to gain access to and efficiently retain iodine may therefore have played a crucial role in human evolution.
Turn-of-the-last-century America was plagued with goiter, an unsightly enlargement of the thyroid gland visible on the front of the neck. As many as a third of the inhabitants of some parts of the country (e.g., the Great Lakes, AKA the "goiter belt," and much of the Midwest) were affected. The connection between goiter and deficiency of iodine wasn't made until a family doctor in Cleveland, Ohio, conducted a homespun experiment on schoolgirls in a nearby community in 1916. Despite objections from local residents, Dr. David Marine administered what we now recognize as a very large dose of iodine: 170-340 mg (170,000 – 340,000 micrograms, mcg) sodium iodide per day to 900 girls. Virtually none of the girls receiving iodine supplementation developed goiters, compared to 22% of the control group not receiving iodine (Zimmerman MB 2008).
Mothers from the same era, often deficient in iodine, gave birth to severely impaired babies afflicted with far below average intelligence, consigned to a brief, disabled life. These children were known by the harsh name of "cretins," the disease known as "cretinism."
The recognition of the importance of iodine launched it into the realm of public health, too large an issue to leave to individuals, families, or physicians to remedy on their own. Much debate ensued in the mid-twentieth century on how to best ensure that the U.S population receive a minimum quantity of iodine in their diets. Table salt (sodium chloride) became the agreed vehicle for iodine in 1924, though iodization was deemed voluntary, not mandatory.
During the 1960s and 70s, most Americans willingly complied by liberally shaking the salt shaker over anything and everything. Overt iodine deficiency largely became a thing of the past, goiters a rarity. FDA guidelines suggest iodine content in salt of 45 mg/kg; this means that slightly over one half teaspoon of salt per day, or 3000 mg (1,150 mg sodium), provides the Recommended Daily Allowance of iodine of 150 mcg per day.
Coincident with the widespread application of the salt shaker was the recognition of the dangers of hypertension. Clinical studies made it clear that liberal use of salt increased blood pressure, fluid retention, even osteoporosis.
The public health message reversed its focus and began to urge reducing use of table salt. Salt use was demonized as the cardiovascular dangers of hypertension gained public recognition. Somehow, the issue of iodine was forgotten. (This has created some peculiar public health collisions. While the American Heart Association advises reduction of salt use, and the American Medical Association has even urged the FDA to remove salt from the "generally recognized as safe" designation, others like UNICEF and the charitable International Council for the Control of Iodine Deficiency Disorders both advocate for increased salt use worldwide.)
Fast forward to the 21st century and many health-conscious people proudly declare their assiduous avoidance of salt, certainly iodized table salt. Others have turned to alternative preparations of sodium chloride, such as sea salt (very little iodine content), Kosher salt (no iodine), and potassium chloride-based salt substitutes (no iodine).
So what's become of the iodine?
Maybe your iodized salt isn't so iodized
Even people who use iodized salt are getting less iodine than expected.
Iodine deficiency is on the rise. The NHANES data of Americans' health has revealed a quadrupling of iodine deficiency in the period between 1971 and 1992, with 11% of the population now clinically iodine deficient as judged by urinary levels of iodine (Hollowell JG et al 1998). Regional variation in incidence seems to have been smoothed over, with no specific areas of the country standing out more than others, unlike the past (likely due to the globalization of the food supply).
A recent study (Dasgupta PK et al 2008) suggests that, even among people who use the salt shaker for cooking and food, daily iodine intake is only around 45 mcg per day. Interestingly, a detailed analysis of several brands of commercially-available salt showed that, after opening, iodine is lost rapidly from the product, especially if stored in humid conditions (see figure); within 10-20 days after opening, iodine content is dramatically reduced, even nearly gone, under conditions of high humidity. Their analysis also showed that, even if the salt is labeled "iodized," it usually contains substantially less than the FDA-suggested 45 mg/kg.
Loss of iodine over time with exposure to air with specified humidity levels, no light, 22 +/- 1 °C.
From Dasgupta PK et al 2008.
The majority of salt used in processed foods is not iodized. While dairy products and baked foods (bread and related products) were formerly substantial sources of iodine, iodine content of these foods has dropped 70% over the past 20 years due to changing practices by dairy producers and bakers (Dasgupta PK et al 2008). Add to this the currently popular notion of "buy local" and we might therefore expect to see regions with greater proportions of their population with goiter, much as in the early 20th century.
In short, even people who are using iodized table salt and eat common processed foods may not be getting the iodine content they need. In addition, the public health message to limit salt use is accelerating a gradual and insidious return of iodine deficiency.
Iodine deficiency is inevitably followed by underactive thyroid function, reductions in thyroid hormone levels and hypothyroidism. Ironically, we might predict that iodine deficiency is apt to primarily afflict the health conscious, the people most likely to avoid salt and follow the "buy local" practice.
So history repeats itself.
What quantity of iodine is necessary for ideal health?
There remains no question that iodine is necessary for health, specifically thyroid health. Deficiency over any length of time leads to a thyroid gland that enlarges, or "hypertrophies," an attempt to overcompensate by growing larger and better able to extract the little iodine available from the body. If iodine deficiency continues, production of thyroid hormones, T3 and T4 (the "3" and "4" referring to the number of iodine atoms per molecule of T3 and T4), begins to suffer, production drops, clinical hypothyroidism ensues.
One of the difficulties in the world of iodine is that 20th century overuse of iodized salt led to smugness over the ease of iodine replacement. Use iodized salt, goiters are essentially erased - end of story. Clinical research involving iodine during the period focused almost exclusively on questions of delivering similar public health efforts for iodine replacement in third world countries to relieve endemic goiter, affecting as much as 2-3 billion people even today.
There is no debate over the fact that even the current RDA for iodine of 150 mcg per day for non-pregnant adults is sufficient to prevent or reverse goiter.
What is curiously missing are answers to the questions: What is the quantity of iodine necessary for ideal thyroid function? What is the quantity of iodine necessary for perfect overall health?
Specifically, dose-escalating studies for iodine that track thyroid function have not been thoroughly explored. If the RDA for iodine of 150 mcg yields some improvement of thyroid measures, would 300 mcg, 600, 900, even 10,000 mcg further improve thyroid function? Sadly, these studies have not yet been done.
Should we take a lesson from the Japanese, who, through their dietary reliance on seaweed (e.g., kelp, kombu, nori, etc.), have iodine intakes 30- to 100-fold higher (5,280-13,800 mcg per day) without excessive thyroid disease and reduced incidence of fibrocystic breast disease and breast cancer (Patrick L 2008)?
Despite nearly 80 years of public health efforts, you are left with the impression that there are many stones yet unturned in the area of iodine and its role in health. The optimal dose of iodine for health seems to be one of them.
Iodine deficiency as a coronary risk factor
Little argument remains that iodine deficiency is an important factor that leads to disordered thyroid function.
But can iodine deficiency act as a coronary risk factor?
Dr. Stephen Hoption Cann is author of the most thorough review to date on whether iodine and iodine deficiency play a role in cardiovascular disease. (Hoption Cann SA, Hypothesis: Dietary Iodine Intake in the Etiology of Cardiovascular Disease. J Amer Coll Nutr 2006;25(1)1-1.)
In his introductory comments, Dr. Hoption Cann states:
"Iodine-containing thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are important metabolic regulators of cardiovascular activity with the ability to exert action on cardiac myocytes, vascular smooth muscle, and endothelial cells. Numerous studies of patients with spontaneously occurring hypothyroidism and hyperthyroidism have demonstrated that thyroid hormones can have profound effects on the heart and cardiovascular system."
Dr. Hoption Cann describes an early observation on the connection between goiter and coronary plaque:
". . . subjects who died from coronary sclerosis [coronary disease] often had goitre. . . 250 Finnish subjects who had died from coronary heart disease were age and sex-matched to controls who died from other causes. The risk of death from coronary heart disease was found to be significantly higher in individuals with goiter (odds ratio = 3.53 . . ."
We tracked Dr. Hoption Cann down to seek his answers on some issues of particular concern to us. Here are his responses to our questions.
TYP: What is your background--areas of research, areas of interest, etc.?
SHC: I have a BSc in human biology from the University of Victoria, Canada. From that same University I obtained my PhD studying the relationship between nutrition, immunology and cancer. I completed my postdoctoral studies at the University of British Columbia in epidemiology. I am presently an Adjunct Professor in the School of Population and Public Health at the University of British Columbia. My research interests are studying trace elements and their role in disease, particularly the trace element iodine, and the study of the beneficial effects of fever.
TYP: How did you come upon the iodine/cardiovascular disease question?
SHC: I have been researching iodine and its association with cancer and other diseases and noted that it was a common treatment in the past for all variety of cardiovascular conditions.
TYP: Since publication of your review, have you learned anything new re: iodine and its relationship with cardiovascular disease?
SHC: Iodine reduces the viscosity of the blood and also acts as an antioxidant, which may be the primary mechanisms for its beneficial effects on cardiovascular disease.
TYP: Could you share with us your personal views on iodine, i.e., your opinions based on all you know about iodine, though not necessarily fully worked out in the scientific experience? Especially helpful would be your sense for the trends in deficiency beyond what the most recent NHANES tells us, preferred methods for individual supplementation (as opposed to public health measures), etc.
SHC: Even in countries considered iodine sufficient, there will be subgroups within the population that are iodine deficient. Unfortunately, at this time it is rare that iodine deficiency is confirmed in subjects with thyroid problems, and many patients may receive thyroid hormones when they are in need of an increase in dietary iodine. This will continue to be a problem until measures of iodine are incorporated in the routine testing of subjects with suspected thyroid issues.
There are few iodine rich-foods other than iodized salt and seafood, but iodine is especially high in seaweed.
TYP: What is your opinion (not recommendation, as I understand how sketchy the clinical data are) regarding the daily iodine dose requirement for humans?
SHC: I believe that the intake of 150 ug [micrograms] per day is adequate for thyroid function. But the more intriguing question is: What benefits do higher levels have on human health?
Doses in the range of 5 mg [5000 µg] up to 50-100 mg [50,000-100,000 µg] have been used for the treatment of fibrocystic breast disease, to improve cerebral functioning, lessen fatigue, and reduce respiratory infections, but research on these topics is only beginning and cannot be generally recommended at this stage.
Normal thyroid hormone levels may be seen in subjects with large iodine intakes (in milligram and gram quantities). Examples of [groups consuming] milligram quantities include patients on the iodine-rich drug amiodarone or the Japanese, who consume large quantities of iodine-rich seaweed. A small percentage of those individuals may develop hypothyroidism, or less commonly, hyperthyroidism, at those higher levels, which returns to normal when iodine intake is reduced.
Often, patients, when starting to take larger levels of iodine (5 mg and higher), will have increased TSH values, but the levels of T3 and T4 will be normal, and as mentioned, a small number will have elevated TSH but develop a reversible hypothyroidism.
TYP: Where do you see this issue going in the next few years?
SHC: In the past, iodine was used to treat a wide variety of cardiovascular diseases. The routine doses were in the milligram to gram range - with doses varying from 1,000 to as much as 50,000 times the current RDA.
While the current RDA is an adequate level for iodine intake, there may be further therapeutic benefits derived from higher iodine levels in patients with cardiovascular disease. Research on elevated iodine levels and its relationship to various diseases is starting to gain increasing study, but it will take some time before these much higher levels can be approved for study in cardiovascular disease.
TYP: Thank you, Dr. Hoption Cann, for sharing your insights with us.
Is there a role for iodine in the Track Your Plaque program?
No question remains: Iodine is essential for health. Just as deficiency in vitamin C will lead to teeth falling out, open sores over the body, and eventually death, so will iodine deficiency lead to debilitating disease. Simply meeting the Recommended Daily Allowance (RDA) of 150 mcg per day will keep goiter from developing and maintain thyroid hormone production at a "normal" level for the majority of people.
But does the RDA of 150 mcg per day suit everyone perfectly? Are there people or conditions that increase the need for iodine? In particular, do the observations in Japanese and small clinical trials suggest that we should follow their lead and boost our iodine intake to match, i.e., daily intakes in the milligram range?
Another interesting question: Athletes and persons engaged in heavy physical effort lose considerably more iodine than other people in their perspiration, increasing need for iodine (Smyth PP, Duntas LH 2005; Mao IF et al 2001). Vegetarians also have substantially greater likelihood of iodine deficiency than carnivorous people (Remer T et al 1999). What quantity of iodine per day is sufficient in these people?
Does alleviating goiter also mean that thyroid function is optimized? Goiter may simply represent the grossly visible manifestation of hypothyroidism (and other thyroid conditions). Is there an intake of iodine that can further improve thyroid function, even after goiter is reversed or suppressed?
To further complicate the situation, what is the quantity of iodine required in the presence of now ubiquitous environmental blockers of thyroid function, such as bromine (baked products and other processed foods; pool water); bisphenol A (from polycarbonate plastics, plastics with recycling code 7, microwaveable plastic, and canned foods); perchlorates (fertilizers, explosives such as in fireworks); polychlorinated biphenyls (pesticides, PCBs), polybrominated diphenyl ethers (flame retardants in carpeting and other consumer products)? All of these substances have been shown to block either iodine or thyroid action (Blount BC et al 2006; Schmutzler C et al 2007). How should this factor into our decisions on dose of iodine?
As Dr. Hoption Cann points out, despite all we know about the human need for iodine, there is still much about this nutrient we do not know. We desperately await clarification on these issues. Be assured that Track Your Plaque remains on the forefront of the discussion. We are not necessarily waiting for a consensus, nor should we heed the rants of the alternative "fringe" eager for an answer and offer one that pleases. Until then, our advice is that attention to iodine should be part of an overall effort towards maintaining ideal thyroid health. That effort includes:
* Assessment of thyroid hormone status: This includes measurement of free T3, free T4, and TSH. Should these be abnormal, thyroid antibodies (thyroid peroxidase antibody, thyroid-binding globulin antibody) should also be assessed to determine whether an autoimmune attack of the thyroid is underway.
* Assessment of iodine intake: While some advocate urinary ("spot" or 24-hour urine collection) testing or iodine skin testing, we remain undecided on their validity and practical utility, particularly given the presence of environmental iodine blockers. More data are clearly needed here to help us create a useful solution to assess iodine adequacy.
* An assessment of potential thyroid symptoms: This needs to be made by you and your health provider. Are you abnormally fatigued, intolerant to cold, cold hands and feet, experience habitually foggy thinking, sleeping more, etc.?
* Assess body temperature: Take oral temperature first upon arising (not after brushing your teeth, making the bed, drinking coffee, etc., first thing). This approximation of the body's lowest overnight temperature yields important insight into the adequacy of thyroid status. Oral temperatures consistently <97.6 F suggest hypothyroidism; consistently <97.0 F almost certainly reflects hypothyroidism.
* Iodine intake: If all above measures are normal and hypothyroidism is not suggested, then simply adhering to the RDA of 150 mcg per day for adults or thereabouts is likely sufficient. If there is any indication of hypothyroidism, then strong consideration should be given to an increase in iodine intake to the 1000 mg per day range, preferably from an iodine supplement such as kelp tablets, a form that approximates the Japanese experience. Toxicity from this dose is rare, confined principally to people who have unusual thyroid disorders, such as toxic nodular goiter (Pennington JA 1990); this is best decided with the assistance of your healthcare provider. Also, note that there may be a slight increase in TSH when higher doses of iodine are taken (Clarke CD et al 2003).
Obtaining iodine through the use of iodized salt is both unreliable and unhealthy, since salt increases blood pressure, causes fluid retention, and can accelerate osteoporosis, and iodine in salt is inconsistent and poorly absorbed.
Note that many multivitamins or multi-minerals contain somewhere around the RDA for iodine.
Keep in mind that, if hypothyroidism is present, iodine intake may need to be individualized by your healthcare provider. Rarely, someone with low thyroid will develop abnormal thyroid responses to iodine. This occurs because of the iodine deficiency present before correction perturbs thyroid function; adding iodine can actually worsen the situation temporarily. Iodine replacement can therefore only occur alongside monitoring of thyroid function by you and your health provider. |
