Should people with adrenal fatigue be tested for iodine deficiency and bromide toxicity?

Adrenal fatigue and iodine deficiency share a lot more in common than the fact that most physicians don't believe they exist or that they are not a significant problem in the United States.  These conditions share treatments, symptoms, and a host of other interesting commonalities.  In this blog article I will discuss these commonalities as well as provide evidence that people with adrenal fatigue should be tested for iodine deficiency and bromide toxicity.

Adrenal Fatigue

Adrenal fatigue is a syndrome where the adrenal glands produce insufficient levels of the adrenal hormones cortisol and aldosterone or an altered circadian rhythm of cortisol release.  Adrenal fatigue is thought to be the product of excessive stress, poor stress management, and nutritional deficiency.  In addition to these factors that are thought to be at the root of adrenal fatigue, the reliance on energy drinks and caffeine to provide energy are also thought to be relevant.

Iodine deficiency and bromide toxicity

Iodine deficiency and bromide toxicity go hand in hand.  Iodine and bromide are known as halides, a group of elements that can substitute for one another in specific tissues in the body.  Fluoride, chloride, iodide and bromide are the primary halides with astatide being a less commonly seen halide in biology.  Iodide and chloride have biological value to humans while fluoride and bromide do not and can potentially be toxic.  In a person with sufficient iodine/iodide there tends to be no issue, but when a person is not getting sufficient levels of this nutrient or the other halide chloride, bromide can accumulate in the body tissues that store them, including the thyroid and stomach.

Bromide is thought to be a neurotoxin and it's use as a sedative provides support for this notion as overdose of sodium bromide can lead to neurological issues.  The use of bromide in prescription and OTC medicines was ceased in the 1970s because bromide's half-life(12 days in humans) made it difficult to dose.  Bromide is ubiquitous in modern society.  It is found in some citrus drinks and bread and bakery products but it is primarily an environmental toxin.  Bromide is used as a flame retardent in mattresses, carpets, and upholstered furniture and can also be found in plastics, car upholstery, pool and hot tub chemicals, pesticides, and certain medications including atrovent.  Since bromide toxicity is unlikely to occur in someone sufficient in iodine that isn't taking large doses of bromide-based medications, we will consider the two more or less the same for this discussion.  While it is possible that someone could be deficient in iodine and not have bromide toxicity, it is unlikely given our current environment.

Bromide competes with iodide in the thyroid and the goitrogenic effect of bromide is enhanced under conditions of iodine deficiency(1, 2).  Under iodine deficient conditions, up to 40% of the iodide in the thyroid can be replaced by bromide.  With sufficient iodide supply, a constant iodide to bromide ratio is established in the thyroid(2).  Very high bromide intake shortens the half-life of iodine in the thyroid of both iodine sufficient and iodine deficient rats to about 1/3rd of the value in controls and increases whole body loss of iodine via the kidneys(2).  This is a problem because bromide's serum half-life in humans is 12 days compared to iodine's which is approximately 10 hours in iodine sufficient people and significantly lower in those with iodine deficiency(3).  This is the primary reason it takes high doses and long periods of time to improve an iodine deficiency and bromide toxicity.  In addition, bromide's half-life is increased significantly in salt deficient diets and can be shortened with increased salt consumption(2).

The interesting thing about iodine deficiency and bromide toxicity is that increasing iodine intake increases bromide excretion in the urine.  This is more than likely initiated first by iodine replacing bromide on receptors of cells in target tissues.  This will lead to an increase in serum bromide until the kidneys filter bromide out of the blood and into the urine.  This is an important process and one I believe to be the primary link between iodine deficiency/bromide toxicity and adrenal fatigue as bromide has a long half-life in serum and the kidneys can only filter out so much bromide at a time.  Once kicked off of receptors and in to the blood, bromide can mess with electrolyte balance and cause a host of other problems.  On the surface, it doesn't appear that these conditions are related in anyway.  When you take a look at some of the common symptoms between the two, a potential relationship begins to emerge.  Below is a list of the common symptoms of adrenal fatigue and iodine deficiency/bromide toxicity:

Common symptoms include:
Fatigue
Electrolyte imbalance
Irritability
Depression/anxiety
Hormonal imbalance
Frequent urination
Brain fog
Diarrhea/constipation
Skin problems/dermatitis
Dream changes
Sleep problems

As you can see, that is quite a laundry list of symptoms.  It is important to realize that a person who experiences either adrenal fatigue or iodine deficiency/bromide toxicity may not have all of those symptoms and may have separate symptoms that are not listed.  These are just the common symptoms that tend to be reported in people with adrenal fatigue and/or iodine deficiency/bromide toxicity.  In addition to these symptoms, both adrenal fatigue and bromide toxicity have similar treatments as well.  These treatments include high doses of salt, vitamin C, and magnesium.  As you can see, a relationship begins to emerge just by looking at common symptoms and treatments.  Let's take a look at some of the science to identify how these seemingly unrelated conditions can have such a strong relationship.

Adrenal fatigue, iodine deficiency, bromide toxicity, and electrolyte imbalance

In his book Adrenal fatigue: The 21st century stress syndrome, Dr. James Wilson points out that many of the symptoms of adrenal fatigue are related to an electrolyte imbalance(4).  This is primarily due to low levels of the mineralocorticoid aldosterone.  When sodium levels in the body become too low, aldosterone is secreted by the adrenal glands and acts on the kidneys to reabsorb sodium and water and excrete potassium in the urine.  Aldosterone can be stimulated in multiple ways including via adrenocorticotropin hormone, the renin-angiotensin system, or simply by high potassium levels.  Since adrenocorticotropin hormone is also responsible for secretion of cortisol, it appears to be the link between cortisol and aldosterone in adrenal fatigue.  However, the link between aldosterone and the renin-angiotensin system appears to be the link between iodine deficiency/bromide toxicity and adrenal fatigue.

The renin-angiotensin system helps regulate blood pressure via fluid and electrolyte balance.  When blood pressure is low, the kidneys secrete renin which converts angiotensinogen in to angiotensin I.  Angiotensin I is then converted to angiotensin II which acts on blood pressure by constricting blood vessels as well as signalling the adrenal glands to secrete aldosterone.  Aldosterone then signals the kidneys to recycle sodium and water in to the blood to bring blood pressure back up.  In situations where aldosterone is low, sodium is wasted and blood pressure drops further.  Needless to say, low levels of renin will have the same effect since renin helps to stimulate aldosterone release.  In adrenal fatigue, aldosterone levels are typically low which causes salt wasting in the urine which then leads to an imbalance in the ratio of sodium to potassium.  In adrenal fatigue, licorice root is given to allow cortisol to attach to mineralocorticoid receptors and mimic the effects of aldosterone on the kidneys by recycling sodium and dumping potassium via the urine.

Increasing sodium consumption will help with any symptoms associated with a low sodium to potassium ratio; however, administration of sodium chloride in the form of salt decreases renin activity.  It seems logical that this is mediated by an effect of high sodium levels causing decreased plasma renin activity(PRA) in response to an increased sodium to potassium ratio.  This does not appear to be the case, however.  In humans, PRA is suppressed by sodium chloride but not sodium bicarbonate(5).  The effect of salt intake on PRA appears to hold true for bromide as well.  PRA decreased by nearly 50% with the administration of sodium chloride and sodium bromide but not with sodium bicarbonate or nitrate.  In addition, lysine monohydrochloride but not lysine glutamate had a similar effect, indicating a renal effect of bromide and chloride on renin activity rather than of sodium(6).  Whether this holds true for all of the halides has not been elucidated.  Regardless, high serum levels of bromide appear to have a very strong effect on sodium wasting via a reduction in PRA.


The intake of salt in the form of sodium chloride is a very powerful therapy in both adrenal fatigue and bromide toxicity.  In the treatment of adrenal fatigue, salt is used to relieve the symptoms caused by electrolyte imbalance as well as to nourish the adrenals.  In bromide toxicity, salt is used to increase the excretion of bromide.  One of the primary ways of removing bromide from the body is with the use of sodium chloride.  Increased sodium chloride intake increases bromide loss via the urine in dogs and humans and improves bromide induced dermatitis in humans(7).  Increased intake of sodium chloride in rats considerably reduces the half-life of bromide.  In 2 studies by the same authors, administering sodium in the form of 5 different salts, including sodium chloride and bicarbonate, had the same effect on the rate of bromide excretion which was proportional to sodium excretion in all 5 cases under the same sodium intake.  The authors concluded that the excretion of bromide is dependent on sodium intake rather than chloride(8, 9, 4). In addition, the proportion of bromide and sodium excretion are constant at a given sodium intake and increase with the amount of sodium ingested.

This does not mean that chloride does not also have an effect on bromide excretion.  In addition to being a halide and competing with bromide on receptors in target tissues, the sum of chloride and bromide in extracellular fluid remains constant at 110mmol/l(2).  Increasing one will cause a concomitant drop in the other as it is excreted via the urine.  In addition, bromide half-life in rats varied with chloride intake from 2.5 days with high chloride intake to 25 days under low chloride intake(10).  There doesn't appear to be a synergistic effect of sodium and chloride on bromide excretion nor does it make sense to use a different form of sodium such as sodium bicarbonate in terms of increasing bromide excretion.  However, there may be benefit to using sodium bicarbonate for bromide excretion to avoid the negative effect of reducing PRA.  As you will see shortly, PRA has a very strong impact on sleep quality.

Decreased PRA is associated with increased wakefulness and a decrease in sleep efficiency index.  PRA activity is higher during non-REM sleep, but PRA had no relationship with cortisol levels(11).  Multiple studies have established a strong link between PRA and sleep stage.  Specifically, PRA drops as someone enters REM sleep and increases during non-REM sleep(12, 13, 14, 15), with entering REM sleep leading to a near complete cessation of renin release(13).  In addition, peak levels of renin occurred during the transition from deep sleep to light sleep and the initiation of rises in PRA occurred in the transition from REM to stage 2.  All sleep disturbances and irregularities were reflected in deviations from the normal PRA curve.  Finally, both provoked and spontaneous awakenings blunted the rise of PRA found in deep sleep(14). Given the fact that sleep disturbances are both a strong contributor to and a primary symptom of adrenal fatigue, these relationships provide strong evidence that adrenal fatigue and iodine deficiency/bromide toxicity are related by changes in sleep quality.

Another interesting relationship worth exploring is that of magnesium with PRA.  High plasma magnesium levels have a strongly positive relationship with the release of renin by the kidney of dogs(16) as well as rats(17, 18) and humans(19).  However, this relationship seems to be flipped in people with hypertenson(19, 20) and may be a result of a decreased pool of intracellular magnesium due to abnormal intracellular magnesium metabolism(21).  Interestingly enough, while magnesium has an effect on renin release, it appears to decrease aldosterone release in rats(17) and humans(19).  In addition, magnesium deficient rats have higher levels of aldosterone secretion than magnesium sufficient rats(17).  One thing most users of supplemental magnesium notice, particularly those with adrenal fatigue, is an improvement in sleep quality.  Magnesium is also used in the treatment of iodine deficiency and bromide toxicity, further strengthening their relationship to adrenal fatigue.

Conclusion

All of the evidence described above points to a strong relationship between adrenal fatigue, iodine deficiency, and bromide toxicity.  It is difficult to draw hard conclusions with this evidence since a lot of it is not done in humans, but there is certainly enough evidence to support the notion that people with adrenal fatigue should be tested for iodine deficiency and bromide toxicity.  While there is strong evidence that they are related, we do not know whether one causes the other or they share a separate variable; whether they are related in a large number of cases or only a few; and how iodine deficiency and bromide toxicity relate to low or altered cortisol levels.  In addition to the effects of bromide on sodium loss, iodine is found in significant concentrations in the adrenals and there is the potential for there to be a direct effect of iodine deficiency on adrenal function, but this has not been studied.  A few other questions emerge as well.  One question worth answering is if bromide and sodium excretion levels are constant at a given sodium intake, does this mean being in a low sodium state increases the likelihood of bromide accumulation in the blood and, in a state of iodine deficiency, in the cells as well?  Could the natriuresis of fasting associated with low carb diets exacerbate this effect with inadequate sodium intake?  Are the negative effects of very low carb diets on sleep and thyroid function caused by iodine deficiency and/or bromide toxicity and can this be avoided with adequate iodine and salt intake?

There are other avenues worth exploring with the relationship between adrenal fatigue, iodine deficiency, and bromide toxicity.  Digestive problems are associated with both adrenal fatigue and bromide toxicity.  Since bromide concentrates in the gastric mucosa, is secreted into the stomach, and is known to replace chloride in other tissues, there is the potential that hydrobromic acid could be produced rather than hydrochloric acid and interfere with digestion.(1).  In addition, given that the sodium calcium exchanger is highly expressed in the smooth muscle cells of the intestinal wall, could a drop in sodium levels caused by increased exposure to bromide slow peristalsis and impact digestion by increasing the amount of time food spends in the digestive tract?  Is a reduction in the sodium to potassium ratio a contributor to poor digestion in adrenal fatigue?  As you can see, there are many unanswered questions in this relationship.  At this point it seems prudent to begin testing people with adrenal fatigue for iodine deficiency and bromide toxicity in integrative/functional medicine clinics to help provide some of the answers clinical research is unlikely to answer.

For more information on adrenal fatigue, consult Adrenal fatigue: The 21st century stress syndrome by Dr. James Wilson.

For more information on iodine deficiency, consult Iodine: Why you need it, why you can't live without it by Dr. David Brownstein.

For more information on properly supplementing with iodine consult this blog.

Iodine part 3: Factors affecting iodine status, testing and supplementiation

Over the previous two parts of this blog series we've discussed the roles of iodide/iodine in the body as well as how changes to the food system have negatively impacted iodine status.  In the final blog in this series we will discuss how certain things impact iodine status, how you can test your iodine status, and what you need to know about supplementing with iodine.  This information is directly from the protocol used in the Iodine Project and is the work of Dr. Abraham, Dr. Flechas, and Dr. Brownstein.  If you are considering iodine supplementation and have any sort of thyroid issues you should use iodine under the care of a doctor of integrative medicine.

At the end of the last blog we discussed the removal of iodine from bread back in the 70s.  As a result, Americans are excreting 50% less iodine than they did back then.  To make matters worse, they replaced iodine with something called bromine.  Bromine, iodine, fluorine, chlorine, and astatine belong to a class of chemical elements called halogens.  The halogens are highly reactive elements that can react with other compounds by stealing an electron.  When they do this they are called halides and can interchangeably bind to the receptors on your cells.  Chloride and iodide are both important for health, fluoride is often used to prevent cavities, and bromide doesn't appear to be necessary and can be potentially harmful.  Whether bromide is toxic or not, I believe it is, it is certainly problematic for people low in iodide, as is fluoride.  While there is no hard evidence to indict bromide at very low levels, high levels are certainly toxic.

Where do we find bromide?

As mentioned above, you can find bromide in bread and other bakery products since iodine was replaced with bromide.  You can also find brominated vegetable oil(BVO) in citrus flavored soft drinks like Mountain Dew, some energy drinks, and formerly in Gatorade.  In 2013, an online petition asked PepsiCo to stop putting BVO in Gatorade.  The impetus for the petition was that Europe, India, and Japan do not allow BVO for use as a food additive as they regard it as unsafe.  Since Gatorade is sold in those countries, there is already a formula without BVO so there is no reason to put a potentially toxic substance in it.  The petition was successful and Pepsi removed the BVO from the citrus Gatorade flavors in 2013.  Bromide-based pesticides are also used on the food supply, mostly in strawberries.

Despite there being some uses in the food supply, bromide is primarily an environmental toxin.  Bromide can be found in plastics, certain medications(Atrovent and some anesthetics), bromine pool and hot tub treatments, and as a fire retardant in mattresses, carpets, and upholstery/car upholstery.  Adding evidence that bromide is primarily an environmental toxin, a study performed in 1997 found that in healthy adults living in Beijing, the lungs had the highest tissue levels of bromine(1).  Furthermore, the authors stated that the tissue levels of bromine in subjects from this study were significantly lower than people from other countries.  While it is certainly possible that the lungs just happen to be an area where bromine accumulates, it seems unlikely that an ingested substance would specifically accumulate in the lungs, especially one that can interchangeably bind to iodide receptors in the body.  Since Asian cultures tend to eat high levels of iodide in the form of seaweed, iodide may "boot" bromide from the body with the exception of bromide's point of entry or areas where the sodium iodide symporter(NIS) is lacking.

Bromide toxicity

Bromide was used over the counter as a sedative and remedy for headaches until 1975 when it was removed from over the counter use as well as prescription medicine due to chronic toxicity(2).  Bromide's extremely long half life in the blood of 12 days causes levels to build up in the body over time and makes it difficult to dose.  Most of the acute side effects associated with bromide use are neurological in nature, but chronic toxicity affects the endocrine and reproductive systems in animals(3).  In rats and mice, bromide toxicity has been shown to effect the pituitary gland, adrenal gland, thyroid gland, prostate gland, testes, and ovaries with very high doses.  Probably the most important gland to look at in regard to bromide toxicity is the thyroid gland given bromide's classification as a goitrogen.

Goitrogens

Goitrogens are substances that interfere with thyroid function and can lead to goiter.  In the case of bromide and the other halides, low intake of iodide causes the other halides to take up space on the NIS, blocking iodide uptake.    Studies in rats have shown bromide to take the place of iodide in the thyroid with a concomitant drop in thyroid hormones with high bromide intakes(4, 5) as well as reducing the half-life of iodine by 2/3rds(5).  Cruciferous vegetables such as broccoli, kale, and cauliflower are also considered goitrogens.  Their effects are mediated by glucosinolates that can form thiocyanates that compete with iodide at receptors on the symporter or goitrins that directly interfere with thyroid hormone synthesis(6). In addition to competing with iodide at the thyroid, bromide also causes elimination of iodide from the skin(7), but there is no evidence cruciferous vegetables do the same.  Cooking inactivates some of the goitrogens found in cruciferous vegetables.

One has to be careful to not put the horse before the cart when looking at the goitrogenic effects of food.  There are many beneficial effects to eating cruciferous vegetables including cancer prevention(8) as well as meeting your nutrient needs for the day.  High exposure to goitrogens merely means your iodine needs increase and that low to moderate iodine intake is not sufficient(9, 10, 11).  Since there are no beneficial effects to being exposed to bromide, it should be avoided altogether and your exposure to elements that may contain it(Pools, plastics in computers, and fire retardant materials in furniture and upholstery) should be considered when calculating your daily need for iodide.  In addition, while fluoride appears to be beneficial when applied to the teeth, there is no evidence of it being beneficial when ingested.  This is a problem because most of the water supply in the United States is fluoridated.

Testing for iodine sufficiency

All of this evidence points to the importance of determining whether you are iodine sufficient or not.  There are far too many factors to make a blanket recommendation for an RDA for iodine.  People who eat high levels of goitrogenic foods, work in in the furniture industry, work with bromide-based chemicals, use Atrovent, or spend a lot of time in their car probably have a higher iodine requirement than people who don't fit any of that criteria.  One of the least effective ways to measure iodine is in the serum.  Iodine, like magnesium, is primarily found inside cells.  Measuring your iodine levels by measuring the amount of iodine in your blood would be like measuring the amount of gas in your car by how much is in your fuel line.  Your fuel line will be full up until the point your gas tank becomes empty, at which point your fuel line will empty almost immediately.  The current standard for measuring iodine sufficiency is the urinary iodine spot and 24 hour loading test.

The urinary iodine spot test measures the iodine level in your urine upon awakening and is used as a reference value.  The 24 hour urinary iodine loading test involves taking 50mg of Iodoral after the spot test and collecting your urine for 24 hours, including the first urination on the next day.  The amount of iodine in your urine is used to determine what percentage of the iodine you retained in your body.  Healthy people excrete 90% of ingested iodine in the urine, so people with levels lower than that are said to be deficient in iodine as their body attempts to retain more.  In addition, you can also measure bromide and fluoride levels in the urine to identify whether or not you have high levels of either halide.  There are no randomized clinical studies supporting the use of this test to determine iodine sufficiency.  However, the physicians in the Iodine Project who have been using this test as well as treating patients with iodine find that the level of iodine excreted in the urine is inversely related to the severity of symptoms and that the test and symptoms improve over time with proper supplementation iodide/iodine(12, 13, 14,) (Note: Dr. Abraham, referenced in 12 & 13, makes Iodoral and therefore has a financial interest in both iodine supplementation and the test, which uses 50mg Iodoral as the iodine load).  You can order the 24 hour urinary iodine lading test from FFP laboratories and do not need a doctor's prescription.

Supplementing with iodine

Seaweed, fish, eggs, dairy and iodized salt are the primary sources of iodine in the diet.  The iodine content of seaweed varies by the type of seaweed and the iodine content of dairy depends on the diet of the animal was well as the type of teat cleanser the farmer uses as iodine based teat dips cleansers absorb in to the udder and get in to the milk.  However, chlorine can also be used and may increase competition with iodine as it is also a halogen.  While I think seaweed is probably sufficient for getting your iodine needs, the other foods are probably not going to get you to an adequate intake.  If you don't eat seaweed, the only way you are going to meet your iodine needs is through supplementation.  If you are deficient in iodine, supplementation is probably your only option.  I tend to recommend food over supplementation in most cases; magnesium, fish oil, and iodine are the only exceptions.  Let's take a look at supplementing with iodine.  (Note:This information is taken from the recommendations of Dr. Abraham and Dr. Brownstein of the Iodine Project. This is from their practical experience working with thousands of patients, there are no randomized clinical trials supporting this protocol.  I have experience with it and will discuss that in part 4)

Dosage

The dosage of iodine you choose is dependent on many factors including exposure to goitrogens.  There are iodine deficient people supplementing with 150mg of iodine(3 orders of magnitude higher than the RDA) with no ill effects.  This level of intake is pretty severe and more than likely unsafe unless doing so under the supervision of a physician.  The smartest approach to determining your dosage of iodine is to start a little above the RDA(200mcg) and double it every couple of weeks.  As long as you also take the companion supplements that will be discussed later you can probably start safely at double this number.  Since you will be starting at such a low dosage, it will probably not be possible for you to use Iodoral until you reach 4mg of iodine(1/4 of a 12.5mg Iodoral).  You can use any brand of potassium iodide until then, just make sure you determine your dose by the amount of iodide and not the total amount of potassium iodide.

Research by Eskin et al, found that iodide and iodine each seem to accumulate more in different tissues with iodide accumulating more in the thyroid and iodine accumulating more in the breast tissue of rats(15).  Because of these findings and the fact that so may tissues seem to require iodine/iodide, the best course of action is to supplement with both as soon as possible.  The only products I know of that contain both are Lugol's solution and Iodoral, but there are more than likely other options or combinations you can use to get both in supplement form.  As always, you should discuss supplementation with your doctor and if you have a thyroid condition you should be using iodine supplementation under their supervision.

One of the primary determinants of the dosage that is best for you is the presence of bromine related detoxification symptoms.  The bromine related detoxification symptoms can be found here.  If you experience any of these symptoms, you are clearing bromine from your tissues faster than your detoxification system can remove them.  Many people ignore these symptoms if they are minor(I did) and work up to a dosage of 50mg over time.  At a dosage of 50mg, the doctors of the Iodine Project state that most people will reach iodine sufficiency in 3 months.  Of course, there will be variability in this number and that will be dependent on your score on the 24 hour iodine excretion test.  Taking this test at regular intervals is a good idea to make sure iodine supplementation is working.  In some instances there are other issues such as a defective symporter that can increase the time it takes to reach iodine sufficiency.  There are companion supplements to take that cover these issues and some of the other issues that may arise.

Companion supplements

Selenium
Selenium plays an important role in the thyroid.  It supports efficient thyroid hormones synthesis and is also needed to convert T4 to the active T3.  Supplementing with iodine while deficient in selenium can make a thyroid problem worse and vice versa.  Chris Kresser wrote a terrific article covering the use of selenium that can be found here.  You will want to get approximately 200mcg of selenium.  It's best to get a selenium complex that contains multiple forms of selenium.

Vitamin C
Vitamin C is a powerful antioxidant and is very useful in supporting the liver while the body detoxes.  Based on case reports and the experience from physicians in the Iodine Project, vitamin C also helps improve a defective sodium iodide symporter(16).  Aim for 3000mg or more of vitamin C per day depending on the severity of your detox symptoms and be sure to spread the dosage out throughout the day as much as possible.  If you take too much vitamin C at one time you could experience loose stools.  It is also important to taper down your dosage slowly if you decide to stop taking it as a sharp drop in vitamin C intake can simulate the symptoms of vitamin C deficiency.

Magnesium
Magnesium helps the body detox and is used in over 300 enzymatic reactions.  Since most people are probably deficient in magnesium it is a good idea to take it in supplement form.  Aim for 500mg of elemental magnesium per day of a more time released form of magnesium.  I use Jigsaw Magnesium w/SRT which is dimagnesium malate but other people have gotten good results from magnesium glycinate or citrate.  Magnesium oxide often causes loose stools so use it at your discretion.  If you have any sort of kidney pathology you should discuss magnesium supplementation with your doctor.

Vitamins B2 & B3
The doctors in the Iodine Project have found that supplementing with vitamins B2 and B3 help increase the absorption of iodine.  Aim for 100mg of B2 as riboflavin and 500mg of B3 (Not niacinamide) in a time released form per 50mg of iodine.  The doctors of the Iodine Project have a formula called ATP cofactors that they use with their patients.  This dosage of B2 and B3 will definitely turn your urine bright yellow.

Salt
Salt is used to help support the adrenals and speed up the excretion of bromide.  The doctors of the Iodine Project have found that supplementing with 1/2 tsp of unrefined celtic sea salt dissolved in to a glass of water 2 times a day has helped with bromide detox symptoms.  In addition, bromide half-life has been shown to be dependent on sodium intake in rats(17).  The sodium in salt is also used to increase iodide uptake by powering the sodium iodide symporter.

Conclusion

Over the course of this three part series on iodine we have discussed why the RDA for iodine is low, how environmental exposure to bromide increases iodine needs, how factors in the diet can contribute to low iodine status, how changes to the food system have decreased the amount of iodine we consume, and how to safely supplement with iodine.  The protocol used by the doctors in the Iodine Project is based off their practical experience treating thousands of people as well as the experience of thousands more from the Curezone and Yahoo Iodine groups.  I am currently halfway through using this protocol and will give my personal take in part 4 of this blog series once I have completed the high dose phase and enter a maintenance dose.  The results thus far have been pretty amazing.  If you decide to implement an iodine protocol it's wise to consult a physician familiar with using high dosage iodine.

Part 1    Part 2

Iodine part 2: Where did it go and and why the RDA may be inadequate

In my last blog on iodine located here, we went over the many functions of iodine in the body and iodine's potential role in cancers of the stomach, ovaries/cervix, and the breast.  Needless to say many people may wonder if they are getting enough iodine in their diet.  While you may get enough iodine based on the very low RDA value, if you aren't eating seaweed or plenty of salt you are probably deficient from an optimal health standpoint.  The truth of the matter is, iodine has been slowly removed from the diet and our health has suffered as a result.  Let's take a look at how our diets have changed with regard to iodine.

Where did the iodine go?

In the early 1900s, landlocked areas in the US (the Great Lakes, midwest, and northwest mountainous regions) experienced an epidemic of goiter, swelling of the thyroid gland due primarily to iodine deficiency.  These regions have soil that is deficient in iodine as there is no access to the sea, the predominant source of iodine.  Since the soil is deficient in iodine, plants grown in that soil are deficient in iodine as well.  As a result, the people in these areas became iodine deficient and, in response, their necks swelled as their thyroid glands grew to trap more iodine from the bloodstream.

Map of the goiter belt

Taken from learnendocrinology.blogspot.com

In order to fight this goiter epidemic, iodide was added to salt because salt consumption was fairly stable at the time.  This successfully solved the goiter epidemic, but did it solve the iodine deficiency problem?  There is no way of knowing for sure, however, a study done in Italy in 2006 found that despite there being a very low prevalence of goiter in Piedmont school children, 39% had low urinary iodine excretion levels suggesting that the absence of goiter may not indicate iodine sufficiency(1).  There are a couple of important ways iodine has been removed from the diet and levels are lower today than they were 40 years ago.

One of the ways that iodine has been removed from the US diet is via poor food recommendations given out by the USDA.  It is currently considered good practice to reduce salt and egg consumption to help improve the risk of heart disease.  Removing these two products from the diet greatly diminishes the iodine content of the diet as they are 2 of the more significant sources of iodine.  In addition, most people have made the switch from iodized salt to sea salt because they have been told that sea salt is better.  The sea salt most people consume does not contain any source of iodine or iodide, which is plainly written in small letters on every bottle. It's also ironic that most people who consume sea salt are consuming refined sea salt which can be seen when looking at the color of the salt.  If it's white and clean looking you are essentially just eating rocks of table salt without iodine added, all of the beneficial minerals that make sea salt healthy have been removed in the refining process.  So not only are you not getting any iodine, you aren't getting any of the benefits from sea salt either.

Another interesting fact that people don't realize is that up until the 1970s, iodated bread conditioners were used in breads to increase shelf life.  Each slice of bread contained 150mcg of iodine, an amount equivalent to the RDA for adults.  However, due in large part to a study performed in 1948 on rats by Wolff and Chaikoff(2), iodine was slowly being removed from the medicine cabinet and our food supply.  In the study, the authors concluded that when serum levels of iodine reached a certain level, the thyroid stopped making thyroid hormones, an effect now called the Wolff-Chaikoff effect.  This is a temporary phenomenon, perhaps being an artifact of the body adapting to a change in the internal environment that reverses itself in 2 days.  The problem is that they never measured blood levels of the thyroid hormones in this study, and these findings have never been confirmed in humans.  So while the thyroid gland may have temporarily stopped making thyroid hormones, we have no idea if this reflected a drop in circulating serum thyroid hormones.  In addition, attempts to reproduce the Wolff-Chaikoff effect in rats have failed.

Two of the biggest problems with the findings of the Wolff and Chaikoff studies is that iodine had been used liberally in medicine up until that point successfully for many conditions and the Japanese, who are considered much healthier than most populations, consume enormous quantities of iodine from seaweed in comparison to the RDA and the findings of the Wolff-Chaikoff study.  In a later paper published by Wolff when he was with the National Institute of Health(NIH), Dr. Wolff identified consumption of iodine in excess of 200mcg as problematic and levels above 2000mcg(2mg) as potentially harmful(3).  What is odd about these recommendations is that the vast majority of Americans would consume well above 200mcg by simply eating 2 slices of bread, and there was no epidemic of thyroid disorders back when this was the standard.  In fact, thyroid disorders have actually increased since iodine consumption has been reduced.  It doesn't end there, when you look at the levels of iodine consumed by the Japanese, these recommendations look even more foolish.

It is currently estimated that the Japanese consume an average of 1-3mg of iodine per day in the form of seaweed(4).  Judging by the data they compiled, two things are evident.  First, while the average consumption of iodine by the Japanese is between 1-3mg/day, there appears to be large variability in consumption levels.  The largest study in this review contained 4138 subjects and found a mean urinary iodine content of 3300mcg/L.  Since the average person urinates 2L/day, this would lead to a daily urinary excretion of 6600mcg of iodine per day which would indicate an intake of 7333mcg/day, 37 times what is considered harmful in the Wolff paper.  Secondly, as the Japanese have adopted more of a Western diet, iodine consumption has dropped considerably as can be seen by the fact that iodine consumption is much higher in the older Japanese generation in comparison to younger ones(4).  In addition, Japanese people who move to the United States have much higher rates of the diseases reported in part 1 of this blog than do Japanese people remaining in Japan(4).

One final example of the use of high levels of iodine can be found by perusing the iodine forums on curezone.  Led by Drs. Abraham, Brownstein, and Flechas; many people are ignoring the recommendations of Wolff-Chaikoff and using very high doses of iodine to reverse many of the issues discussed in part 1 of this blog series.  These people are using 50mg, 100mg, and even 150mg of iodine successfully to help with a range of issues.  This has spawned many books including Dr. Brownstein's, Iodine: Why you need it, why you can't live without it as well as The Iodine Crisis by Lynne Farrow.  In the Iodine Crisis, Farrow reports many of the cases of successful use of high dose iodine found on curezone as well as at her site www.breastcancerchoices.org.

There is no doubt iodine consumption has decreased substantially since these changes have been implemented to our food system.  The National Health and Nutrition Examination Survey (NHANES) has looked at nutritional intake since 1971.  Between 1971 and 1999, urinary iodine excretion dropped by 50%(5).  However, researchers consider the US population to be iodine sufficient because the level of iodine found in the urine indicates that iodine consumption approximates the 150mcg RDA for adults.  That is, of course, assuming you believe 150mcg to be an adequate amount of iodine.  One of the odd things about this data, however, is that the urinary iodine excretion from the 1970s would indicate significant iodine excess by the Wolff criteria.  Despite the potential iodine excess back then and more appropriate iodine intake according to Wolff now, thyroid disorders as well as breast cancer rates have increased substantially over this time period.  Breast cancer rates in the 1970s were 1 in 20 and have increased to in 1 in 7 today.

If iodine sufficiency is attained at 150mcg or iodine per day, you would assume that higher intakes would just lead to more iodine excretion in the urine.  A study done by Koutras et al. in 1964 found that with increasing iodine intakes up to 800mcg/day, the body accumulates up to 7mg of iodine over the course of 12 weeks with no change in thyroid output(6).  This would indicate that not only is 150mcg of iodine per day not adequate to become iodine sufficient, the iodine is being used by tissues other than the the thyroid gland.

Conclusion

Changes to the food system have substantially decreased the iodine intake of people in the United States.  While urinary iodine excretion levels indicate iodine sufficiency, the data currently used to recommend iodine intake is not adequate.  It seems foolish to use a single study performed in rats as a basis for recommending the intake of any nutrient for humans.  While it seems safe to say that the RDA of iodine is adequate to prevent goiter, it seems like a pretty big jump to use it as the basis for total body iodine sufficiency based on a study in rats.  Further studies are needed to identify the level of iodine in the diet necessary for optimal health.  Given that the Japanese as well as other Asian cultures consume far more iodine than Americans and tend to have better health outcomes indicates that higher levels of iodine intake are, at the very least, tolerated very well and, at best, better for your health.  This wide range of tolerable iodine intake coupled with the temporary nature of the Wolff-Chaikoff effect indicates that this effect may merely be the body adapting to a rapid change in iodine intake and not due to the damaging effects of high iodine intake.

In the final installment of this series we will look at the iodine loading test, how to safely use high levels of iodine from food or supplements, and factors that may increase your iodine needs.  While removing iodine from bread may have been a bad idea, what they replaced it with may have made matters far worse.

Part 1

Iodine: Do you get enough and is the RDA adequate?

A month or so ago I decided I was going to do an article on iodine, and lo and behold Science Daily publishes a story on iodine deficiency being on the rise in developed countries.  For the most part, iodine deficiency is thought to only affect people in undeveloped countries because the US added iodide to salt back in the 1920s to combat goiter in landlocked states that didn't have access to soil or foods rich in iodine.  It worked, but perhaps this is one of the answers to increasing iodine deficiency in developed countries; who uses iodized salt any more?  In this two part series we will look at the roles of iodine in the body and how and why iodine levels have declined over the past forty years.  Let's take a look at iodine, element number 53 on the periodic table of elements and something I've found to be critically important to health and wellbeing.

Iodine vs Iodide

You will often see iodine and iodide used interchangeably when referring to the biological roles of iodine.  Iodine refers to the atom iodine(I) or the molecule iodine(I₂) while iodide is the negatively charged ion of iodine (I^-).  Most of the iodine on the planet is in the iodide form as it is water soluble.  Molecular iodine(I₂) is toxic and should not be consumed orally.  Iodide(I^-) is taken up by the thyroid where it is converted to iodine (I) and added to tyrosine to make the thyroid hormones T3 and T4, a process we will discuss in depth a little later.  Unless specifically noted, I will use iodine for both iodine(I) and iodide(I^-) within this article.

What foods contain Iodine?

Iodine is found in high concentrations in seawater, so foods that come from the ocean tend to be the best sources of iodine.  This includes sea vegetables such as seaweeds as well as fish.  Iodine is also found in many land foods such as broccoli, spinach, milk, and eggs.  The caveat with land foods is that the soil that they are grown in or, in the case of animals, the soil that the foods they eat are grown in must be high in iodine.  This is why it's important to rotate crops, if you continually grow spinach in the same soil it will deplete that soil of iodine and decrease the iodine content of foods grown in that soil.  Taking it a step further, animals who eat food from iodine deficient soil will also be deficient in iodine.  This is why looking up the nutrient contents of foods can be deceiving, while nutritionata may state that a food has x amount of a nutrient, there's no way they can tell what the condition of the soil the food was grown in is like.

A perfect case of this is the goiter belt, an area that encompasses the Great Lakes, Midwest, and mountainous areas where the soil is deficient in iodine.  People in the goiter belt are particularly prone to goiter, an enlargement of the thyroid gland.  As these people become deficient in iodine, their thyroids enlarge in order to trap more iodine from the circulation.  In 1924, iodized salt was introduced successfully to combat goiter in these areas.  In fact, the FDA recommendation of 150 mcg per day of iodine appears to be the dose of iodine necessary to prevent goiter.  This doesn't, however, mean that this is the optimal dosage for human health.

Thyroid gland and enlarged thyroid gland (Goiter)

Taken fromhttp://nandabooks.blogspot.com/2012/10/nursing-care-plan-for-goiter-assessment.html

Iodine and thyroid function

Iodine plays a significant role in thyroid function.  Thyroxine(T4) and triiodothyronine(T3) are the two hormones secreted from the thyroid gland that help regulate cellular metabolism(Energy production).  They get the names T4 and T3 because the number corresponds with the number of iodine atoms contained within each.  While T4 is the most abundant thyroid hormone, T3 is the far more active one.  T4 is broken down to T3 inside cells by selenium containing enzymes where it increases energy metabolism.

Iodide is trapped by the sodium iodide symporter of the cells of the thyroid gland from the bloodstream and imported in to the thyroid where it is converted to iodine.  In the case of iodine/iodide deficiency, the thyroid lacks one of the key components it needs to make thyroid hormones.  This causes an increase in thyroid stimulating hormone (TSH), a hormone that signals the thyroid to make more T4.  In an effort to trap more iodine from the bloodstream, the thyroid gland enlarges and produces a goiter.  In mild iodine deficiency, TSH levels may be normal because the body compensates by converting more T4 in to T3.  In this instance there may be a goiter present in someone with normal TSH levels.  However, the cells of the body require selenium to convert the inactive T4 in to the active T3, so if the person is selenium deficient this conversion cannot happen.  Selenium's role in converting T4 to T3 make it essential in protecting the thyroid while supplementing iodine.  In the acute sense, if a person with a goiter is given sufficient iodine and selenium the goiter will go away.  If the goiter has been untreated for five or more years, iodine therapy may not be able to get rid of the goiter.

Side view of a person with a goiter

Taken from http://www.taytan.com/images/goiter.jpg

Given that thyroid hormones regulate energy metabolism in all of your cells, you can see how important getting sufficient iodine is.  Cells that have insufficient thyroid hormones won't produce energy properly and, therefore, won't be able to perform their role in the body.  Muscle cells won't contract properly, neurons won't fire properly, and all cells will not be able to replicate properly.  Any process that requires energy will be affected, which is nearly every process.  As such, every system can be affected including the digestive system, immune system, nervous system, endocrine system, basically every system of the body.  The role of iodine doesn't end at the thyroid hormones, however, let's take a look at other roles iodine plays in the body.

Roles of iodine in the body

While most people associate iodine with the thyroid hormones, iodine also has other functions outside of this role.  A sodium iodide symporter (Primary transporter of iodine in to cells) has been found in the stomach mucosa and thymus gland(Part of the adaptive immune system).  In addition, the mammary glands of lactating mothers and the salivary glands concentrate amounts of iodine equivalent to the thyroid gland.  Finally, the skin, joints, arteries, bone, cervix, and choroid plexus all take up significant amounts of iodine(1).

Researchers have theorized that iodine may have an antioxidant effect in humans (1, 2).  This hypothesis comes from studies in animals that have shown an antioxidant role of iodide in the brain of rats(3) as well as the eyes of rabbits(4).  Furthermore, iodine deficiency has been show to increase oxidative damage in the thyroids of rats and mice as evidenced by an increase in the expression of antioxidant defense genes(5).  In humans, the thyroid and breast both concentrate large quantities of iodide and a have a highly efficient ability to neutralize hydrogen peroxide(H₂O₂), a potent free radical, by donating an electron from the iodide to the H₂O₂.  In the thyroid, the remaining iodine combines with tyrosine to make the thyroid hormones(6). It is theorized that low iodide leads to high levels of thyroid stimulating hormone (TSH) which produces higher levels of H₂O₂ that, since they are not being used to help produce thyroid hormones, cause oxidative stress to the thyroid gland.  This could be the beginning pathology that leads to thyroid cancer(7, 8).

There is strong epidemiological evidence that points to iodine deficiency playing a role in breast (1, 8, 9, 10), gastric(8, 11, 12, 13)  and ovarian cancers (10).  While there is conflicting evidence showing no role of iodine deficiency with gastric cancers(14) and the role of iodine deficiency hasn't been studied often in ovarian cancer, the role of iodine deficiency in breast cancer appears to have strong support and little evidence to contradict it.  People with iodine deficiency induced goiter are three times more likely to be diagnosed with breast cancer than the general population(1).  Furthermore, researchers have found a significant difference in urinary iodine excretion rates and women with breast cancer(9).  Urinary iodine content is a valid way of identifying iodine intake, has been used in multiple studies(10), and is a way to determine iodine sufficiency; something that will be discussed in part two of this blog.

In a study on iodine and breast cancer cells, molecular iodine induced apoptosis in 4 out of 5 breast cancer cell lines(15).  Apoptosis is programmed cell death and is a necessary measure the body uses to get rid of abnormal cells.  One of the hallmarks of cancer cells, along with higher levels of oxidative stress, is that they somehow manage to become resistant to apoptosis.  In vitro, iodine induces apoptosis in tumor cells while providing protective effects in non-tumor cells(16).  In an analysis published in the Journal of American Physicians and Surgeons in 2006, Miller provided a very thorough analysis of the association between iodine deficiency and fibrocystic breast disease(1). The two primary studies referenced in this analysis showed a 70% success rate in treating fibrocystic breast disease with iodine.  All of this evidence points to an important role of iodine in breast health.

Recommendations for iodine intake

The US RDA for iodine is 150mcg for adults, with an increase to 220mcg for pregnant women and 290mcg for lactating women.  The discrepancy between the RDAs is due to the nutritional needs of the fetus during pregnancy and developing child during breast feeding.  These numbers appear to be the amount of iodine required to prevent goiter in the general population and to prevent cretinism and mental retardation in the children of pregnant and nursing mothers.  The problem is that these numbers do not necessarily reflect what is optimal.  This is the problem with some of the RDAs of micronutrients as most were developed to prevent diseases of malnutrition such as rickets and scurvy and do not necessarily reflect what is optimal to human health.  In addition, the RDAs are merely snapshots in time and do not reflect increased nutritional needs that may occur due to changes in the environment as well as the food environment.  This is very important as certain environmental changes can increase or decrease your need for specific nutrients, particularly iodine.

Conclusion

As you can see, iodine has many roles in the human body.  While it's role in the thyroid hormones is critical to human health, it is important not to be myopic and ignore the other roles it plays in the body.  In part two of this series we will discuss environmental and food factors that may contribute to iodine deficiency as well as a new grass roots campaign forming over the internet with doctors and patients that are bucking conventional wisdom and using milligram doses of iodine to combat many of the health issues discussed above.  While iodine's role in health is important, as is any essential nutrient that you may become deficient in, it is important to not look at single nutrients as a panacea for all of the worlds ills.  Rather, you should look to optimize your life by living a healthy lifestyle and look to get optimal levels of all essential nutrients.  The question being asked in these blogs and by iodine researchers and physicians who routinely use it is if the RDA is sufficient for optimal health and not just to treat goiter.

Part 2