Category Archives: Hypothyroidism - Page 2

Carbohydrates and the Thyroid

Mario’s post last Thursday (Low Carb High Fat Diets and the Thyroid, Aug 18, 2011), looking at a series of studies cited in a July 1 post by Anthony Colpo, elicited a reply from Anthony.

The exchange turned out to be a blessing, because it is generating some insights on topics of fundamental importance.

Low-Carb Dangers

A motivating factor for our book was Paul’s bad experience with very low carb dieting. We felt obliged to warn the Paleo community that it was possible to become deficient in glucose and that this could be dangerous. We’ve blogged about “Zero Carb Dangers” (see especially Dangers of Zero-Carb Diets, II: Mucus Deficiency and Gastrointestinal Cancers; Danger of Zero-Carb Diets III: Scurvy; Dangers of Zero-Carb Diets, IV: Kidney Stones). Our work has persuaded many in the Paleo and low-carb communities to eat more “safe starches” including white rice. We recommend a carb intake that approaches the body’s total glucose utilization.

We do recommend ketogenic diets and low-carb diets as therapies for many neurological disorders and some infections, but believe that even ketogenic diets should generally include at least 200 glucose calories per day.

So when we consider claims that low-carb diets can be dangerous, it’s not without sympathy.

At the same time, given the therapeutic potential of low-carb and ketogenic dieting, and the likelihood that humans are evolutionarily adapted to a range of macronutrient intakes, we don’t think it’s appropriate to repudiate low-carb entirely.

This places an onus on us to closely examine the evidence, understand precisely when a low-carb diet passes from healthy to unhealthy, and make clear recommendations for how much dietary glucose is needed in different circumstances to avoid negative consequences.

The Issue of Low-Carb and the Thyroid

One problem that sometimes occurs on low-carb diets is a syndrome called “euthyroid sick syndrome,” characterized by low T3 and high reverse T3 hormone levels and elevated cortisol.

Here’s our friend and gracious podcast host, Danny Roddy:

[A low-carb] diet will lead to an elevation of catabolic stress hormones, while [a high-carb diet] has been shown to increase thyroid hormone triiodothyronine (T3), increase testosterone, and decrease cortisol, the anti-hair, pro-misery stress hormone (here, here, here (PDF), & here).

And here’s Anthony Colpo in his July 1 post:

[D]ecreasing carbohydrate intake to low levels results in diminished levels of T3 and/or increased rT3, something most aspiring fat-burners wish to avoid desperately.

Few things are more essential to good health than proper thyroid function. So this is clearly an issue we have to investigate and understand. It could impact our prescription for the minimum level of carb intake needed for good health.

Why Mario’s Post Emphasized Omega-6 Fats

Anthony seemed to think that Mario’s emphasis on the dangers of high-omega-6 diets was intended as a denial that low-carb specifically could be the cause of thyroid trouble. No.

The studies in question compared low-carb high-fat diets with other diets. In some but not all studies, thyroid function was impaired on the low-carb high-fat diet.

In looking at the studies cited by Anthony plus a few others, Mario found that thyroid function was impaired on all of the low-carb high-omega-6 diets but none of the (admittedly few) low-carb high-saturated-fat diets.

This led him to emphasize the role of the fatty acid type, rather than the amount of carbohydrates. It is also supportive of Perfect Health Diet claims that high omega-6 is toxic whereas high saturated fat is not.

Mario did not have space to treat the dangers of glucose deficiency for the thyroid, especially since the studies he was examining did not provide compelling evidence about the effects of dietary carbohydrate restriction (once the possibility of PUFA toxicity was accounted for). So he didn’t venture into this question, other than to assert the importance of “moderate” carb consumption.

But now we will – in the remainder of this post, and two upcoming guest posts.

Let’s explore the circumstances under which we might expect low-carb diets to cause “euthyroid sick syndrome.”

The Limits to Glucose Production

Let me begin by revisiting the initial post in our Zero-Carb Dangers series (Dangers of Zero-Carb Diets, I: Can There Be a Carbohydrate Deficiency?, Nov 10, 2010). I’ve been meaning to correct that post for some time, and this seems a good occasion.

That post emphasized size of the liver as a limit on its ability to synthesize glucose from protein. There is, indeed, a physical limit to the liver’s ability to manufacture glucose from protein. As long as unlimited fat is available for energy production and unlimited protein is available as a gluconeogenic substrate, the limit is determined by the oxygen supply to the liver and is about 400 g / 1600 calories per day.

However, this theoretical limit is never reached in healthy humans, except in some diabetics (as Nigel Kinbrum pointed out). The liver’s conversion of protein to glucose is controlled hormonally; insulin and glucagon are the most important players, with insulin inhibiting gluconeogenesis and glucagon promoting it.

Diabetics can have very high rates of gluconeogenesis because their pancreatic beta cells may no longer produce insulin even as their pancreatic alpha cells continue to produce glucagon.

In normal healthy humans, basal hormone levels are balanced so that during fasting or starvation, the liver and kidneys manufacture minimal but sufficient glucose while sparing protein as much as possible.

In a normal person, the liver and kidneys together never produce more than about 100 g / 400 calories glucose per day from protein. In the absence of hormonal dysregulation, this is a fairly hard limit.

Glucose Utilization and Glucose Deficiency

We discussed this in the book, and I won’t repeat the evidence. Suffice it to say that everyone consumes at least 600 glucose calories per day, a majority by the brain but also extensive amounts for structural components of the body – glycosylated proteins which coat every cell, and glycoproteins which are major components of mucus, joint lubricants, and connective tissue – and for immune function (since glucose is needed to produce the reactive oxygen species that kill pathogens).

Because limited research has been done on this subject, it’s possible that we’ve underestimated the body’s glucose needs. It could be as high as 800 glucose calories per day. It’s not likely to be lower.

This is for sedentary healthy people. Two factors may substantially increase glucose utilization:

  • Infection. Many pathogens consume glucose – indeed, people with parasitic infections can sometimes have great difficulty obtaining enough glucose from food – and the immune system also consumes glucose.
  • Athletic activity. Exercise can consume large amounts of glucose.

Let’s look at athletic activity. The Mayo Clinic lists the amount of calories burned per hour of exercise of various kinds, and the most intense types of exercise, such as running or cycling at race speeds (>20 mph), may burn 1,200 calories per hour. Most of these calories come from fat, but 30-40% may come from glycogen, and glucose is consumed to replace the glycogen. Thus, a runner or cyclist may burn up to 400 glucose calories per hour of training.

In a cyclist, runner, or swimmer who trains 2 hours per day, therefore, glucose needs may be quite a bit higher than in our sedentary healthy person. Such an athlete may be consuming ~1500 glucose calories per day.

Yet at most 400 calories of glucose per day can be manufactured from protein. It’s clear that athletes need to eat a fair amount of carbohydrate to avoid a glucose deficiency.

Anthony Colpo is a cyclist and athlete who routinely engages in intense endurance exercise. His unusually high glucose utilization is presumably what made him vulnerable to glucose deficiency syndromes – and therefore more sensitive than others to the dangers of low-carb diets.

The Basis for Our Carbohydrate Consumption Recommendations

Let’s go back to our sedentary healthy person, and let’s consider the minimum dietary glucose that person needs to avoid difficulty.

First let’s consider a person who eats a large amount of protein – 600 calories per day, about double the intake of an average American.

Roughly 200 calories per day may be needed for structural uses, leaving 400 calories per day for possible conversion to glucose.

But if protein consumption is lower, there may not be enough substrate to create 400 glucose calories per day. This may lead to hormonal changes that try to conserve protein by limiting gluconeogenesis.

Now let’s look on the glucose side. If 600-800 glucose calories are utilized by the body daily, and at most 400 of those can be manufactured from protein and at most ~300 can be displaced by ketones, then someone on a zero-carb diet is living right on the margin of glucose deficiency.

And this is before athletic activity or infections are considered.

If 200 glucose calories per day are consumed, and if 400 protein calories are consumed, and if MCT oil (a ketogenic substrate) is consumed to make it easier to generate ketones to displace glucose, then one might just barely meet the body’s structural glucose and protein needs on a ketogenic diet. This is why we recommend that ketogenic diets include at least 200 calories from starch.

But it’s not really desirable to live on the margin of glucose deficiency, especially if you’re not making it easy for your body to generate ketones. For this reason, our normal diet recommends 400 calories or more from starches.

The Trouble with Vegetables

We generally advise not counting vegetables as carb calorie sources. This often puzzles diabetics who note that vegetables have some sugar – typically, about 80 calories per pound – and that consuming vegetables raises their blood sugar levels.

The reason we recommend not counting vegetable calories is that digestion of vegetable matter is an energy-intensive process that consumes glucose. Gut cells consume glucose directly, and also vegetables have a lot of fiber which causes gut bacterial activity which in turn leads to immune activity which consumes glucose. This glucose consumption by the gut and immune system occurs over an extended period of time after vegetables are eaten – perhaps 6 hours. But vegetable sugars are digested quickly – mainly in the first hour. So you can have a surge of blood sugar due to vegetable sugars, even if the vegetables make no net contribution to daily glucose balance.

So it’s really starches and fruits that are the useful sources for meeting the body’s carb needs.

What Happens When There is a Glucose Deficiency?

When the body is deficient in glucose, the hormonal milieu changes to help maintain body functions while conserving glucose and protein.

Two of the important hormones are cortisol and T3.

T3, the most active thyroid hormone, has a strong effect on glucose utilization. T3 stimulates glucose transport into cells, and transport is the limiting factor in glucose utilization in many cell types. In hyperthyroidism, a condition of too much T3, there are very high levels of glucose utilization. Administration of T3 causes elevated rates of glycolysis regardless of insulin levels.

The body can reduce T3 levels by converting T4 into an inactive form called reverse T3 (rT3) rather than active T3. High rT3 levels with low T3 levels lead to reduced glucose transport into cells and reduced glucose utilization throughout the body.

Cortisol is a hormone that helps prevent hypoglycemia, a condition of low blood glucose. It reduces glucose utilization and increases gluconeogenesis.

So the syndrome of low T3, high rT3, and high cortisol can be understood as a diagnostic pattern of a systemic glucose deficiency.

What Is “Euthyroid Sick Syndrome”?

Euthyroid sick syndrome is defined as “a state … where the levels of T3 and/or T4 are at unusual levels, but the thyroid gland does not appear to be dysfunctional.” Specifically, “Reverse T3 are generally increased signifying inhibition of normal Type 1 enzyme or reduced clearance of reverse T3. Generally the levels of Free T3 will be lowered.”

Wikipedia’s list of causes includes:

  • Fasting, starvation (PAJ: These induce glucose deficiencies, especially if there is insufficient protein available to sustain even the normal 400 calories/day glucose synthesis.)
  • Sepsis (PAJ: Infection increases glucose requirements.)
  • Trauma (PAJ: Fabrication of structural glycoproteins and protein glycosylation is increased during wound repair.)
  • Malignancy (PAJ:  Cancers consume large amounts of glucose.)
  • Hypothermia (PAJ:  Shivering, like endurance exercise, consumes glycogen.)
  • Cirrhosis (PAJ: Damage to the liver may reduce its ability to synthesize glucose, forcing glucose conservation.)
  • Chronic renal failure (PAJ: The kidney is the other organ besides the liver that synthesizes glucose from protein. So kidney damage will reduce the body’s ability to synthesize glucose.)

Looking at this list, it seems that euthyroid sick syndrome may be just another name for a systemic glucose deficiency.

If glucose deficiency is the cause, then obviously low carb diets are going to be a risk factor for euthyroid sick syndrome.

This is not to say that low carb diets will automatically lead to euthyroid sick syndrome. A sedentary person free of infections may be quite normal and healthy on a very low carb diet. This is why most low carbers do not experience the condition.

But if other risk factors, like infection, cancer, or endurance exercise, are present, then the odds of developing euthyroid sick syndrome on a low carb diet may become quite high.

Diagnostic Value of rT3:T3 Ratio for Low-Carb Dieters

Here’s an interesting implication of today’s analysis.

The ratio of rT3 to T3 may have diagnostic value for glucose status and therefore for the presence of infections or cancers. It might not be a bad idea for low-carb dieters to monitor these hormone levels, and to eat enough “safe starches” to keep their rT3:T3 ratio at normal levels.

The rT3:T3 ratio is likely to be of much greater clinical value to low-carbers than to the average high-carb American. So even though doctors rarely test for it, low-carb dieters may find it quite useful.

Are High-Carb Diets Without Risk?

In the wake of Anthony’s reply I was amused by a Twitter conversation between @DannyRoddy and @StabbyRaccoon – two of the smartest and nicest people on the Web.

As noted above, Danny believes that high-carb diets might be beneficial by creating above-normal T3 levels:

I believe the real question is: what range radically increases T3?…

I’m more concerned where CHO starts dramatically increasing T3.

Stabby paid me the honor of valuing my opinion:

maybe Paul … could look into it.

Alright, let’s look (briefly) into it.

In the quote from Danny on potential risks of low-carb diets, he cited several papers. One of them was this:

To evaluate the effect of changes in dietary carbohydrate (CHO) and excessive caloric consumption on circulating thyroid hormone levels, six normal weight subjects were fed five separate diets: three isocaloric diets with 20%, 40%, or 80% CHO and two hypercaloric (+2000 calories) diets with 20% or 40% CHO for 5 days each as outpatients. T4, T3, and rT3 concentrations were measured in plasma samples collected on the morning of the sixth day. At least 1 week of the subjects’ usual diets intervened between each experimental diet.

Mean T4 and rT3 levels were similar after all diets. Pair-wise comparisons among all five diets revealed significantly (P < 0.005) increased T3 concentrations after both hypercaloric diets compared to the iso-20 and iso-40 diets, and after the iso-80 compared to the iso-20 diet. A multiple regression analysis of the data revealed the highest correlation of T3 levels with total calories (r = 0.68; P < 0.001) rather than with the intake of CHO (r = 0.46; P < 0.025), fat (r = 0.49; P < 0.02), or protein (r = 0.30; P = NS).

I haven’t read the full study yet and find this abstract mildly puzzling. On the one hand, the multiple regression analysis shows that fat, not carbohydrate, is the most effective macronutrient at raising T3. Maybe Danny should eat a high-fat diet to raise his T3.

On the other hand, the normo-caloric 80% carb diet had more T3 than the normo-caloric 20% carb diet. So maybe carbs do increase T3 more than fat.

Now, hypercaloric (positive energy balance) diets are associated with a variety of diseases including obesity and metabolic syndrome. Stephan Guyenet has argued that positive energy balance is itself inflammatory and damaging, and that high-reward foods which induce overeating may directly cause metabolic diseases.

In this study, T3 concentrations were increased similarly on both hypercaloric (2000 excess calories) 20% and 40% carb diets and normo-caloric 80% carb diets. Could it be that some of the ill effects of hypercaloric diets will also be present on normo-caloric high-carb diets?

Of course, with any hormone we have to ask what the right amount is. Usually both too much and too little are problematic. This is certainly true of thyroid hormones.

High T3 concentrations are characteristic of the disease hyperthyroidism and have negative effects. One of the effects of high T3 levels is enhanced transport of glucose into cells. For instance:

Pre-treatment of these cells with T3 moreover substantially enhances the stimulatory effect of insulin such that at maximally effective hormone concentrations the effects of T3 and insulin on glucose transport are more than additive and indeed nearly multiplicative …

The extra glucose transported into cells is disposed of through glycolysis. Glycolysis is the characteristic metabolism of cancer cells, so high T3 might promote the cancer phenotype.

Indeed, hyperthyroidism increases the risk of ovarian cancer by 80%.

Glycolysis also occurs in the cytosol, making glucose and downstream energy substrates like pyruvate and lactate available to bacteria. Thus, high T3 may promote bacterial infections.

Indeed, thyroid storms can cause sepsis.

Those who have been following CarbSane’s exposition of the dangers of lipotoxicity may be interested to find that high T3 not only increases circulating glucose levels and rates of glycolysis, but also circulating free fatty acid levels:

Hyperthyroidism, which was induced by administration of tri-iodothyronine (T3) to rats for 2, 5 or 10 days, increased fasting plasma concentrations of glucose, insulin and free fatty acids. Administration of T3 for 2 or 5 days increased the rates of glycolysis at all insulin concentrations studied …

Elevated free fatty acids seem to be the primary cause of diabetes.  Here elevated free fatty acids are associated with high glucose and with a hormonal trait – high T3 – associated with high-carb diets.

(Aside: This kind of evidence is why we have to be a bit cautious in assuming that free fatty acid levels, and thus diabetes risk, are higher on low-carb high-fat diets. Recently CarbSane and I had a brief discussion on this topic: see this post on her blog and the comment thread. She leans toward the idea that more dietary fat = more free fatty acids and thus more lipotoxicity; to me the issue is far from clear, as the need to dispose of glucose will tend to inhibit drawdown of free fatty acids. I think that moderate carb consumption, near the body’s glucose utilization, rather than high carb consumption may minimize lipotoxicity. However, concerns over lipotoxicity might lead us to revisit our suggestion of ketogenic diets for diabetes.)

Getting back to the question Stabby asked me to look into: I have only a provisional response. I have given only the most superficial of looks at the literature. I am mainly tossing out topics for further investigation (hopefully by others!).

But at a glance, I don’t see any obvious reasons to change the judgment of our book that moderate carb consumption, close to the body’s glucose utilization needs, is optimal. In my judgment, “dramatically increasing T3” by eating a high carbohydrate diet (if, indeed, a high-carb diet does this) is probably undesirable. Rather, it’s best to eat a moderate amount of carbohydrate that keeps T3 at physiologically normal, healthy levels. Both too much and too little T3 – and, perhaps, too much and too little dietary carbohydrate – may be dangerous.


In regard to Anthony Colpo, I’d like to extend an olive branch, and reiterate the following points:

  • The purpose of Mario’s post last Thursday was not to show that Anthony was right or wrong, but to find out whether we were right or wrong.
  • Although we are more sympathetic than Anthony to low-carb diets, we agree that they have risks. Yes, it is possible to become glucose deficient.
  • I stand by Mario’s post. I don’t believe there are any errors in it.
  • Nothing Mario said contradicted the main points of Anthony’s July 1 post to which it linked. Mario (and we) endorsed “moderate” carb consumption, not very low carb diets, and Mario’s focus on the dangers of high-omega-6 diets should not be construed as a denial of the dangers of very low-carb diets.

Anthony and I exchanged increasingly cordial emails over the weekend, are sending each other copies of our books, and I hope we will be on good terms even if our diet ideas and study interpretations are not identical.

In regard to rT3:T3 ratio, it might be interesting to compile some data on rT3:T3 ratios and carb intake among low-carbers. It may be that studying how rT3:T3 ratio varies with carb consumption will give us a clearer idea of optimal carbohydrate intake. I would expect there would be some “plateau region” of carb intake over which rT3 is low and T3 levels are stable. At very high carb intakes, T3 might be elevated in order to promote glucose disposal; at very low carb intakes, the euthyroid sick syndrome of elevated rT3 and depressed T3 might hold.

Finally, a look at upcoming posts. Yes, long as this post was, we’re not done exploring these issues.

Anthony cited some more papers in his reply to Mario, and Mario will respond in detail: what do those studies prove? The purpose of this is to evaluate our diet to see if our advice is sound, not to feature any disagreements Mario may have with Anthony, or to prove anyone wrong.

In the post after that, we’ll have a fascinating personal story from Gregory Barton. Gregory’s experience connects euthyroid sick syndrome to the vexing issue of high LDL on Paleo diets, and as such ties in with some points Chris Masterjohn has made on the role of thyroid hormone in LDL pathways. As such it may help us reach some closure on two of the outstanding problems that have troubled the low-carb Paleo community.

And if we’re not tired of the issue after those posts, commenter Valtsu has been sending me references to papers discussing links between infections and euthyroid sick syndrome. It looks like toxins and inflammatory cytokines released during infections can disrupt the ability of the hypothalamus to regulate thyroid hormone levels. This could have implications for other diseases besides euthyroid sick syndrome – including obesity, which often features disruption of the hypothalamus’s regulation of energy utilization.

So I think this little controversy is leading us to some productive discoveries. Therefore, I’d like to thank Anthony for raising the issues in the first place. Out of disagreement may come insight.

Low Carb High Fat Diets and the Thyroid

Last year we ran a series on “Zero-Carb Dangers,” which are health problems that can appear if carb intake – or carb+protein intake, since protein can to some degree make up for a deficit of glucose – are too low. Anthony Colpo has recently argued that hypothyroidism should be added to the list of potential zero-carb dangers; and that low-carb high-fat diets in general might create a risk of hypothyroidism. Similar arguments have been made by Matt Stone and others. Our resident thyroid expert, Mario Renato Iwakura, decided to look more deeply into the matter. What does the literature say? Here’s Mario.

There have been anedoctal reports on low carb forums about people becoming hypothyroid after following a low carb, high fat diet. Anthony Colpo recently wrote a blog post about carbohydrate, fat and protein intake and their effects on thyroid hormone levels, concluding that a high fat or high protein diet is detrimental and that a high carbohydrate diet is good for the thyroid [1].

What I will try do demonstrate here is that the sole conclusion we can draw from the literature, including the studies cited by Anthony and others, is that a high polyunsaturated fat (PUFA) diet is detrimental to thyroid health. There is no evidence that a diet, such as the Perfect Health Diet, that is high in saturated and monounsaturated fat, low in PUFA, and provides sufficient, moderate levels of protein and carbohydrate, has any detrimental effect on the thyroid. On the contrary, I believe that such a diet is optimal for thyroid health.

What Has Been Tested: High PUFA Diets

Colpo’s post is extensive and covered most, but not all, relevant studies published to date about the subject. Many of those studies have problems like short duration or calorie restriction. But in almost all, with the exception of one study by Jeff Volek and collaborators [2], the fat used in the high fat diet was predominantly polyunsaturated fat from vegetable oils. An example is the Vermont long term study [3]:

“The long-term study of fat overfeeding included four subjects studied before and after overeating fat for 3 mo. The excess fat in these diets averaged 895 kcal/d consisting of margarine, corn oil, a corn oil colloidal suspension, and fat enriched soups and cookies.  The ratio of saturated to unsaturated fatty acids in these diets was ~1:2.5.”

This ratio is precisely that found in corn oil. So, this diet’s fat  was probably 13.5% saturated, 29% monounsaturated, and 57.5% polyunsatured.

Or in Ullrich et al 1985 [4]:

“One diet was high in polyunsaturated fat (HF), with 10%, 55%, and 35% of total calories derived from protein, fat, and carbohydrate, respectively.”

Polyunsaturated Fat and the Thyroid.

Let’s look at the literature, starting with two studies not cited by Anthony.

In 1995, Vasquez et al tested four very low calorie diets, with variable amounts of carbs, fats and protein, in 48 obese women for 28 days [5]. All diets were in liquid form, and fat was predominantly PUFA. The composition of the four diets was:

50P/10C 50P/76C 70P/10C 70P/86C
Energy (kcal) 590 590 615 615
Protein (% cal) 35.5 33.7 45.8 43.0
Fat (% cal) 57.8 15.1 48.1 4.1
Carb (% cal) 6.7 51.2 6.1 52.9
T3 Day 0 2.0 2.2 1.6 1.8
T3 Day 28 1.1 1.7 1.0 1.4
Variation -45% -23% -37% -22%

T3 thyroid hormone levels decreased on all of these severely calorie restricted diets. However, when PUFA was high (50P/10C and 70P/10C) the decrease in T3 was much larger than when PUFA was low (50P/76C and 70P/86C).

In a 1992 paper, Vasquez et al compared two very low calorie diets (600kcal/day), one ketogenic and the other nonketogenic [6]. The fat sources were soybean oil and refined and stabilized vegetable oils.

Ketogenic Nonketogenic
Protein 35% 34%
Fat 58% 15%
Carbs 9% 51%
T3 Day 0 1.4 1.5
T3 Day 28 0.8 1.3
Variation -43% -13%

The various studies cited by Colpo also show decreases in T3 levels in diets high in PUFA. In Ullrich et al 1985 [4], a study of healthy young adults, although TSH, T4, and rT3 did not change significantly, T3 levels on a high polyunsaturated diet decreased more than on a high protein diet:

“The triiodothyronine (T3) declined more (P less than .05) following the HF diet than the HP diet (baseline 198 micrograms/dl, HP 138, HF 113). Thyroxine (T4) and reverse T3 (rT3) did not change significantly. Thyroid-stimulating hormone (TSH) declined equally after both diets”

In the Vermont study [3], where the low carb diet was high in PUFA fat, that was the case too:

“During maintenance eating, levels of T3 (triiodothyronine) were higher on the high-carb diet. When subjects on the low-carb diet began eating the higher-carb mixed weight gain diet, their T3 levels rose. T3 levels among those who went from the high-carb maintenance diet to the mixed diet remained unchanged. In contrast to T3, serum concentrations of T4 were unchanged by overeating or changes in dietary composition.” [1]

Low-PUFA High-Fat Diets and the Thyroid: Lack of Direct Evidence

Unfortunately we don’t have human studies comparing diets high in saturated fat and polyunsaturated fat and their effect on thyroid hormones synthesis. Neither do we have studies showing what happen to T3 levels after a high saturated/monosaturated fat diet is eaten. We will have to rely on indirect evidence.

Indirect Evidence: Calories Required to Maintain Weight.

There is a connection between thyroid activity and obesity. Reduced thyroid activity reduces energy expenditure (“calories out”) and promotes weight gain; normal thyroid function tends to promote normal weight. So we can use the vast number of obesity studies as indirect evidence for the effects of different types of diet on the thyroid.

Anthony emphasized this relationship in his post, noting findings of the Vermont study on overfeeding:

“Again, that both groups gained weight should come as no surprise. However, the group overfed the mixed diet required more calories (2,625 kcal/m2 per day) to maintain their new heavier weights than did the group overfed fat (1,840 kcal/m2 per day). Baseline differences in metabolism between the two groups were ruled out, as there was no difference in total calories required to maintain initial lean weights.”

So the high-PUFA diet promoted weight gain: it caused excess weight to be retained at a lower calorie intake. This is consistent with reduced thyroid activity.

Is this effect due to a high-fat diet generally, or to high-PUFA diets only? Some insight into this question may be found in a blog post by Stephan Guyenet [7]. Rats fed isocaloric diets in which the fat source was varied among three groups – a beef tallow group (primarily saturated fat, 3% PUFA), an olive oil group (primarily unsaturated, 10-15% PUFA), and a safflower oil group (78% PUFA) – had highly variable weight gains. The olive oil group gained 7.5% more weight than the beef tallow group, and the safflower oil group 12.3% more weight.  This is exactly the same pattern found in the Vermont overfeeding study in man: reduced energy expenditure as the consumption of PUFA increases.

Since 1945, it has been known that men fed a high carbohydrate and then a high saturated fat diet needed about the same amount of calories to mantain their weight in cold temperature [18]. Here is the data, expressed in terms of the percentage of baseline calorie intake that the men had to eat to maintain their weight:

The high-fat diet consisted largely of butter and cream; the high-carbohydrate diet of extra sugar. When eating the butter and cream, subjects had to eat more calories to maintain weight than when eating the sugary diet – 202% of baseline calorie intake vs 191%. Every subject had to increase calories when eating high-fat. This suggests higher thyroid hormone levels on the high-saturated fat diet than on a high-carb diet.

The Volek Study

Anthony cited a study by Jeff Volek and others [2] on body composition and hormonal responses to a carbohydrate-restricted diet and said that:

Upon commencement of the low-carbohydrate diet a small calorie deficit and a significant increase in protein intake occurred, resulting in a mean 3.3 kilogram fat loss and a 1.1 kilogram lean mass gain. There was a significant increase in total T4 (+10.8%), but for some reason the researchers did not directly measure T3 nor rT3. They instead tested T3 uptake, an indirect measure of thyroxine binding globulin (TBG) in the blood, which tells us little of any real value about changes in actual thyroid hormone levels. The researchers also measured IGF-1, glucagon, total and free testosterone, sex hormone-binding globulin (SHBG), insulin-like growth factor-I (IGF-I), and cortisol. The only significant change noted was a reduction in insulin following the low-carbohydrate diet.

The Volek study is very interesting because it was not calorie restricted (only carbohydrate was restricted) and was done in normal-weight man. The amount of polyunsaturated fat increased a little (from 6 to 11% of calories), but was still low; saturated and monosaturated fats were the main fats of the low carb-high fat diet. Although he did not directly measured T3 nor rT3 we have indirect evidence that they were not impaired.

One very well known fact is that hypothyroid patients, even when taking T4 hormones, usually struggle to lose fat. This occurs because, when thyroid hormones are low, especially when T3 (triidothyronine) is low [8], the basal metabolism is decreased. If the LCHF diet was impairing the thyroid these healthy normal weight men, who had been advised to eat enough calories to maintain their weight during the intervention, should have struggled to lose fat mass. In fact they lost 3.3 kg (7.3 pounds) in 6 weeks on an 8% reduction in calorie intake. The control group did not lose any weight despite an 11% reduction in calorie intake.

More, testosterone levels usually decrease when thyroid hormones are low [9][10]. IGF-1 levels are also decreased in hypothyroidism [11][12]. Glucagon levels are higher in hypothyroid patients [13]. Sex hormone-binding globulin (SHBG) is low in hypothyroidism [14][15][16]. But none of these parameters changed during the LCHF diet.

So this diet which was low in carb (8% of calories) and moderately high in protein (30%) and PUFA (11%) does not seems to affect the thyroid if saturated and monosaturated fat (50% of calories) are the main fat of the diet. Let’s compare the fatty acid profile of the Volek diet with that of human milk:

Saturated Monounsaturated Polyunsaturated
Volek diet 41% 41% 18%
Human milk 47.5% 40.5% 12%

Not too much difference. Perhaps PUFA intake needs to be higher than 11% of calories or 18% of fat to impact the thyroid.

Effects of high fat and thyroid responses to cold.

In 1945, Mitchell et al published two articles comparing the effects of proteins versus carbohydrates and fat versus carbohydrate on man’s tolerance to cold exposure [18][19]. Carbohydrate does better than protein, but worse than fat, at maintaining internal temperature as measured by rectal temperature.

On the first experiment, five men consumed a high protein diet (41% P, 40% F, 19% C) and five a high carbohydrate diet (11% P, 41% F, 48% C) for 5.5 months. Food intake was adjusted to mantain a constant body weight.

The effect of decrement in rectal and mean skin temperature during eight hour exposure to cold with light clothing:

Rectal Temp Skin Temp
High Protein 1.63 5.21
High Carb 1.05 3.65
Significance P=0.017 P=0.0096

On the second experiment, five men consumed a high fat diet (10% P, 73% F, 17% C) and five a high carbohydrate diet (10% P, 23% F, 67% C) for 56 days. Food intake was adjusted to maintain a constant body weight. The excess fat of the high fat group was provided by butter and cream.

Decrement in rectal temperature from the first two hour to the last two hours of 6 hours exposures to -20º F (-29º C), with variable number of intervening meals:

Number of intervening meals Difference 

0 and 1 meal


0 and 2 meals

None One Two
High Carb 0.71 0.72 0.68 -0.01 0.02
High Fat 0.60 0.36 0.33 0.24 0.27
Significance None P=0.034 P=0.018 P=0.083 




* These probabilities pertain only to the high fat diet

What is clear here, is that 6 hours exposures to -20º F decreased rectal temperature equally in both groups if no meal was ingested. Eating a high carb meal between the intervention did not produced any alteration. But, eating a high fat meal cut the decrement in rectal temperature in half.

Thyroid hormones are responsible for basal metabolic rate and heat production.

So, if a high saturated fat diet maintains body temperature better than a high carbohydrate diet when the body is subjected to cold, it would seem fair to assume that the thyroid functions better on this high saturated fat diet.


A diet with sufficient but not excess protein, moderate carbohydrate comprising a minority of calories, and high intake of saturated and monounsaturated fat but low intake of polyunsaturated fat would seem to be optimal for thyroid function. But this is the Perfect Health Diet!


[1] Anthony Colpo. Is a Low Carb Diet Bad For Your Thyroid?.

[2] Volek JS et al. Body composition and hormonal responses to a carbohydrate-restricted diet. Metabolism. 2002 Jul;51(7):864-70.

[3] Danforth E Jr et al. Dietary-induced alterations in thyroid hormone metabolism during overnutrition. J Clin Invest. 1979 Nov;64(5):1336-47.

[4] Ullrich IH et al. Effect of low-carbohydrate diets high in either fat or protein on thyroid function, plasma insulin, glucose, and triglycerides in healthy young adults. J Am Coll Nutr. 1985;4(4):451-9.

[5] Vazquez JA et al. Protein metabolism during weight reduction with very-low-energy diets: evaluation of the independent effects of protein and carbohydrate on protein sparing. Am J Clin Nutr. 1995 Jul;62(1):93-103.

[6] Vazquez JA et al. Protein sparing during treatment of obesity: ketogenic versus nonketogenic very low calorie diet. Metabolism. 1992 Apr;41(4):406-14.

[7] Whole Health Source. Vegetable Oil and Weight Gain.

[8] Danforth E Jr, Burger A. The role of thyroid hormones in the control of energy expenditure. Clin Endocrinol Metab. 1984 Nov;13(3):581-95.

[9] Cavaliere H et al. Serum levels of total testosterone and sex hormone binding globulin in hypothyroid patients and normal subjects treated with incremental doses of L-T4 or L-T3. J Androl. 1988 May-Jun;9(3):215-9.

[10] Kumar A et al. Hypoandrogenaemia is associated with subclinical hypothyroidism in men. Int J Androl. 2007 Feb;30(1):14-20. Epub 2006 Jul 24.

[11] Akin F et al. Growth hormone/insulin-like growth factor axis in patients with subclinical thyroid dysfunction. Growth Horm IGF Res. 2009 Jun;19(3):252-5. Epub 2008 Dec 25.

[12] Soliman AT et al. Linear growth, growth-hormone secretion and IGF-I generation in children with neglected hypothyroidism before and after thyroxine replacemen. J Trop Pediatr. 2008 Oct;54(5):347-9. Epub 2008 May 1.

[13] Stanická S et al. Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy. Clin Chem Lab Med. 2005;43(7):715-20.

[14] Dittrich R et al. Thyroid hormone receptors and reproduction. J Reprod Immunol. 2011 Jun 3.

[15] Krassas GE et al. Thyroid function and human reproductive health. Endocr Rev. 2010 Oct;31(5):702-55. Epub 2010 Jun 23.

[16] Carani C et al. Multicenter study on the prevalence of sexual symptoms in male hypo- and hyperthyroid patients. J Clin Endocrinol Metab. 2005 Dec;90(12):6472-9. Epub 2005 Oct 4.

[17] Bandini LG et al. Metabolic differences in response to a high-fat vs. a high-carbohydrate diet, Obes Res. 1994 Jul;2(4):348-54.

[18] Mitchell HH, Glickman N, et al. The tolerance of man to cold as affected by dietary modification; carbohydrate versus fat and the effect of the frequency of meals. Am J Physiol. 1946 Apr;146:84-96.

[19] Mitchell HH, Glickman N, et al. The tolerance of man to cold as affected by dietary modifi-cation; proteins versus carbohydrate and the effect of variable protective clothing. Am J Physiol. 1946 Apr;146:66-83.

[20] Smith RE et al. Metabolism and cellular function in cold acclimation. Physiol Rev. 1962 Jan;42:60-142.


Iodine and Hashimoto’s Thyroiditis, Part 2

Mario Renato Iwakura’s guest series on the place of iodine and selenium supplementation in treatment of hypothyroidism continues. This is part 2. Thank you Mario! – Paul

In Part I (Iodine and Hashimoto’s Thyroiditis, Part I, May 24, 2011) we looked at evidence from animal studies that iodine is dangerous to the thyroid only when selenium is deficient or in excess, and that optimizing selenium status allows the thyroid to tolerate a wide range of iodine intakes. In fact, there were some hints (such as an improved CD4+/CD8+ T cell ratio) that high iodine, if coupled with optimal selenium, might actually diminish autoimmunity.

If that holds in humans too, we should expect that populations with healthy selenium intakes should see a low incidence of thyroid disease and no effect from iodine intake on the incidence of Hashimoto’s thyroiditis. Is that the case?

Korean Study

Dr. K [1] quotes a Korean study [3] of Hashimoto’s patients. Half restricted iodine intake to less than 100 mcg/day, the other half ate their normal seaweed and iodine. Of the 23 patients who restricted iodine, 18 (78%) became euthyroid in the sense of having TSH below 4.43 mIU/L, while only 10 (46%) of the 22 that did not restrict iodine became euthyroid. There was no measurement of symptoms at all, and no report of thyroid antibody titers after iodine restriction, so we don’t know if the iodine restriction relieved the underlying autoimmune disorder.

The selection of subjects for the two groups was odd. Group 1, the iodine restricted patients, had an extremely wide range of starting TSH, averaging 38 mIU/L but with a standard deviation of 82 mIU/L. Since all subjects began with TSH above 5 mIU/L, it’s clear that many of the Group 1 members had TSH near 5 and others had TSH well over 100 mIU/L. In comparison, Group 2, the controls, averaged a TSH of 11 mIU/L with a standard deviation of 11 mIU/L – less than 1/7 the standard deviation of Group 1. Few Group 2 members had a TSH above 30.

Table 2 presents the results. Mean TSH in Group 1 was reduced a little, but it did not even come close to normal. Since 78.3% of Group 1 had TSH below 4.43 mIU/L after 3 months, the other 21.7% had to have averaged a TSH above 102.2 mIU/L at the conclusion of the study. The standard deviation of Group 1 TSH at the end of 3 months of iodine restriciton was 71 mIU/L.

Meanwhile, Group 2 members still had a much lower standard deviation at the end of the study: 19 mIU/L.

A conclusion of this study was that “the initial serum TSH concentration was significantly lower in the recovered patients than in the non-recovered patients, which suggests that the possibility of recovvery is increasingly rare as the initial hypothyroidism becomes more severe.” Since Group 1 originally had a much larger fraction of members with very low TSH than Group 2 (plus a few with extremely high TSH to raise the average TSH), and the definition of recovery was a reduction of TSH to 4.43, perhaps it is not surprising that a higher fraction of Group 1 recovered.

Further calling into question the conclusion that lower iodine intake is beneficial is another observation. Looking at Table 1, we see that Group 2 (controls) had, at baseline, much higher iodine intake and higher urinary iodine excretion. Despite this, goiter size, TSH, antimicrosomal (MSAb) and antithyroglobulin (TGAb) antibodies were all lower!

A Japanese Study

A similar study with similar results was done in Japan [4].

In Asia, high iodine intake is due to high consumption of seaweed. Seaweed is high in naturally produced bromine compounds [5][6][7], arsenic [9][12][13], and mercury [9], and can accumulate radioactive iodine [8][9][10][11]. All these substances are known to interfere with thyroid function.

Bromide levels in urine in Asia are very high and are associated with seaweed consumption [6][7]. Values of 5 to 8.1 mg/l have been observed among Japanese, and 8 to 12 mg/l among Koreans.

It is quite possible that any benefits from “iodine restriction,” i.e. seaweed restriction, were due to reduced intake of bromine, arsenic, mercury, and radioactive iodine.

A China Study

Dr. Kharrazian [2] cites a study done in China [14] comparing three different areas: one with iodine deficiency (Panshan), another where iodine is more than adequate (Zhangwu) and a third where iodine is excessive (Huanghua). More than adequate and excessive iodine was associated with increased risk for subclinical and overt hypothyroidism.

But, another study [15], done in the same regions, showed that, coincidentally, Huanghua, the region with excessive iodine, and Zhangwu, the region with more than adequate iodine, had lower median serum selenium concentrations than Panshan, where iodine was deficient. Blood selenium concentrations were 83.2, 89.1 and 91.4 microg/L, respectively. So iodine consumption was inversely related to selenium consumption. Was it lower iodine, or higher selenium, that was beneficial?

TPOAb antibody levels were inversely associated with selenium levels. Patients with the highest TPOAb antibodies (>600 UI/ml) had lower selenium levels than patients with moderate and lower TPOAb antibodies (respectively 83.6, 95.6 and 92.9 UI/ml). [15]

Studies from Brazil, Sri Lanka, Turkey, and Greece

Dr K also cites a rise in Hashimoto’s incidence in Brazil, Sri Lanka, Turkey and Greece after salt iodinization began. Are these countries deficient in selenium? Well, lets see:

Brazil: The study was done in São Paulo, a city with a large Brazilian-Japanese population. Brazilian-Japanese have significant lower levels of Se than Japanese living in Japan [16].

Greece: Selenium status is one of the lowest of the Europe [17].

Turkey: Selenium status of Turkish children is found to be unusually low, only 65 ng/ml in boys and 71 ng/ml in girls [18]. Turkey is characterized by widespread iodine deficiency and marginal selenium deficiency [19].

Sri Lanka: Significant parts of the Sri Lankan female population may be selenium deficient [20].

One study, done in Egypt, measured iodine excretation in urine and its relation with thyroid peroxidase antibody (TPOAb) [21]. Although the abstract said that a significant correlation was found, this is far from reality, as we can see from Fig. 2.

Another study from Brazil [2] measured urinary iodine excretation and serum TPOAb and TgAb antibodies from 39 subjects with Hashimoto’s, none of whom were receiving treatment at the time of the study. Both antibody titers had no obvious correlation with urinary iodine.

Two discordant epidemiological studies

From the Netherlands, we have a prospective observational study looking at whether the female relatives of 790 autoimmune thyroid disease patients would progress to overt hypothyroidism or hyperthyroidism [22].

Although the relationship was not considered statistically significant, they found that women with high iodine intake (assessed through questionnaires) were 20% less likely to develop thyroid disorders.

Another study from western Australia (a region that has previously been shown to be iodine replete) measured urinary iodine concentration (UIC) of 98 women at 6 months postpartum and checked their thyroid status both postpartum and 12 years later [23]. UIC at 6 months postpartum predicted both postpartum thyroid dysfunction and hypothyroidism  12 years later:

The researchers concluded:

The odds ratio (OR) of hypothyroid PPTD with each unit of decreasing log iodine was 2.54, (95%CI: 1.47, 4.35), and with UIC < 50 lg/l, OR 4.22, (95%CI: 1.54, 11.55). In the long term, decreased log UIC significantly predicted hypothyroidism at 12-year follow-up (p = 0.002) … The association was independent of antibody status.

In short, the more iodine being excreted (and thus, presumably, the more in the diet and in the body), the less likely were hypothyroid disorders – not only at the time, but also 12 years later.

Dangers of selenium supplementation in iodine deficiency.

Selenium supplementation when iodine and selenium deficiencies are both present  can be dangerous, as the experience in northern Zaire, one of the most severely iodine and selenium deficient population in the world, shows [25].

Schoolchildren and cretins were supplemented for 2 months with a physiological dose of selenium (50 mcg Se per day as selenomethionine). Serum selenium was was very low at the beggining of the study and was similar in schoolchildren and in cretins (343 +- 190 nmil/L in schoolchildren, n=23, and 296 +- 116 nmol/L in cretins, n=9). After 2 months of selenium supplementation, the massive decrease in serum T4 in virtually every subject can be seen in fig. 4 below:

In schoolchildren, serum free thyroxin (fT4) decreased from 11.8 +- 6.7 nmol/L to 8.4 +- 4.1 nmol/L (P<0.01); serum reverse triiodothyronine (rT3) decreased from 12.4 +- 11.5 nmol/L to 9.0 +- 7.2 nmol/L; mean serum T3 and mean TSH remained stable. In cretins, serum fT4 remained the same or decreased to an undetectable level in all nine cretins; mean serum T3 decreased from 0.98 +- 0.72 nmol/L to 0.72 +- 0.29 nmol/L, and two cretins who were initially in a normal range of serum  T3 (1.32-2.9 nmol/L) presented T3 values outside the lower limit of normal after selenium supplementation; mean serum TSH increased significantly from 262 mU/L to 363 mU/L (p<0.001).

Another previous similar trial, this time done in 52 schoolchildren, reached the same results: a marked reduction in serum T4 [26][27]. This previous trial “was shown to modify the serum thyroid hormones parameters in clinically euthyroid subjects and to induce a dramatic fall of the already impaired thyroid function in clinically hypothyroid subjects” [27].

What stands out is the difference in the results between euthyroid schoolchildren and cretins/hypothyroids. Two months of selenium supplementation was probably not enough time to affect significantly the thyroid of the euthyroid schoolchildren (althougt already impacted T4 and fT4). But, in cretins and hypothyroids, where the thyroid was already more deficient, the impact was evident.

Conclusion and What I Do

Iodine and selenium are two extremely important minerals for human health, and are righly emphasized as such in the Perfect Health Diet book and blog. I believe they are fundamental to thyroid health and very important to Hashimoto’s patients.

A survey of the literature suggests that Hashimoto’s is largely unaffected by iodine intake. However, the literature may be distorted by three circumstances under which iodine increases may harm, and iodine restriction help, Hashimoto’s patients:

  1. Selenium deficiency causes an intolerance of high iodine.
  2. Iodine intake via seaweed is accompanied by thyrotoxic metals and halides.
  3. Sudden increases in iodine can induce a reactive hypothyroidism.

All three of these negatives can be avoided by supplementing selenium along with iodine, using potassium iodide rather than seaweed as the source of iodine, and increasing iodine intake gradually.

It’s plausible that if iodine were supplemented in this way, then Hashimoto’s patients would experience benefits with little risk of harm. Anecdotally, a number have reported benefits from supplemental iodine.

Other evidence emphasizes the need for balance between iodine and selenium. Just as iodine without selenium can cause hypothyroidism, so too can selenium without iodine. Both are needed for good health.

A few months after I was diagnosed with Hashimoto’s I started 50 mg/day iodine plus 200 mcg/day selenium. If I were starting today, I would follow Paul’s recommendation to start with selenium and a low dose of iodine, and increase the iodine dose slowly. I would not take any kelp, because of potential thyrotoxic contaminants.

Currently I’m doing the following to try to reverse my Hashimoto’s:

  1. PHD diet and follow PHD book and blog advices to enhance immunity against infections, since infections seems to be implicated in Hashimoto’s pathology [28][29][30]. I give special attention to what Chris Masterjohn calls “traditional superfoods”: liver and other organs, bones and marrow, butter and cod liver oil, egg yolks and coconut, because these foods are high in minerals, like iodine, zinc, selenium, copper, chromium, manganese and vanadium, all of which seems to play a role in thyroid health [31];
  2. High dose iodine (50mg of Lugol’s) plus 200 mcg selenium daily. These I supplement because of their vital importance to thyroid and immune function;
  3. 3 mg LDN (low dose naltrexone) every other day to further increase immunity. LDN resources are listed below [32][33][34][35][36];
  4. Avoiding mercury and other endocrine disruptors. When I removed 9 amalgams (mercury), my TPO antibodies increased for 3 months and took another 6 months to return to previous values. I also avoid fish that have high and medium concentrations of mercury. Cod consumption increased my TPO antibodies;
  5. 1g of vitamin C daily. Since it seems to confer some protection against heavy metal thyroid disfunction [37], improve thyroid medication absorption [38] and there is some evidence that it could improve a defective cellular transport for iodine [39];
  6. Donating blood 2 to 3 times per year. In men, high levels of iron seems to impact thyroid function [40].

Final Thanks

I would like to make a special thanks to Paul Jaminet for giving me the opportunity to write this essay, for gathering many, many papers for me, and for having the patience to revise both posts and suggest many changes that made the text clearer; and to Emily Deans who kindly sent me one key study that Paul could not get.


[1] Dr Datis Kharrazian. Iodine and Autoimmune Thyroid — References.

[2] Marino MA et al. Urinary iodine in patients with auto-immune thyroid disorders in Santo André, SP, is comparable to normal controls and has been steady for the last 10 years. Arq Bras Endocrinol Metabol. 2009 Feb;53(1):55-63.

[3] Yoon SJ et al. The effect of iodine restriction on thyroid function in patients with hypothyroidism due to Hashimoto’s thyroiditis. Yonsei Med J. 2003 Apr 30;44(2):227-35.

[4] Kasagi K et al. Effect of iodine restriction on thyroid function in patients with primary hypothyroidism. Thyroid. 2003 Jun;13(6):561-7.

[5] Gribble GW. The natural production of organobromine compounds. Environ Sci Pollut Res Int. 2000 Mar;7(1):37-47.

[6] Zhang ZW et al. Urinary bromide levels probably dependent to intake of foods such as sea algae. Arch Environ Contam Toxicol. 2001 May;40(4):579-84.

[7] Kawai T, Zhang ZW et al. Comparison of urinary bromide levels among people in East Asia, and the effects of dietary intakes of cereals and marine products. Toxicol Lett. 2002 Aug 5;134(1-3):285-93.

[8] Leblanc C et al. Iodine transfers in the coastal marine environment: the key role of brown algae and of their vanadium-dependent haloperoxidase. Biochimie. 2006 Nov;88(11):1773-85.

[9] van Netten C et al. Elemental and radioactive analysis of commercially available seaweed. Sci Total Environ. 2000 Jun 8;255(1-3):169-75.

[10] Hou X et al. Iodine-129 in human thyroids and seaweed in China. Sci Total Environ. 2000 Feb 10;246(2-3):285-91.

[11] Toh Y et al. Isotopic ratio of 129I/127I in seaweed measured by neutron activation analysis with gamma-gamma coincidence. Health Phys. 2002 Jul;83(1):110-3.

[12] Miyashita S, Kaise T. Biological effects and metabolism of arsenic compounds present in seafood products. Shokuhin Eiseigaku Zasshi. 2010;51(3):71-91.

[13] Cleland B et al. Arsenic exposure within the Korean community (United States) based on dietary behavior and arsenic levels in hair, urine, air, and water. Environ Health Perspect. 2009 Apr;117(4):632-8. Epub 2008 Dec 8.

[14] Chong W, Shit Xg, Teng WP, et al. Multifactor analysis of relationship between the biological exposure to iodine and hypothyroidism. Zhongua Yi Za Zhi. 2004 Jul 17:84(14):1171-4.

[15] Tong YJ et al. An epidemiological study on the relationship between selenium and thyroid function in areas with different iodine intake. Zhonghua Yi Xue Za Zhi. 2003 Dec 10;83(23):2036-9.

[16] Karita K et al. Comparison of selenium status between Japanese living in Tokyo and Japanese brazilians in São Paulo, Brazil. Asia Pac J Clin Nutr. 2001;10(3):197-9.

[17] Thorling EB et al. Selenium status in Europe–human data. A multicenter study. Ann Clin Res. 1986;18(1):3-7.

[18] Mengüba? K et al. Selenium status of healthy Turkish children. Biol Trace Elem Res. 1996 Aug;54(2):163-72.

[19] Hincal F. Trace elements in growth: iodine and selenium status of Turkish children. J Trace Elem Med Biol. 2007;21 Suppl 1:40-3.

[20] Fordyce FM et al. Selenium and iodine in soil, rice and drinking water in relation to endemic goitre in Sri Lanka. Sci Total Environ. 2000 Dec 18;263(1-3):127-41.

[21] Alsayed A et al. Excess urinary iodine is associated with autoimmune subclinical hypothyroidism among Egyptian women. Endocr J. 2008 Jul;55(3):601-5. Epub 2008 May 15.

[22] Strieder TG et al. Prediction of progression to overt hypothyroidism or hyperthyroidism in female relatives of patients with autoimmune thyroid disease using the Thyroid Events Amsterdam (THEA) score. Arch Intern Med. 2008 Aug 11;168(15):1657-63.

[23] Stuckey BG et al. Low urinary iodine postpartum is associated with hypothyroid postpartum thyroid dysfunction and predicts long-term hypothyroidism. Clin Endocrinol (Oxf). 2011 May;74(5):631-5. doi: 10.1111/j.1365-2265.2011.03978.x.

[24] American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Hyperthyroidism and Hypothyroidism.

[25] Vanderpas JB et al. Selenium deficiency mitigates hypothyroxinemia in iodine-deficient subjects. Am J Clin Nutr. 1993 Feb;57(2 Suppl):271S-275S.

[26] Contempré B et al. Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population. Clin Endocrinol (Oxf). 1992 Jun;36(6):579-83.

[27] Contempré B et al. Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium. J Clin Endocrinol Metab. 1991 Jul;73(1):213-5.

[28] Benvenga S et al. Homologies of the thyroid sodium-iodide symporter with bacterial and viral proteins. J Endocrinol Invest. 1999 Jul-Aug;22(7):535-40.

[29] Wasserman EE et al. Infection and thyroid autoimmunity: A seroepidemiologic study of TPOaAb. Autoimmunity. 2009 Aug;42(5):439-46.

[30] Tozzoli R et al. Infections and autoimmune thyroid diseases: parallel detection of antibodies against pathogens with proteomic technology. Autoimmun Rev. 2008 Dec;8(2):112-5.

[31] Neve J. Clinical implications of trace elements in endocrinology. Biol Trace Elem Res. 1992 Jan-Mar;32:173-85.

[32] David Gluck, MD. Low Dose Naltrexone information site.

[33] LDN Yahoo Group.

[34] LDN World Database. Where LDN users share their experience with various diseases.

[35] Those Who Suffer Much Know Much. A colection of LDN users testimonies.

[36] Elaine A. More. The Promise Of Low Dose Naltrexone Therapy: Potential Benefits in Cancer, Autoimmune, Neurological and Infectious Disorder.

[37] Gupta P, Kar A. Role of ascorbic acid in cadmium-induced thyroid dysfunction and lipid peroxidation. J Appl Toxicol. 1998 Sep-Oct;18(5):317-20.

[38] Absorption of thyroid drug levothyroxine improves with vitamin C. The Endocrine Society. News Room.

[39] Abraham, G.E., Brownstein, D.. Evidence that the administration of Vitamin C improves a defective cellular transport mechanism for iodine: A case report. The Original Internist, 12(3):125-130, 2005.

[40] Edwards CQ et al. Thyroid disease in hemochromatosis. Increased incidence in homozygous men. Arch Intern Med. 1983 Oct;143(10):1890-3.


Iodine and Hashimoto’s Thyroiditis, Part I

Mario Renato Iwakura is a Brazilian engineer and Hashimoto’s thyroiditis patient who is intimately familiar with the hypothyroidism literature. Mario has graciously agreed to do a guest series on the place of iodine and selenium supplementation in treatment of hypothyroid disorders. I’m very excited to have Mario’s thoughts, as he’s extremely smart and passionately engaged with the science. — Paul

Most doctors believe that iodine supplementation will aggravate autoimmune (Hashimoto’s) thyroiditis. This view is supported by observations that the incidence of Hashimoto’s hypothyroidism tends to increase in populations that increase their iodine intake. (The incidence of hyperthyroidism, on the other hand, increases as iodine intake decreases.). However not all epidemiological studies support this association [1][2][3][4].

Dr. Datis Kharrazian (“Dr. K”), whose 2010 book “Why Do I Still Have Thyroid Symptoms?”[5] is popular among Hashimoto’s patients, vehemently opposes the use of iodine in Hashimoto’s [5][6][7]. Chris Kresser of The Healthy Skeptic [8] has argued this point of view in his post “Iodine for hypothyroidism: like gasoline on a fire?”. And there’s little doubt that some patients have experienced bad consequences from high-dose iodine.

On the other side, doctors such as Dr. Guy E. Abraham [9], Dr. David Brownstein [10], Jorge D. Flechas [11] and Dr. David Derry [12] have claimed success prescribing high doses of iodine for Hashimoto’s and for breast and thyroid cancers.

Can these experiences by reconciled? What we will try to do is demonstrate that iodine acts synergistically with selenium, and that it is imbalances between the two that damage the thyroid.

First, Some Background

Thyroid peroxidase or thyroperoxidase (TPO) is an enzyme expressed mainly in the thyroid that liberates iodine for addition onto tyrosine residues on thyroglobulin (TG) for the production of the thyroid hormones thyroxine (T4) or triiodothyronine (T3).

The human body normally has low levels of auto-antibodies against both TG and TPO, which serve some physiological function. Autoimmune thyroiditis features high levels of these auto-antibodies, leading to immune attacks on the thyroid.

High levels of  thyroid auto-antibodies are positively associated with hypothyroidism symptoms [13][14]. TPO antibodies and TSH levels are strongly associated with progression of subclinical hypothyroidism to overt hypothyroidism [3], as can be see in Table 3 below:

Selenium Can Cure An Iodine Excess

Dr. K said in his book and site that “iodine stimulates the production and activity of the thyroid peroxidase (TPO) enzyme” [5][7]. Since TPO is a target of autoimmune attack in Hashimoto’s patients, this might worsen the disease [5][6][7]. In his book he also states that excessive iodine will shut down TPO activity [5], but he neither cites a reference nor states what level of iodine intake will cause this to happen.

In fact, excess iodine combined with selenium insufficiency will reduce (not increase, not shut down) TPO activity [15]. Let’s look at a study that had seven groups: normal iodine and lab-chow selenium only (NI), excess iodine and lab-chow selenium only (EI), and five groups with excess iodine and steadily increasing levels of selenium added to water (IS1 to IS5). TPO activity was reduced by excess iodine (EI), but returned to control levels (NI) with moderate selenium (IS1 and IS2). With excess iodine and excessive selenium (IS3 to IS5), TPO activity was also decreased, as we can see from table 2 below.

Some other studies have also demonstrated this reduced TPO activity at high iodine intakes [23][24].

This study [15] also showed a picture (fig. 1) of thyroid follicles from rats receiving normal iodine diet (NI), excessive iodine (EI) and excessive iodine plus 0.2 mg/L selenium (IS2). Thyroid follicles from the excessive iodine group (EI) are enlarged, a characteristic of goiter. But, there is virtually no difference between the first and last picture! If selenium and iodine are increased together, no goiter occurred.

Note that the IS2 level of selenium, which protects against iodine toxicity, corresponds in a person who drinks 1-2 liters per day to a selenium dose of 200 to 400 mcg per day – which happens to be the Perfect Health Diet “plateau range” for selenium.

Selenium Can Cure Autoimmunity

Another paper, also from China, looked at the effects of selenium in an animal model of iodine induced autoimmune thyroiditis [16].

There were three groups of mice, a healthy control group, and groups with iodine induced autoimmune thyroiditis without (AIT) and with (AIT+Se) selenium. The AIT+Se group was given high iodine (AIT only) for 8 weeks to induce the disease, and then, for 8 weeks more, they were given iodine plus selenium. After 8 weeks of selenium supplementation their thyroid follicles were almost fully recovered, as we can see below, even though high-dose iodine had continued:

The AIT group has enlarged cells characteristic of goiter and dead tissue; the AIT-Se group thyroid section resembles a normal thyroid. Thyroid weight doubled in the AIT group, proof of goiter, but returned to normal after selenium supplementation.

Before selenium was given to the AIT+Se group, serum TgAb antibodies were elevated, but they returned to normal after selenium supplementation:

An interesting aspect of this study was the changing population of immune cells. A specialized subpopulation of T cells, negative regulatory T cells or Tregs, helps establish and maintain self-tolerance by suppressing response to self-antigens and suppressing excessive immune responses deleterious to the host. Deficits in Treg cell numbers or function lead to autoimmune diseases [17].

In this study, CD4+CD25+Foxp3+ Treg Cells were reduced by high iodine, but returned much of the way toward normal after 8 weeks of selenium even though high iodine intake continued. The implication is that selenium-iodine balance may be needed to maintain proper Treg cell populations, and that selenium supplementation may restore normal regulation of autoimmunity.

The researchers concluded:

“In the present study, we observed that Se supplementation increased the frequency  of CD4+CD25+Foxp3+ T cells and enhanced expression of Foxp3 in vivo. These changes were accompanied by suppressed TgAb titers and reduced thyroiditis. Thus the benefit of Se treatment may be due to the increase of CD4+CD25+ regulatory T cells.”

Under What Circumstances Does Excess Iodine Induce Autoimmunity?

In the previous study high doses of iodine were used to induce autoimmune thyroiditis. Let’s look more closely into the circumstances in which that happens.

It’s often said that excessive iodine in Hashimoto’s triggers an immune response characterized by proliferation of T lymphocytes, a disrupted Th1/Th2 axis, and altered CD4/CD8 levels. Pathogenesis of autoimmune disease is believed to begin with the activation of T cell autoaggression (turning them into “allergized T cells”).

Our next study, also from China, showed that excess iodine can indeed cause such an autoimmune pathology, but only if there is a deficiency in selenium [18].

Mice in 5 groups were orally administrated different combinations of iodine and selenium for 30 days. Four groups had no selenium but varying amounts of iodine in their water:  0 μg/L (group I), 1500 μg/L (group II), 3000 μg/L (group III), and 6000 μg/L (group IV). The fifth group had 6000 μg/L iodine plus 0.3 mg/L selenium (group V).

In Group IV, high-dose iodine at 6000 μg/L caused a proliferation of lymphocytes. But this was completely abolished by the addition of selenium to water in Group V:

Normally there are relatively stable population of T cells and their subgroups in tissue till immune function is in disorder. As we can see from Fig. 1, increasing iodine increased T lymphocytic reproductive activity, and was clearly high in group IV. But group V, which also received selenium, had the same values as the control group (I).

Subjects with Hashimoto’s also have a lower ratio of CD4+ to CD8+ lymphocytes than controls [19][20]. From fig. 2, we can see that iodine supplementation in groups II and III actually increased the CD4+ to CD8+ ratio, until the onset of autoimmune symptoms at very high doses in Group IV when the ratio decreased. However, group V, which had the highest iodine intake but with selenium as well, had the highest CD4+ to CD8+ ratio of all groups.  This suggests that high-dose iodine and selenium together may actually diminish the autoimmune syndrome compared to the low levels in the controls.

Another marker of autoimmune thyroiditis is the relative strength of the Th1 and Th2 responses, as indicated by the markers interferon-gamma and interleukin-4 (Th2). Th1(IFN-γ)/Th2(IL-4) ratios are increased in Hashimoto patients [21][22], and related with severity of Hashimoto’s disease [22].

As we can see from Fig. 3, the group with the highest iodine intake but no selenium (IV) was the only group that had clearly higher Th1/Th2 ratio. High iodine plus selenium in group V had similar Th1/Th2 ratios than control group (I).

The researchers concluded:

“The results revealed that there was no significant difference in the immunotoxicity between interventional group (group V) and control group (group I), indicating that adequate selenium has a favorable interventional effect on excessive iodine intake.”


Excess iodine intake can cause an autoimmune thyroiditis that bears all the characteristics of Hashimoto’s. However, in animal studies this occurs only if selenium is deficient or in excess. Similarly, in animal studies very high iodine intake can exacerbate a pre-existing autoimmune thyroiditis, but only if selenium is deficient or in excess.

With optimal selenium status, thyroid follicles are healthy, goiter is eliminated, and autoimmune markers like Th1/Th2 ratio and CD4+/CD8+ ratio are normalized over a wide range of iodine intake. It seems that optimizing selenium intake provides powerful protection against autoimmune thyroid disease, and provides tolerance of a wide range of iodine intakes.

In the next post in this series (Iodine and Hashimoto’s Thyroiditis, Part 2, May 26, 2011), we’ll transition from animals to humans. Does epidemiological evidence suggest that these animal findings are transferable to humans?


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