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.

Leave a comment ?


  1. At least half the recent posts on Anthony Colpo’s blog bash someone. He’ll find some reason to lob insults at someone.

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

    This is fairly consistent with my experience that I do best on a diet with some meat and a very large amount of vegetables, but regardless of the volume of food I consume I generally experience better satiety if I include 200 calories of starch per meal. This almost seems to have the effect of a “switch” in the sense that I otherwise don’t experience “better” satiety with more starch versus other calorie sources, so long as this basic requirement is met. This isn’t inviolable for me, but it’s a general trend.


  3. Hi Paul,

    Excelent post!

    I want to say that I have no personal disagreement with Colpo or anyone else!

    I’m only a subclinical hypothyroid person due to Hashimoto’s seeking to my n=1 best approaches while trying to reverse my condition, and it happens that your PHD has been helping me a lot!

    Finally, let’s not forget the effect thyroid hormones on longevity! It may be wise not try to increase them too much, certanly not by overfeeding!

  4. Hi Chris,

    200 starch calories per day was sort of a magic level for me — it made acute glucose deficiency symptoms go away — and 200 starch calories per meal is about what I eat now (400-600 per day) and seems to work well for me.

    I think the satiety / lack of hunger signals a well nourished body, and glucose deficiency stimulates hunger. But 400-600 starch calories a day should be enough to eliminate the deficiency and the hunger for most non-athletes.

  5. I’m glad we’re looking into this further. Obviously I am also puzzled by that abstract as well. That the hypercaloric diets didn’t have a difference in T3 levels but the 80% carb iso diet produced higher T3 than the 40 and 20 is odd and suggests that the difference is not in carbohydrate intake, since it’s roughly the same amount of carbs as between 40% and 80% on the isocaloric diets. The conclusion I am leaning towards is what I suggested to Danny. That an 80% carb diet is also a low protein diet, and a protein-restricted diet can elevate thyroid activity. Ray Peat says that tryptophan and cystine reduce T3 and some animal studies suggest it. Like you mentioned, that’s not to say it’s desirable as Peat suggests, but it could be explanatory, if it is indeed true.

    Stephan’s latest post reminded me of an important distinction with regards to Mario’s post. I don’t think that it is linoleic acid itself that is inhibiting T4 to T3 conversion, but excessive inflammation. And excessive linoleic acid, while it doesn’t necessarily cause more excessive inflammation, does reduce the amount of DHA in the cells and impairs anti-inflammatory signaling. It’s all about the ratio, or more specifically the “omega-3 index”. If omega-3 intake is equally poor on a high and a moderate LA diet then I doubt there will be a difference. You’ve probably read it but Chris Kresser makes the point for various cytokines causing hypothyroid symptoms

    I suspect that that you suspect that too.

    It’s great to see so many minds debating and researching. Cheers.

  6. Carbohydrates and the Thyroid | Low Carb Daily - pingback on August 24, 2011 at 12:27 pm
  7. Fantastic post, Paul. I see euthyroid sick syndrome (ESS) frequently in my practice, and anecdotally it almost always appears concurrently with chronic infection or autoimmunity. I run a full thyroid panel on all of my patients and will be adding rT3 shortly. After a few months I’ll have some initial clinical data to work with.

    As Stabby pointed out, inflammatory cytokines suppress thyroid hormone production in several ways. They suppress pituitary production of TSH, T4 to T3 conversion and cellular sensitivity to T3.

    I’ve seen significant improvements in T3 levels by addressing the underlying cause of inflammation in ESS patients.

    And for whatever it’s worth, I do generally see improvements when patients with thyroid issues switch from a VLC to moderate (i.e. 100-175g) carb diet.

  8. Amazing post Dr. Jaminet. Like in real life, your writing comes off as so cordial and serene; even when you’re making me critically examine my own positions.

    I just wanted to clarify a few things about my stance on CHO and T3:

    About my exchange with SR. Many doctors will accept a bottom barrel FT3 number as being ‘in range’ when the person has obvious manifestations of hypothyroidism (euthyroid). When I told SR that I wanted to “radically increase T3” with diet, I meant that I wanted to push T3 levels as high as they would go without becoming hyper, which would probably not happen unless I was taking meds or had an autoimmune issue.

    My stance on this subject is largely motivated my 4+ years experimenting with low-carb and very low-carb (zero) diets. While I completely believe that one can survive on VLC diets (0-PHD range) I found that nagging symptoms I had had for years went away with upping my carbohydrate consumption (fruit) to Mark Sisson’s danger zone (300-400).

    To be more specific: high anxiety, low libido, toe fungus, poor sleep, puffiness, persistent bloating and mild depression were literally obliterated by this approach. My breath improved as well, possibly signaling better digestion or modified gut ecology.

    Given my heavy self-experimentation over the years, I found that thyroid seemed to be key in all my issues. Perhaps this is why I’m so fond of Ray Peat. When you take into account that structure and energy are interconnected and that fueling the body at a cellular level is paramount, Peat’s ideas become much clearer.

    I should be more careful in my wording as I know these things are highly variable. Perhaps its because I see so many on LC Paleo dieters with similar, persistent problems like mine.

    Once again, amazing article and I really appreciate you taking the time to explore this area.

  9. Paul,

    This post exemplifies why this is one of my top three favorite nutrition/health blogs (along with Stephan Guyenet’s and Chris Masterjohn’s).

    I appreciate your open-mindedness and willingness to carefully consider evidence countering what you have written earlier.

    Also I am happy you reacted to Anthony Colpo’s criticism with an olive branch. Whether one likes Anthony’s style or not, his arguments are always worth considering and often offer valuable insights. (His book on cholesterol is still the best book available in my opinion.)

    Looking forward to future installments of this series.


  10. Paul,

    I hope that my role in this controversy isn’t misconstrued as trying to stoke the fire. My intention is always to get feedback from the experts I trust in order to elucidate a topic that puzzles me since I am certainly not on ya’ll’s level to do so myself. Just like Stabby, I value your in-depth, thorough, well thought out perspective on topics such as in this article and in your book. However, I equally value Anthony Colpo’s knowledge. If it was not for his “Great Cholesterol Con,” I would have never overcome the Lipid Hypothesis mindset and never even considered your book and diet, which has already helped me tremendously. For both your books (and Colpo’s diet book: “Fat Loss Bible”), I owe you both a debt of gratitude. Unfortunately for me, this particular topic is one of the few disagreements between your diet approaches I was trying to resolve in my mind since it has large implications for myself and others whom I seem to be a filter for diet and health advice. Unlike other commenters here, I even enjoy Colpo’s feistiness, which sure livens up my week from reading his articles. I also equally appreciate your nice demeanor and friendly website and following. If I caused this controversy then I apologize. Yet, if a few great minds came together to meet and share ideas from this, then I also see it as being tremendously beneficial for everybody involved especially the readers like me on such an important issue for our health.

  11. the first question i would ask is what is the normal conversion of T4 to T3? Is it a 1:1 conversion or is something lost in the process? For example my recent Free T4 was1.24( range.89-1.76, and Free T3 was 2.6(range 2.3-4.2. TSH was 1.7(range .35 to 5.5)

    I eat starches in form of rice and potatoes on a daily basis- not sure how much
    Thanks, very interesting subject, and appreciate your objectivity in trying to find answers and not being tied to an ideological viewpoint.

  12. Jaybird,

    On my part, I do not think you are responsible for any controversy! On the contrary, I think that this ‘controversy’ ended into a great discution!

  13. A quick question back to Chris K. In your comment you said you would be supplementing rT3. Isn’t that the version of T3 that Paul mentioned as being the problem? What form of T3 is optimal to supplement here (not that I would ever take T3 because of longevity considerations)

  14. Thanks Mario.

    I sure have learned a lot!

  15. You need to seriously take into account the source of carbs and the immune response to them. Everything else you talked about will be heavily influenced by this.
    This is speaking from personal experience, i reversed hashimoto’s tyroiditis on myself. And the thing that helped most was going keto at first, and then slowly reintroducing other stuff (some veggies and very little fruit) but not grains or starches, that would again fuel inflammation which quickly reflected on the thyroid. The next big part was taking massive doses of fish oil, i believe this was equally important as the rest of the diet put together. All the while i trained heavily in martial arts and did weightlifting. Just when my tests came back normal, even the antibodies went negative, i had a big tragedy in my family which resulted in the most stressful time of my life. I kept with the plan and the thyroid stayed ok. This must’ve been the hardest test.
    Hopefully i will get a chance to repeat my results on someone else (i’m a molecular biologist, we’re used to testing stuff out on ourselves), when i do i hope to write a bit more about this.
    I find your information here sound,but contradictory in parts to my experience, hence i believe there’s much more to it.

  16. How do ideas about physiological insulin resistance relate to rt3 preventing glucose uptake? Can we not make a similar interpretation? What if one experiences no symptoms of hypothyroidism while having a higher than normal rt3 level? How also then would we factor in Petro’s and Lucas’ posts revolving around mitochondria and fuel oxidation–as related again to t3/rt3?

  17. Aaron,

    I’ll be testing rT3 levels, not supplementing with it.

  18. Chris

    Have you seen high range t3 with a hi rt3 or is this not possible?

    Is it a possibility with high cortisol/stress hormone levels?


  19. Sorry, I just saw that you haven’t been checking rt3 in clinic as part of your regular t panel.

  20. Hi, I just wanted to add an anecdote. A few years ago tests indicated I had developed a slight hypothyroidism. Then I had a pregnancy, and a few weeks after giving birth I started a zero-carb diet (by which I mean eating just meat — for me this is profoundly more health-promoting than a VLC diet of meat and non-starchy vegetables, as the former relieves my mood problems and normalizes my weight, but the latter does not). A few months later I tested thyroid levels again, and I no longer had hypothyroid as evidenced by TSH, but my T3 levels were slightly below normal. I continued the diet, and several months further along was retested. Now all the thyroid tests are normal. So, I think I may have had a bit of ESS at a certain point, and I’m not sure why — perhaps the stress of pregnancy and nursing, or maybe because there were still residual omega 6 FAs in my body. Maybe it was somehow left over from having hypothyroidism which hadn’t completely healed. Who knows? But all of it it did normalize over time on a ZC diet for me.

  21. @Thea, I too have found so far the best results with Hashimotos eating an auto-immune paleo diet + daily omega 3 supplement. My waistline and TSH is the best since being diagnosed 2 years ago. I exclude dairy, grains(including rice), legumes, seeds, nuts, alcohol. However – I find a moderate carb diet is best as well. I tend to use a gram per kilo bw per day a good way to measure – I find 75 – 100 grams carbs which equals 1.5 – 2 grams per kilo per day works for me. I tried lower carb, but get the lump feeling in my throat – slight thyroid inflammation. It goes when I eat enough carbs, starchy veg make me feel good.

    Infractions seem to quickly make things worse. My canaries are dishydrotic eczema and Raynauds – both will appear and tell me quickly if I’ve eaten the wrong thing.

  22. Julianne, which starchy vegetables do you eat? Assuming potatoes?

  23. No not potatoes – I cut nightshades as well, although I’ve added back a little tomato paste for flavour.

    I eat kumara and other sweet potatoes, and pumpkin and other winter squash. I also eat a banana when I go to the gym

  24. The quote from Danny Roddy states that one of the effects of a high carb diet is increased testosterone. I find this interesting because I believe a lower carb diet may have increased mine. After a year on a whole foods paleo style diet my total testosterone level was 827(52yo male) and was flagged as high on some general blood screening I had done. Unfortunately, I don’t know my T level previous to this diet but when I did some research into whether this was a problem I found there was a positive correlation with testosterone and HDL. My HDL had increased 50% (from 52 to 78) on this diet. We’ve all read the numerous reports of people greatly increasing HDL when switching to a higher saturated fat paleo diet so I wonder how many have also increased total testosterone. If testosterone levels increase on both low carb and high carb then obviously it’s not the carbs. My guess would be a reduction in neolithic agents of disease such as excessive pufa’s, grains, sugar, etc. Any thoughts?

  25. Paul, you are way too nice 😉

  26. I really enjoy following along as the paleo bloggers debate the data. Nice work Paul, both in engaging in debate in a respectful manner and in going over the data as it relates to the PHD.

  27. Paul you’re the best. I’m glad you addressed Colpo’s post without insults. I think he has a lot to offer even if I turned my nose up at him when I was completely obsessed by low carb.

  28. Just wanted to mention Dr Kruse recommends a low carb diet with 50g of protein 30 mins upon waking to restore leptin sensitivity. You will have high reverse T3 if not leptin sensitive. So perhaps this 50g protein – 200 calories goes towards providing needed glucose.

  29. “At least half the recent posts on Anthony Colpo’s blog bash someone. He’ll find some reason to lob insults at someone.”

    Yeah, really, he likes dishing it out but seems he can’t take it.
    Probably a lack of SAFA in his diet. Would make me cranky as well. 😉

    And sorry, Paul, but I really don’t think it’s such a big deal to use the word “bash”. Colpo needs to lighten up dramatically!


  30. That Dr Kruse leptin sensitivity protocol includes max 50g carb – 200 carb calories. But I think lower the better is recommended.

  31. This is really interesting.

    I’ve been my opinion on sugar and carbs has really oscillated a lot as I read more posts and books. I honestly have no idea exactly how much I’m getting right now because I don’t count calories, but I’d assume it’s somewhere in the 100g range. Not including vegetables, I probably get most of my carbs from raw mlik (my main divergence from the paleo crowd) and some from nuts, nut butters, and some fruit.

    I was eating sweet potatoes pretty regularly until a few months ago. Maybe I should pick that up again…

    On another note, I’m always a bit skeptical when the dialog surrounding this kind of things gets really technical. I think understanding specific components and processes in the body is important, but at times I feel like we forget that there’s still a lot we don’t know for sure. It’s often far too easy to come to conclusions based on incomplete information, even when it seems pretty clear cut.

    Keep up the good work!


  32. Just a brief question: I am not to count carbs from vegetables does it even apply to those higher in sugar/starch like carrots and green peas and bell peppers?

  33. A second question – sorry…I have just read that women suffering from PCOS should keep their carbohydrate intake below 80 g. I am not the typical PCOS sufferer as I am neither overweight nor diabetic but before finally conceiving my first child my doctor told me that my ovaries looked like I did suffer from it.
    Here is the link:
    Peggy Emch isn´t a medical doctor but what she evidently did some research…What carb intake would you recommend for someone with fertility issues and (possible) PCOS?

  34. Nice tone, Paul.

    I just can’t read anything from Colpo without seeing him make egomaniacal who’s-your-daddy!-faces while writing. He’s an embodiment of the phrase “my opinions might change, but not the fact that I’m right”.

    I’m always interested in reading more on the subject of thyroid!

  35. Posts like these are the reason this site is one of the top places for balanced nutrition info on the interweb. Great work! On the downside, you made me think too hard too early in the morning. I need more coffee!

  36. Excellent post, Paul. Anthony Colpo could learn some humility if he visited these parts often.

    I have no doubt he’s an intelligent guy, but he seems to suffer from what Chris Masterjohn described in his recent post about diet dogma: taking personal experience and applying it to everyone. So if he happened to suffer from poor thyroid function when he went low carb, everyone will and low carb must be evil! I find that approach quite irritating and it takes away quite a lot of his credibility. It probably didn’t occur to him that his endurance exercise dramatically increased his glucose requirements and was the main reason for his suffering, rather than low carb itself. Also, his constant insistence that no real ‘athlete’ can thrive on low carb bugs me. Maybe not endurance athletes as your post so eloquently demonstrates, but bodybuilders can and do. His constant references to low carb ‘sucking the big one’ for building muscle are quite irritating to be honest, when there are plenty of examples of real world people using such a diet to build muscle, without steroid use which the professional bodybuilders on high carb diets constantly abuse. Just a visit to Mark McManus’ “Musclehack” site will get you acquainted with plenty of people who gain muscle eating his version of low carb, the MANS diet. It’s basically VLC for most of the week and then carb loading for one day to replenish muscle glycogen. I believe the Metabolic Diet by Mauro Di Pasquale was the pioneer of such carb cycling diets and produced great results for many people who didn’t want to abuse steroids. An approach like yours where one consumes LC instead of VLC seems to work well too, at least for me. The concept behind the ‘carb loading’ in carb cycling diets is to replenish muscle glycogen and I find I can do that effectively by maintaining a constant LC intake of around 100g everyday, without having to go VLC and then load up on carbs. Off topic, but since Colpo was being discussed, I just felt like sharing it.

  37. this post is amazing, and making me change my views….

    where does protein fall into the starch equation? and when you have ESS, how do you go about correcting it besides 200g starch a day? i read a study earlier saying that pro-inflammatory cytokines are greatly reduced via endurance exercise and thus, enhances the hypothalamus, and probably controlling for leptin/thyroid.

    seems youre at opposite ends with Dr Kruse though. His big direction is high rT3=leptin resistance, no question about it eat lots of protein and keep carbs at or below 50g/day.

    You say high rT3 means ESS and other thyroid problems/deficiencies but don’t mention the significance, if any is applicable, to leptin or a low carb diet.

    slightly confused…

  38. Is there anything wrong with getting my carbs in the form of pure gluccose (rice syrup)? I just do not enjoy safe starches. I can eat them without health problems but I like my meat/fish with vegetables much more without added rice/potatoes. I do like fruit but from what I understand they shouldn`t provide me with more than 200 kcal. I would enjoy coconut milk smoothies with rice syrup…Might this be an option?

  39. It would be great if some long term low carbers could get their hormones tested and evaluted agaisnt their diet and activity level. I think that would shed some serious light on this issue. What we have is many younger paleos coming forth with these sex hormone and thyroid issues all of a sudden, and some of them seem to be fixing these with high carb paleo diets. On the other hand, I know much of the consensus of young people at AHS was that we were not impressed by the physiques of some of the older, long term low carb guru’s such as Cordain and Eades physiques. Sure, activity levels play a major role in leaness, but so do sex and thyroid hormones.

    Personally, higher carbs seems to improve these things for me like Danny, but I dont have evidence for it yet. Fats also help, I definitely can’t be too low in these. But more fat doesn’t do it for me the way more carbs does.

    That said, Jeff pointed out something that I;ve been on to for a while as well… HDL and Testosterone are always postively correlated. Saturated Fats raise HDL, so higher fat should = higher T. But for some reason this isn’t the case for some? Also, Paul noted in his HDL post that higher potassium excretion was correlated with high HDL, so tubers such as potatoes and sweet potatoes, which are to my knowledge the highest dietary sources of potassium around, also should help HDL and testosterone and this is certainly true in my case going off of symptoms.

    We have all these short term studies but no long ones. We have anectodes from both sides of the board, but what are the variables? Are these folks with good thyroid and sex hormones on high fat doing something different that those whose dropped arent? I think we will continue to have these questions until we really dig digger with the evidence we have in long term long carb dieters.

  40. I can’t help but feel this is all a little too reductionist, especially since the evidence isn’t so clear. Studies are pretty inconsistent with hormone level measurements and diets, and people have inconsistent symptoms/feelings with different blood levels. We don’t know optimal levels of thyroid, and we would perhaps come to a different dietary conclusion for every single-hormone-based article written–ie, finding a diet that optimizes testosterone wouldn’t necessarily be the same for t3: now what do you do? Anyway, I don’t think Colpo’s thyroid articles have airtight coherency by any means.

  41. @John,

    I don’t think it’s reductionist especially when if the thyroid is not optimally functioning, many other parts of the body that have a hand in wellbeing suffer as well. I think this is a very important issue especially for folks who see this diet as a long term thing.

  42. Bill,

    The thyroid itself is often not the problem when someone has symptoms of hypothyroidism, and people experience symptoms at different blood levels. So, finding a diet to “optimize” lab numbers only goes so far–it’s of course complicated. Men feel great when they inject testosterone: what you do then when studies show max test with one macro ratio, max t3 with another? We always end up failing when we consider something to be the “master” hormone/protein/chemical.

    Peter posted OD cortisol numbers [low normal] in the comments section of some post.

  43. My wife and I have been VLC for a couple years now, myself probably a little longer than her and I tend to eat more saturated fat too. She recently stopped taking birth control and her menstrual cycle just stopped. Also for years and years, maybe as long as the past decade, she’s been chronically constipated, depressed, and always tired and wanting to sleep 10+ hours. She’s been thru tons of tests and no doctor can find anything wrong with her. I started doing some research on her results from multiple blood tests and found her TSH has been slowly increasing and was at 3.13. We started checking her basal body temperature in the mornings and she’s usually around 96.

    I started to suspect possible hypothyroidism so we presented this info to her endocrinologist and he actually got mad at me and asked who the doctor was here, that’s not it he said.

    Both of us have also avoided salt for most of our lives as well as most packaged/processed foods that might contain salt. So we started supplementing Iodine, starting about a month ago and slowly increasing the dosage each week, as well as eating about 200-400 carb calories a day from white rice, taro, and cassava (all covered in pastured butter). Some mornings now her temperature has reached as high as 98.2 and her constipation has suddenly improved a lot.

    I’m not sure how big of a part the higher carb intake is playing in this apparent recovery, but it’s a little too early to declare her cured anyway because we’re also still waiting to see if her hormones correct themselves. Her estradiol and progesterone were both very low, and her prolactin about double the normal upper limit, but we’re hoping her body will correct itself soon without the need for synthetic hormones. Multiple doctors keep suggesting getting back on birth control but we’re going to start thinking about having a child in the next couple of years so we need to figure out what’s going on with her body now.

    I decided to get some blood tests done on myself and found my TSH was 3.87 and although I have had no symptoms of hypothroidism, I started supplementing Iodine too. I was already eating that many carbs for a few months now to help with a chronic fungal infection in my gut that had caused acne for most of my life. Paul’s advice appears to have helped me cure that as well.

  44. What happens in a book is not instructive to what happens in human. I detailed the hormone cascade in my Hormone 101 blog. reverse T 3 is a competive inhibitor at the cellular level. When it is high it completely shuts down T4 and T3 function. It completely demolishes glucose utilization. This can happen on a high carb, low carb, high fat or low fat diet and a diet of low to high protein. I have seen and treated all these conditions. The reason is what is occurring centrally at the leptin receptor and the hypocretin neurons. There are several reasons for this. Often leptin sensitivity is different centrally, at the liver level, and also at the peripheral muscle layer. This is very evident when the hypothalamus is very disordered when the cardiac CRP is elevated as it is in acute sepsis or infection and ESS. The leptin receptor has 6 possible “inception” sites that all confer a distinct biologic responses based upon a cornucopia of dietary inputs. Each one of these leptin receptors are tied to specific neurons by direct wiring and complex neurotransmitter connections. This increases the variations of the neurobiology even further. Leptin neurons act directly on the Lateral Hypothalamic Area (LHA) and regulate hypocretin gene translation and changes its control over the dopamine tracts that SG spoke of. The dopamine tracts are “outflow only tracts” and have no bearing of control of the hypocretin neurons or on the leptin receptor directly. Dr. Meyers at Michigan has shown rather definitely that leptin is the master controller of all energy balance. Insulin plays a small role. Dr Lustig totally swung and missed this at AHS and I told him so and I will be soon posting why after his theory is in print in the Journal of pediatrics. LHA Leptin receptor neurons also densely innervate the LHA where they directly synapse with the hypocretin neurons, but not MCH neurons, Dr Meyers has shown and said in Orlando in June of 2010 that direct leptin action via LHA Leptin receptor mediated neurons regulates gene expression in hypocretin neurons. He also believes as I do that leptin contols the whole wiring circuits of all energy balance. These findings have shown us leptin’s massive role for LHA leptin action in the modulation of hypocretin neurons, suggesting the importance of LHA Leptin receptor neurons in the regulation of hypocretin signaling that is crucial to leptin action and complete metabolic control of energy balance and all glucose homeostasis. This includes the action of the thyroid. The thyroid answers to central leptin status. I think if you read my pocket reference to endocrinology in my hormone 101 post this is obvious. This story has been what happens in the brain. I see this daily in my clinic and the clinical testing meshes with this work from the benchtop. I think it is ridculous to think one diet over the other dictates this or that. The brain is what controls it all.

  45. Dr Kruse can you condense that to easily understandable. Why do you do low carb for leptin sensitivity if diet type doesn’t make a difference if that’s what I’m understanding from your above comment?

  46. Hunter,

    What steps did you take that helped with your acne?

  47. Tony’s blog post is a trip. I think he has most of the other blogger beat on testosterone levels except maybe Nickoley and Taubes.

    I really appreciate your tone and refusal to ramp up the heat or attack others. It reminds me of what a soccer referee told my son once, “Play the ball not the other player”.


  48. Sue I don’t recommend a diet that is always low carb. To reset leptin sensitivity to get on the road of optimal the reset last 6 to 8 weeks. This is not a way someone has to eat forever. I have said that clearly in my own blog and made it very clear on the monster thread at MDA. I think you mischaracterized what i said about it here. The reset is a short experience one undertakes until clinical thresholds are met.

  49. @Kate, read my question to Paul about acne near the bottom of the errata page:

    Basically, I just follow the PHD and completely cut out sugar except for a handful or 2 of berries each day, maybe a banana at most. Avoiding sugar is the key, healing your gut after that can be accomplished thru many tools.

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