Category Archives: Hypothyroidism

Matt Farina’s Recovery from Hypothyroidism

Matt Farina is in the process of using the Perfect Health Diet to recover from hypothyroidism, and wanted to report his progress to PHD readers. Here’s Matt! – Paul Jaminet

My hypothyroidism was discovered in 2012. I was age 30 at the time and had just moved to a new part of the UK and enlisted with a new doctors surgery. The condition was discovered by accident when a nurse at the new surgery noticed I had an irregular heart beat. I was sent for blood tests in April 2012 where it was discovered that I had an underactive thyroid. My serum TSH was 11.3. We retested a week later and it was similar, 11.7. Free T4 was 11.1 and 11.6 pmol/l, on the low side.

The doctor asked if I had any of the common symptoms of hypothyroidism; I said I was tired in the day and had brain fog in the morning. I regularly go to the gym and run 10k and half marathon races, so the tiredness was noticeable. My mood was sometimes a little unstable too.

The doctor prescribed 50 mcg levothyroxine, and I began taking it daily. In July 2012, we remeasured. With the levothyroxine, my TSH had fallen to 3.0 and my free T4 had risen to 17.6 pmol/L – right in the middle of the normal range. Nevertheless, my hypothyroidism symptoms, such as brain fog and tiredness, persisted.

In early 2013, I relocated to a new part of the country and found a new doctor. They remeasured and my TSH was now 2.71. In July 2013, it was 2.6. I was still taking 50 mcg levothyroxine daily.

In early 2014, I moved again, and found a new doctor. My TSH had risen a little, to 3.3.

I decided to start researching causes and cures of hypothyroidism, and started to listen to podcasts from Ben Greenfield and Robb Wolf. Through them, I noticed that some people were successfully curing hypothyroidism through the Paleo diet. This really piqued my interest and I wanted to know more.

In May 2014, I sent Ben Greenfield an email saying I was considering starting a Paleo diet to overcome my hypothyroidism and I really wasn’t expecting a reply considering how busy he must be. He kindly responded very quickly saying, “I would say Paleo may be a bit dangerous, ideally I encourage you to follow a diet closer to this one.” He linked to the Perfect Health Diet.

A new set of blood tests were taken a few days after Ben’s email which showed a significant decrease in serum free T4 and an increase in TSH levels; free T4 was down to 12.1 and TSH was up to 6.42.

The doctor wanted to double my daily dose of levothyroxine to 100 mcg per day. I asked him why he thought I had hypothyroidism, and whether he would recommend that I change my diet to help overcome it. His responses shocked me. He said my hypothyroidism “could be genetic” and “unfortunately it’s just who you are.” He also said that he wouldn’t recommend any dietary changes because I didn’t show symptoms of food intolerance.

I decided that I would stick with the 50 mcg dose of levothyroxine, and see if diet could help me. I started the Perfect Health Diet the next day – June 2, 2014.

The first 3 months on the Perfect Health Diet yielded weight loss and other health benefits. I was never over weight but I dropped a jean size, started noticing stomach muscles and people were commenting on me losing weight in my face. As I intermittently fasted in the mornings, my clarity of thinking improved at work in the mornings with reduced brain fog. Other benefits included easier breathing through my nose, reduced tiredness in the day, and no more heart palpitations. The first few weeks were a little tough as my body was becoming fat adapted but that soon passed. The diet left me feeling satiated the vast majority of the time and the food I was having were truly delicious combinations. I used the Perfect Health Diet audiobook to scrub up on knowledge while I was at the gym.

After 3 months on the Perfect Health Diet, in late August 2014, I had a set of blood tests. My serum free T4 was back to normal at 18.0 and my TSH had dropped to 5.25. Nevertheless, my doctor still wanted to double my levothyroxine dose to 100 mcg. I politely declined as I knew the diet was working and that there would be even better results to come.

After 6 months on the Perfect Health Diet, in November 2014, free T4 was up again to 19.2 pmol/L and TSH had dropped again to 3.78. At this point the doctor had no comment except to say that I should stay at 50 mcg of levothyroxine daily.

At my next test, in March 2015, free T4 was up again to 19.9 pmol/L and TSH had dropped to 2.08. I continued to take 50 mcg levothyroxine daily, though in retrospect this would have been a good time to begin dropping the dose.

At my 12 month anniversary of adopting the Perfect Health Diet, in June 2015, I was tested again. This time free T4 was 27.6 pmol/L – well above normal – and TSH was only 0.12. I was now overdosing on thyroid hormone.

The doctor suggested cutting my levothyroxine dose in half, to 25 mcg per day, but I’ve decided to drop levothyroxine entirely and see if I show hypothyroidism symptoms. If I do I’ll try small doses of levothyroxine to see what works for me. I’m eagerly looking forward to my next blood test in three months to see if I am back to normal.

I fully intend to continue the Perfect Health Diet indefinitely, and I hope my story helps other people overcome their hypothyroidism.

Back in May 2014, when I first learned about PHD and the hope that it gave for natural thyroid healing, and heard my doctor say that hypothyroidism was genetic and incurable and that I would be living with it for the rest of my life, I left the doctors office feeling sad. If diet could heal hypothyroidism, then many people were being misled by their GPs.

Now I feel hope. I know hypothyroidism can be healed. Thanks for you hard work Paul, it’s really appreciated.

Neu5Gc and Autoimmunity: Hashimoto’s Hypothyroidism

In Part I of this series, I reviewed the biology of Neu5gc (“Neu5gc, Red Meat, and Human Disease: Part I,” January 14, 2015). Now it’s time for Part II: a look at whether mammalian meats (beef, lamb, pork, dairy) may help provoke Hashimoto’s hypothyroidism.

Background on Autoimmunity

If you only care about health and what to eat, skip to the next section; but for those who want to understand mechanisms, here is the key background:

  • Neu5gc is abundant in nearly all mammals, but is absent in humans, ferrets, and new world monkeys.
  • Neu5gc is a sialic acid. It provides the terminal end of the carbohydrates which coat cells and glycoproteins. Cells need to be coated in these acids, because in water acids become ions and give the cells a charge, which repels other cells. When sialic acids are bound by antibodies, the charge is lost, and cells clump or aggregate. In fact, clumping of cells after pig serum was injected into humans was the first sign that humans form antibodies to pig cells. The main antigens in pig cells are “alpha-gal” and Neu5gc.
  • Although humans cannot manufacture Neu5gc due to a mutation that occurred 3 million years ago, we retain the ability to utilize it. So Neu5gc from food can appear on the surface of human cells.
  • To generate a broad-spectrum immune response, the DNA of B cells is re-arranged to create novel combinations of segments on the light- and heavy-chain portions of antibodies. This enables the body to generate more than 10^12 different antibodies. [1] To avoid generating antibodies to human antigens, any B cells that generate antibodies while still in bone marrow are destroyed. But Neu5gc from food doesn’t reach bone marrow, so there is nothing to stop the formation of white blood cells capable of generating antibodies to Neu5gc.

So Neu5gc has the potential to accumulate in human cells, especially intestinal cells which are directly exposed to food; and we can form antibodies to Neu5gc, which then may react to human cells which have incorporated Neu5gc into their carbohydrate coat.

One might think that this would be enough to generate autoimmunity, but more is needed. Although everyone has antibodies that can react to Neu5gc, the “preimmune repertoire” of antibodies binds to Neu5gc with very low affinity, and “low concentrations of anti-Neu5Gc antibodies do not seem to have any effect on Neu5Gc containing cells.” [4] In order to make high affinity antibodies, B cells must be repeatedly stimulated by Neu5gc-containing antigens.

The best stimulation is provided by bacterial cell wall components. As one paper states,

Bacteria are potent immunogens because they express a number of factors that can act as immune stimulants. Gram-negative bacteria universally produce endotoxins that have been shown to be powerful immune system modulators through the Toll-like receptor 4 (TLR4) on a variety of human immune cells. Lipoproteins on Gram-positive and Gram-negative cell surfaces can also interact with TLR2, resulting in release of cytokines involved in B cell and T cell proliferation. In addition, bacterial DNA has been known for many years to have the capability to stimulate the immune system. [2]

So to generate autoimmunity against Neu5gc incorporated in human cells, B cells must first be triggered to form high-affinity anti-Neu5gc antibodies by meeting bacterial pathogens who have incorporated Neu5gc into their cell walls.

This can happen because some bacteria do incorporate sialic acids from their local environment into their cell walls; and thus gut bacteria will incorporate Neu5Gc from food into cell walls.

A primary reason for doing this is that, by coating themselves in sialic acids acquired from their host, they look like a “host cell” and are shielded from immune attack. [5] Many pathogens have learned this trick:

Many pathogens secrete a sialidase that releases sialic acid from [nearby cells] … [O]ther sialic acid-utilizing bacteria, such as the respiratory pathogen H. influenzae, lack genes for a sialidase …. Presumably free sialic acid is made available to such pathogens by other, sialidase-expressing bacteria living in the same niche, or … by host sialidases that are activated in the course of inflammation. [3]

Among the pathogens known to use host sialic acids to shield themselves from human immunity is Neisseria gonorrhoeae, the pathogen that causes gonorrhea. It is possible that gonorrhea infection could lead to autoimmunity through this mechanism.

To date, the published research on this topic has focused on the possibility of pathogens incorporating Neu5Ac, the primary human sialic acid, from human cells into their cell walls, and subsequently triggering autoimmunity against Neu5Ac. There has been little study of the possibility that gut pathogens will incorporate Neu5Gc from food into their cell walls, potentially triggering autoimmunity against Neu5Gc incorporated in human cells.

Yet a recent study [4] comparing the levels of Neu5Gc antibodies in human blood against the prevalence of Hashimoto’s hypothyroidism suggests that this may be a significant pathway for autoimmunity.

Hashimoto’s Hypothyroidism and Neu5Gc Antibody Levels

This is one paper in which it’s almost enough just to present the data. Here are levels of anti-Neu5Gc antibodies in patients with hypothyroidism vs healthy controls:

Neu5gc hashis fig 1

This is Figure 1. [4] Patients with Hashimoto’s have, on average, 7-fold higher anti-Neu5Gc antibody levels than the general population. Patients with hypothyroidism, some of whom have Hashimoto’s and some don’t, have an intermediate level of anti-Neu5Gc antibodies.

Here are antibody levels in the healthy population (Figure 2a):

Neu5gc hashis fig 2a

Few healthy patients had more than 16 mcg/mL of anti-Neu5Gc antibodies, and none had more than 24 mcg/mL.

Here are antibody levels in Hashimoto’s patients (Figure 2c):

Neu5gc hashis fig 2c

Only 3% of Hashi’s patients had less than 12 mcg/mL of anti-Neu5Gc antibodies, and 57% had more than 24 mcg/mL.

This is a very good separation of the two groups. It looks like if you can generate large numbers of anti-Neu5Gc antibodies, then you are almost certain to get Hashimoto’s hypothyroidism.

About 50% (in this study, 47.9%) of hypothyroidism cases are autoimmune in origin. The 52.1% of hypothyroid patients who didn’t have Hashimoto’s generally had low levels of anti-Neu5Gc antibodies, similar to the healthy controls. This observation strengthens the association between anti-Neu5Gc antibodies and autoimmune hypothyroidism. It looks like anti-Neu5Gc antibodies are strongly linked to autoimmunity.

Adding plausibility, “both autoantigens related to Hashimoto disease [thyroid peroxidase and/or thyroglobulin] are glycoproteins and N-linked carbohydrates containing sialic acids have been detected in both molecules.” [4] So it’s possible Neu5Gc is incorporated directly into thyroid peroxidase and thyroglobulin.

The study authors state, “this is the first study investigating the association of anti-Neu5Gc antibodies with autoimmune diseases such as hypothyroidism.” [4]

They also tested for anti-Neu5Gc antibodies in rheumatoid arthritis patients, but found no connection there. Rheumatoid arthritis patients do not have elevated levels of anti-Neu5Gc antibodies.

Their paper has not yet been cited by any other papers. It looks like the investigation of Neu5Gc-mediated autoimmunity is at its very beginnings.

Jim Beecham’s Experience

Jim Beecham, MD, responded to my previous post with a personal story:

I read with interest your post about Neu5Gc. I am anxious to read Part 2 which I understand is coming. Meanwhile I have been doing a little research on the subject.

I suffered badly with childhood asthma, and I still get a sort of asthmatic tightness of my breathing once in a while. In the past few weeks have I realized this is on days after I eat cheese and/or beef. This has ceased upon my cutting out red meat and dairy this past week.

I also get hypothyroid symptoms of cold face and backs of hands from time to time. I wonder if this is also linked to Neu5Gc …

In a second comment Jim added:

Here’s another thought re: Neu5Gc…which I cannot prove but think is likely.

When an upsurge of titer of anti-Neu5Gc antibodies float in body fluids, they have opportunity cause inflammatory reaction.

One researcher postulated this mechanism for hemolytic uremic syndrome.

My own experience is I develop a groin ‘heat rash’ type reaction and irritable bladder a day or so after eating too much cheese and red meat.

Jim’s personal experiences add further evidence that Neu5Gc-driven inflammation and autoimmunity is a real phenomenon.

The paper linking Neu5Gc to hemolytic uremic syndrome is [6].


There’s an excellent chance that Hashimoto’s hypothyroidism is brought about by a complex of factors:

  1. An infection in the gut by bacterial pathogens that acquire Neu5Gc from food (primarily beef and pork) and incorporate it into their cell walls.
  2. A leaky gut that (a) allows Neu5Gc from food to enter the body for subsequent incorporation into human cells, such as thyroid cells, and (b) creates either a systemic invasion of Neu5Gc-bearing gut pathogens, or a “metabolic endotoxemia” in which Neu5Gc-bearing cell wall components of gut bacteria enter the body, triggering formation of high-affinity anti-Neu5Gc antibodies.
  3. Significant consumption of beef and pork, providing the Neu5Gc to drive the autoimmune process.

If this is the case, then the strategy for overcoming Hashi’s would involve:

  1. Improving gut barrier integrity and mucosal immunity,
  2. Normalizing or diversifying the gut flora, and
  3. Reducing dietary Neu5Gc by replacing beef, dairy, lamb, and pork with seafood and bird meats.

Neu5Gc-mediated autoimmunity does not play a role in rheumatoid arthritis, but it may play a role in other autoimmune diseases. The most likely organ to be affected is the gut, which is directly exposed to food; endothelial cells, which line blood vessel walls, and immune cells which circulate in blood, as blood is the next location after the gut exposed to food molecules entering the body; and lastly organs which interact closely with the blood, such as the thyroid. Hemolytic uremic syndrome is a condition of endothelial cell dysfunction.

So: it looks like reduction of mammalian meats, replacing them with seafood and bird meats, may be a prudent part of a “Hashimoto’s protocol.” In autoimmune disorders affecting the gut, blood vessels, or immune cells, it may be worth trying a 30-day elimination of mammalian meats.

Perfect Health Retreat

We have a few spots remaining for the May 2-9 Perfect Health Retreat, and will soon be taking reservations for the October retreat, either October 3-10 or 10-17 (or both). If you are interested, visit here for more info or email me at



[1] “Generation of Antibody Diversity,” in Alberts B, Johnson A, Lewis J, et al., Molecular Biology of the Cell, 4th edition, New York: Garland Science; 2002,

[2] Harvey HA, Swords WE, Apicella MA. The mimicry of human glycolipids and glycosphingolipids by the lipooligosaccharides of pathogenic neisseria and haemophilus. J Autoimmun. 2001 May;16(3):257-62.

[3] Severi E, Hood DW, Thomas GH. Sialic acid utilization by bacterial pathogens. Microbiology. 2007 Sep;153(Pt 9):2817-22. Full text:

[4] Eleftheriou P et al. Prevalence of anti-Neu5Gc antibodies in patients with hypothyroidism. Biomed Res Int. 2014;2014:963230.

[5] Varki A, Gagneux P. Multifarious roles of sialic acids in immunity. Ann N Y Acad Sci. 2012 Apr;1253:16-36. Full text:

[6] Löfling JC et al. A dietary non-human sialic acid may facilitate hemolytic-uremic syndrome. Kidney Int. 2009 Jul;76(2):140-4.


High LDL on Paleo Revisited: Low Carb & the Thyroid

One of the more mysterious conditions afflicting low-carb Paleo dieters has been high serum cholesterol. Two of our most popular posts were about this problem: Low Carb Paleo, and LDL is Soaring – Help! (Mar 2, 2011) enumerated some cases and asked readers to suggest answers; Answer Day: What Causes High LDL on Low-Carb Paleo? (Mar 4, 2011) suggested one possible remedy.

On the first post, one of the causes suggested by readers was hypothyroidism – an astute answer. Raj Ganpath wrote:

Weight loss (and VLC diet) resulting in hypothyroidism resulting in elevated cholesterol due to less pronounced LDL receptors?

Kratos said “Hypothyroidism from low carbs.” Mike Gruber said:

I’m the guy with the 585 TC. It went down (to 378 8 months or so ago, time to check again) when I started supplementing with iodine. My TSH has also been trending up the last few years, even before Paleo. So hypothyroidism is my primary suspect.

Those answers caused me to put the connection between hypothyroidism and LDL levels on my research “to do” list.

Chris Masterjohn’s Work on Thyroid Hormone and LDL Receptors

Chris Masterjohn has done a number of blog posts about the role of LDL receptors in cardiovascular disease. His talk at the Ancestral Health Symposium was on this topic, and a recent blog post, “The Central Role of Thyroid Hormone in Governing LDL Receptor Activity and the Risk of Heart Disease,” provides an overview.

His key observation is that thyroid hormone stimulates expression of the LDL receptor (1). T3 thyroid hormone binds to thyroid hormone receptors on the nuclear membrane, the pair (a “dimer”) is then imported into the nucleus where it acts as a transcription factor causing, among other effects, LDL receptors to be generated on the cell membrane.

So higher T3 = more LDL receptors = more LDL particles pulled into cells and stripped of their fatty cargo. So high T3 tends to reduce serum LDL cholesterol levels, but give cells more energy-providing fats. Low T3, conversely, would tend to raise serum cholesterol but deprive cells of energy.

Other Pieces of the Puzzle

Two other facts we’ve recently blogged about help us interpret this result:

We can now assemble a hypothesis linking low carb diets to high LDL. If one eats a glucose and/or protein restricted diet, T3 levels will fall to conserve glucose or protein. When T3 levels fall, LDL receptor expression is reduced. This prevents LDL from serving its fat transport function, but keeps the LDL particles in the blood where their immune function operates.

If LDL particles were being taken up from the blood via LDL receptors, they would have to be replaced – a resource-expensive operation – or immunity would suffer. Apparently evolution favors immunity, and gives up the lipid-transport functions of LDL in order to maintain immune functions during periods of food scarcity.

High LDL on Low Carb: Good health, bad diet?

Suppose LDL receptors are so thoroughly suppressed by low T3 that the lipid transport function of LDL is abolished. What happens to LDL particles in the blood?

Immunity becomes their only function. They hang around in the blood until they meet up with (bacterial) toxins. This contact causes the LDL lipoprotein to be oxidized, after which the particle attaches to macrophage scavenger receptors and is cleared by immune cells.

So, if T3 hormone levels are very low and there is an infection, LDL particles will get oxidized and cleared by immune cells, and LDL levels will stay low. But if there is no infection and no toxins to oxidize LDL, and the diet creates no oxidative stress (ie low levels of omega-6 fats and fructose), then LDL particles may stay in the blood for long periods of time.

If LDL particles continue to be generated, which happens in part when eating fatty food, then LDL levels might increase.

So we might take high LDL on Paleo as a possible sign of two things:

  • A chronic state of glucose deficiency, leading to very low T3 levels and suppressed clearance of LDL particles by lipid transport pathways.
  • Absence of infections or oxidative stress which would clear LDL particles by immune pathways.

The solution? Eat more carbs, and address any remaining cause of hypothyroidism, such as iodine or selenium deficiency. T3 levels should then rise and LDL levels return to normal.

Alternatively, there is evidence that some infections may induce euthyroid sick syndrome, a state of low T3 and high rT3, directly. And these infections may not oxidize LDL, thus they may not lead to loss of LDL particles by immune pathways. So such infections could be another cause of high LDL on Paleo.

Gregory Barton’s Experience

Gregory Barton is an Australian, 52 years old, living in Thailand, where he keeps goats, makes goat cheese and manages a large garden which can be seen on

Gregory left a comment with an intriguing story, and I invited him to elaborate in a post. Here’s Gregory’s story. – Paul

Gregory’s Writing Begins Here

One of the claims of low carb dieting is that it will normalize the symptoms of metabolic syndrome. Blood pressure, blood sugar and blood lipids, it is claimed, will all come down on a low carb diet, in addition to weight. For most people this happens. But there is a significant minority of people on Paleo and other low carb diets whose blood lipids defy this claim. (See the list of low-carb celebrities with high LDL in this post.)

Why should this happen? Why should some people’s lipids fall on low carb while other people’s lipids rise? Suboptimal thyroid might be the proximate cause for lipids rising on a low carb or paleo diet. Broda Barnes and Lawrence Galton have this to say about thyroid disorders:

“Of all the problems that can affect physical or mental health, none is more common than thyroid gland disturbance. None is more readily and inexpensively corrected. And none is more often untreated, and even unsuspected.”  — Hypothyroidism: The Unsuspected Illness

I went very low carb in April in an effort to address metabolic issues, eating as little as 15grams carbohydrate per day. I had great results with blood pressure, sleeping, blood sugar and weight loss. But lipids bucked the trend.

I had expected triglycerides and cholesterol to drop when I cut the carbs, but they did the opposite: They surged. By July my total cholesterol was 350, LDL 280, and triglycerides bobbed around between 150 and 220.

I did some research and found several competing theories for this kind of surge:

  1. Saturated fat: The increase in saturated fat created a superabundance of cholesterol which the liver cannot handle. Also, Loren Cordain has claimed that saturated fat downregulates LDL receptors.
  2. Temporary hyperlipidemia: The surge in lipids is the temporary consequence of the body purging visceral fat. Jenny Ruhl has argued that within a period of months the situation should settle down and lipids should normalize.
  3. Hibernation: The metabolism has gone into “hibernation” with the result that the thyroid hormone T4 is being converted into rT3, an isomer of the T3 molecule, which prevents the clearance of LDL.
  4. Malnutrition: In March, Paul wrote that malnutrition in general and copper deficiency in particular “… is, I believe, the single most likely cause of elevated LDL on low-carb Paleo diets.”
  5. Genetics: Dr. Davis has argued that some combinations of ApoE alleles may make a  person “unable to deal with fats and dietary cholesterol.”

I could accept that saturated fat would raise my cholesterol to some degree. However, I doubted that an increase in saturated fat, or purging of visceral fat, would be responsible for a 75% increase in TC from 200 to 350.

There are two basic factors controlling cholesterol levels: creation and clearance. If the surge was not entirely attributable to saturated fat, perhaps the better explanation was that the cholesterol was not being cleared properly. I was drawn to the hibernation theory.

But what causes the body to go into hibernation? According to Chris Masterjohn, a low carb diet could be the cause. Although he does not mention rT3, he warns,

“One thing to look out for is that extended low-carbing can decrease thyroid function, which will cause a bad increase in LDL-C, and be bad in itself. So be careful not to go to extremes, or if you do, to monitor thyroid function carefully.”

If low carb is the cause, then higher carb should be the cure. Indeed, Val Taylor, the owner of the yahoo rT3 group, commented that “it is possible that the rT3 could just be from a low carb diet.” She says, “I keep carbs at no lower than 60g per day for this reason.”

Cortisol and Getting “Stuck” in Hibernation

So what about temporary hyperlipidemia? Bears hibernate for winter, creating rT3, but manage to awaken in spring. Why should humans on low carb diets not be able to awaken from their hibernation? There are many people who complain of high cholesterol years after starting low carb.

A hormonal factor associated with staying in hibernation is high cortisol. It has been claimed that excessively high or low cortisol, sustained over long periods, may cause one to get “stuck” in hibernation mode. One of the moderators from the yahoo rT3 group said:

High or low cortisol can cause rT3 problems, as can chronic illness. It would be nice if correcting these things was all that was necessary. But it seems that the body gets stuck in high rT3 mode.

James LaValle & Stacy Lundin in Cracking the Metabolic Code: 9 Keys to Optimal Health wrote:

When a person experiences prolonged stress, the adrenals manufacture a large amount of the stress hormone cortisol. Cortisol inhibits the conversion of T4 to T3 and favours the conversion of T4 to rT3. If stress is prolonged a condition called reverse T3 dominance occurs and lasts even after the stress passes and cortisol levels fall. (my emphasis)

What I Did

First, I got my thyroid hormone levels tested. A blood test revealed that I had T4 at the top of the range and T3 below range. Ideally I would have tested rT3, but in Thailand the test is not available. I consulted Val Taylor, the owner of the yahoo rT3 group, who said that low T3 can cause lipids to go as high as mine have and, “as you have plenty of T4 there is no other reason for low T3 other than rT3.”

I decided to make these changes:

  1. Increase net carbs to ~50 grams per day. Having achieved my goals with all other metabolic markers I increased carbs, taking care that one hour postprandial blood sugar did not exceed 130 mg/dl.
  2. Supplement with T3 thyroid hormone.
  3. In case the malnutrition explanation was a factor, I began supplementing copper and eating my wife’s delicious liver pate three times per week.

I decided to supplement T3 for the following reasons:

  • The surge in TC was acute and very high. It was above the optimal range in O Primitivo’s mortality data.
  • I increased carbs by 20-30g/day for about a month. TC stabilized, but did not drop.
  • The rT3 theory is elegant and I was eager to test my claim that the bulk of the cholesterol was due to a problem with clearance rather than ‘superabundance’.

What happened?

I started taking cynomel, a T3 supplement, four weeks ago. After one week triglycerides dropped from 150 to 90. After two weeks TC dropped from 350 to 300 and after another week, to 220. Last week numbers were stable.

Based on Paul’s recent series on blood lipids, especially the post Blood Lipids and Infectious Disease, Part I (Jun 21, 2011), I think TC of 220 mg/dl is optimal. As far as serum cholesterol levels are concerned, the problem has been fixed.

I believe that thyroid hormone levels were the dominant factor in my high LDL. Saturated fat intake has remained constant throughout.

My current goal is to address the root causes of the rT3 dominance and wean myself off the T3 supplement. I hope to achieve this in the next few months. My working hypothesis is that the cause of my high rT3 / low T3 was some combination of very low carb dieting, elevated cortisol (perhaps aggravated by stress over my blood lipids!), or malnutrition.

Another possibility is toxins: Dr Davis claims that such chemicals as perchlorate residues from vegetable fertilizers and polyfluorooctanoic acid, the residue of non-stick cookware, may act as inhibitors of the 5′-deiodinase enzyme that converts T4 to T3. Finally, Val Taylor claims that blood sugar over 140 mg/dl causes rT3 dominance. I couldn’t find any studies confirming this claim, and don’t believe it is relevant to my case. Val recommends low carb for diabetics to prevent cholesterol and rT3 issues but warns not to go under 60g carb per day.

Issues with T3 Supplementation

There are some factors to consider before embarking upon T3 supplementation:

  1. Preparation: In order to tolerate T3 supplement you have to be sure that your iron level and your adrenals are strong enough. This requires quite a bit of testing. I’ve read of people who cut corners with unpleasant results.
  2. Practicalities: T3 supplementation requires daily temperature monitoring in order to assess your progress. People who are on the move throughout the day would find this difficult.
  3. Danger: Once you get on the T3 boat you can’t get off abruptly. Your T4 level will drop below range and you will be dependent on T3 until you wean yourself off. If you stopped abruptly you could develop a nasty reaction and even become comatose.

My advice for anyone doing very low carb

As Chris Masterjohn said, in the quote above, if you are going to do very low carb, check your thyroid levels. I would add: Increase the carbs if you find your free T3 falling to the bottom of the range. It might be a good idea to test also for cortisol. A 24-hour saliva test will give you an idea whether your cortisol levels are likely to contribute to an rT3 issue. It might also be a good idea to avoid very low carb if you are suffering from stress – such as lipid anxiety!

Gregory Barton’s Conclusion

I also think my experience may help prove thyroid hormone replacement to be an alternative, and superior, therapy to statins for very high cholesterol. Statins, in the words of Chris Masterjohn,

“… do nothing to ramp up the level of cholesterol-made goodies to promote strength, proper digestion, virility and fertility.  It is the vocation of thyroid hormone, by contrast, to do both.”

Paul’s Conclusion

Thanks, Gregory, for a great story and well-researched ideas. The rapid restoration of normal cholesterol levels with T3 supplementation would seem to prove that low T3 caused the high LDL levels.

However, I would be very reluctant to recommend T3 supplementation as a treatment for high LDL on Paleo.  If the cause of low T3 is eating too few carbs, then supplementing T3 will greatly increase the rate of glucose utilization and aggravate the glucose deficiency.

The proper solution, I think, is simply to eat more carbs, to provide other thyroid-supporting nutrients like selenium and iodine, and allow the body to adjust its T3 levels naturally. The adjustment might be quite rapid.

In Gregory’s case, his increased carb consumption of ~50 g/day was still near our minimum, and he may have been well below the carb+protein minimum of 150 g/day (since few people naturally eat more than about 75 g protein). So I think he might have given additional carbs a try before proceeding to the T3.

Gregory had a few questions for me:

GB: What if one is glucose intolerant and can’t tolerate more than 60 grams per day without hyperglycemia or weight gain?

PJ: I think almost everyone, even diabetics, can find a way to tolerate 60 g/day dietary carbs without hyperglycemia or weight gain, and should.

GB: What if raising carbs doesn’t normalize blood lipids and one finds oneself ‘stuck in rT3 mode’?

PJ: I’m not yet convinced there is such a thing as “stuck in rT3 mode” apart from being “stuck in a diet that provides too few carbs” or “stuck in a chronic infection.” If one finds one’s self stuck while eating a balanced diet, I would look for infectious causes and address those.

Finally, if I may sound like Seth Roberts for a moment, I believe this story shows the value of a new form of science: personal experimentation, exploration of ideas on blogs, and the sharing of experiences online. It takes medical researchers years – often decades – to track down the causes of simple phenomena, such as high LDL on low carb. We’re on pace to figure out the essentials in a year.

Mario Replies: Low Carb Diets and the Thyroid, II

We’ve been looking at papers put forth by Anthony Colpo in support of his idea that low-carb diets can cause “euthyroid sick syndrome” (see his original post on July 1 and a post expanding his case on August 20).  I gave my general perspective on this issue last week: Carbohydrates and the Thyroid, Aug 24, 2011. Briefly, an extreme low-carb diet can create a glucose deficiency, especially if endurance exercise or infection increases glucose requirements, and glucose deficiency invokes the body’s glucose conservation measures, which primarily consist of lower T3 and higher rT3 hormone levels – two hormonal markers of euthyroid sick syndrome. I also offered my view, unchanged from our book, on what level of dietary carbohydrate intake is needed to avoid a glucose deficiency.

Now it’s time to look more closely at the evidence to see if my perspective is consistent with the literature. Our thyroid expert, Mario Renato Iwakura, has been looking into Anthony’s papers to see if they report any negative effects from Perfect Health Diet-level carb intakes. In his first post (Low Carb High Fat Diets and the Thyroid, Aug 18, 2011), he showed that studies cited in Anthony’s July 1 post were generally very high omega-6 diets and therefore did not refute our diet, which prescribes low omega-6 intake. Anthony’s August 20 rebuttal cited a few more experiments which were not high in omega-6, and today Mario is going to look specifically at the issue of carbs. How much carbohydrate intake is needed to avert a glucose deficiency as indicated by decreased T3 and increased rT3?

Mario had assistance from JS Stanton of who reviewed the post pre-publication and contributed some helpful suggestions. Without further ado, here’s Mario! – Paul

After my post on low carb diets and thyroid function, Anthony Colpo wrote a reply that I will address with this post.

First, let me say that neither I nor Paul ever said that:

  1. A high carbohydrate diet has detrimental effects on the thyroid;
  2. Low-carb diets have any “metabolic advantage”; or
  3. A very low carbohydrate diet is healthy or good for the thyroid.

Second, Anthony has been making a case that low-carb diets can produce a condition called “euthyroid sick syndrome,” characterized by low T3 and high rT3. Anthony seems to have supposed that my post was intended to reply or refute his July 1 post. It was not; my post was intended as a treatment of thyroid health generally, and was designed to answer the question of whether the studies Anthony had cited in any way refuted the Perfect Health Diet prescription for thyroid patients.

In the developed world, most cases of hypothyroidism – up to 90% – are diagnosed as Hashimoto’s autoimmune thyroiditis. Hashimoto’s is a complex disease, whose causes are too complex to explore in this post, but in my opinion it is generally caused by exogenous toxins (gluten, mercury, bisphenol-A, bromide, etc) that disrupt gut flora and cause gut permeability and disturbed immunity that allows infections to enter the body and take root in thyroid tissue, after which in susceptible persons an autoimmune attack on the thyroid can develop.

Which infections are associated with Hashimoto’s is still an object of study, but we do know that many of the likely pathogens benefit from high gut, serum, or cellular glucose levels  and therefore we can suspect that a high carbohydrate diet might promote the disease and a low, but not too low, carbohydrate diet, such as PHD, might be therapeutic.

So even if some thyroid-related problems, like euthyroid sick syndrome, may become more likely on a low-carb diet, others, like Hashimoto’s, may be relieved by a low-carb diet. It is therefore necessary to look closely at each condition and at the literature to see which diet optimizes thyroid health – and whether specific thyroid disorders demand different diets.

In looking at the papers cited by Anthony, I’ll borrow his section headings so that readers have an easier time finding the part of his post that I am responding to.

“Here Comes the Boom!”

Anthony, in an attempt to refute my assertation that PUFA may cause thyroid impairment on LCHF diets, cites two papers.

The first was Danforth E Jr et al. [1] This paper reported a number of experiments with multiple low-carb diet variations. In all studies, provided fat was rich in omega-6 fats:

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. [1]

However, there was a single experiment which was low in both fat and carb. Anthony wrote:

However, as you scan through the above paper, you will notice that one of the groups followed a zero-carb diet consisting of nothing but lean meat, fish, fowl, and vitamin and mineral supplements. In other words, they ate next to no PUFA.

This particular diet was actually a “protein-supplemented modified fast” consisting of:

a 6-wk period during which the subjects received a protein-supplemented modified fast including 1.2 g/kg ideal weight per d of lean meat, fish, or fowl. This was supplemented by 25 meq/d of potassium bicarbonate and citrate and 200 mg of calcium as carbonate, plus vitamins and iron. [1]

So an 80-kg man would have gotten 100 g lean meat. 100 g chicken breast supplies 165 calories total, 32 calories from fat and 133 from protein. So this “zero-carb diet” provided at most a few hundred calories per day. Anthony’s conclusion:

During this very low PUFA diet, T3 concentrations fell steadily and at six weeks were equivalent to those found after 7 days of fasting (88 ng/dl)!

Here’s the data from the study:

The initial concentration of T3 in these subjects was 155 ng/dl, fell to 87 ng/dl during the 7-d fast, and then rose to 146 ng/dl with refeeding. Initial rT3 concentrations were 25 ng/dl, rose with fasting to 57 ng/dl, and then fell again to 24 ng/dl with refeeding. Slower but similar changes in the concentrations of T3 and rT3 to those of fasting occurred with administration of a protein-supplemented modified fast for 1 wk. During the first week of the diet, T3 concentrations fell from 166 to 109 ng/l and rT3 concentrations rose from 31 to 53 ng/dl. [1]

In short: On a 7-day modified fast providing 130 protein calories per day, the fall in T3 levels is significantly less than on a 7-day true fast.

As the modified fast was continued, T3 concentrations continued to fall and at 6 wk were equivalent to those found after 1 wk of fasting (88 ng/dl). rT3 concentrations, however, returned to their initial values as the fast was continued (39 ng/dl). [1]

So even after 6 weeks, the rT3:T3 ratio was lower on the modified fast (39/88) than after 1 week on the true fast (57/87).

This all looks consistent with Perfect Health Diet arguments that we need at least 200 starch calories and at least 600 carb+protein calories to prevent a glucose deficiency; with Paul’s argument that high rT3 and low T3 is the body’s response to a glucose deficiency; and with the idea that mitigating the glucose deficiency by carb or protein intake will lower the rT3:T3 ratio. It does not speak at all to Perfect Health Diet-style low carb (400 calories from starches, adequate protein) being unhealthy.

Anthony next discusses Bisschop PH et al. [2] He even e-mailed Bisschop to be sure the diet was low in PUFA. But what diet caused a significant decrease in T3 levels? A diet supplying only 2% carbohydrate out of 2483 total calories, or 49.66 calories = 12.41g of carbohydrate. Again, Perfect Health Diet recommends 400 calories (100g) carbohydrate, and argues that, because the amount of glucose that can be manufactured from protein is hormonally limited, even if dietary protein is sufficient at least 200 readily digestible glucose calories should be eaten to avert the risk of a glucose deficiency.

Anthony quoted the following passage from Bisschop PE et al:

Apparently, isocaloric carbohydrate deprivation induces a catabolic state with respect to protein metabolism compared with diets with a normal composition and compared with starvation. This catabolic reaction to carbohydrate deprivation is associated with decreased insulin secretion. Apparently, exogenous carbohydrates and/or insulin induced by exogenous carbohydrates are required for a proper utilization of dietary proteins. [2]

Anthony goes further and says that low carb diets “suck the big one for building muscle”:

So what does explain the reduction in T3 seen on the low-carb diet? Well, remember how I said that Dr. Bisschop and his team also measured urinary nitrogen excretion in the male subjects? Urinary nitrogen excretion is a long-standing and widely employed marker for protein (as in, lean tissue) breakdown. Low-carb diets have repeatedly been shown to increase nitrogen excretion, which is one reason why they suck the big one for building muscle.

The carbohydrate deprivation diet comprised 2% of carbs and 15% of protein. On a 2483 calorie diet, this is only 420 carb+protein calories – insufficient to meet the minimum Paul estimated of 600-800 calories per day to avoid a glucose deficiency. The body simply isn’t being given enough amino acids to meet the body’s glucose requirements. Muscle breakdown necessarily follows.

But, let’s see what happens when you provide more carb+protein. The Volek study [3] provided 8% carbs (184 calories) and 30% protein (704 calories) – still low-carb, but now enough carb and protein to avert a glucose deficiency. Here is Table 2 from Volek et al [3]:

The subjects in the Volek study were asked to maintain their current level of physical activity and to consume adequate dietary energy to maintain body mass. And yet fat mass was significantly (P < .05) decreased (-3.4 kg) and lean body mass significantly increased (+1.1 kg) at week 6.

Lesson: if you don’t want to lose muscle on a VLCD, eat extra protein and at least a bit of carbs!

“Why The Volek Study Proves Absolutely Nothing …”

Anthony wrote:

The study headed by Jeff Volek  is the only one allegedly showing no change in thyroid hormone levels on a low-carb diet, so of course it is eagerly cited by Mario as proof that I’m wrong. Just one wee problem: Volek et al didn’t even measure levels of T3, the critical thyroid hormone in question! Instead, as I explained in my article, the pro-low-carb and Atkins-sponsored Volek team chose to only measure T3 uptake, a test also known as “resin-binding T3 uptake”.

This, of course, is just fine by Mario, who happily extrapolates the results of unrelated studies examining the relationship between thyroid hormones and a bunch of other hormones; studies, I should point out, that did not involve low-carb diets.

The Volek study [3] was cited because it was unique: the only low-carb study that didn’t use a high PUFA diet. As for the failure to measure T3, I agree this was a flaw. However, you cannot reasonably argue that T3 may have decreased with no detectable effect on the human body. You absolutely cannot say that T3 can decrease with no effect on testosterone, IGF-1, glucagon, sex hormone-binding globulin (SHBG), fat mass, or lean body mass. Maybe in an alien body or in another parallel universe … but not in humans.

Anthony next cites Otten MH et al [4]. Study subjects were taken through a succession of diets, eating each diet for only 72h. The two diets that caused the greatest changes in T3 and rT3 were the first two: a diet of 100% fat and another of 50% fat and 50% protein.

Paul has argued that gluconeogenesis is hormonally limited and can generate at most 400 glucose calories per day; this is why zero-carb diets are dangerous. So it is no surprise that these zero-carb diets produce the elevated rT3 – depressed T3 pattern that is the body’s response to a glucose deficiency. Again, this does not argue against Perfect Health Diet-style low carb.

What is interesting about Otten et al is that the diet of 50% carbohydrate and 50% fat showed a decrease of 24% in T3 and an increase of 34% in rT3. It looks like even high-carb diets can induce high rT3 and low T3 if the diet is unbalanced and deficient in protein.

Perhaps the problem is not so much low-carb, but malnourishment in general! High rT3 and low T3 reduce metabolism and may help conserve protein during malnourishment, regardless of whether the threat to protein stores comes from dietary restriction of carbs or protein.

“Fifty Grams I Tell Ya, FIFTY GRAMS!!”

Anthony proceeds to comment on a study, Spaulding SW et al. [5], which was cited by Stabby in the comments. In this study, only fifty grams of carbohydrate on a high fat diet was enough to restore T3 levels to normal:

As anticipated, total fasting resulted in a 53% reduction in serum T3 in association with reciprocal 58% increase in rT3. Subjects receiving the no-carbohydrate hypocaloric diets for two weeks demonstrated a similar 47% decline in serum T3 but there was no significant change in rT3 with time. In contrast, the same subjects receiving isocaloric diets containing at least 50 g of carbohydrate showed no significant changes in either T3 or rT3 concentration. [5]

Anthony’s comment is this:

Mario and Stabby jump on this finding as if it is proof that only fifty grams of carbohydrate is needed to maintain optimal carbohydrate levels. In doing so, they totally ignore the fact that this result was hardly a universal finding. They totally ignore all the other studies showing T3 reductions at higher carbohydrate intakes.

Based on Paul’s view of things, it would be no surprise that this was not a universal finding. Paul estimates that 200 calories of dietary carbs, plus 400 calories from gluconeogenesis, is barely sufficient to prevent a glucose deficiency in a sedentary healthy person. Any perturbation – exercise, infection, protein restriction limiting the availability of substrates for gluconeogenesis – might induce a glucose deficiency.

But it is significant that when circumstances are right, 200 calories per day of carbs can eliminate the T3 drop and rT3 rise that is associated with glucose deficiency. So Spaulding et al is a positive contribution to the debate, and once again it tends to confirm Perfect Health Diet’s analysis.

Anthony cited several other studies in which 200 carb calories was insufficient to prevent a rise in T3. First, Mathieson et al [6]:

Ruth Mathieson and her colleagues from Virginia Polytech and State University placed fourteen obese free-living women on 530-calorie/day diets containing either 44 grams or 94 grams daily of carbohydrate. Both diets caused significant reductions in T3, with the ketogenic diet causing the largest decline.

Recall that Paul believes that 200 carb calories and 600 calories of carb+protein are the bare minimum needed to prevent a glucose deficiency, even when all circumstances are favorable. These diets only had 530 calories total. As carb+protein intake was insufficient to maintain glucose status, it is no surprise that the diets induced a fall in T3.

The other study cited by Anthony was Serog et al [7]. Anthony writes:

Serog et al examined four isocaloric (mean intake 2800 calories/day) diets lasting 1 week each. In two of these, a standard diet containing 45 percent carbohydrate was consumed. The remaining two diets were either low- or high-carbohydrate, and were consumed by all the subjects in random order between the two standard diet phases.

Average carbohydrate intake in grams was 250 grams on the standard diet, 71 grams on the low-carbohydrate diet, and 533 grams on the high-carbohydrate diet. On the standard and high-carbohydrate diets, T3 levels did not change, ranging from 163.3 to 169.5 ng. They declined on the low-carb diet to a mean 148.6 ng. Mirroring these changes, rT3 rose significantly only on the low-carb diet.

What was the fat used? You bet! Soy oil! From Table 1, composition of the Normal Protein Hypocaloric Diet (NHD): protein was provided as casein (14g), skimmed milk (34g), and soy (22g); fats were from soy (16g, 9g linoleic acid); carbohydrates were primarily dairy sugars.

Finally, Anthony cited a study by Davidson and Chopra [8] which found that T3 levels increased as carbohydrate intake increased from 20% toward 80% of energy. Paul himself discussed this study in last week’s post, in response to a cite by Danny Roddy. Paul’s observation was that high T3 levels are harmful to health, and that T3 may be elevated on the 80% carb diet in order to dispose of excess glucose (T3 stimulates glycolysis), so this could indicate a mechanism by which high-carb diets are health impairing. It does not prove that 80% carb diets are healthier than 20% carb diets.


Yes, it is possible to develop a glucose deficiency on low-carb diets. If this occurs, the body will conserve glucose by reducing T3 and increasing rT3.

However, there is as yet no evidence that T3 and rT3 will exit normal ranges when following Perfect Health Diet guidelines.

Until a well-designed study provides contrary evidence, I stand by my assertion that 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 is optimal for thyroid function. But this is the Perfect Health Diet!


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

[2] Bisschop PH, et al. Isocaloric carbohydrate deprivation induces protein catabolism despite a low T3-syndrome in healthy men. Clin Endocrinol (Oxf). 2001 Jan;54(1):75-80.

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

[4] Otten MH et al. The role of dietary fat in peripheral thyroid hormone metabolism. Metabolism. 1980 Oct;29(10):930-5.

[5] Spaulding SW et al. Effect of caloric restriction and dietary composition of serum T3 and reverse T3 in man. J Clin Endocrinol Metab. 1976 Jan;42(1):197-200.

[6] Mathieson RA, et al. The effect of varying carbohydrate content of a very-low-caloric diet on resting metabolic rate and thyroid hormones. Metabolism, May, 1986; 35 (5): 394-8.

[7] Serog P, et al. Effects of slimming and composition of diets on V02 and thyroid hormones in healthy subjects. Am J Clin Nutr. 1982 Jan;35(1):24-35.

[8] Davidson MB, Chopra IJ. Effect of carbohydrate and noncarbohydrate sources of calories on plasma 3,5,3?-triiodothyronine concentrations in man. J Clin Endocrinol Metab. 1979 Apr;48(4):577-81.