Thursday, January 14, 2016

Thyroid and Low-Carb: What Do Thyroid Hormones Do?

There's much too-ing and fro-ing over thyroid hormones and low-carb diets on the interwebs, in the paleo and now endurance communities, as low-carb or ketogenic diets have become popular.

Typical was this post by Anthony Colpo from a few years ago: "Is a Low Carb Diet Diet Bad For Your Thyroid?"
"Over the years, an abundance of research has gathered to indicate that, for those who wish to maintain optimal thyroid function, very low-carbohydrate diets aren’t a wise idea."
He then goes through a bunch of studies which all, pretty much, detail that thyroid hormones go down on a low-carb diet.

OK.  But insulin, another hormone, also goes down on a low-carb diet.  And we know that's one of the features of the low-carb diet as regards insulin, as a high insulin level (hyperinsulinemia, if you're wearing a white coat) is a bad thing.

I just listened to a podcast interview with Dr. Tamsin Lewis on Endurance Planet, where she makes the following points about a ketogenic diet:
"– ...signal that body is in high stress state
"– can create thyroid problems
"– TSH increase; T3, T4 decrease
"– cortisol up..."
Burning off waste fuel
But neither she nor Colpo state what these thyroid hormones do.  We know what insulin does, it's part of the body's system for regulating glucose.  Working properly, it signals that the body should dispose of a glucose bolus: eat some glucose—toxic in too-high amounts (known as hyperglycemia)—and your body needs to get rid of it.  It does so mainly by signalling the cells to start burning glucose instead of fat, and to turn up the metabolic rate to increase glucose disposal. Some glucose is also turned into fat, but the majority of it is burned off—used as fuel, or literally burned off like waste gas at an oil well.

The other interesting thing to note about low-carb diets and thyroid hormones, as Jimmy Moore notes in the introduction to this podcast ("Do Low-Carb Diets Lower Thyroid Function? Let’s Ask The Experts!" is:
"However, two of the top low-carb nutritional health researchers in the world — Dr. Stephen Phinney and Dr. Jeff Volek — say this phenomenon with low thyroid while on a low-carbohydrate diet promoted by people in the Paleo community like Kresser and Paul Jaminet is “a myth” and has not manifested itself in any of the research subjects in their numerous studies of people who are properly following a well-formulated low-carb diet with adequate calories over the past three decades."
So those are two pretty extreme positions: the folks who claim that you shouldn't go on a low-carb diet say it will negatively impact your thyroid hormones, and the folks who actually tell people to eat a low-carb diet and study what happens never see adverse effects from it.

So, for starters, what do thyroid hormones actually do in the body?  Why are they important?

That turns out to be a tough question to answer.

But first, a quick primer on thyroid hormones.  There are three, which work in the following manner:

Thyroid-Stimulating Hormone is produced in the brain, and is a love-letter to the thyroid telling it to produce the next hormone.  TSH is important in some of the pathological states.

T4 is produced by the thyroid, and is converted into the next hormone:

T3.  This is the active form (supposedly) of the hormone.

(Basically—remember, this is insanely complex.)

T4 and T3 together are known as thyronines, and they do the following, according to Wikipedia:
"The thyronines act on nearly every cell in the body. They act to increase the basal metabolic rate, affect protein synthesis, help regulate long bone growth (synergy with growth hormone) and neural maturation, and increase the body's sensitivity to catecholamines (such as adrenaline) by permissiveness. The thyroid hormones are essential to proper development and differentiation of all cells of the human body. These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds. They also stimulate vitamin metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis."
So a lot, and many things can go wrong.  But we're going to ignore most of this stuff, as like most biological processes, you'll go insane if you get into the details too much, as it's nearly fractal in complexity.  The important part for this discussion is that italicized by me in the quote above.

 I found this terrific-sounding paper from 1983: "The Role of Thyroid Hormones and Insulin in the Regulation of Energy Metabolism" by Dr. Elliot Danforth, Jr., but unfortunately, despite describing the various ups and downs of thyroid hormones, he states:
"The physiological significance of these nutritionally-induced alterations in thyroid hormone metabolism however are still unknown."
He does, however, concur with this statement from the Jimmy Moore podcast above:
"Dr. Phinney believes the primary point of contention revolves around consuming an adequate amount of calories with your low-carbohydrate nutritional intake in order to normalize thyroid and metabolic function without the necessity for consuming added sources of dietary glucose. Dr. Volek concurs stating that it’s calorie-restriction that brings on this low thyroid effect, not limiting carbohydrates."
Dr. Danforth agrees, stating that:
"Therefore, the concentrations of total, free, and production rates of the potent thermogenic hormone, T3 , is increased by overfeeding and decreased by underfeeding in concert with the changes in resting metabolism that are found in these conditions."
Starve yourself, and thyroid hormones go down.  So don't do that.* (That's a good reaction for the thyroid hormones to have, btw, as we'll see...)

Then I found this paper: "Effect of Thyroid Hormones on Oxidative and Nonoxidative Glucose Metabolism in Humans".  I've not yet read the full text, but the summary is pretty clear:
"...T4 treatment increased basal energy expenditure (+8%), glucose disposal (+31%), and oxidation (+87%) but decreased nonoxidative glucose metabolism (-30%) and was without effect on lipid oxidation. During the euglycemic clamp, T4 treatment enhanced insulin-induced glucose disposal (+16%), glucose oxidation (+34%), and inhibition of lipid oxidation (-66 vs. -40%); nonoxidative glucose metabolism was stimulated to a similar extent before and after T4. During hyperglycemia, 3,5,3'-triiodothyronine (T3) did not affect glucose disposal but increased carbohydrate-induced lipogenesis at both insulin infusion rates...."
T4 causes the body to burn glucose, and turns up the metabolism to do so.  T3 enhances storage of glucose as fat.  So both hormones are in the business of getting rid of excess glucose, just like insulin.

In fact, they not only work in concert with insulin to dispose of excess—toxic—glucose, they make insulin work better:

 "Thyroid hormone potentiates insulin signaling and attenuates hyperglycemia and insulin resistance in a mouse model of type 2 diabetes."
"...Single injections of T3 (7 ng·g⁻¹ i.p.) rapidly and markedly attenuated hyperglycemia. Treatment with T3 (14 ng·g⁻¹·day⁻¹, 18 days) dose-dependently attenuated blood glucose and increased insulin sensitivity in db/db mice. Higher doses of T3 (28 ng·g⁻¹·day⁻¹) reversed insulin resistance in db/db mice. T3 also increased insulin levels in plasma and the neurogenic differentiation factor (an insulin synthesis transcription factor) and insulin storage in pancreatic islets in db/db mice....
"...T3 potentiated insulin signaling, improved insulin sensitivity, and increased insulin synthesis, which may contribute to its anti-diabetic effects. These findings may provide new approaches to the treatment of type 2 diabetes...."
So if you're healthy, and you go on a low-carb/ketogenic diet, and your thyroid hormones go down a bit, that's perfectly normal.

It's not a sign, as various Paleo folks suggest, of some underlying need for glucose for proper thyroid function.  What's important isn't the absolute hormone level, as Colpo suggests in his post, it's the appropriate hormone level.

The same level of thyroid hormones is no longer needed on a low-carb diet.  

And this is what the research shows, as even the low-carb diet advocates Rosedale and Westman have found:
"Interestingly, this study cohort exhibited a reduction in circulating free T3, the secreted form of thyroid hormone thought to mediate most of thyroid actions. Paralleling this reduction in circulating free T3, 9 patients of this study cohort that had basal body temperatures measured before and after intervention showed a significant decrease (p=0.004) in basal body temperature of 0.182 degrees C."
As the paper on thyroid's role in glucose disposal makes clear, this is exactly what you'd expect to see.

T3 is referred to as a thermogeniccausing or pertaining to the production of heat—hormone in that study from 1983, because it raises the metabolism. Your body is burning off waste fuel, like those oil wells above.  So it's hardly surprising that if you lower carbohydrate consumption that T3 and body temperature are reduced, as it's now working normally.  It no longer needs to burn off toxic excess glucose.

In fact, the most in-depth study of the long-term safety of a low-carb, ketogenic diet I've found was conducted at Johns Hopkins Childrens Center, studying the treatment of epilepsy using a keto diet:
"The evidence is based on a study of 101 patients ages 2 to 26 years treated with the ketogenic diet for a minimum of 16 months and for up to eight years at Hopkins Children’s between 1993 and 2008."
The term "thyroid" isn't even mentioned, and the diet was found to be without side effects.

But, and here's a big but, Kresser, Jaminet, and Lewis aren't exactly wrong.  As I said above, the human body is insanely complicated, and there are many things that can go wrong.

For Lewis' observations, if you are carbohydrate-dependent, and you go on a low-carb diet, your body is going to go into panic mode.  This isn't bad, but it can be miserable, just like doing the first run when you start running can be horrible—my first run sure was.  If you are carb-dependent, and there are people who are unable—through atrophy of the fat-burning system—to burn fats, going low-carb is going to be miserable at first.  And your body is going to produce cortisol, which is a stress hormone that induces the body to convert muscle to glucose.  Because your broken body is dependent on glucose.  This is part of the fix, however, not part of the underlying problem.  It used to be thought that this was a week-to-three week process, but we know now that it likely takes months, if not years, to build the fat-burning system up to where it could be.  And while you may not feel flu-like symptoms for months instead of a week or two, you may have reduced energy.  I didn't find it that way, but it's possible.

Clearly hormones produced by the thyroid should go down on a low-carb diet, but what about TSH?  It's unclear what that TSH going up might mean, as one study of centenarians found they had lower-than-normal TSH levels, another found normal levels, and a third found high levels.  Go figure.

What did seem important, from that first link in the paragraph above, was the rate of auto-immune thyroid disease:
"Autoantibodies positivity was found in 4.16% of centenarians and in 10.4% and 13.6% of old and young controls. Thus, the incidence of thyroid autoantibodies was lower in centenarians than in old controls."
As far as the divergence of opinion between the ketogenic diet promoters and the anti-ketogenic Paleo gurus, I suspect it's simply a matter of confounders that are not being properly accounted for.

Many of the people in the Paleo community, like myself, come to it because they have one of the diseases that the conventional medical system does a lousy job of treating: metabolic syndrome and autoimmune conditions.

And the two are inter-related:
"Diabetic patients have a higher prevalence of thyroid disorders compared with the normal population (Table 1). Because patients with one organ-specific autoimmune disease are at risk of developing other autoimmune disorders, and thyroid disorders are more common in females, it is not surprising that up to 30% of female type 1 diabetic patients have thyroid disease. The rate of postpartum thyroiditis in diabetic patients is three times that in normal women. A number of reports have also indicated a higher than normal prevalence of thyroid disorders in type 2 diabetic patients, with hypothyroidism being the most common disorder.
Hypothyroidism is when your thyroid underproduces thyroid hormones.  It is typically—unless you're deficient in iodine—an auto-immune condition: your body is destroying your thyroid.  If your thyroid hormone production is deranged, and they work in concert with insulin, then it's not surprising that hypothyroid and diabetes often go together.

"Thyroid hormones are positively associated with insulin resistance early in the development of type 2 diabetes"
And:
"Studies have found that diabetes and thyroid disorders tend to coexist in patients. Both conditions involve a dysfunction of the endocrine system. Thyroid disorders can have a major impact on glucose control, and untreated thyroid disorders affect the management of diabetes in patients. Consequently, a systematic approach to thyroid testing in patients with diabetes is recommended."
(There's another thyroid disease that causes overproduction of thyroid hormones, which is also an autoimmune condition, just to make things really interesting.)

Diabetes is a disease, essentially, of a failure to process carbohydrates.  It's hardly surprising, therefore, that both organs involved in producing hormones to dispose of carbs may be involved.

Now it's entirely possible that if you're marginally hypothyroid, and you reduce glucose production, therefore reducing thyroid hormones further, you may have additional problems.  And this may be what Kresser and Jaminet are seeing in the people they refer to, although the Rosedale/Westman study mentioned above was not a study of healthy people, but sick ones:
"Patients were referred for the treatment of diabetes, cardiovascular disease, excessive weight, fatigue, and other chronic diseases of aging."
But what I suspect is happening, is that people who are more carbohydrate dependent do worse initially on a low-carb diet, and may be underconsuming calories, leading to the hypothyroid-like symptoms.  The thyroid reduces metabolic rate in the absence of food, to reduce the body's need to metabolize its tissues, thereby lengthening the time one can go without food.  This has clear evolutionary advantages, obviously.

But I've not found any indication that carbohydrates are required or even beneficial for thyroid health, as the role of the thyroid, in partnership with the pancreas where insulin is produced, is in disposing of glucose.

Both Kresser and Jaminet recommend increasing "safe" carbohydrates consumption a bit for people who seem to have hypothyroid conditions on a low-carb diet, and while this is likely effective in resolving symptoms, it may not resolve the underlying condition.  But if that's where you are, it's worth a shot, as they both advocate a minimal increase well within the bounds of what I'd consider a reasonable level of carbohydrates.

The other confounder in the opposite direction is that reduction in carbohydrates may lead to a reduction of autoimmune thyroiditis symptoms, as a commonly-consumed source of carbohydrates is wheat, and wheat appears to be pretty clearly causal in auto-immune thyroiditis, as both Kresser and Jaminet note.  Jaminet has a category of starch called "safe starches", and while some people don't seem to do well with potatoes, it's a pretty good list.

I don't find the argument for a dietary requirement for safe starches very compelling; but as I said above, this stuff is insanely complicated, and there may well be a class of people who have a requirement for dietary starch.  If you have issues, experiment.

But I think the long-term goal for a healthy diet should be getting to the point where you have no dependency on glucose intake.  It doesn't appear to be necessary, and there are benefits to weaning yourself off that dependency.

* Under-eating can be an issue on a low-carb/ketogenic diet, as appetite can be suppressed.  But I've never heard of anyone starving to death as a result of a ketogenic diet, so I suspect that it's a short-term phenomenon.