The previous generation of myths about low carb diets were focused on organ systems. They warned of things like kidney dysfunction, and osteoporosis.
As these myths became untenable, new myths have swiftly taken their place: myths, for example, about hormone systems, and gut bacteria.
In previous posts, such as here, and here, we dispelled misinformation arising from fears about cortisol.
In this post we address fears about thyroid.
The idea that ketogenic diets are “bad for thyroid” is spouted in keto-opposed and keto-friendly venues alike.
Despite rampant parroting, it is difficult to find evidence to support this idea.
The only evidence that we found even suggestive of this idea is the fact that T₃, the most active thyroid hormone, has repeatedly been shown to be lower in ketogenic dieters.
However, this lowered T₃ is not a sign of “hypothyroid”. In fact, it has a beneficial function!
In this article, we explain why lower T₃ on a ketogenic diet is beneficial, rather than a sign of dysfunction or cause for alarm.
In Brief:
Low T₃ is not hypothyroid.
Diagnosis
Let’s first clear up some confusion about “low thyroid”.
Diagnosis is a tricky business.
Diseases manifest in unwanted symptoms, and diagnosis is the art of determining the cause.
Sometimes symptoms are very good discriminators.
They are easy to verify, and they have only one or two common causes.
Other times symptoms are common in a variety of illnesses, and by themselves don’t help diagnosis much.
Hypothyroid tends to be a cluster of these indiscriminate symptoms, and therefore, a lot of people are tempted, in understandable desperation, to diagnose themselves with it.
Ideally in medical research we want to find indicators and predictors of diseases:
things we can measure that discriminate well between diseases, or predict the imminent manifestation of those diseases.
Often they are measures that are not readily apparent to a patient, for example blood levels of various substances.
To verify a suspicion of hypothyroid, we measure thyroid hormones in the blood.
As we have seen again and again, there are often different ways to measure something, and symptoms or outcomes correlated with one measure may or may not correlate with the others.
Hypothyroid
The most common thyroid measures are the levels of TSH (thyroid stimulating hormone), T₄ (a relatively inactive form of thyroid hormone), and T₃ (the more active form).
TSH acts on the thyroid gland causing T₃ and T₄ to be produced.
Further T₃ can be generated out of T₄.
Hypothyroid is a problem in the gland, where not enough T₃ and T₄ are being produced.
It is indicated by high values of TSH (along with low T₃ and T₄).
It is my suspicion
that supplementing thyroid hormone in the general case of hypothyroidism may be as foolish as supplementing insulin in Non-Insulin-Dependent Diabetes.
Insulin is appropriate in (aptly named) Insulin-Dependent Diabetes, just as thyroid hormone would remain appropriate in Hashimoto’s.
The situation is analogous to high insulin in a Type II (Non-Insulin-Dependent) Diabetic:
In that case, insulin at normal amounts is not effectively reducing blood sugar as it would in a healthy body, so more and more gets produced to have the needed effect.
In the case of hypothyroid, more and more TSH is produced, because TSH is what acts on the thyroid gland to produce T₃ and T₄.
In other words, when you have low T₃ and T₄ levels, this signals more TSH to be created, in order to cause more T₃ and T₄ to be made in the gland.
Low T₃ by itself, without high TSH or low T₄, has been studied extensively, and has various names, including “nonthyroidal illness syndrome” (NTIS) [1].
On modern, high carb diets, it appears to happen only in cases of critical illness [1].
Whether low T₃ in critical illness is adaptive or not is a point of controversy [1].
Clearly, either there is a disruption in production caused by the illness,
or the body has a functional reason for not raising T₃; that is,
that low T₃ helps recovery in some way.
The adaptive hypothesis would be supported if supplementing T₃ caused harm.
Unfortunately, results have been mixed.
The mixed results are probably an artefact of the lumping together of the various situations in which NTIS occurs.
Although NTIS occurs with starvation,
ketogenic diets, which share some metabolic similarities with starvation, have not so far been included in this area of research.
However, research in calorie, carbohydrate, and protein restriction indicates that in these cases, as with starvation [1], lower T₃ is adaptive.
Lower T₃ spares muscle in conditions of weight loss or inadequate protein.
In weight loss, starvation, or protein deficiency conditions, lowered T₃ is thought to be a functional response that protects against muscle loss [2], [3].
When a diet creates a calorie deficit, or is low in protein, this creates a catabolic state (one in which the body tends to be breaking things down, rather than building them up).
If the body does not respond to this by lowering T₃, then lean mass would be lost.
Moreover, if T₃ is supplemented by a well-meaning person who interpreted this adaptation as a detrimental “hypothyroid” condition, this also results in loss of lean mass, as shown by Koppeschaar et al. [4].
Supplementing T₃ decreases ketosis, and increases the insulin-to-glucagon ratio [4], which, as we have previously discussed is tightly correlated with glucose production.
This suggests that supplementing T₃ induces gluconeogenesis;
as Koppeschaar et al. put it: “It must be concluded that triiodothyroxine also directly influenced glucose metabolism”.
Not only are T₃ levels lower in calorie restriction, but T₃ receptors are downregulated [1], [5], suggesting a second mechanism by which the body adapts away from T₃ use under ketogenic conditions.
If you are on a low-carb diet in which you are losing weight, and your T₃ is low, don’t assume you should correct this with supplementation.
Lowered T₃ has a purpose, and supplementing it defeats the purpose.
Other research has shown a correlation between lower T₃ and higher ketosis [6], and
between lower T₃ and very low carbohydrate levels [7], [8], [9].
It’s all very consistent.
In other words, the more ketogenic a weight loss diet is the better it spares muscles, and lowered T₃ is thought to be part of the mechanism, because it is both correlated with higher βOHB, correlated with muscle sparing, and because supplementing with T₃ reverses the muscle sparing effect.
As alluded to above, T₃ will also be lowered in a situation where weight is not being lost, and carbs are not ketogenically low, if protein is inadequate [10].
This further underscores the function of T₃ lowering: to spare protein for lean mass.
We are not aware of a study showing the effects of a protein adequate, ketogenic maintenance diet (i.e. not calorie restricted) that measured T₃. Therefore, we are not certain whether lowered T₃ would continue in that context [11].
However, insofar as it may continue, that could be beneficial:
Low T₃ is associated with longevity.
It’s possible that the lower T₃ found in ketogenic dieters is an indicator of a lifespan increasing effect.
First, T₃ is associated with longevity.
Low T₃ has been found in the very long-lived [12].
This does not appear to be simply an effect of old age, though,
because the correlation also shows up in a genetic study of longevity [13].
Moreover, just as with moderately elevated cortisol,
low T₃ is found in animals who have their lifespans experimentally increased,
and therefore (again, as with elevated cortisol)
the low T₃ is hypothesised to be part of the mechanism in increasing lifespan [13], [14].
Conclusion
There is no evidence that we are aware of indicating that ketogenic diets cause hypothyroid, or negatively impact thyroid function.
The fact that T₃ is lower in ketogenic dieters is probably part of the mechanism that protects lean mass when fat is being lost.
Moreover, low T₃ may possibly even be an indicator of a life extending effect, an effect we have suggested elsewhere when examining the cortisol profile of ketogenic dieters.
References:
[1] | Evidence type: review
Economidou F1, Douka E, Tzanela M, Nanas S, Kotanidou A.
Hormones (Athens). 2011 Apr-Jun;10(2):117-24.
(Emphasis ours) |
Ketogenic metabolism most closely resembles starvation, though, of course, with the important difference that it is nutritionally complete and there is no reason to believe it would be unhealthy indefinitely. — Amber
[2] | Evidence type: experiment
Kaptein EM, Fisler JS, Duda MJ, Nicoloff JT, Drenick EJ.
Clin Endocrinol (Oxf). 1985 Jan;22(1):1-15.
(Emphasis ours) |
[3] | Evidence type: experiment
Yang MU, van Itallie TB.
Am J Clin Nutr. 1984 Sep;40(3):611-22.
(Emphasis ours) |
[4] | Evidence type: experiment
Koppeschaar HP, Meinders AE, Schwarz F.
Int J Obes. 1983;7(2):133-41.
(Emphasis ours) |
[5] | Evidence type: review
Schussler GC, Orlando J.
Science. 1978 Feb 10;199(4329):686-8.
“Fasting decreases the ratio of hepatic nuclear to serum triiodothyronine (T₃) by diminishing the binding capacity of nuclear T₃ receptors. In combination with the lower serum T₃ concentration caused by fasting, the decrease in receptor content results in a marked decrease in nuclear T₃-receptor complexes. The changes in T₃ receptor content and circulating T₃ in fasted animals appear to be independent synergistic adaptations for caloric conservation in the fasted state. Unlike changes in hormonal level, the modification of nuclear receptor content provides a mechanism that may protect cells with a low caloric reserve independently of the metabolic status of the whole animal.” |
[6] | Evidence type: controlled experiment
Spaulding SW, Chopra IJ, Sherwin RS, Lyall SS.
J Clin Endocrinol Metab. 1976 Jan;42(1):197-200.
|
So at least in a very low calorie situation, T₃ becomes low only when the diet is sufficiently low in carbohydrate to be ketogenic, and its level correlates with ketogenesis.
We are not told whether any of the diets were protein sufficient, but in this case it doesn’t matter. The very low calories make it catabolic, and only when carbohydrate is at ketogenically low levels does the protein sparing effect occur. —Amber
[7] | Evidence type: controlled experiment
Mathieson RA, Walberg JL, Gwazdauskas FC, Hinkle DE, Gregg JM.
Metabolism. 1986 May;35(5):394-8.
(Emphasis ours) |
[8] | Evidence type: controlled experiment
Pasquali R, Parenti M, Mattioli L, Capelli M, Cavazzini G, Baraldi G, Sorrenti G, De Benedettis G, Biso P, Melchionda N.
J Endocrinol Invest. 1982 Jan-Feb;5(1):47-52.
(Emphasis ours) |
[9] | Evidence type: controlled experiment
Azizi F.
Metabolism. 1978 Aug;27(8):935-42.
(Emphasis ours) |
Note that in this case, “refeeding” was with an 800 calorie diet, i.e., for protein, 200g. So the refeeding diet is still low calorie, and thus still catabolic —Amber
[10] | Evidence type: controlled experiment
Otten MH, Hennemann G, Docter R, Visser TJ.
Metabolism. 1980 Oct;29(10):930-5.
“Short term changes in serum 3,3′,5-triiodothyronine (T₃) and 3,3’5-triiodothyronine (reverse T₃, rT₃) were studied in four healthy nonobese male subjects under varying but isocaloric and weight maintaining conditions. The four 1500 kcal diets tested during 72 hr, consisted of: I, 100% fat; II, 50% fat, 50% protein; III, 50% fat, 50% carbohydrate (CHO), and IV, a mixed control diet. The decrease of T₃ (50%) and increase of rT₃ (123%) in the all-fat diet equalled changes noted in total starvation. In diet III (750 kcal fat, 750 kcal CHO) serum T₃ decreased 24% (NS) and serum rT₃ rose significantly 34% (p < 0.01). This change occurred in spite of the 750 kcal CHO. This amount of CHO by itself does not introduce changes in thyroid hormone levels and completely restores in refeeding models the alterations of T₃ and rT₃ after total starvation. The conclusion is drawn that under isocaloric conditions in man fat in high concentration itself may play an active role in inducing changes in peripheral thyroid hormone metabolism.” |
Here, finally, is a study that is explicitly a maintenance diet. It says mostly what we would expect. It was a bit surprising, and contrary to some previous findings, that in the half carb, half fat diet, this high a carbohydrate level would still allow lower T₃. The authors suggest that this is evidence that high fat alone is responsible. Our interpretation, in contrast, is that it is the zero protein condition that led to the lower T₃. In the body of the paper, the authors, to their credit, acknowledge that they are speculating. We would love to see this example followed by more researchers. —Amber
[11] | Ebbeling et al. did make T₃ measurements, on a ketogenic diet intended to be weight stable, but the subjects were losing weight while on the ketogenic phase, and therefore no conclusion about T₃ in weight stable, protein adequate conditions can be drawn from that study.
Ebbeling CB, Swain JF, Feldman HA, Wong WW, Hachey DL, Garcia-Lago E, Ludwig DS.
JAMA. 2012 Jun 27;307(24):2627-34. doi: 10.1001/jama.2012.6607.
(Emphasis ours) |
[12] | Evidence type: observational
Baranowska B1, Wolinska-Witort E, Bik W, Baranowska-Bik A, Martynska L, Broczek K, Mossakowska M, Chmielowska M.
Neurobiol Aging. 2007 May;28(5):774-83. Epub 2006 May 12.
(Emphasis ours) |
[13] | Evidence type: observational
Rozing MP1, Westendorp RG, de Craen AJ, Frölich M, Heijmans BT, Beekman M, Wijsman C, Mooijaart SP, Blauw GJ, Slagboom PE, van Heemst D; Leiden Longevity Study (LLS) Group.
J Gerontol A Biol Sci Med Sci. 2010 Apr;65(4):365-8. doi: 10.1093/gerona/glp200. Epub 2009 Dec 16.
“BACKGROUND: |
[14] | Evidence type: experiment
Fontana L, Klein S, Holloszy JO, Premachandra BN.
J Clin Endocrinol Metab. 2006 Aug;91(8):3232-5. Epub 2006 May 23.
“CONTEXT: |
this is all much too interesting for a rushed comment, so I will just say, bravo(!) and rush down to open presents.
Rain check. happy time-off work everyone :p
Thank you, raphi. I hope you enjoyed the day! 🙂
Nice job as always.
Did you read this:
http://edwardjedmonds.com/thyroid-function-and-saturated-fat/
You probably did, but just in case…
Thank you. No, I hadn't seen that. 🙂
Following from Michael Frederik's link, it's interesting to see that lowered T3 promotes uncoupling. This mechanism might reconcile 2 things observed on LC diets:
1) excess cellular energy is effectively dispersed which is advantageous for weight maintenance (or gain!) in a food environment that is unfavorable to mitochondrial health. However, I don't know if the uncoupling occurs more so through UCP upregulation, ATPase reversing its role or simply more proton back-decay into the mitochondrial matrix.
2) Heat! I tolerate the cold much better. This seems to contradict the conventional adage that hypothyroid makes people cold. Actually, this would (partly?) explain why lowered T3 on well formulated LC diets aren't followed by lethargy or cold intolerance but actually quite the opposite. Cool stuff.
Please school me and fill in the details 😀
From Cite 7: "3,5,3'-triiodothyronine (T₃), and 3,5,3'-triiodothyronine (rT₃). "
From Cite 10: "3,3',5-triiodothyronine (T₃) and 3,3'5-triiodothyronine (reverse T₃, rT₃)"
Both seem to be typos and are so in the originals.
Curious.
I am, though, going to discontinue my 5 micrograms of T3. Will that
have any effect on my frequent migraines? I hope so.