The Effect of Ketogenic Diets on Thyroid Hormones

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.

Low T₃ is not hypothyroid.


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.


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].


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.



Evidence type: review

Economidou F1, Douka E, Tzanela M, Nanas S, Kotanidou A.
Hormones (Athens). 2011 Apr-Jun;10(2):117-24.

(Emphasis ours)

“The metabolic support of the critically ill patient is a relatively new target of active research and little is as yet known about the effects of critical illness on metabolism. The nonthyroidal illness syndrome, also known as the low T₃ syndrome or euthyroid sick syndrome, describes a condition characterized by abnormal thyroid function tests encountered in patients with acute or chronic systemic illnesses. The laboratory parameters of this syndrome include low serum levels of triiodothyronine (T₃) and high levels of reverse T₃, with normal or low levels of thyroxine (T₄) and normal or low levels of thyroid-stimulating hormone (TSH). This condition may affect 60 to 70% of critically ill patients. The changes in serum thyroid hormone levels in the critically ill patient seem to result from alterations in the peripheral metabolism of the thyroid hormones, in TSH regulation, in the binding of thyroid hormone to transport-protein and in receptor binding and intracellular uptake. Medications also have a very important role in these alterations. Hormonal changes can be seen within the first hours of critical illness and, interestingly, these changes correlate with final outcome. Data on the beneficial effect of thyroid hormone treatment on outcome in critically ill patients are so far controversial. Thyroid function generally returns to normal as the acute illness resolves.”


It remains controversial whether development of the aforementioned changes in thyroid metabolism reflects a protective mechanism or a maladaptive process during illness.

If these changes constitute an adaptation mechanism, then treatment to restore thyroid hormone levels to the normal range could have deleterious effects. In contrast, if these changes are pathologic, treatment may improve an otherwise poor clinical outcome. Current literature data indicate that:

Starvation-induced decrease in serum T₃ concentrations most likely reflects a process of adaptation.

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


Evidence type: experiment

Kaptein EM, Fisler JS, Duda MJ, Nicoloff JT, Drenick EJ.
Clin Endocrinol (Oxf). 1985 Jan;22(1):1-15.

(Emphasis ours)

“The relationship between the changes in serum thyroid hormone levels and nitrogen economy during caloric deprivation were investigated in ten obese men during a 40 d, 400 kcal protein-supplemented weight-reducing diet. This regimen induced increases in the serum levels of total T₄, free T₄ and total rTT₃and decreases of total T₃, while serum TSH remained unchanged. There were progressive decreases in total body weight and urinary losses of total nitrogen and 3-methylhistidine, with the early negative nitrogen balance gradually returning towards basal values during the 40 days. Subjects with the largest weight loss had the most increase in the serum levels of total T₄ and free T₄ index and the greatest decrease in T₃. The magnitude of the increase of the nitrogen balance from its nadir was correlated with the extent of the reduction of T₃ and increase of T₃ uptake ratio and free T₄ levels. The decrease in the urinary excretion of 3-methylhistidine correlated with the increase in free T₄ and rT₃ levels. Nadir serum transferrin values were directly related to peak rT₃ values, and the lowest albumin concentrations occurred in subjects with the highest total T₄ and free T₄ index values. Further, the maximum changes in the serum thyroid hormone levels preceded those of the nutritional parameters. These relationships suggest that: (1) increases in serum rT₃ and free T₄ and reductions in T₃ concentrations during protein supplemented weight reduction may facilitate conservation of visceral protein and reduce muscle protein turnover; and (2) the variation in the magnitude of these changes may account for the heterogeneity of nitrogen economy.”


Evidence type: experiment

(Emphasis ours)

“Although the rate of fat loss was relatively constant throughout the study, wide interindividual variations in cumulative protein (nitrogen) deficit were observed. Total nitrogen losses per subject ranged from 90.5 to 278.7 g. Cumulative nitrogen loss during the first 16 days tended to correlate negatively with initial mean fat cell size and positively with initial lean body mass. Most notable was the strong negative correlation between the size of the decrease in serum triiodothyronine over the 64-day study and the magnitude of the concurrent cumulative N deficit. During severe caloric restriction, one's ability to decrease circulating serum triiodothyronine levels may be critical to achievement of an adaptational decrease in body protein loss.


Evidence type: experiment

(Emphasis ours)

“Metabolic responses during a very-low-calorie diet, composed of 50 per cent glucose and 50 per cent protein, were studied in 18 grossly obese subjects (relative weights 131-205 per cent) for 28 d. During the last 14 d (period 2) eight subjects (Gp B) served as controls, while the other ten subjects (Gp A) in the low T₃ state were treated with triiodothyronine supplementation (50 micrograms, 3 times daily). During the first 14 d (period 1) a low T₃-high rT₃ state developed; there was an inverse relationship between the absolute fall of the plasma T₃ concentrations and the cumulative negative nitrogen balance as well as the beta-hydroxybutyrate (βOHB) acid concentrations during the semi-starvation period, pointing to a protein and fuel sparing effect of the low T₃ state. Weight loss in the semi-starvation period was equal in both groups; during T₃ treatment the rate of weight loss was statistically significant (Gp A 6.1 +/- 0.3 kg vs Gp B 4.2 +/- 0.2 kg, P less than 0.001). In the control group there was a sustained nitrogen balance after three weeks; in Gp A the nitrogen losses increased markedly during T₃ treatment. Compared to the control group, on average a further 45.4 g extra nitrogen were lost, equivalent to 1.4 kg fat free tissue. Thus, 74 per cent of the extra weight loss in the T₃ treated group could be accounted for by loss of fat free tissue. During the T₃ treatment period no detectable changes occurred regarding plasma triglycerides and plasma free fatty acids (FFA) concentrations; the plasma βOHB acid concentrations decreased significantly as compared to the control group. Plasma glucose concentrations and the immunoreactive insulin (IRI)/glucose ratio increased in Gp A in the T₃ treatment period, reflecting a state of insulin resistance with regard to glucose utilization. Our results warrant the conclusion that there appears to be no place for T₃ as an adjunct to dieting, as it enhances mostly body protein loss and only to a small extent loss of body fat.


"The plasma βOHB concentration declined significantly during T₃ treatment. In accordance with the results of Hollingsworth et al. we observed a decline of the plasma uric acid levels; this decline occurred simulataneously with the decrease in the βOHB levels in the T₃ treated group; as renal tubular handling of uric acid and ketones are closely linked during fasting, this might implicate a diminished renal reabsorbtion of ketones.

"It is known that renal conservation of ketones prevents large losses of cations during prolonged starvation without T₃ treatment; since ammonium is the major cation excreted in established starvation, the increased renal reabsorbtion of ketone bodies also minimizes nitrogen loss."


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."


Evidence type: controlled experiment

Spaulding SW, Chopra IJ, Sherwin RS, Lyall SS.
J Clin Endocrinol Metab. 1976 Jan;42(1):197-200.
“To evaluate the effect of caloric restriction and dietary composition on circulating T₃ and rT₃, obese subjects were studied after 7—18 days of total fasting and while on randomized hypocaloric diets (800 kcal) in which carbohydrate content was varied to provide from 0 to 100% calories. As anticipated, total fasting resulted in a 53% reduction in serum T₃ in association with a 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. The decline in serum T₃ during the no-carbohydrate diet correlated significantly with blood glucose and ketones but there was no correlation with insulin or glucagon. We conclude that dietary carbohydrate is an important regulatory factor in T₃ production in man. In contrast, rT₃, concentration is not significantly affected by changes in dietary carbohydrate. Our data suggest that the rise in serum rT₃ during starvation may be related to more severe caloric restriction than that caused by the 800 kcal diet.”

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


Evidence type: controlled experiment

Mathieson RA, Walberg JL, Gwazdauskas FC, Hinkle DE, Gregg JM.
Metabolism. 1986 May;35(5):394-8.

(Emphasis ours)

“Twelve obese women were studied to determine the effects of the combination of an aerobic exercise program with either a high carbohydrate (HC) very-low-caloric diet (VLCD) or a low carbohydrate (LC) VLCD diet on resting metabolic rate (RMR), serum thyroxine (T₄), 3,5,3'-triiodothyronine (T₃), and 3,5,3'-triiodothyronine (rT₃). The response of these parameters was also examined when subjects switched from the VLCD to a mixed hypocaloric diet. Following a maintenance period, subjects consumed one of the two VLCDs for 28 days. In addition, all subjects participated in thrice weekly submaximal exercise sessions at 60% of maximal aerobic capacity. Following VLCD treatments, participants consumed a 1,000 kcal mixed diet while continuing the exercise program for one week. Measurements of RMR, T₄, T₃, and rT₃ were made weekly. Weight decreased significantly more for LC than HC. Serum T₄ was not significantly affected during the VLCD. Although serum T₃ decreased during the VLCD for both groups, the decrease occurred faster and to a greater magnitude in LC (34.6% mean decrease) than HC (17.9% mean decrease). Serum rT₃ increased similarly for each treatment by the first week of the VLCD. Serum T₃ and rT₃ of both groups returned to baseline concentrations following one week of the 1,000 kcal diet. Both groups exhibited similar progressive decreases in RMR during treatment (12.4% for LC and 20.8% for HC), but values were not significantly lower than baseline until week 3 of the VLCD. Thus, although dietary carbohydrate content had an influence on the magnitude of fall in serum T₃, RMR declined similarly for both dietary treatments.”


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)

“The effect of different hypocaloric carbohydrate (CHO) intakes was evaluated in 8 groups of obese patients in order to assess the role of the CHO and the other dietary sources in modulating the peripheral thyroid hormone metabolism. These changes were independent of those of bw. Serum T₃ concentrations appear to be more easily affected than those of reverse T₃ by dietary manipulation and CHO content of the diet. A fall in T₃ levels during the entire period of study with respect to the basal levels occurred only when the CHO of the diet was 120 g/day or less, independent of caloric intake (360, 645 or 1200 calories). Moreover, reverse T₃ concentrations were found increased during the entire period of study when total CHO were very low (40 to 50 g/day) while they demonstrated only a transient increase when CHO were at least 105 g/day (with 645 or more total calories). Indeed, our data indicate that a threshold may exist in dietary CHO, independent of caloric intake, below which modifications occur in thyroid hormone concentrations. From these results it appears that the CHO content of the diet is more important than non-CHO sources in modulating peripheral thyroid hormone metabolism and that the influence of total calories is perhaps as pronounced as that of CHO when a “permissive” amount of CHO is ingested.”


Evidence type: controlled experiment

(Emphasis ours)

“To assess the effect of starvation and refeeding on serum thyroid hormones and thyrotropin (TSH) concentrations, 45 obese subjects were studied after 4 days of fasting and after refeeding with diets of varying composition. All subjects showed an increase in both serum total and free thyroxine (T₄), and a decrease in serum total and free triiodothyronine (T₃) following fasting. These changes were more striking in men then in women. The serum T₃ declined during fasting even when the subjects were given oral L-T₄, but not when given oral L-T₃. After fasting, the serum reverse T₃ (rT₃) rose, the serum TSH declined, and the TSH response to thyrotropin-releasing hormone (TRH) was blunted. Refeeding with either a mixed diet (n = 22) or a carbohydrate diet (n = 8) caused the fasting-induced changes in serum T₃, T₄, rT₃, and TSH to return to control values. In contrast, refeeding with protein (n = 6) did not cause an increase in serum T₃ or in serum TSH of fasted subjects, while it did cause a decline in serum rT₃ toward basal value.

The present data suggest that: (1) dietary carbohydrate is an important factor in reversing the fall in serum T₃ caused by fasting; (2) production of rT₃ is not as dependent on carbohydrate as that of T₃; (3) men show more significant changes in serum thyroid hormone concentrations during fasting than women do, and (4) absorption of T₃ is not altered during fasting.”

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


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


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)

“Participants Overweight and obese young adults (n=21).

Interventions After achieving 10 to 15% weight loss on a run-in diet, participants consumed low-fat (LF; 60% of energy from carbohydrate, 20% fat, 20% protein; high glycemic load), low-glycemic index (LGI; 40%-40%-20%; moderate glycemic load), and very-low-carbohydrate (VLC; 10%-60%-30%; low glycemic load) diets in random order, each for 4 weeks.”


“Hormones and Components of the Metabolic Syndrome (Table 3)

Serum leptin was highest with the LF diet (14.9 [12.1 to 18.4] ng/mL), intermediate with the LGI diet (12.7 [10.3 to 15.6] ng/mL) and lowest with the VLC diet (11.2 [9.1 to 13.8] ng/mL; P=0.0006). Cortisol excretion measured with a 24-hour urine collection (LF: 50 [41 to 60] μg/d; LGI: 60 [49 to 73] μg/d; VLC: 71 [58 to 86] μg/d; P=0.005) and serum TSH (LF: 1.27 [1.01 to 1.60] μIU/mL; LGI: 1.22 [0.97 to 1.54] μIU/mL; VLC: 1.11 [0.88 to 1.40] μIU/mL; P=0.04) also differed in a linear fashion by glycemic load. Serum T₃ was lower with the VLC diet compared to the other two diets (LF: 121 [108 to 135] ng/dL; LGI: 123 [110 to 137] ng/dL; VLC: 108 [96 to 120] ng/dL; P=0.006).


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)

“It is well known that physiological changes in the neuroendocrine system may be related to the process of aging. To assess neuroendocrine status in aging humans we studied a group of 155 women including 78 extremely old women (centenarians) aged 100-115 years, 21 early elderly women aged 64-67 years, 21 postmenopausal women aged 50-60 years and 35 younger women aged 20-50 years. Plasma NPY, leptin, glucose, insulin and lipid profiles were evaluated, and serum concentrations of pituitary, adrenal and thyroid hormones were measured. Our data revealed several differences in the neuroendocrine and metabolic status of centenarians, compared with other age groups, including the lowest serum concentrations of leptin, insulin and T₃, and the highest values for prolactin. We failed to find any significant differences in TSH and cortisol levels. On the other hand, LH and FSH levels were comparable with those in the elderly and postmenopausal groups, but they were significantly higher than in younger subjects. GH concentrations in centenarians were lower than in younger women. NPY values were highest in the elderly group and lowest in young subjects. We conclude that the neuroendocrine status in centenarians is markedly different from that found in early elderly or young women.”


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.


The hypothalamo-pituitary-thyroid axis has been widely implicated in modulating the aging process. Life extension effects associated with low thyroid hormone levels have been reported in multiple animal models. In human populations, an association was observed between low thyroid function and longevity at old age, but the beneficial effects of low thyroid hormone metabolism at middle age remain elusive.


We have compared serum thyroid hormone function parameters in a group of middle-aged offspring of long-living nonagenarian siblings and a control group of their partners, all participants of the Leiden Longevity Study.


When compared with their partners, the group of offspring of nonagenarian siblings showed a trend toward higher serum thyrotropin levels (1.65 vs157 mU/L, p = .11) in conjunction with lower free thyroxine levels (15.0 vs 15.2 pmol/L, p = .045) and lower free triiodothyronine levels (4.08 vs 4.14 pmol/L, p = .024).


Compared with their partners, the group of offspring of nonagenarian siblings show a lower thyroidal sensitivity to thyrotropin. These findings suggest that the favorable role of low thyroid hormone metabolism on health and longevity in model organism is applicable to humans as well.


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.


Caloric restriction (CR) retards aging in mammals. It has been hypothesized that a reduction in T₃ hormone may increase life span by conserving energy and reducing free-radical production.


The objective of the study was to assess the relationship between long-term CR with adequate protein and micronutrient intake on thyroid function in healthy lean weight-stable adult men and women.


In this study, serum thyroid hormones were evaluated in 28 men and women (mean age, 52 +/- 12 yr) consuming a CR diet for 3-15 yr (6 +/- 3 yr), 28 age- and sex-matched sedentary (WD), and 28 body fat-matched exercising (EX) subjects who were eating Western diets.


Serum total and free T₄, total and free T₃, reverse T₃, and TSH concentrations were the main outcome measures.


Energy intake was lower in the CR group (1779 +/- 355 kcal/d) than the WD (2433 +/- 502 kcal/d) and EX (2811 +/- 711 kcal/d) groups (P < 0.001). Serum T₃ concentration was lower in the CR group than the WD and EX groups (73.6 +/- 22 vs. 91.0 +/- 13 vs. 94.3 +/- 17 ng/dl, respectively) (P < or = 0.001), whereas serum total and free T₄, reverse T₃, and TSH concentrations were similar among groups.


Long-term CR with adequate protein and micronutrient intake in lean and weight-stable healthy humans is associated with a sustained reduction in serum T₃ concentration, similar to that found in CR rodents and monkeys. This effect is likely due to CR itself, rather than to a decrease in body fat mass, and could be involved in slowing the rate of aging.”


  1. 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

    1. Thank you, raphi. I hope you enjoyed the day! :-)

  2. Nice job as always.
    Did you read this:
    You probably did, but just in case...

  3. 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 :D

  4. 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.

    I am, though, going to discontinue my 5 micrograms of T3. Will that
    have any effect on my frequent migraines? I hope so.


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