It’s been thought that very-low-carb-high-fat ketogenic diets followed over the long-term will mess up with your hormones. Critics of low-carb nutrition advocate that keto diets lower the thyroid activity, decrease testosterone levels and affect other hormones throughout the body. What’s the evidence?
And what about the global massive iodine deficiency, regardless of the type of diet? Isn’t that more indicative of thyroid issues and overall poor health?
Under my n=1 keto-experiment, which is been going for more than 10 months, I was able to double my testosterone levels, from ~400 ng/dL to 843 ng/dL with dietary interventions and other lifestyle interventions.
I tweaked my testosterone levels between May 2014 and July 2014. I suspect that prior to starting the keto nutrition at the end of Sept. 2013, my T levels were below 200 ng/dL. And I have a couple of reasons to believe so, but I will talk about it in The Testosterone R(x), which I will be releasing in the near future.
Back to the Thyroid
If you’re a healthy human being and consume an eucaloric diet (where you eat food to meet your daily energy expenditure), your thyroid hormones T3 and T4 will show values in the normal range of 80-170 ng/dL for T3 and 4.5-12.5 ug/dL for T4. This happens regardless of the diet you eat.
Now let’s focus on the ketogenic diet and/or other variations of very low carbohydrate diets. If you maintain a state of ketosis for the longer-term you will most likely reduce the caloric intake because one of the biggest benefits of this approach is the “no hunger, no cravings” protocol.
If you’re like me, you can go days without eating. (When I’m involved in strenuous projects, I’m completely draw-in and I forget about food. That did not happen when I was not in ketosis).
So, I do not always meet my caloric intake for the day.
What’s all this got to do with the Thyroid Hormones?
Let’s see some possible correlations between thyroid activity, food intake and carbohydrate intake.
The Literature – Variability of Conclusions
1. Effect of Caloric Restriction and Dietary Composition on Serum T3 and Reverse T3 in Man
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.
Is lower T3 always indicative of disease state? I would say no. T3 is adjusted according to the needs of the body and it’s implicated in the feedback mechanism that goes between the hypothalamus (especially the regulation of food intake) and the thyroid.
Isocaloric diets containing at least 50g carbs are diets with the same number of calories, which is 800 kcals (in this case). So, is T3 not having a strong correlation with low calorie diets, but with the amount of carbs in the diet? What about Baltimore Longitudinal Study of Aging? We’ll see about it later.
2. Effect of dietary composition on fasting-induced changes in serum thyroid hormones and thyrotropin
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.
I do agree with their conclusion but I do not seem to empathize with their urgency to raise T3. It may be just my own interpretation, but I do not think low T3 is bad, as long as the thyroid function is normal and as long as the signaling TSH -> TRH and T4 concentration work properly.
We know from biochemistry textbooks that T3 works like a catalyst, increasing or decreasing the speed with which chemical reactions take place all over the body. Isn’t it normal that lower or no food intake leads to lower T3 levels, as long as everything else is in normal boundaries?
Serum levels of T3 and T4 are inter-connected because T4 (thyroxine) flows in much higher concentrations in the blood and is converted to T3 (active form of thyroid hormone) whenever needed. In fasted states, as there is not much need of high T3, there will be higher levels of circulating T4 (as it’s not converted).
3. Metabolic responses in grossly obese subjects treated with a very-low-calorie diet with and without triiodothyronine treatment
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 (BOHB) 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 BOHB 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.
Special thanks to Amber from Paleohacks for suggesting these articles. T3, as previously explained, speeds up processes throughout the body. It increases the usage of glucose, as well as fatty acids. However, where glucose is not available, it will promote gluconeogenesis by breaking down lean tissue (see first pic). It would be unnatural to supplement with T3 for lower T3 levels under caloric restricted regimens.
4. Isocaloric carbohydrate deprivation induces protein catabolism despite a low T3-syndrome in healthy men
Dietary carbohydrate content is a major factor determining endocrine and metabolic regulation. The aim of this study was to evaluate the relation between thyroid hormone levels and metabolic parameters during eucaloric carbohydrate deprivation.
We measured thyroid hormone levels, resting energy expenditure (by indirect calorimetry) and urinary nitrogen excretion in six healthy males after 11 days of three isocaloric diets containing 15% of energy equivalents as protein and 85%, 44% and 2% as carbohydrates.
In contrast to the high and intermediate carbohydrate diets, carbohydrate deprivation decreased plasma T3 values (1·78 ± 0·09 and 1·71 ± 0·07 vs. 1·33 ± 0·05 nmol/l, respectively, P < 0·01), whereas reverse T3, T3 uptake and free T4 levels increased simultaneously compared to the other two diets. TSH values were not different among the three diets. Although dietary carbohydrate content did not influence resting energy expenditure, carbohydrate deprivation increased urinary nitrogen excretion (10·91 ± 0·67 and 12·79 ± 1·14 vs. 15·89 ± 1·10 g/24 h, respectively, P = 0·03).
Eucaloric carbohydrate deprivation increases protein catabolism despite decreased plasma T3 levels. Because it has previously been shown that starvation decreases plasma T3 levels, resting energy expenditure and nitrogen excretion, these discordant endocrine and metabolic changes following carbohydrate deprivation indicate that the effects of starvation on endocrine and metabolic regulation are not merely the result of carbohydrate deprivation.
What is eucaloric carbohydrate deprivation?
It’s a feeding regimen where subjects are given food to meet their daily requirements, but these diets are restricted in carbohydrates. For example, if my TEE (total energy expenditure) is 2,500kcals and I eat a eucaloric carbohydrate deprived diet, I will eat 2,500kcals with macronutrient partitioning de-favoring carbs. Thus, I will eat foods high in fat and high in protein.
However, in this study there were 6 subjects following three different diets (for 11 days each):
D1 – High-Carb-Diet (15% protein, 85% carbs)
D2 – Control-Diet (15% protein, 44% carbs, 41% fat)
D3 – Low-Carb-Diet (15% protein, 2% carbs, 83% fat)
This is a very challenging study as it shows a certain relationship between carbohydrate intake and T3 levels. After following the low carb diet for 11 days, subjects show increased urinary nitrogen excretion. I believe 11 days is not enough time to totally shift to being a fat-adapted person and rely mostly on fat oxidation for energy. Their body was still looking for sugar after 11 days on very-high-fat-very-low carb diet, hence the breakdown of lean tissue (natriuresis). Plus, 15% protein is not enough under their design, if you ask me.
If they would have kept going with the protocol, I suspect that natriuresis would have slowed down. To suppress this effect, I would have increased protein intake to 20-30% of total calories and I believe that endogenous protein breakdown would have slowed down.
The low carb diet did lower T3 levels compared to the other diets but did not decrease TSH levels, which show correlation between T3 and carbohydrate when subjects are fed eucaloric diets.
5. The human metabolic response to chronic ketosis without caloric restriction: Physical and biochemical adaptation
To study the metabolic effects of ketosis without weight loss, nine lean men were fed a eucaloric balanced diet (EBD) for one week providing 35-50 kcal/kg/d, 1.75 g of protein per kilogram per day and the remaining kilocalories as two-thirds carbohydrate (CHO) and one-third fat. This was followed by four weeks of a eucaloric ketogenic diet (EKD)–isocaloric and isonitrogenous with the EBD but providing less than 20 g CHO daily. Both diets were appropriately supplemented with minerals and vitamins. Weight and whole-body potassium estimated by potassium-40 counting (40K) did not vary significantly during the five-week study.
Nitrogen balance (N-Bal) was regained after one week of the EKD. The fasting blood glucose remained lower during the EKD than during the control diet (4.4 mmol/L at EBD, 4.1 mmol/L at EKD-4, P less than 0.01). The fasting whole-body glucose oxidation rate determined by a 13C-glucose primed constant infusion technique fell from 0.71 mg/kg/min during the control diet to 0.50 mg/kg/min (P less than 0.01) during the fourth week of the EKD. The mean serum cholesterol level rose (from 159 to 208 mg/dL) during the EKD, while triglycerides fell from 107 to 79 mg/dL. No disturbance of hepatic or renal function was noted at EKD-4.
These findings indicate that the ketotic state induced by the EKD was well tolerated in lean subjects; nitrogen balance was regained after brief adaptation, serum lipids were not pathologically elevated, and blood glucose oxidation at rest was measurably reduced while the subjects remained euglycemic.
In this case, when they were given higher protein intake (1.75g per kg of bodyweight), there was no major nitrogen loss. Compared to the previous study, the subjects were given fair amount of protein to start becoming adapted to a high-fat-very-low-carb regimen.
6. Metabolic differences in response to a high-fat vs. a high-carbohydrate diet.
Energy expenditure was measured in a group of 7 subjects who received two isocaloric isonitrogenous diets for a period of 9-21 days with a 4-10-day break between diets. Diet 1 was a high-fat diet (83.5 +/- 3.6% of total energy). Diet 2 was a high carbohydrate diet (83.1 +/- 3.7% of total energy). Resting and postprandial resting metabolic rate were measured by open circuit indirect calorimetry 2-4 times during each metabolic period. Total energy expenditure (TEE) was measured by the doubly labeled water method over an 8-13-day period.
The respiratory quotient was measured 2-4 hours after a meal during each metabolic period for the calculation of total energy expenditure by the doubly labeled water method. Levels of total T3 (TT3), T3 uptake, free thyroid index and T4 were measured at the end of each metabolic period. No significant changes in resting metabolic rate (RMR) were apparent on the two diets (1567 +/- 426 kcal/d high-fat diet and 1503 +/- 412 kcal/d high-carbohydrate diet n=7, p<0.15). Total energy expenditure measured in 5 subjects was significantly higher during the high-carbohydrate phase of the diet (2443 +/- 422 vs. 2078 +/- 482 kcal/d p<0.05). Activity estimated from TEE/RMR was greater on the high-carbohydrate diet but only approached statistical significance (p<0.06).
Total T3 was significantly lower and free thyroid index and T3 uptake were significantly higher at the end of the high fat diet in comparison to the high-carbohydrate diet. These data suggest that individual tolerance to a high-fat diet varies considerably and may significantly lower TEE by changing levels of physical activity. The explanation for changes in thyroid hormone levels independent of changes in metabolic rate remains unclear.
Lower T3 in high-fat diet => Lower TEE
Higher T3 in high-carb diet => Higher TEE
There is correlation between carbs and T3 levels but a higher TEE may yield more ROS (reactive oxygen species). However, the high-fat diet, even with the lower TEE, lead to more weight loss. The subjects may not have been able to adapt to the diet because of its short duration of only a few days. Many of them reported nausea and lethargy (possibly effects of keto-adaptation).
7. The effect of varying carbohydrate content of a very-low-caloric diet on resting metabolic rate and thyroid hormones
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.
This study shows correlation between T3 and carb content, as well as T3 and calorie restriction. When on the high-carb diet, the subjects show lower T3 levels, but not as low as the ones when they follow a low-carb diet, thus strengthening the correlation between carbohydrate intake and T3 levels. However, this still does not mean that lower T3 levels are sign of a disease state or that something is wrong in the body.
Aging and Thyroid Levels
8. Effect of Long-Term Calorie Restriction with Adequate Protein and Micronutrients on Thyroid Hormones
Caloric restriction (CR) retards aging in mammals. It has been hypothesized that a reduction in T(3) 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.
DESIGN, SETTING, AND PARTICIPANTS:
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.
MAIN OUTCOME MEASURES:
Serum total and free T(4), total and free T(3), reverse T(3), 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 T(3) 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 T(4), reverse T(3), 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 T(3) 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.
I find this very interesting mostly because of the duration of the study as well as their conclusion. They point out the previously mentioned stronger correlation between T3 levels and carbohydrate intake but as you can see, TSH and T4 remain similar among the groups regardless of the different caloric intake, carbohydrate intake and overall design of the groups’ protocols.
I would suspect that this shows that lower T3 is not indicative of a malfunctioning thyroid, but it still remains unclear whether this is true or not.
You can check the full article and the references section. I’d be interesting to see other perspectives on this.
9. Evaluation of neuroendocrine status in longevity
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.
I find this study more relevant due to its higher sample size. Centenarians show lower T3, insulin, leptin, and prolactin compared to younger subjects, while there are no differences in TSH and cortisol levels.
Other studies that I have read show differences between cortisol levels in various aging groups. It’s interesting that NPY were highest in the elderly because as far as I know NPY (neuropeptide Y) stimulates feeding and promotes lipogensis.
10. Low Serum Free Triiodothyronine Levels Mark Familial Longevity: The Leiden Longevity Study
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.
nonagenarians = people living in their nineties
Same as the previous study, they link lower thyroid activity with increased lifespan. Here’s the full article.
To better understand the connection between thyroid activity and carbohydrate intake, one must have knowledge of how this gland functions and how its function is tied to processes throughout the entire body.
These studies show stronger correlation between the thyroid active hormone T3 and carbohydrate intake (higher-carb => higher T3) and they also show correlation between caloric intake and T3 levels. Subjects restricting calories (hypocaloric diet) have lower circulating T3 levels regardless of the type of macronutrient partitioning.
A hyper-active thyroid gland can speed up metabolism 60% to 100% according to Guyton.
Complete lack of thyroid secretion usually causes the basal metabolic rate to fall 40 to 50 per cent below normal, and extreme excesses of thyroid secretion can increase the basal metabolic rate to 60 to 100 per cent above normal.
Although the rate of protein synthesis is increased, at the same time the rate of protein catabolism is also increased. The growth rate of young people is greatly accelerated. The mental processes are excited, and the activities of most of the other endocrine glands are increased.
Intermittent fasting will most likely decrease T3 levels, but it should not affect TSH levels and T4 levels. If this were true all people fasting would suffer from hypothyroidism and many of us would have goiters.
What I’d like to draw attention to is iodine intake. Without proper iodine intake your thyroid may not function normally and this is the case where you’d see lower T3 levels as well as Lower T4 and TSH.
Iodine is very important because it is required to make thyroid hormones (T1, T2, T3, T4). Iodine binds with tyrosine to makes these hormones.
To prevent hypothyroidism, goiter and dwarfism, countries throughout the world have added iodine to salt (iodized salt).
Even though this is not the most efficient form to get iodine in the body, as Dr. Brownstein believes only 10% of iodine from iodized salt is absorbed, the protocol of iodized salt managed to eradicate the epidemic of hypothyroid related disorders for several decades.
However, we may be on a downward sloping curve because we fear to consume salt. We are constantly being bombarded by message to reduce the intake of sugar, salt, and fat.
(Again) Table salt (even iodized) may not be the best choice for iodine intake. I would instead eat seafood (kelp, seaweed) as it is rich in this extremely important nutrient. If that’s not possible I’d supplement with kelp extract or other products that provide a good source of iodine.
I would personally not worry for lower T3 levels under well formulated ketogenic diets and/or when following fasting/IF protocols as long as TSH and T4 are within normal ranges. Again, to make sure there is good function of the thyroid gland, I would ensure appropriate iodine intake.
As I said, I will lay down a complete Thyroid Protocol (Rx) as well as a Testosterone Protocol (Rx). However, I’m still conducting active research and experimentation on both of them and will let you know as soon as I finish them.
Later Edit: T-(Rx) is up and running. Following the link…
This has been a very long post and if you’ve made it so far, please share your thoughts in either of the comment sections below.
Hint: You might as well check the newer studies in the Further Readings section.
Spaulding, S. W., Chopra, I. J., Sherwin, R. S., & Lyall, S. S. (1976). Effect of caloric restriction and dietary composition on serum T3 and reverse T3 in man. The Journal of Clinical Endocrinology & Metabolism, 42(1), 197-200.
Azizi, F. (1978). Effect of dietary composition on fasting-induced changes in serum thyroid hormones and thyrotropin. Metabolism, 27(8), 935-942.
Koppeschaar, H. P., Meinders, A. E., & Schwarz, F. (1982). Metabolic responses in grossly obese subjects treated with a very-low-calorie diet with and without triiodothyronine treatment. International journal of obesity, 7(2), 133-141.
Bisschop, P. H., Sauerwein, H. P., Endert, E., & Romijn, J. A. (2001). Isocaloric carbohydrate deprivation induces protein catabolism despite a low T3‐syndrome in healthy men. Clinical endocrinology, 54(1), 75-80.
Phinney, S. D., Bistrian, B. R., Wolfe, R. R., & Blackburn, G. L. (1983). The human metabolic response to chronic ketosis without caloric restriction: physical and biochemical adaptation. Metabolism, 32(8), 757-768.
Bandini, L. G., Schoeller, D. A., & Dietz, W. H. (1994). Metabolic Differences in Response to a High‐Fat vs. a High‐Carbohydrate Diet. Obesity research, 2(4), 348-354.
Mathieson, R. A., Walberg, J. L., Gwazdauskas, F. C., Hinkle, D. E., & Gregg, J. M. (1986). The effect of varying carbohydrate content of a very-low-caloric diet on resting metabolic rate and thyroid hormones. Metabolism, 35(5), 394-398.
Fontana, L., Klein, S., Holloszy, J. O., & Premachandra, B. N. (2006). Effect of long-term calorie restriction with adequate protein and micronutrients on thyroid hormones. The Journal of Clinical Endocrinology & Metabolism, 91(8), 3232-3235.
Baranowska, B., Wolinska-Witort, E., Bik, W., Baranowska-Bik, A., Martynska, L., & Chmielowska, M. (2007). Evaluation of neuroendocrine status in longevity. Neurobiology of aging, 28(5), 774-783.
Rozing, M. P., Westendorp, R. G., de Craen, A. J., Frölich, M., Heijmans, B. T., Beekman, M., … & van Heemst, D. (2009). Low serum free triiodothyronine levels mark familial longevity: the Leiden Longevity Study. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, glp200.
Further Readings (newer studies):
Kumar, S., & Kaur, G. (2013). Intermittent fasting dietary restriction regimen negatively influences reproduction in young rats: a study of hypothalamo-hypophysial-gonadal axis. PloS one, 8(1), e52416.
Fond, G., Macgregor, A., Leboyer, M., & Michalsen, A. (2013). Fasting in mood disorders: neurobiology and effectiveness. A review of the literature. Psychiatry research, 209(3), 253-258.
Li, C., Ostermann, T., Hardt, M., Luedtke, R., Broecker-Preuss, M., Dobos, G., & Michalsen, A. (2013). Metabolic and psychological response to 7-day fasting in obese patients with and without metabolic syndrome. Forschende Komplementärmedizin/Research in Complementary Medicine, 20(6), 413-420.
Chausse, B., Solon, C., Caldeira da Silva, C. C., Masselli dos Reis, I. G., Manchado-Gobatto, F. B., Gobatto, C. A., … & Kowaltowski, A. J. (2014). Intermittent Fasting Induces Hypothalamic Modifications Resulting in Low Feeding Efficiency, Low Body Mass and Overeating. Endocrinology.
Moreno, B., Bellido, D., Sajoux, I., Goday, A., Saavedra, D., Crujeiras, A. B., & Casanueva, F. F. (2014). Comparison of a very low-calorie-ketogenic diet with a standard low-calorie diet in the treatment of obesity. Endocrine, 1-13.
Agnihothri, R. V., Courville, A. B., Linderman, J. D., Smith, S., Brychta, R., Remaley, A., … & Celi, F. S. (2014). Moderate weight loss is sufficient to affect thyroid hormone homeostasis and inhibit its peripheral conversion. Thyroid, 24(1), 19-26.
Ortiz-Bautista, R. J., Aguilar-Salinas, C. A., & Monroy-Guzmán, A. (2013). Caloric restriction: positive metabolic effects and cellular impact. Clinical cases, 81, 430-435.
Redman, L. M., & Ravussin, E. (2011). Caloric restriction in humans: impact on physiological, psychological, and behavioral outcomes. Antioxidants & redox signaling, 14(2), 275-287.
Trexler, E., Smith-Ryan, A., & Norton, L. (2014). Metabolic adaptation to weight loss: implications for the athlete. J Int Soc Sport Nutr, 11, 7.