Could the ketogenic diet induce a shift in thyroid function and support a metabolic advantage in healthy participants? A pilot randomized-controlled-crossover trial

Abstract

Background The ketogenic diet (KD) has been shown to result in body mass loss in people with disease as well as healthy people, yet the effect of the KD on thyroid function and metabolism are unknown. Objective We aimed to determine the effects of a KD, compared with an isocaloric high-carbohydrate low-fat (HCLF) diet, on resting metabolic rate and thyroid function in healthy individuals. Design Eleven healthy, normal-weight participants (mean(SD) age: 30(9) years) completed this randomized crossover-controlled study. For a minimum of three weeks on each, participants followed two isocaloric diets: a HCLF diet (55%carbohydrate, 20%fat, 25%protein) and a KD (15%carbohydrate, 60%fat, 25% protein), with a one-week washout period in-between. Importantly, while on the KD, the participants were required to remain in a state of nutritional ketosis for three consecutive weeks. Crossover analyses and linear mixed models were used to assess effect of diet on body mass, thyroid function and resting metabolic rate. Results Both dietary interventions resulted in significant body mass loss (p<0.05) however three weeks of sustained ketosis (KD) resulted in a greater loss of body mass (mean (95%CI): -2.9 (-3.5, -2.4) kg) than did three weeks on the HCLF diet (-0.4 (-1.0, 0.1) kg, p < 0.0001). Compared to pre-diet levels, the change in plasma T3 concentration was significantly different between the two diets (p = 0.003), such that plasma T3 concentration was significantly lower following the KD diet (4.1 (3.8, 4.4) pmol/L, p<0.0001) but not different following the HCLF diet (4.8 (4.5, 5.2) pmol/L, p = 0.171. There was a significant increase in T4 concentration from pre-diet levels following the KD diet (19.3 (17.8, 20.9) pmol/L, p < 0.0001), but not following the HCLF diet (17.3 (15.7, 18.8) pmol.L, p = 0.28). The magnitude of change in plasma T4 concentration was not different between the two diets (p = 0.4). There was no effect of diet on plasma thyroid stimulating hormone concentration (p = 0.27). There was a significantly greater T3:T4 ratio following the HCLF diet (0.41 (0.27, 0.55), p < 0.0001) compared to pre-diet levels but not following the KD diet (0.25 (0.12, 0.39), p = 0.80). Conclusions Although the diets were isocaloric and physical activity and resting metabolic rate remained constant, the participants lost more mass after the KD than after the HCLF diet. The observed significant changes in triiodothyronine concentration suggest that unknown metabolic changes occur in nutritional ketosis, changes that warrant further investigation. Trial registration Pan African Clinical Trial Registry: PACTR201707002406306 URL: https://pactr.samrc.ac.za/.

Cross‐sectional associations between healthy eating index and thyroid function in U.S. male Adults, NHANES 2007–2012

“…Although there is no doubt that iodine intake significantly affects thyroid function, several epidemiological studies have found that diet intake (not related to iodine) could also play a role. It was found by Stella Iacovides et al that a ketogenic diet decreased T3 levels and increased T4 levels, while a high-carbohydrate, low-fat diet did not affect thyroid function (Iacovides & Maloney, 2022).…”

“…Although there is no doubt that iodine intake significantly affects thyroid function, several epidemiological studies have found that diet intake (not related to iodine) could also play a role. It was found by Stella Iacovides et al that a ketogenic diet decreased T3 levels and increased T4 levels, while a high‐carbohydrate, low‐fat diet did not affect thyroid function (Iacovides & Maloney, 2022 ). Alessio Basolo et al reported that a high‐protein overfeeding led to plasma TSH, FT3, and FT4 decrease, while a low‐protein overfeeding resulted in a reduction in plasma TSH and increase in plasma FT3 (Basolo et al, 2019 ).…”

Obesity and Obesity-Related Thyroid Dysfunction: Any Potential Role for the Very Low-Calorie Ketogenic Diet (VLCKD)?

“…Regarding the effect of VLCKD on the thyroid function of healthy individuals, in 2022, Iacovides et al addressed the effects of two types of diets on thyroid function and body mass in eleven healthy participants [ 17 •]. To assess the impact of diet on body mass and thyroid function, they conducted a randomized, crossover study with two isocaloric diets: a low-carb diet and a VLCKD [ 17 •]. In response to the two diets, plasma TSH and T4 levels remained constant.…”

“…In response to the two diets, plasma TSH and T4 levels remained constant. However, plasma T3 concentrations decreased more on VLCKD than on the low carb diet ( p = 0.003), and it was associated with more significant body mass loss [ 17 •]. The study suggests that nutritional ketosis may shift in the T3:T4 circulating ratio, resulting in an increase in inactive T4 and a decrease in active T3 without a change in TSH.…”

“…While the exact mechanism by which KD improves the health of these patients is not fully understood, it is believed that switching from glucose to ketone body metabolism favorably affects the regulation of certain neurotransmitters, oxidative stress, and ion channels [ 13 – 16 ]. Based on current evidence, the effectiveness of KD extents to various pathologies, including impaired glucose control [ 17 •, 18 ], obesity [ 17 •, 19 , 20 ], polycystic ovary syndrome [ 11 , 14 , 21 , 22 ], cancer [ 23 , 24 ], and psoriasis [ 25 ]. KD has been studied as a tool to preserve muscle mass in the context of weight loss programs [ 8 , 26 , 27 ].…”