Thyroid function and therapeutic carbohydrate restriction

Sarah Rice BSc. (Hons), MCOptom (UK), MHP, NNP

Introduction

A recent study by Vranjić et al. (2025) reviews the complex interplay between the ketogenic diet (KD) and thyroid function, emphasising the metabolic, hormonal, immune, and individual factors that mediate this relationship (1). 

The relationship between metabolic health and thyroid function is complex and bidirectional, where non-thyroidal illness describes the condition whereby the hypothalamic-pituitary-thyroid system and thyroid hormone metabolism are abnormal due to non-thyroidal diseases (2). Studies suggest that glycaemic control and thyroid function are interrelated, with abnormal TSH concentrations occurring in poorly controlled type 2 diabetes and an increased risk of autoimmune thyroid disease occurring in type 1 diabetes (2, 3). The bidirectional relationship between obesity and thyroid disease also reflects this complexity (3). Insulin resistance is implicated in the development of thyroid dysfunction and disease, where higher circulating levels of insulin can cause increased thyroid proliferation, and conversely, insulin resistance and type 2 diabetes may develop secondary to thyroid disease (3, 4). This complex relationship extends to the influence of nutritional ketosis on metabolic pathways, which may modulate thyroid hormones (1).

A metabolic advantage in healthy individuals?

A small study looking at the effect of nutritional ketosis on healthy participants utilised three weeks of isocaloric diets (crossover), comparing a ketogenic diet to a high-carbohydrate, low-fat diet (5). They found that the KD resulted in more weight loss, with no change in resting metabolic rate (RMR). Compared to pre-diet levels, plasma TSH and T4 were unchanged, while plasma T3 concentration was significantly lower following the KD diet (T3 unchanged on the low-fat diet). Nutritional ketosis may contribute to a metabolic advantage via the influence of thyroid hormones on metabolic pathways related to energy storage and expenditure, including lipid and carbohydrate metabolism. Thyroid hormones mediate metabolic rate and adaptive thermogenesis, playing a significant role in determining bodyweight. An interesting observation was that the shift in hormones that occurred in this study is similar to the effect seen in cold exposure, suggesting that nutritional ketosis drives similar changes in the metabolic activity of brown adipose tissue as seen with cold stimulation (5).

Improvements in Hashimoto’s thyroiditis using TCR

Hashimoto’s thyroiditis (HT) is an autoimmune endocrine condition and the most common form of thyroiditis. At its core, HT is an inflammatory disorder with key features including the production of proinflammatory cytokines (TNF-alpha; interleukin-6) leading to an increase in extracellular fluid levels and water retention, which is observed as an increase in water content in the thyroid tissue. Research suggests potential benefits of TCR for thyroiditis via mechanisms that include decreasing inflammation and improving insulin sensitivity, which contribute to improved metabolic markers in this population.

In this study from Huang et al. (2024), MRI scans were used to assess thyroid composition to determine dietary effects. After 6 months, it was observed that patients in the reduced-carbohydrate group had significant reductions in thyroid water content, along with a decrease in thyroid antibodies (TPOAb and TgAb) (6).

Thyroid Hormone Regulation under the KD

The KD alters several hormonal pathways: leptin and insulin levels decrease, reducing TRH and TSH secretion and deiodinase activity, while cortisol transiently increases during early adaptation, potentially suppressing the HPT axis. Ghrelin may rise, but its effect is minor compared to leptin and cortisol (1). Adequate protein is important for hormone synthesis, and fat quality may also influence inflammation and thyroid function. The microbiome and nutrient absorption, paying attention to selenium, iodine, and zinc, are other important components of a successful dietary approach (1).

The KD consistently leads to reduced circulating triiodothyronine (T3) levels, often without a compensatory rise in thyroid-stimulating hormone (TSH), suggesting a non-pathological, adaptive downregulation of thyroid activity (1). This reduction is primarily due to decreased deiodinase activity, resulting from lower insulin and glucose levels, which impairs the conversion of thyroxine (T4) to active T3. Reverse T3 may increase, further reducing active thyroid hormone availability. These changes mimic the physiological response to fasting or caloric restriction and are generally not associated with overt hypothyroidism in the absence of symptoms. In fact, studies consistently show TSH remaining in range during nutritional ketosis despite decreasing T3 concentration (1).

Individual Variability

Genetic polymorphisms (e.g., DIO2 Thr92Ala, APOA2, PPARA) influence individual responses to KD, affecting T3 conversion, fat metabolism, and ketogenesis efficiency (1). Sex-based differences are notable: women are more susceptible to reproductive and thyroid disruptions caused by increased leptin sensitivity and changes in thyroxine-binding globulin (TBG) that are mediated by oestrogen. Progesterone may also influence thyroid hormone sensitivity via changes to body temperature and RMR occurring in a cyclical manner. During nutritional ketosis, changes in T3 concentration may exacerbate cyclical features of thyroid metabolism in sensitive women. Shifting hormones, such as during perimenopause or with oral contraceptive use, may influence laboratory readings, yielding normal total T4 with low free T4 and symptoms of hypothyroidism (1). 

Thyroid hormone regulation under intermittent fasting

Fluctuations in thyroid hormones during fasting appear to be temporary adaptations, with similar changes observed under conditions of carbohydrate restriction (1, 7). Reducing insulin resistance may improve the sensitivity of thyroid hormones as part of the metabolic improvements that can occur during intermittent fasting as well as reduce inflammatory markers, which may have a role in managing Hashimoto’s thyroiditis (6, 7). 

Conclusion

TCR induces adaptive changes in thyroid hormone metabolism, with potential benefits in inflammation and autoimmunity. Variations in responses to dietary changes suggest individualised dietary strategies and appropriate monitoring of relevant metrics are key. Further long-term, controlled studies are needed to clarify the safety and efficacy of TCR in diverse thyroid phenotypes, particularly in the ketogenic range.

Resources

Women are particularly vulnerable to thyroid hormone fluctuations and dysregulation due to the cyclical fluctuations and interactions that occur in response to reproductive hormone changes. Perimenopause represents a transitional state where thyroid hormones may fluctuate in response to other hormonal changes. Nutrition Network is launching a new course where you can learn more about how hormonal fluctuations impact metabolic health: Menopause and perimenopause:

Science, Strategies & Lifestyle tools to Optimise Women’s Hormones.

References

1. Vranjić, P. et al. (2025) “Ketogenic Diet and Thyroid Function: A Delicate Metabolic Balancing Act,” Current Issues in Molecular Biology, 47(9), p. 696. Available at: https://doi.org/10.3390/cimb47090696.
2. Iwamoto, Y. et al. (2022) ‘Effect of Hyperglycemia-Related Acute Metabolic Disturbance on Thyroid Function Parameters in Adults’, Frontiers in Endocrinology, 13, p. 869869. Available at: https://doi.org/10.3389/fendo.2022.869869.
3. Cywes, R. et al. (2023) ‘Chapter 3 – Endocrine’, in T.D. Noakes et al. (eds) Ketogenic. Academic Press, pp. 107–203. Available at: https://doi.org/10.1016/B978-0-12-821617-0.00010-3.
4. Rezzonico, J. et al. (2008) ‘Introducing the Thyroid Gland as Another Victim of the Insulin Resistance Syndrome’, Thyroid®, 18(4), pp. 461–464. Available at: https://doi.org/10.1089/thy.2007.0223.
5. Iacovides, S. et al. (2022) ‘Could the ketogenic diet induce a shift in thyroid function and support a metabolic advantage in healthy participants? A pilot randomized-controlled-crossover trial’, PLoS ONE, 17(6), p. e0269440. Available at: https://doi.org/10.1371/journal.pone.0269440.
6. Huang, X.-S. et al. (2024) “MRI quantitative assessment of the effects of low-carbohydrate therapy on Hashimoto’s thyroiditis,” Endocrine Connections, 1(aop). Available at: https://doi.org/10.1530/EC-23-0477.
7. Shkorfu, W. et al. (2025) ‘Intermittent Fasting and Hormonal Regulation: Pathways to Improved Metabolic Health’, Food Science & Nutrition, 13(8), p. e70586. Available at: https://doi.org/10.1002/fsn3.70586.