There is a growing need to identify predictive factors to forecast weight loss outcomes for individuals living with obesity undergoing medical nutrition therapy. Although the effect of thyroid function on weight has been well described in the literature, its impact on weight loss trajectory for this population of patients remains uncertain (8–14). Our study suggest that baseline thyroid function plays a significant role on weight loss outcomes, with a negative correlation between baseline TSH levels and the amount of weight loss after 6 weeks. No correlation was noted between fT3 levels and the amount weight loss. Therefore, baseline TSH could serve as a predictive variable and merit incorporation into future prediction models.
Precisely, our data shows a negative correlation at week 6 between baseline TSH levels and absolute weight loss, with a β-coefficient of -0.473 (Table 3). In other words, for every decrease of 1 mIU/L of TSH, there is an additional 0.473 lbs of weight loss after 6 weeks of VLED. This translates to a significant mean weight loss difference of 1.3 lbs or 0.8% of total body weight loss (TBWL) between extreme TSH quantiles. This weight loss difference persisted at week 12 (Table 2). Studies have shown that individuals using a VLED achieve weight loss of 3 lbs per week on average (18). Therefore, the additional weight loss by unit of TSH decrease represents close to 4% of an individuals’ total weight loss after 6 weeks, which is clinically relevant.
Although the % of TBWL remained statistically significant between extreme TSH quantiles, there was no clear correlation between baseline TSH levels and absolute weight loss at week 12. These findings reflect the anticipated weight loss rate within VLED programs. Indeed, studies on VLED suggest that the rate of weight loss is higher in the first 6 weeks following the initiation of the diet (19). Therefore, the effect of baseline TSH levels on weight loss is expected to be more pronounced within this treatment period. Additionally, the levels of fT4 and fT3 are expected to fluctuate with weight loss due to associated changes in deiodinase activity (20). fT4 has a half-life of 7 days, which will reflect a change in TSH levels in 4–6 weeks (21). Hence, baseline TSH levels could better represent an individual’s baseline thyroid function within the initial 6 weeks of VLED.
When expressed in terms of absolute amount of weight loss, our study did not demonstrate a statistically significant difference between baseline TSH quantiles at week 6 and week 12. A possible explanation could be the variance in the mean initial weight between the groups. In fact, the participant’s mean weight in the lower TSH quantile was 276.16 ± 52.67lbs compared to 282.74 ± 63.70 lbs in the highest TSH quantile (Table 1). It has been well established that initial weight impacts weight loss outcomes (22). Therefore, the mean weight difference between the TSH quantiles could potentially skew our results. Nevertheless, studies have suggested that the percentage of weight loss might be a more sensitive predictor of weight loss outcomes than absolute weight, as it is the least influenced by initial weight, as found in our study (23). Accordingly, the % of TWBL is the most often used metric in clinic and research settings.
Contrary to previous findings, our study did not demonstrate a correlation between baseline fT3 levels and weight loss outcomes. Although there was a statistically significant difference in absolute weight loss at week 6 and week 12 between fT3 quantiles, there was no clear trend of progressive increase in weight loss with higher fT3 levels. As such, no significant difference was noted between extreme fT3 quantiles. Additionally, there was not significant difference in the % of TBWL between fT3 quantiles. The inconsistency of this finding is expected due to the potential variability in fT3 levels within individuals. For instance, serum fT3 follows a circadian rhythm with approximately 10% higher concentrations in the morning (24). Furthermore, the immunoassays frequently used by laboratories are highly susceptible to interference by various factors (e.g., heterophil antibodies, medications), rendering them to be an unreliable tool in clinical settings (25). Consequently, the American Thyroid Association does not recommend the use of fT3 levels as a therapeutic target for individuals with thyroid disorders (26). Although fT3 could potentially play a role in weight loss at the cellular level, its dosage is variable and should not be used as a predictor for weight loss outcomes in this population.
The mechanism underlying our findings remains unclear. It has been described that thyroid hormones regulate resting energy expenditure by acting both in peripheral tissues and the central nervous system. For instance, thyroid hormones play a role in ATP-dependent metabolic cycles such as lipid and glucose homeostasis in the liver, promote adipocyte proliferation, and regulate feeding behaviors in the hypothalamus (27, 28). We hypothesize that euthyroid individuals with lower baseline TSH levels have a higher circulating fT4 and fT3, and thus, a higher resting metabolic rate. These individuals might therefore be more responsive to lower energy diets and experience greater weight loss. This finding aligns with the results found by Tagliaferri et al. who also observed that higher TSH levels affects energy expenditure in patients with obesity and subclinical hypothyroidism (29). However, further research is needed to understand how normal thyroid function regulates weight changes in this population of patients.
To our knowledge, this study boasts the largest sample size investigating the impact of baseline thyroid function on weight loss outcomes in euthyroid individuals living with obesity. Nevertheless, some limits merit mention. Firstly, obesity is a complex multifactorial disease, making it impossible to control for all potential confounding factors (e.g., sleep apnea status, diabetes pharmacotherapy, etc.). Secondly, the participants in this study were individuals enrolled in a weight management program with weekly visits who adhered to the recommended diet. The negative correlation between baseline TSH and weight loss outcomes might be attenuated in a clinic setting. Thirdly, most participants in our study presented with a baseline TSH level within the lower half of the normal range for the laboratory, which might indicate a potential selection bias as higher TSH levels are typically expected with increased BMI. This could have skewed the results. Lastly, fT4 levels were not collected in the cohort used for this study. Some participants could present with undiagnosed subclinical hypothyroid. fT4 levels is also more stable than fT3 levels and could potentially better represent thyroid function than TSH.
In conclusion, our study demonstrated that a lower baseline TSH level is associated with greater weight loss at both 6 and 12 weeks following a medical weight management program utilizing VLED therapy, with a significant negative correlation observed week 6. Conversely, a higher baseline fT3 level was not associated with increased weight loss. Therefore, baseline TSH could serve as a predictive variable that merits incorporation into future prediction models. Moreover, our findings prompt a crucial clinical inquiry into whether supplementing euthyroid individuals with elevated baseline TSH could improve their weight loss outcomes. Further research is essential to address this pertinent clinical question.