According to the most recent data of the Centers for Disease Control and Prevention, approximately two-thirds of adults are overweight (body mass index [BMI] > 25 kg·m−2) and ~38% of the adult U.S. population is obese (BMI > 30 kg·m−2) (1). This clearly represents a health epidemic with wide-ranging health implications on the average American. Rarely are overweight and obese adults found without comorbid conditions. Typically, obese adults often have hypertension, atherosclerosis, type 2 diabetes, dyslipidemia, arthritis, and/or failing joints. The link between obesity and thyroid dysfunction (including autoimmune thyroid disease, the main cause of hypothyroidism in adults) has been studied (2–4). The prevalence of autoimmune thyroid disease in obese adults is estimated to be between 10% and 60% (5), and overweight and obese individuals are at high risk for hypothyroidism and thyroid hormone replacement (THR) (6). There is a bidirectional relationship between thyroid dysfunction and obesity; changes in body weight, body composition, and total and resting energy expenditure independently of physical activity (2,3,5,7–12) can result from the disruption of normal thyroid function. Conversely, a direct link between obesity and thyroid dysfunction can also occur, via the disruption of signaling in the hypothalamic–pituitary–adrenal axis (3,4,13,14).
According to IMS data, Synthroid® (levothyroxine) has been one of the most commonly prescribed drugs in the United States for the past several years, with an estimated 126 million prescriptions written in 2017. Given the epidemic proportion of obesity and the prevalence of prescription THR (6,15), it is crucial to understand how THR may affect weight loss efforts and body composition changes of those who are trying to improve their health.
Taking into consideration the very complex role the thyroid plays in weight regulation and metabolism, we reviewed the differences in body composition changes in those taking and not taking THR in nonsurgical weight loss studies published in the past 5 yr. We thoroughly reviewed the literature (PubMed) using search terms including but not limited to T4, thyroid hormone, thyroid replacement, diet, calorie restricted diet, very low calorie diet (VLCD), weight loss, BMI, body fat, bone mass, muscle mass, lean body mass, and free fat mass. We were unable to find sizable (>50 participants) weight loss studies providing detailed data on the differences in adults taking versus not taking THR, particularly with outcome measures beyond weight and BMI.
Here we report no effect of THR on the results of a 9-wk intense weight reduction program focused on lowering subcutaneous and visceral adipose tissue. We assessed changes in body weight, BMI, % body fat, visceral fat, and metabolic age and increases in % body water to provide a clear picture of weight and metabolic-related outcomes in participants with or without prescription THR medications. We find that the 20Lighter Program (T20LP) outcomes were not affected by THR, and meaningful improvements were achieved in physiologic and metabolic end points, including those directly linked to cardiovascular disease risk and overall health.
MATERIALS AND METHODS
Subjects and Program Overview
This was a retrospective review of data from 2200 participants completing T20LP (Boston, MA) by December 31, 2017. This study protocol was reviewed and approved by the Institutional Review Board, and consent was obtained from all participants. T20LP, a commercial doctor-supervised weight loss and metabolic health program, included 6 wk of a patent-pending structured VLCD and 3 wk of a customized transition back to a normal dietary intake. Each participant engaged in once a day home weigh-ins, daily messaging with the supervising doctor, proprietary vitamin/mineral supplementation, daily journaling, and at least three in-person office visits for body composition analysis and consultation with a staff member (initial baseline, ~days 40–42, and ~days 60–63). Participants were encouraged (but not required) to engage in light physical activity (walking, etc.) but to avoid beginning highly strenuous exercise until they entered the transition phase of the program (weeks 6–9).
Structured VLCD and Transition
The 6-wk VLCD on T20LP included no prepackaged food items. The goal of 500 to 850 calories per day was achieved with freshly prepared lean proteins, low carbohydrate vegetables, and fruits. T20LP does not permit canned items, processed foods, deli meats, and preprepared food items commonly found at grocery stores and restaurants during the 6-wk VLCD duration. The VLCD eliminated wheat, corn, dairy, oil, and sugar. The dietary intake during the transition period gradually increased from the VLCD to an end point (including total calories per day and the recommended amount of protein each day) customized for each participant based on gender, age, and average daily activity level. Overall, it ranged from ~1200 to 2000 calories each day and from ~70 to 150 g of protein. For the duration of the 9-wk program, no artificial sweeteners were permitted; only stevia, a plant-derived sweetener, was allowed.
Body Composition Analysis
T20LP included body composition analysis measured via a class 2 medical device with bioelectrical impedance analysis with bipolar foot electrodes (Tanita Corporation, Chicago, IL) at each office visit to monitor participant progress. End points of interest assessed at each follow-up visit include weight, BMI, % body fat, % body water, visceral fat rating, and metabolic age. These end points were calculated using the proprietary Health Edge Software (Tanita Corporation).
Comparison of Groups
In addition to the calculation of the mean at baseline and at the 60-d end point in each group, we also compared the mean change over 60 d between groups. We did this additional comparison to minimize the effect of a higher proportion of males in the non-THR group and females in the THR group that may affect the overt magnitude of improvements (a man who is 280 lb at baseline is likely to lose more weight than a woman who is 200 lb at baseline). We assessed the change over 60 d as a % improvement (change/baseline value × 100). This allows us to compare improvements between the groups in a way that avoids a bias in favor of the non-THR group that had a higher proportion of male participants.
Baseline demographic values (age and BMI) are reported as median ± SD. All outcome data are shown as mean ± SEM. To assess for significance of each outcome from baseline to 60 d, a Wilcoxon matched-pairs signed rank test was used. To assess for significance between participants taking prescription thyroid meds (THR) and those not taking prescription thyroid medications (non-THR) groups, a D’Agostino and Pearson (DAP) normality test was used to show the presence of normality in the population of means. If the population of means passed the DAP normality test (parametric), subsequent statistical analysis was done via an unpaired t-test with Welch’s correction. If the means failed the DAP normality test (nonparametric), subsequent statistical analysis was done via a Mann–Whitney U-test. In all cases, the statistical significance threshold was P < 0.05.
A total of 2200 participants completed the first 6 wk of T20LP by December 31, 2017. Baseline age (54.0 ± 9.5 yr), BMI (34.1 ± 6.1 kg·m−2), comorbidities, history, and prescription medications were typical of metabolic syndrome (Table 1). At the start of T20LP, 23.7% of participants reported no comorbidities, 35.9% reported one comorbidity, 22.1% reported two comorbidities, and 18.3% reported three or more comorbidities (Table 1). Comorbidities included hypertension, dyslipidemia or triglyceridemia, type 2 diabetes, previous treatment for cancer, at least one previous heart attack, joint replacement or reconstructive surgery, arthritis, gout, epilepsy, angina, atrial fibrillation, and sleep apnea requiring a CPAP machine, among others. At the start of T20LP, 222 (10.1%) of the 2200 participants reported taking prescription THR. Baseline age (THR, 52.5 ± 9.0 yr; non-THR, 55 ± 9.6 yr), BMI (THR, 34.4 ± 6.1 kg·m−2; non-THR, 34.2 ± 6.7 kg·m−2), comorbidities, history and prescription medications, and other characteristics were similar between groups (Table 1).
Overview of Outcomes for THR and Non-THR Groups
From baseline to 60 d, both non-THR and THR groups showed similar clinically relevant and statistically significant changes in the most basic weight loss outcome measurements (pounds lost and BMI reduction). The non-THR group’s weight was reduced from a baseline of 238.7 ± 2.9 to 205.2 ± 2.8 lb at 60 d. The THR group’s weight at start of program was 234.2 ± 6.3 and 204.2 ± 4.7 lb at 60 d. Both of these reductions were statistically significant (P < 0.0001 and P = 0.0003, respectively) (Fig. 1A).
BMI, a standardized measure of height and weight, was reduced for both groups. For the non-THR group, the values were 35.2 ± 0.16 pts at baseline and 30.3 ± 0.17 pts at 60 d. For the THR group, the values were 35.1 ± 0.26 pts at baseline and 30.6 ± 0.16 pts at 60 d. Reductions in both groups were statistically significant (P < 0.0001) (Fig. 1B).
As we looked into more complex body composition changes over 60 d, we continued to see significant improvements. % Body fat (the percentage of body weight that is fat) in the non-THR group dropped from 41.1% ± 0.28% to 34.7% ± 0.27%, and the THR group saw a reduction from 42.3% ± 0.26% to 36.1% ± 0.22% at 60 d. Both of these reductions were statistically significant (P < 0.0001) (Fig. 1C).
The measure of visceral fat, measured by a proprietary Tanita Corporation algorithm as a visceral fat rating (range 1–59), showed reductions for both groups. Non-THR visceral fat rating was reduced from 18.0 ± 0.46 to 13.2 ± 0.41 pts, and THR was reduced from 17.0 ± 0.27 to 12.8 ± 0.25 pts. Both changes were statistically significant (P < 0.0001) (Fig. 1D).
More nuanced and less often reported % body water represents tissue hydration, a gauge of intracellular water. The non-THR group showed an increase of % body water from 41.4% ± 0.08% to 44.8% ± 0.09%, and the THR increased from 39.8% ± 0.09% to 42.9% ± 0.09%. This increase was still statistically significant in both groups (P < 0.0001) (Fig. 1E).
Lastly, metabolic age, a proprietary Tanita Corporation measure indicating at what age level a user’s BMR is rated (range 12–90 yr; younger representing a more efficient metabolism, older representing less efficient), also showed significant improvements in both groups. The non-THR group went from 80.1 ± 0.56 yr at baseline to 64.3 ± 0.64 yr at 60 d. The THR group also showed an impressive drop from 78.9 ± 0.66 to 64.3 ± 0.64 yr at 60 d. Both reductions were statistically significant (P < 0.0001) (Fig. 1F).
Comparison of THR and Non-THR Groups
To compare the improvements between groups to assess for any advantage in the non-THR group or disadvantage in the THR groups, we compared the mean change in each outcome.
The % of body weight lost during the study did not different between groups. The non-THR group lost a mean of 14.0% ± 0.22%, and the THR group lost a mean of 12.8% ± 0.30%. This small difference did not meet statistical significance (P = 0.0712) (Fig. 2A). The % of BMI reduction was the same between groups. The mean % reduction in BMI for non-THR group was 13.92% ± 0.24% versus 12.86% ± 0.31% in the THR group, which is not a statistically significant result (P = 0.1394) (Fig. 2B).
Similar to body weight and BMI, body fat and visceral fat reductions did not differ between groups. Reduction in % body fat in the non-THR group was 15.62% ± 0.39%, slightly more than the 14.61% ± 0.34% reduction of the THR group, but this difference was not statistically significant (P < 0.3917) (Fig. 2C). The % visceral fat decrease in the non-THR group was 26.3% ± 0.39% versus 24.6% ± 0.44% in the THR group, again a small numerical difference but not a statistically significant result (P > 0.1425) (Fig. 2D).
No statistical significance was found between the groups for improvement in body water. The mean increase in % body water in the non-THR group was 8.09% ± 0.127% and 7.86% ± 0.129% for the THR group. Following other outcomes, these means were not statistically different (P = 0.5512) (Fig. 2E).
The last outcome measure, metabolic age, is a metabolism-focused rather than physiologic measurement. The values of % metabolic age reduced were 19.76% ± 0.127% for the non-THR group and 18.47% ± 0.316% for the THR group, not a statistically significant difference (P = 0.3327) (Fig. 2F).
Obesity and thyroid diseases have approached alarming rates in the United States (1,6,15), and as the population ages, these two health issues are increasingly concomitant. A direct relationship between thyroid dysfunction and obesity is well known and has been described in the literature for many years. Thyroid dysfunction causes changes in body weight, body composition, and total and resting energy expenditure independently of physical activity (2,3,5,7–12). Conversely, there is also a direct link between obesity and thyroid dysfunction, as it is also known that obesity can cause thyroid dysfunction through the disruption of signaling in the hypothalamic–pituitary–adrenal axis (3,4,13,14). In either case, the “chicken or the egg” conundrum leaves us with a subset of the population with low metabolic rates and high levels of body fat, at risk for obesity-related health issues. To complicate matters, there are differing opinions and contradictory evidence as to whether prescription THR causes weight loss or perpetuates weight gain in those with hypothyroidism (16–18). In addition, we found references in the literature to weight loss in THR patients being attributed to loss of excess edematous water rather than reduction of body fat (16,17). Given this preponderance of contradictory information, we sought to provide a clear picture of the physiological and metabolic changes occurring during T20LP with granular information beyond commonly used outcome measures.
Unlike previous studies, our data show both statistically significant and clinically meaningful changes in all outcome measures for both THR and non-THR groups. The presence of THR medications did not prevent successful weight loss, reduced adiposity, and did not preclude favorable changes in body composition or metabolism. Both physiological and metabolic changes for each group independently were impactful.
Our study indicates that participants who take prescription THR do equally as well on T20LP as those not taking prescription THR. References in the literature attribute weight loss by THR patients to reduction of excess edematous fluid rather than body fat (16–18). Our data clearly demonstrate that T20LP causes a dramatic reduction in % body fat and visceral fat in participants taking THR on par with participants without a hypothyroid disorder. We received anecdotal reports of THR clients that frequency of urination was increased throughout the program and reports that their faces and hands felt “less puffy.” This could be a result of a decrease in myxedema in the THR group; however, it did not significantly affect the overall improvements in body composition.
To our knowledge, this is the first large-scale study quantifying body composition changes specifically in participants on prescription THR medications. This study is also the first to demonstrate a clinically relevant improvement in not only body weight and BMI but also intracellular water, body fat, and visceral fat. Although reduction of body weight is important, body weight alone is not an adequate measure of reduction in disease risk and improvement in overall health (19). Visceral fat is a well-characterized direct marker of cardiovascular and metabolic disease risk in both young and old humans (20,21), and in our opinion, weight loss programs should move away from body weight and toward end points such as visceral fat to truly gauge the value of the program in a participant’s health. In totality, our data show that an intense doctor-supervised weight loss program including a structured VLCD produces clinically meaningful improvements in physiologic and metabolic end points, including those directly linked to cardiovascular disease risk reduction and metabolic syndrome, and improvements in overall health in adults taking prescription THR.
The 20Lighter Program is a commercial weight loss and metabolic health program. Participants were not compensated for participation, and no outside funding was used in this study. The authors thank Linda Tighe, Maria Lee, and Krista Curry for their help in study data collection. The results and views of the current study do not constitute endorsement by the American College of Sports Medicine.
The authors declare competing financial interests: Gerald C. Dembrowski and Jessica W. Barnes report ownership interest in an organization that may gain or lose financially through this publication.
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