Reasons for this recommendation include that it is:. Levothyroxine contains T 4 thyroxine , which is converted in the body to more biologically active, T 3. For most individuals, taking levothyroxine T 4 will sufficiently treat hypothyroidism but a small percentage of individuals don't efficiently convert T 4 to T 3.
Levothyroxine is generally well tolerated and side effects are often attributable to the wrong dosage, which can manifest as symptoms of either hypothyroidism or hyperthyroidism. Cytomel liothyronine contains T 3 , which is the active hormone from which the levothyroxine is converted to by deiodinase enzymes in our bodies. While Cytomel is indicated and FDA approved to treat hypothyroidism, it generally isn't recommended as first-line therapy by most medical guidelines.
Successful treatment of hypothyroidism and normalization of TSH thyroid-stimulating hormone with Cytomel alone generally requires high doses, putting some individuals at risk for hyper thyroidism in some tissues. In addition, Cytomel often needs to be taken multiple times a day since it has a short half-life, resulting in fluctuating levels in the body. Effects of the drug can wear off fairly quickly.
If you take Cytomel once daily and notice symptoms of hypothyroidism getting worse as the day progresses, speak to your doctor about the possibility of splitting your dosages throughout the day. One clinical study recommended to take Cytomel two to three times daily but if the dose cannot be divided evenly, give the larger dose at bedtime. While not a first-line option for hypothyroidism, Cytomel may be an appropriate choice in those who cannot efficiently convert T 4 to T 3 and is often used in combination with levothyroxine.
A variety of studies have shown improved symptoms and quality of life in those combining Cytomel and levothyroxine versus those taking levothyroxine alone. It is important to talk to your doctor regarding the best time to take Cytomel and levothyroxine if both have been prescribed to you. There is no single recommended method of dosing. The most important thing is to stay consistent! A small change in how you normally take Cytomel and levothyroxine can make a big difference in absorption and overall effect.
The most common recommendation for individuals is to take both medications at the same time , in the morning on an empty stomach, about minutes before food with a full glass of water.
If you are prescribed to take Cytomel more than once daily, subsequent doses should be taken on an empty stomach as well if possible. After 3 months, patients were switched from levothyroxine in the morning to placebo and vice versa for another 3 months. Double-blind study medication was provided by the hospital pharmacy, which performed the randomization. Commercial levothyroxine sodium tablets Thyrax Duotab, 0.
Every patient received study capsules containing a similar dose of levothyroxine as before entry into the trial. Placebo and levothyroxine capsules were visually identical. Patients were instructed by a research nurse to take the morning capsule on an empty stomach half an hour before breakfast and the bedtime capsule at night just before going to bed.
At baseline and every 6 weeks, patients were seen in our clinics by a research nurse. At these visits, blood samples were obtained to determine plasma thyrotropin, FT 4 , T 3 , creatinine, and lipid levels, and blood pressure, heart rate, and body weight were measured. The remaining capsules in the containers were counted to check for compliance. Quality-of-life questionnaires were completed by patients at baseline, at 3 months, and at the end of the study.
Blood samples were drawn on the morning of the planned visit to the research nurse. Capsules were not withheld on the day of blood sampling. Serum thyrotropin levels reference range, 0. Levels of FT 4 reference range, Three QOL questionnaires Item Short Form Health Survey, Hospital Anxiety and Depression Scale, and Item Multidimensional Fatigue Inventory and a specific questionnaire about symptoms of hypothyroidism and hyperthyroidism were completed by patients at baseline, at 3 months, and at the end of the study.
Patients completed the questionnaires under the supervision of a research nurse. After the trial ended, patients were free to choose at what time of day they preferred to continue taking levothyroxine, in the morning or at bedtime. One year after the trial, we asked every patient at what time he or she was taking the levothyroxine tablet. The primary end point was a change in thyroid hormone variables thyrotropin, FT 4 , and total T 3 [TT 3 ] levels between 12 weeks of morning levothyroxine intake and 12 weeks of bedtime levothyroxine intake.
Secondary end points were changes in QOL measured by 3 questionnaires , thyroid symptom score, body mass index, heart rate, and serum lipid and creatinine levels. The direct treatment effect among all variables was measured by performing an independent-samples t test between the differences of week 12 and week 24 in the first group started with morning levothyroxine and the second group started with bedtime levothyroxine.
All P values were 2-sided and were not adjusted for multiple testing. All calculations were performed using commercially available statistical software SPSS To calculate the sample size, we assumed that a difference in thyrotropin level of 1.
From previous results in a pilot study, we calculated that the standard deviation of the difference between morning and bedtime administration would be between 2. Between April 1, , and November 30, , a total of consecutive patients with primary hypothyroidism were assessed for study eligibility. Ultimately, patients met the inclusion criteria and gave written informed consent. Fifteen randomized patients withdrew their consent shortly after enrollment in the trial and had baseline data only.
The baseline characteristics of these patients did not differ from those of patients who completed the trial. Baseline characteristics of the 2 groups are given in Table 1. There were differences between the 2 groups in the proportions of male patients, levothyroxine dosages, and thyrotropin levels. On average, patients missed a mean SD of 1.
Because there were no severe symptoms related to hypothyroidism or hyperthyroidism, no patient required a change in levothyroxine dosage during the trial. Results of the primary outcomes are summarized in Table 2 and in Figure 2. Among the group that received morning levothyroxine first, the mean SD thyrotropin level decreased from 2. In contrast, among the group that received bedtime levothyroxine first, the mean SD thyrotropin level increased from 2.
When overall changes were compared between the 2 groups, bedtime levothyroxine intake was found to have a direct treatment effect, with a decrease in thyrotropin level of 1. The mean SD FT 4 level in the group that received morning levothyroxine first increased from 1. In the group that received bedtime levothyroxine first, the mean SD FT 4 level decreased from 1. Therefore, bedtime levothyroxine intake resulted in a direct treatment effect, with an increase in FT 4 level of 0.
Changes in TT 3 levels were similar to changes in FT 4 levels. In the group that received morning levothyroxine first, the mean SD TT 3 level increased from In the group that received bedtime levothyroxine first, the mean SD TT 3 level decreased from In this case, the direct treatment effect of bedtime levothyroxine was an increase in TT 3 level of 6.
No first-order carryover effect was found for thyrotropin, FT 4 , or TT 3 levels. There were no differences between the 2 study groups in serum creatinine or lipid levels, blood pressure, body mass index, or heart rate. These results are summarized in Table 2.
Hypothyroidism symptoms were unchanged between the 2 periods, despite improved thyroid hormone profiles, nor was there a difference in hyperthyroidism symptoms.
When asked at the end of the trial before the randomization code was broken , 34 of 90 patients said that they felt better during the period of morning intake of levothyroxine, 31 patients preferred the period of bedtime intake, and 25 patients indicated no preference. At 1 year after completion of the trial, more than half of the patients still preferred bedtime intake of levothyroxine. We performed this large, randomized, double-blind crossover trial among 90 patients to address whether levothyroxine taken at bedtime instead of in the morning improves thyroid hormone levels.
The primary outcomes show a decrease in thyrotropin level of 1. Despite the change in thyroid hormone levels, the patient QOL did not differ. Bedtime levothyroxine intake could be more convenient for patients, as they do not have to postpone breakfast. After our study was completed, more than half of the patients decided to continue with bedtime intake of levothyroxine. How can the bioavailability effects of levothyroxine be explained?
An interval of 30 minutes between taking levothyroxine and eating breakfast may be too short to prevent interference with gastrointestinal absorption of levothyroxine. Moreover, many patients drink coffee in the morning, often instead of eating breakfast, 6 or may take other medications that interfere with levothyroxine absorption. In contrast, most patients in our study stated that they had eaten no food or snacks for several hours before bedtime, this being their usual routine.
Bowel motility is slower at night, resulting in more prolonged exposure of levothyroxine to the intestinal wall and, consequently, in better bioavailability. Thyroid hormone level changes did not translate into QOL changes. There are various explanations for this observation. Patients with hypothyroidism taking adequate doses of levothyroxine ie, those whose thyrotropin level is in the reference range can still have significant impairment in psychological well-being and cognitive function compared with control subjects.
Weight gain and inability to lose weight are known to occur in patients with treated hypothyroidism and hyperthyroidism. A trial investigating T 3 supplementation showed that improved QOL was limited to a subgroup of patients with suppressed thyrotropin levels who had lost weight.
In contrast, plasma thyroid hormone levels may not be representative of thyroid hormone levels at the tissue level eg, in the brain ; therefore, they would be unrelated to QOL. Primary outcomes of this study are consistent with results of an earlier pilot study. In a retrospective medical record review of 15 nursing home residents, Elliott 35 observed a nonsignificant decrease in thyrotropin levels when levothyroxine intake was switched from after breakfast to midnight.
The findings in that nonrandomized trial confirm the results of our study. A 3-period crossover design study 36 showed higher thyrotropin levels when levothyroxine was taken at bedtime instead of before breakfast, but there was no change in FT 4 or TT 3 levels, as in our study.
The study also included patients with thyroid cancer, whose thyrotropin levels were maintained at lower levels than those of the rest of the population. Separating the doses can ensure you get the best results from your thyroid drugs. Besides coffee, some other foods, supplements, and medications can affect how well levothyroxine works. These include:. It may be OK to do so but talk with your doctor first.
The usual recommendation is to take it on an empty stomach in the morning. However, you can take it in the evening at least three to four hours after you've eaten. Losing weight with thyroid disease can be a struggle. Our thyroid-friendly meal plan can help. Sign up and get yours free! Wegrzyn NM. Malabsorption of L-T4 due to drip doffee: a case report using predictors of causation. J Acad Nutr Diet.
Eghtedari B, Correa R. In: StatPearls [Internet]. Updated August 6, Cornelis MC. The impact of caffeine and coffee on human health. American Thyroid Association.
Updated Altered intestinal absorption of L-thyroxine caused by coffee. A novel formulation of L-thyroxine L-T4 reduces the problem of L-T4 malabsorption by coffee observed with traditional tablet formulations. Thyroid hormone profile in patients ingesting soft gel capsule or liquid levothyroxine formulations with breakfast. Int J Endocrinol. Levothyroxine interactions with food and dietary supplements-a systematic review.
Pharmaceuticals Basel. Bolk N. Effects of evening vs morning levothyroxine intake. Arch Intern Med. Your Privacy Rights. To change or withdraw your consent choices for VerywellHealth. At any time, you can update your settings through the "EU Privacy" link at the bottom of any page. These choices will be signaled globally to our partners and will not affect browsing data.
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