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    3 Comments for this article
    Obvious and so simple
    sitelle | none

    It seems fairly obvious that levothyroxine should be given and taken on an empty stomach in the morning, and this is how ALL medical doctors order it to be taken.

    Obvious, based on what?
    Linh | Note
    It is NOT so simple. This study makes it not simple:

    1. First of all, this study has been done by medical doctors who also have research degrees. So not ALL medical doctors agree. Traditional recommendation is valid however not proven by studies to be the best recommendation. This study wants to address that.
    2. There were none prior studies made that proves taking in the morning is more effective than in the evening. NONE. Hence this study.
    3. The recommendation that thyroxine should be taken on an empty stomach is correct since calcium and iron prevent absorption of thyroxine. HOWEVER, at bedtime
    your stomach is most likely to be empty as well. Therefore also valid.
    The Primary Takeaway
    Robbie Robot | USC
    This invaluable study has helped invalidate the myth that thyroid replacement hormones (primarily levothyroxine) must be administered in the morning on an empty stomach. This trial establishes the efficacy of levothyroxine taken before bedtime on an empty stomach.

    Also, of importance that there are no adverse concerns regarding QOL if the medication is taken as prescribed, on an empty stomach at bedtime. The key seems to be taking the medication on an empty stomach, with no other medications, vitamins, beverages, etc. And to wait for a minimum of 30 minutes prior to consuming any
    food or beverage (other than water of course) after taking the medication.

    "Empty stomach" defined as no food, beverage, medication, etc. for at least 2 to 3 hours prior to the administration of levothyroxine.
    Original Investigation
    December 13/27, 2010

    Effects of Evening vs Morning Levothyroxine Intake: A Randomized Double-blind Crossover Trial

    Author Affiliations

    Author Affiliations: Department of Internal Medicine, Maasstad Hospital Rotterdam, Rotterdam (Drs Bolk and Berghout and Mss Nijman and Jongste), Department of Endocrinology, Erasmus Medical Center Rotterdam, Rotterdam (Dr Visser), and Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam (Dr Tijssen), the Netherlands.

    Arch Intern Med. 2010;170(22):1996-2003. doi:10.1001/archinternmed.2010.436

    Background  Levothyroxine sodium is widely prescribed to treat primary hypothyroidism. There is consensus that levothyroxine should be taken in the morning on an empty stomach. A pilot study showed that levothyroxine intake at bedtime significantly decreased thyrotropin levels and increased free thyroxine and total triiodothyronine levels. To date, no large randomized trial investigating the best time of levothyroxine intake, including quality-of-life evaluation, has been performed.

    Methods  To ascertain if levothyroxine intake at bedtime instead of in the morning improves thyroid hormone levels, a randomized double-blind crossover trial was performed between April 1, 2007, and November 30, 2008, among 105 consecutive patients with primary hypothyroidism at Maasstad Hospital Rotterdam in the Netherlands. Patients were instructed during 6 months to take 1 capsule in the morning and 1 capsule at bedtime (one containing levothyroxine and the other a placebo), with a switch after 3 months. Primary outcome measures were thyroid hormone levels; secondary outcome measures were creatinine and lipid levels, body mass index, heart rate, and quality of life.

    Results  Ninety patients completed the trial and were available for analysis. Compared with morning intake, direct treatment effects when levothyroxine was taken at bedtime were a decrease in thyrotropin level of 1.25 mIU/L (95% confidence interval [CI], 0.60-1.89 mIU/L; P < .001), an increase in free thyroxine level of 0.07 ng/dL (0.02-0.13 ng/dL; P = .01), and an increase in total triiodothyronine level of 6.5 ng/dL (0.9-12.1 ng/dL; P = .02) (to convert thyrotropin level to micrograms per liter, multiply by 1.0; free thyroxine level to picomoles per liter, multiply by 12.871; and total triiodothyronine level to nanomoles per liter, multiply by 0.0154). Secondary outcomes, including quality-of-life questionnaires (36-Item Short Form Health Survey, Hospital Anxiety and Depression Scale, 20-Item Multidimensional Fatigue Inventory, and a symptoms questionnaire), showed no significant changes between morning vs bedtime intake of levothyroxine.

    Conclusions  Levothyroxine taken at bedtime significantly improved thyroid hormone levels. Quality-of-life variables and plasma lipid levels showed no significant changes with bedtime vs morning intake. Clinicians should consider prescribing levothyroxine intake at bedtime.

    Trial Registration  isrctn.org Identifier: ISRCTN17436693 (NTR959).