Effects of levothyroxine replacement or suppres... - Thyroid UK

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Effects of levothyroxine replacement or suppressive therapy on energy expenditure and body composition


Yet another paper questioning the effect of levothyroxine monotherapy on free T3 levels and, therefore, on metabolism. With that wonderful term "relative tissue hypothyroidism". :-)

Thyroid. 2015 Dec 23. [Epub ahead of print]

Effects of levothyroxine replacement or suppressive therapy on energy expenditure and body composition.

Samuels M1, Kolobova I2, Smeraglio A3, Peters D4, Purnell J5, Schuff KG6.

Author information

1Oregon Health Sciences University , 3181 SW SamJackson Park Road , Portland, Oregon, United States , 97221 , (503) 494-5242 , (503) 494-0165 ; samuelsm@ohsu.edu.

2Oregon Health & Science University, Endocrinology, Diabetes and Metabolism, Portland, Oregon, United States , 206-859-8317 ; irinakolobova@gmail.com.

3Stanford University School of Medicine, Stanford, California, United States , 650-723-4000 ; smeragli@stanford.edu.

4Oregon Health & Science University, Division of Biostatistics, Portland, Oregon, United States , 503-494-9000 ; petersd@ohsu.edu.

5Oregon Health & Science University, Endocrinology, Diabetes and Metabolism, Portland, Oregon, United States , 503-494-9000 ; purnellj@ohsu.edu.

6Oregon Health Sciences University, Medicine/Endocrinology , 3181 SW Sam Jackson Park Road , L-607 , Portland, Oregon, United States , 97239-3098 , (503) 494-1685 , (503) 494-6990 ; schuffk@ohsu.edu.



TSH-suppressive doses of levothyroxine (L-T4) have adverse effects on bone and cardiac function, but it is unclear whether metabolic function is also affected. The objective of this study was to determine whether women receiving TSH-suppressive L-T4 doses have alterations in energy expenditure or body composition.


This study was a cross-sectional comparison among three groups of women: 26 women receiving chronic TSH-suppressive L-T4 doses, 80 women receiving chronic replacement L-T4 doses, and 16 untreated euthyroid control women. Subjects underwent measurements of resting energy expenditure (REE), substrate oxidation, and thermic effect of food by indirect calorimetry; physical activity energy expenditure by accelerometer; caloric intake by 24-hour diet recall; and body composition by dual x-ray absorptiometry.


REE per kilogram lean body mass in the L-T4 euthyroid women was 6% lower than the L-T4 suppressed group and 4% lower than the healthy control group (P=0.04). Free T3 levels were directly correlated with REE, and were 10% lower in the L-T4 euthyroid women compared to the other two groups (P=0.007). The groups of subjects did not differ in other measures of energy expenditure, caloric intake, or body composition.


L-T4 suppression therapy does not adversely affect energy expenditure or body composition in women. However, L-T4 replacement therapy is associated with a lower REE despite TSH levels within the reference range. This may be due to lower fT3 levels, suggesting relative tissue hypothyroidism may contribute to impaired energy expenditure in L-T4 therapy.

PMID: 26700485 [PubMed - as supplied by publisher]


5 Replies

... and yet T4 mono therapy continues to continue !

Without a doubt T4 mono therapy altered my metabolic function.

The addition of T3 reversed the worst of these effects within days (amazing) and I still continue to progress four months after initally starting T3.

It is not just the obvious benefits such as energy levels rising and a return of clear thinking but the smaller ones such as cuts healing quicker, dry skin banishing, sense of smell returning.. the list is endless .......

I have the DI02 genetic polymorphism so was never going to do well on T4 alone anyway but then we don't know how many others have this faulty gene which I believe is actually quite common.

Thank you for posting Helvella,


Well spotted!

As with all these sorts of articles, so frustrating that no link is made with patient experience or whether there might be symptoms!

Of course with a research design like this, they won't have been asked. And then when those 80 women go into their GP's office saying they feel cold all the time, are gaining weight on their usual diet, their heart and digestion are acting up, or any other things we might guess a low REE directly implies, they'll be told there is no evidence in the literature you can get those symptoms with within range TSH!

Very interesting article. I started taking T3(10m and 10m) just three days ago, combined with 25m of thyroxine. I cannot believe how well I feel after this short time, I feel alive again. On my first day I noticed my breathing was so much better (diagnosed with asthma over 30 years, shortly after I was diagnosed with Hashi's ). The third day I found myself running, yes running for a bus and was not out of breath! Other side effects have also gone or are so much better. Sense of taste and smell, swollen tounge, awake feeling refreshed and do not need a cup of coffee to "wake myself up". I have a clear head , more energy and my movements are so much quicker. Like Flower007 the list goes on.

This is really interesting, thank you for posting it, I am actually starting to think I may have had this problem when I was on levothyroxin alone for block and replace therapy of my graves disease 8 years ago and have suffered ever since, slowly building up getting worse, my graves is kicking off again and I insisted on not having my thyroic killed for now and using block and replace again, so need all the study papers I can find in order to ask for a combination T4 and T3 therapy, as this may very well give me my life back if I am right!! Thank you again, really great info xx

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