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Effects of Levothyroxine Replacement or Suppressive Therapy on Energy Expenditure and Body Composition

Are we all mad?

Summary of paper: To maintain resting energy expenditure with levothyroxine (T4) only, you have to suppress TSH. Suppressing TSH has adverse effects on bone and heart. This is (possibly) because on lower doses of T4, fT3 is too low.

Question: Is this further evidence that levothyroxine monotherapy is a wonderful approach which works for everyone? Or does it suggest that T4/T3 combination therapy might be better for some people?

(Usual issue of laughably small cohort.)

Thyroid. 2016 Mar;26(3):347-55. doi: 10.1089/thy.2015.0345. Epub 2016 Feb 3.

Effects of Levothyroxine Replacement or Suppressive Therapy on Energy Expenditure and Body Composition.

Samuels MH1, Kolobova I1, Smeraglio A2, Peters D3, Purnell JQ1, Schuff KG1.

Author information

11 Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University , Portland, Oregon.

22 Department of Internal Medicine, Stanford University School of Medicine , Stanford, California.

33 Division of Biostatistics, Oregon Health and Science University , Portland, Oregon.



Thyrotropin (TSH)-suppressive doses of levothyroxine (LT4) 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 LT4 doses have alterations in energy expenditure or body composition.


This study was a cross-sectional comparison between three groups of women: 26 women receiving chronic TSH-suppressive LT4 doses, 80 women receiving chronic replacement LT4 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 LT4 euthyroid women was 6% lower than that of the LT4-suppressed group, and 4% lower than that of the healthy control group (p = 0.04). Free triiodothyronine (fT3) levels were directly correlated with REE, and were 10% lower in the LT4 euthyroid women compared with 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.


LT4 suppression therapy does not adversely affect energy expenditure or body composition in women. However, LT4 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 LT4 therapy.


PMID: 26700485

PMCID: PMC4790206

DOI: 10.1089/thy.2015.0345

Full paper freely available here:

10 Replies

I really cannot make head or tail of some of these papers. They insist on levothyroxine alone and then go on to say that bones and heart can be affected.

Both are also affected if we aren't diagnosed or on too low doses. This excerpt:

"However, LT4 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 LT4 therapy."

They also refer to 'despite TSH levels within the reference range.....may be due to lower FT3 levels.

If on treatment we should have a TSH of 1 or lower - not somewhere in the reference range. If on too low a dose we will have lower FT3 levels. We cannot win. They should concentrate on removing/resolving clinical symptoms.


You two really are a blast. Are we yet at the point where endos should all be doing the full Manuel - I know nothing

Que ? :D


We all suffer fawlty thyroids?


I dont suffer, not since i ditched the endo and the doc and self treated. :-)


I just managed to get 75 mcg levothyroxine from my GP, 8 month after being diagnosed, and with lots of symptoms.... If that doesn't do it I'll do the same....


All this seems to me to do is back up what is quoted in this forum as best practice. The group on TSH non-suppressed levo had TSH around 2 and FT3 around 10% lower than the other groups. Hence their metabolisms were lower and they were heavier. Duh-h-h! So it is better to have TSH lower than 2 but ideally not suppressed and FT3 higher in range (unless there is cancer involved). Hence metabolism is higher.

So this study is starting to edge towards what this group already knows.

Thank you to all those in this forum who give out great advice and keep us all in advance of the majority of the medical community.

Gillian xx


Well that was worth it wasn't it? I am afraid I gained not a lot from that experiment and I have done a lot of research in my time.



Once again an inadequate undifferentiated small study. However the obvious indication from this result is that in the group, T4-only therapy did not generally supply enough T3 for tissue euthyroidism. So we have the dilemma that to get an adequate level of tissue health, often T4 has to be given in such quantities that TSH is suppressed. Ergo, increased risk of osteoporosis and AF is alleged to occur. You can't therefore win, as I've said before. Either you are well now and may (MAY) have OP and AF later on, because of this (or not) or you suffer now and don't (may not) have OP and AF later. What choice would anyone sensible prefer? Incidentally, doctors should know that the TSH range for therapy patients is not the same as for well subjects. It is lowered significantly. This is simply because you need more T4 to get a given FT3 because the thyroid's direct T3 supply is no longer working. Since both T4 and T3 control TSH production about equally, then the corresponding TSH must be lower than it was when you were well, to get the same level of "health" back. This should be carried into all doctors' surgeries and carefully explained to them as to why a TSH say of 2.5 might just be acceptable in a healthy subject, it is far too high for someone on T4. And indeed for some, suppressed TSH is the desired end result.


Reading this report it seems to me that lots of (so called experts) are wasting a lot of money when it could be put to much better use. i.e. actually treating us properly.

I have been helped by the people on this site and now feel good, thank you for all your help.

1 like

I think this paper is quite generally useful for us, as it supports the kind of advice the forum gives.

The initial hypothesisis is that a group of women with suppressed TSH will be worse off than healthy controls or a 'euthyroid' group, but they end up finding that the suppressed group is more similar to the healthy controls, and the 'euthyroid' group is actually the worst off. They seem to accept this with good grace, rather than just forgetting to notice it in the discussion as some similar studies do

A few choice tidbits are that many of the participants, in all 3 groups including the 'healthy' group had BELOW RANGE freeT3. This is just glossed over as if it was nothing, but I wanted to know more. Below range is surely a very extreme and unexpected result.

Something I also quite liked about this paper is that in the discussion they go into more detail about the set of measures of metabolism they used, and end up casting some doubt on all of them. Their resting measure of metabolism doesn't seem to have any relation to day-long energy use, or to weight gain. But they don't make any overall comments about what this 'metabolism' they are measuring might be.

Still, I did find it interesting that they had such a range of measures, and so we're able to give some kind of quantitative, measurable quality to how much energy a patient has, whatever the actual true thing being measured was. This makes their study a bit more striking and firm in its claims than relying on self report, or more diverse symptoms to asses how hypothyroid someone is. This study is clearly showing that the 'euthyroid' patients are more unlike the controls, and have less energy than the suppressed patients. Also interesting that fT3 correlated best out of the 3 thyroid panel tests with general energy levels.

I do find the use of the term 'euthyroid' in this paper quite creepy. It's used to refer to the Levothyroxine patients who do not have suppressed TSHs. But it's never used to refer to the healthy controls, even though it surely should describe them just as accurately. It suggests that being euthyroid is some kind of ghostly state of being misled by doctors into a ridiculously low dose and low fT3, and living a shadow existence. And all because of the arcane worship of TSH!