That's a substantial fraction of the 11 point lower blood volume in ME/CFS found in one study. Moreover, this was achieved with only 13 days bed rest. I can only imagine the long-term effects of a sedentary lifestyle. It's likely that this is the primary cause of most ME/CFS. Nonetheless, exercise is unlikely to be the optimal treatment.

Note that, though folate and B12 were given IV before and after surgery, it did not have an immediate effect. The NO induced rise in homocysteine was not blunted by the end of surgery. However, postoperative homocysteine was lowered to below baseline on all 3 measurement days. The NO induced rise in homocysteine lasted 2 days postoperatively.

Unsurprisingly, this suggests a lag time between B vitamin administration and homocysteine drop. Thus, what I'd really like to see is a study administering B vitamins 1 day prior to NO use.

This backs up the two studies on fasting glucose in diabetes and per-diabetes. It is also a higher quality study (crossover design).

Brilliant study. Astonishingly, ~500 mcg thyroxine only increased FT3 about 20% in depressed patients. In controls, it nearly doubled FT3 (about 80# increase), Thyroxine doubled total T4 and total T3 in both depressed and controls. That lines up with the FT3 rise in controls, but is still much lower than I'd expect from this dose.

Note that the depressed patients had equal thyroid symptoms before taking thyroxine, so experienced no increase. The pre-treatment depressed patients, treated depressed patients, and treated controls all had an equal number of thyroid symptoms. Thus, only the pre-treatment healthy patients lacked hyperthyroid symptoms. This is interesting because the treatment was 500 mcg thyroxine (average 484 mcg), which you'd expect to cause more symptoms.

This could mean either that the depressed patients had as many symptoms alleviated as they had caused by thyroxine, or that depressed patients simply had lower thyroidergic activity. The latter is supported by the fact that free T3 and free T4 rose 2 or 3 times less in treated depressed patients compared to treated controls (from full text).

It's also possible that the pre-existence of symptoms masked their appearance (in which case increased severity might be expected). I doubt that this is the case. A few symptoms trended toward improvement.

The individual change in REE to a given change in dose varied radically. The dose change was only 50 mcg, which seemed to change TSH about half what they've calculated for 15% REE change. That is to say, it looks like a 50 mcg dose reduction will only raise TSH from 1.0 to 5.0, not to 10.0. This is my personal guesstimate, and will need to be properly calculated from other studies. My point is merely that 50 mcg will not cause the full 15% REE increase. Additionally, the response to 50 mcg may depend on initial TSH.

It looks like TSH changes that remained hyperthyroid (i.e. bellow 1.0) had little effect on REE. This might be because the body is maintaining thyroid status, or that REE is more like an on/off switch. However, this only covers relatively small changes in thyroxine dose.

It is unclear how supraphysiological doses effect REE. It seems likely that the ten times greater dose (500 mcg) used for depression would significantly increase REE.

Note that this was a two week study. It's hard to guess whether greater benefit would occur over longer periods.

This is the same dosage that another study found to be indiscernible from placebo. I suspect a couple things are at play.

The first is that these are treatment-resistant patients, meaning that we already know they are not susceptible to placebo; given that we are effectively comparing combination therapy to SSRIs alone, this means that the SSRI only stage is not experiencing placebo, thus making the therapeutic effect visible by comparison (retrospective comparison, given that there is no control group).

The second is that this is combination therapy. It seems likely that thyroxine is more effective when combined with SSRIs.

Note that this study uses much lower doses than similar studies I've seen, yet had similar results in terms of efficacy rate (roughly 50% responders). I'm not currently certain how the magnitude of effects compares with those studies. Namely, comparing with Pfeiffer et al (350 mcg), Rudas et al (235 mcg) and Bauer et al (482 mcg), and also Bauer et al from 2016 (300 mcg)

This is consistent with the open label data. The dose is also similar. Combining this placebo-controlled trial with the three open-label supraphysiological thyroxine studies that I've seen, that is sufficient for me to conclude efficacy. Namely, combining with Pfeiffer et al (350 mcg), Rudas et al (235 mcg) and Bauer et al (482 mcg)

I would like to see if this study mentions nonresponders. Those three other studies found roughly a 50% response rate. Thus, the effect size in responders may be twice as significant.

This is another study consistent with the 50% remission figure. The dose is also similar: between 235 mcg (Rudas et al) and 482 mcg (Bauer et al).

Thyroxine working in about 50% of patients was also found in Bauer et al. This dose was not quite as high as Bauer, but 235 mcg is still above a full replacement dose.

I'd like to see results on minor depression. However, such studies are unlikely.

This is the highest dose of levothyroxine that I've seen administered. Even treatment for thyroid cancer rarely goes beyond 300 mcg (or even 200 mcg, which is more common).

If this holds true, I'd expect rapid blood volume expansion from thyroid hormone. I'm also interested in whether thyroid hormone stimulates the production of albumin, given its anabolic properties.

Interesting that the diet group worked better. I'd like to see if it's statistically significantly better than the drug group. It's also worth asking whether sodium was the only important dietary change, or if avoiding sodium caused many other dietary improvements.

Fascinating. Neck circumference suggests that sodium intake may indeed be the significant dietary factor. The recommended diet wasn't even very restricted in sodium.

That sounds incredibly high to me. 3000 mg is the absolute maximum intake that could ever be considered 'low' sodium. Under 1500 is usually considered ideal. Would, then, a diet aiming for half the sodium be twice as effective?