14 Matching Annotations
  1. Nov 2020
    1. Fig 1

      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.

    1. Curcumin, but not fish oil, reduces postprandial glycaemic response and insulin demand for glucose control.

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

  2. Apr 2020
    1. RESULTS: The rate of discontinuation due to side effects was significantly higher in the control group than for the patients (38% versus 0%). The severity of the side effects in the controls increased significantly during treatment with T(4). The side effect scores of the patients were higher than those of the controls prior to T(4) treatment, but did not change significantly during the treatment period. Although the serum concentrations of thyroid hormones rose significantly in both groups, concentrations of fT(3) and fT(4) were significantly higher in the controls.CONCLUSIONS: Healthy controls and depressed patients respond significantly differently to supraphysiological T(4). Healthy controls experience higher elevations of thyroid hormones in response to supraphysiological T(4), thus inducing significantly more side effects and discontinuation.LIMITATIONS: Open-label study; groups were studied at different times; in contrast to healthy controls, depressed patients were also taking antidepressants.

      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.

    1. REE decreased approximately 15% when TSH increased between 0.1 and 10 mU/L.

      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.

  3. Mar 2020
    1. The mean percentage removal of stains for test group was significantly higher than control group.

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

    1. l-thyroxine was added in the dose of 100 microm daily for 4 weeks.

      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)

    1. The addition of supraphysiologic doses of L-T4 (300 mcg per day) to an otherwise stable medication regimen of standard treatments resulted in a significant decline in depression scores during the 6-week, double-blind treatment phase. At endpoint (week 6), the mean HamD score showed a group difference of 3.7 points in favor of L-T4. Such difference is generally considered to be clinically meaningful in a short-term treatment trial for major depression. NICE used a 3.0-point difference in HamD change scores as a criterion of clinical significance.27

      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.

    1. L-thyroxine at an average dose of 350 micro g/die. Outcomes were moderate in 39.3% and very good in 21.5%, corresponding to 21-item HAMD scores of < or =16 and < or =8 and clinical judgement. Of all patients, 39.3% had to stop treatment due to nonresponse or side effects.

      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).

  4. Jan 2020
    1. RESULTS: Two patients dropped out of the study owing to side effects. The remaining 7 patients received a final mean dose of T4 of 235 +/- 58 micrograms/day (range: 150-300 micrograms/day). Their scores on the Hamilton Depression Rating Scale had fallen from a mean of 21.1 +/- 4.1 before inclusion in the study to a mean of 8.0 +/- 2.8 at the end of the 8th week. Five patients were full responders, 1 a partial responder, and 1 a nonresponder.CONCLUSIONS: Augmentation with high-dose T4 proved to have an antidepressant effect in more than 50% of the previously treatment-resistant patients with chronic depression and/or dysthymia.

      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.

    1. Thyroxine was added to their antidepressant medication, and the doses were increased to a mean of 482 ± 72 μg/day.

      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).

    1. RESULTS: In the hypothyroid state, the plasma volume measured by dilution of 125I-albumin (APV) was higher than the calculated plasma volume (CPV) from packed red cell mass, suggesting an extravascular escape of albumin. After substitutive therapy, the CPV showed a statistical increase (P < 0.05), whereas APV remained unchanged. Both ERPF and GFR increased after thyroxine therapy (p < 0.05). In the subclinical group, blood volumes and renal function were similar to those found in the other group of patients when in the euthyroid state.

      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.

    1. 22.3 per cent (−10.7; 95% CI, −15.6 to −5.7) in the diet group

      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.

    2. Sleepiness and neck circumference were significantly reduced only in the diet group (p = .007 and p < .001 for the time × group interactions, respectively).

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

  5. Dec 2019
    1. The sodium-restricted diet group received a regimen aiming a maximum intake of 3 g of sodium per day (equivalent to 7.5 g of sodium chloride).

      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?