82 Matching Annotations
  1. Aug 2019
    1. Magnesium reduces the intensity of addiction to opiates and psychostimulants (cocaine, amphetamine, nicotine, and others). It also decreases the auto-administration of cocaine and the relapse into cocaine and amphetamine intake, as well as reducing the experimental addiction to morphine, cocaine and other substances in animals. In heroin addicts, alcohol consumers and other drug abusers, the plasma and intracellular magnesium concentration is lower compared to healthy subjects.

      Precisely what I'd expect. However, I was hoping to find a placebo controlled trial. I'm nearly certain that magnesium show benefit. I'm less confident that such studies will use adequate doses of magnesium for the effects to reach statistical significance.

  2. Jun 2019
    1. But, if you take a supplement containing 1,250 milligrams, your body seems to realize that’s too much—and so, clamps down on absorption at the intestinal lining level, and you end up absorbing less than half.

      (see 45 seconds into video)

      This could be very handy for lowering the pH of the gut (increasing the acidity). As explained in other Greger videos, an acidic gut is desirable because good gut bacteria produce acids and thus are the bacteria that thrive in an acidic environment.

      Currently, I'm taking magnesium citrate, and my concern is that the unabsorbed magnesium is alkalinizing my gut. Vitamic C should be able to counteract this if it is indeed an issue.

  3. May 2019
  4. Mar 2019
    1. SBP, DBP, RR, and weight did not change following T3 administration

      Liothyronine does not raise blood pressure despite the rise in heart rate. The reason that respiratory rate (RR) was not changed may be because the increased cardiac output compensates for the increased oxygen demand.

    1. Each test salad contained 48 g spinach (Spinach; Dole Food Company), 48 g romaine (Hearts of Romaine; Fresh Express), 66 g shredded carrots (Shredded Carrots; Dole Food Company), and 85 g cherry tomatoes

      This doesn't sound like adequate protein to stimulate bile. Therefore, this study does not elucidate whether fat is necessary for lipid soluble nutrient absorption. Nevertheless, it does show that fat is sufficient.

    1. The amount of dietary fat consumed with the hot meal (3 or 36 g) did not affect the increases in plasma concentrations of vitamin E (20% increase with the low-fat spread and 23% increase with the high-fat spread) or alpha- and beta-carotene (315% and 139% with the low-fat spread and 226% and 108% with the high-fat spread).

      This is some of the better evidence that fat is not necessary for lipid bioavailability. I'm trying to find out if bile alone is sufficient.

    1. A single-dose bioavailability study was performed using three commercially available milks (unfortified whole milk and whole and skimmed milk fortified with vitamins A and E).

      They also gave 10 biscuits (full text). This could potentially destroy the entire premise of the study. They estimate that the entire meal contained between 6 and 20 grams of fat, depending on which milk was given. Skimmed milk contains 0.2% fat, so 430ml provides less than a gram. Therefore, the skimmed milk group obtained most fat from the biscuits. Six grams is certainly enough to substantially enable bioavailability.

    1. CONCLUSION: HSP could have the ability of antifatigue and improve the immunomodulation effect in mice.

      I'd like to see a trial of hemp protein for chronic fatigue syndrome.

    1. CONCLUSION: Tolerance to famotidine occurs during continuous administration for 14 days, as previously shown in ranitidine studies.

      This is good for my purposes. It means high doses can be taken for brain effects without disturbing stomach acidity. The question remains, of course, whether coinciding CNS tolerance develops.

    1. We have previously shown that antinociceptive effects of morphine are enhanced in histamine H1 receptor gene knockout mice.

      H1 antihistamines enhance the opioid high in humans. Hospitals sometimes administer antihistamines in combination with opioids. It's not hard to find people online who are using this combination recreationally.

    1. Especially at 250°C, lignans were degraded rapidly in sesame seeds and rye but not in flax seeds.

      Cool. That's about 480 Fahrenheit, which is over a hundred degrees more than I roast my flax (350F). However, they only roasted for three and a half minutes (from full text), compared to the 10 minutes that I use. Nevertheless, heat sensitive degradation tends to be logarithmic, so I'd likely still be fine if I cooked it for an hour (at least for lignans. The omega-3 would probably oxidize, though)

    1. The median exposure to coal tar ointments was 6 months

      At first glance I thought that this study was useful, but I'll need to examine the time frame more closely. Six months after initial use may not be enough time for cancer to develop, so to be useful it should be 6 months of use years ago. I'll have to look at smoking studies to get a better sense of how to interperet the data.

    1. RESULTS: We observed that poor sleep quality was correlated to low total BMD and legs BMD in middle-aged women after adjusting for potential confounders. Furthermore, when we reran the regression models based on menopausal status in middle-aged women, significant associations between BMD and sleep quality were observed in premenopausal and early postmenopausal groups.

      This is exactly what I expected to find. This is why I doubt that there is significant't risk to high dose T3 taken in the morning. In fact, given that hypothyroidism is also associated with increased fracture, I'm inclined to think that thyroid hormones per se play no role whatsoever, but rather the downstream effects.

    1. The peak T3 concentration after LT3 administration during week 6 was 292.8 ± 152.3 ng/dL, rising from a baseline value of 96.1 ± 7.6 ng/dL

      The T3 half-life, therefore, is only 14.25 hours (14 hours and 15 minutes). I calculated this based on taking the peak value and comparing it to the baseline value 22 hours later.

      Since they've been on the same dose during this study period, the baseline value is what's left from yesterday's peak, and can be assumed to be tomorrows trough. Since the drug took 2 hours to peak, there are 22 hours remaining to reach trough/baseline values.

  5. Jan 2019
    1. Clonidine is associated with diminished susceptibility to hypocapnic central apnoea without significant effect on ventilation or upper airway mechanics.

      In other words, clonidine elevates CO2. I'm not yet sure whether this is a good thing.

    1. naltrexone in their drinking water (5 mg/L)

      Based on water intake of 10ml per 100g body mass, that should translate to 0.5 mg/kg. This is one of the few studies using LDN as opposed to ULDN.

    1. ConclusionsThese findings suggest that in patients with HF, sodium intake plays a role in the pathogenesis of SA.

      The question remains, then, for the general population with SA.

    1. CONCLUSIONS: These findings suggest that pharyngeal edema contributes to sleep-disordered breathing in obese patients with severe OSA, hypertension, and diastolic heart failure. Upper airway edema may contribute to the frequent occurrence of OSA in patients with heart disease.

      I suspect it also plays a role in UARS. This study probably selected people with heart failure because the fluid retention leads to a more dramatic response. Hypertension was likely a neccesary ethical consideration. Hypotension is common in UARS; therefore, one is unlikely to find a study administering diuretics to UARS patients. That leaves correlation as the only tool available to confirm this suspicion.

    1. Given parenterally in dosages sufficient to produce clear-cut increases in the metabolic balances, neither norethandrolone nor nandrolone produced any significant effects on independently measured synthesis or degradation of albumin.

      That is rather unfortunate. It appears rather dificult to have in impact on albumin metabolism.

    1. inverse agonist activity was not required for mu-opioid receptor up-regulation and supersensitivity.

      The question, then, is whether the opioid receptors are involved at all in this upregulation. For example, it could be mediated by TLR4 or filamin A.

    1. studies after administration during the day. Full daily doses of both drugs should be prescribed in nocturnal dosing regimens, and not in divided doses over the day, for avoiding excessive sedation and performance impairment.

      A sound argument. This possibly could increase the antidepressant action as well.

    1. Table 1. Analgesic potency of nalorphine compared with morphine for postoperative pain*

      2 mg appears most effective. download PDF here.

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    Annotators

    1. . Ultra-low doses of opioid antagonists (naloxone and naltrexone), which selectively inhibit the excitatory effects

      I would not expect doses this small to impact the opioid receptors.

    1. Treatment effects were more pronounced at discharge

      Symptoms in the treatment group continually improved, whereas symptoms in the placebo group plateaued. Thus, I'm interested in seeing a longer treatment period. Projecting from symptom scores, elimination of symptoms would occur in about 10 days.

    1. RESULTS: At night (sleep), HR, mean arterial blood pressure and diastolic blood pressure were significantly higher in CFS patients as compared with controls (p < 0.01). During daytime, HR was significantly higher among CFS patients (p < 0.05), whereas blood pressures were equal among the two groups.

      I find the increased nighttime blood pressure suprising. Increased heart rate, on the other hand, is exactly what I might expect. Given that it is diastolic pressure that is elevated, I take it that the increased heart rate is the cause. If not, it could be that a stressor, like a hypopnea, is the underlying cause.

    1. 50 mg naltrexone at bed-time.

      Interesting. Conventional doses of naltrexone appear effective for sleep apnea. I'll be interested in seeing if LDN fairs well.

    1. Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2

      I've found elsewhere that mu agonism combined with delta antagonism provides analgesia while minimizing tolerance.

  6. Nov 2018
    1. The proportion of women with UARS is also significantly higher than for OSAS

      This further supports the link to ME/CFS. The ratio in the referenced study is about 2.5 to 1: female to male.

    2. The most frequent symptoms are excessive daytime sleepiness, fatigue and sleep fragmentation. However, UARS patients also present significantly more often with sleep-onset and sleep-maintenance insomnia, postural hypotension, headaches, gastroesophageal reflux, irritable bowel syndrome, anxiety and alpha-delta sleep

      This makes Upper Airway Resistance Syndrome a prime suspect for ME/CFS. I presents many of the same symptoms, and may be the instigating factor. That does not mean, however, that UARS is the only cause, nor that treating UARS is necessarily sufficient to treat ME/CFS; a feedback loop may mean that other factors must be attended to.

    1. Nimodipine controlled the escalation of the morphine dose in 9 patients (65%), and placebo in 4 (28%), the difference being statistically significant (P=0.03). The dose of morphine was reduced from 313±52 to 174±33 mg/day (P<0.001) in the nimodipine group, and from 254±26 to 218±19 mg/day (not significant) in the placebo group.

      Nimodipine reduced morphine dose in already tolerant patients.

    1. The entire article is begging the question. Is there strong evolutionary pressure in favor of intelligence? Is stupidity, like shortness, adaptive? Modern data shows that intelligence impedes reproductive success. Therefore, there is a strong burden of proof on those suggesting that intelligence was ancestrally adaptive.

    1. The full text describes how ultra-low-dose naloxone and naltrexone enhance opioids at very slim dose margins. A mere two fold difference on naltrexone dose can determine efficacy: 2 micrograms is effective whereas 4 is not. What's more, this optimal dose changes with sex, mouse strain, opioid agonist used, etc.; this making precise dosing challenging. The mechanism suggested is that filamin A has two binding sites, where only 1 has the desired effect.

    1. We measure the binding affinity of NLX or naltrexone to FLNA in cell membranes as 4 picomolar, i.e. approximately 200-fold higher than their binding affinity for MOR

      This sentence appears to indicate equal potency between the two drugs.

    2. Naloxone binding to A7 cells was displaced by naltrexone but not by morphine, indicating a target distinct from opioid receptors and perhaps unique to naloxone and its analogs.

      So, naloxone has a 200 times higher potency at Filamin A compared to opioid receptors, but I need clarification on whether naltrexone achieves similar potency.

    1. The nutritional supplement ingestion for 3 weeks was found to increase serum GH levels with 70% relatively to placebo, whereas circulating IGF-I levels did not change.

      Niacin does not appear to elevate IGF-1.

    1. HGH response to clonidine was not correlated with plasma levels of noradrenaline, serum cortisol, free fatty acids, or blood glucose.

      That's surprising, but it does not necessarily mean that the mechanism is not the lowering of FFAs. Clonidine does lower FFAs, but individual responses to FFA reduction may vary in magnitude.

    2. In this test, endogenous depressives showed a significantly reduced HGH response to clonidine as compared to normal controls, neurotic-reactive depressives, and schizophrenics. However, no differences were found between the endogenous depressives and a group of schizoaffective patients.

      It's possible that this is related to the hyper-vigilance observed in depressives.

    1. CONCLUSION: This meta-analysis confirms a medium effect (SMD = 0.62) of sleep deprivation on pain perception. As this meta-analysis is based on experimental studies in healthy subjects, the clinical relevance should be clarified.

      I'll have to look at this meta-analysis more closely, but they are likely looking at total sleep deprivation for one night, or partial sleep deprivation for one or several nights. Partial sleep deprivation tends to deprive more REM sleep via early awaking. I'd expect the greatest effect from SWS deprivation.

  7. Oct 2018
    1. HFT increased lean mass by 1.06 kg ± 1.78 kg, (1.9%), and LFT increased lean mass by .99 kg ± 1.31 kg, (2.0%). HFT strength improvements on the chest press was 9.07 kg ± 6.33 kg, (11%), and hack squat 20.16 kg ± 11.59 kg, (21%). LFT strength improvements on chest press was 5.80kg ± 4.26 kg, (7.0%), and hack squat 21.83 kg ± 11.17 kg, (24 %).

      Those standard deviations look way too high. Two standard deviations out, people are getting weaker. In other words, it looks like they are using group mean and standard deviation as opposed to individual change before and after. In yet other words, the study is under-powered and useless. It looks like HFT is better.

    1. SWS was generally not affected. It is concluded that beta 1 neurotransmission is directly involved in the regulation of PS.

      Full text summary: Beta 1 but not beta 2 is involved in REM sleep generation. High dose propranolol (which is not selective) practically obliterated REM sleep. Selective beta 1 agonism restored REM, while selective beta 2 agonism did not.

    1. Likewise, the significant (P<0.01) increases in mean cross-sectional area (and total muscle volume) were equal in both groups. Finally, strength increases were identical for both groups (PT=25% and NA=26% improvement). The results of this study suggest that muscle rebuilding – for example, hypertrophy – can be initiated independent of any discernible damage to the muscle.

      No benefit of pain.

    1. CONCLUSIONS: After 9 wk of training, the gains in both isometric and dynamic lifting strength were similar for the two arms. A single bout of damaging eccentric work did not enhance the response to conventional strength training and significantly compromised strength gains for several weeks.

      Pain = less gain.

    1. CONCLUSIONS: These data demonstrate improvement in FM-related sleep dysfunction with pregabalin therapy. The majority of this benefit was a direct effect of pregabalin on the patients' insomnia, while the remainder occurred through the drug's analgesic activity.

      Since the pain is caused be SWS interference, it might be difficult to disentangle cause and effect.

    1. Low BP was more prevalent in subjects with upper airway resistance syndrome (UARS) (23%) than in subjects with obstructive sleep apnea syndrome (OSAS) (0.06%), parasomnia (0.7%), restless leg syndrome (0.9%), or psychological insomnia (0.9%).

      That's an extremely high rate of hypotension in UARS. This may be what I have. If UARS causes hypotension, then sleep apnea (SA) may be different because of its link to obesity.

  8. Sep 2018
    1. Ritanserin, 5 mg, produced a substantially larger increase in SWS (51.4%) than either ketanserin, 20 mg (17.2%) or ketanserin, 40 mg (24.4%). Ritanserin has a significantly higher affinity than ketanserin for 5-HT2C receptor binding sites in the human brain and, based on estimates of per cent occupancy by the two compounds at brain 5-HT2A and 5-HT2C receptors, we conclude that SWS in humans is primarily regulated by 5-HT2C receptors.

      This doesn't quite clarify the effect of 5HT2C antagonism in the absence of 5HT2A antagonism.

    1. The use of a prospective sleep diary measure in patients with a psychiatric disorder is recommended.

      I notice that their study does not support their conclusion in the slightest. Firstly, the study does not actually show that a sleep diary is more accurate than the Pittsburgh Sleep Quality Index (PSQI). Secondly, the PSQI may be picking up sleep quality metrics that are hard to measure. Lastly, what matters is subjective experience, so, franky, F*** them for arbitrarily deciding what is a good sleep measure.

    1. Analgesia obtained when 10 mg of morphine was combined with 100 mg of hydroxyzine was significantly superior to that obtained with morphine alone.

      It is interesting to note that they report potentiation of 10mg but not 5mg of morphine. Thus, it is possible that antihistamine potentiation is dependent on dose of opioid, or that antihistamines raise the analgesic ceiling. That is to say, antihistamines may raise the maximum possible effect from opioids without raising the effects of lower doses much. However, antihistamine combination did tend to enhance the effects of lower dose morphine, but the effect was not as dramatic (therefore not reaching statistical significance in a study of this power).

  9. Aug 2018
    1. CONCLUSIONS: These findings suggest that higher standing BP is a biomarker that helps identify persons with combat PTSD who are likely to benefit from prazosin. These results also are consistent with α1AR activation contributing to PTSD pathophysiology in a subgroup of patients.

      This is precisely the results I would expect. However, I completely disagree with their interpretation.

      People with high blood pressure (BP) can tolerate a reduction in BP without instigating compensatory mechanisms. People with normal or low BP would invoke compensation by the sympathetic nervous system in response to alpha blockade. This would counteract the depressant effects of adrenergic antagonism. Indeed, adrenaline and noradrenaline elevate in response to standing, which I find to be an obvious prediction. Thus, the lack of benefit from prazosin in these subjects may be mediated by an increase in adrenergic receptor activation other than the apha1-adrenoreceptor; in particular, the beta-adrenergic receptors are likely at fault. Propranolol, a beta-blocker, is used for PTSD, so this mechanism seems well substantiated.

      The study apparently found benefit for patients with BP over 110 (with more benefit for higher BP). Thus, I would conclude that systolic pressure below 110 induce compensation.

    1. Dizziness or lightheadedness may be more likely to occur in the elderly, who are more sensitive to the effects of phenoxybenzamine. In addition, phenoxybenzamine may reduce tolerance to cold temperatures in elderly patients.

      Increased sensitivity to cold by phenoxybenzamine could be the result of heat dissipation via peripheral vasodilation.

    1. In these two systems, the alpha 1 adrenergic receptor reappearance followed a monoexponential kinetic allowing to determine the half-life of the receptor (23h in vitro, 33h in vivo) as well as the rate of receptor synthesis and degradation.

      Thus, the effective pharmacological half life of phenoxybenzamine is roughly 1 day.

    1. Typical half-lives are greater than 20 hr, a turnover that is slower than that of several other classes of neurotransmitter and hormone receptors (9, 10, 12, 16).

      This is rather fast. It means that tolerance and withdrawal should develop relatively rapidly. This is consistent with the "first dose effects" observed with alpha blockers.

    1. Prazosin had no analgesic effect alone but dose-dependently potentiated morphine analgesia in morphine-naive mice. Another alpha(1)-adrenoceptor antagonist, corynanthine, had similar effects. Prazosin also increased the analgesic potency of the morphine test dose in morphine-tolerant mice. Naloxone-precipitated vertical jumping was not affected, but weight loss was reduced by prazosin. Acutely administered clonidine potentiated morphine analgesia and alleviated opioid withdrawal signs, as expected. We conclude that in addition to the already established involvement of alpha(2)-adrenoceptors in opioid actions, also alpha(1)-adrenoceptors have significant modulatory role in opioid analgesia and withdrawal.

      This is interesting but not exactly surprising, given that both are depressants. What is surprising, however, is the contrast between this and the fact that stimulants also enhance morphine analgesia.

      Potentiation of Opioid Analgesia by Psychostimulant Drugs: A Review00084-0/fulltext)

    1. Graph 2 shows the trend for the diastolic pressure.

      Post-exercise, diastolic pressure is higher than baseline; compression garments exaggerate this effect

    2. Graph 1 shows the systolic pressure data (x-axis in mmHg). It can be noted that the test subjects start from an equal baseline condition, but after performing the swimming test the athletes not wearing the costume in the first control (20-30 mins) have an average systolic pressure that has dropped to approximately 90 mmHg.

      Thus, compression garments may prevent circumstantial hypotension. In this case, one possibility is that the compression is delivering blood to the heart that would otherwise be shunted to the skin for heat dissipation.

    1. Figure 1c. Temperature before and after T3 administration (T3 given at time 0 hours)

      It appears that the liothyronine could have advanced the the phase of circadian temperature. However, since the study had no controls, it is impossible to confirm this hypothesis. Additionally, the day temperature dropped was the same day that TSH returned to normal; though, it could be that some of the apparent drop in TSH was actually a phase advance of TSH circadian rhythm.

    1. Table 2

      These trained athletes have a BP of about 100/60 at rest. This is substantially lower than the roughly 120/80 BP that I've seen elsewhere. This likely limits the drop in BP seen post-exercise.

    1. Hypertension also affects brain capillary density. Similar to the peripheral microcirculation, hypertension causes rarefaction (decrease in number) of capillaries and impaired microvessel formation that can increase vascular resistance

      This is important because it implies that syncope or incomplete syncope as a result of vasodilators may not be dependent on actual blood pressure. It means that it is theoretically possible that vasodilators will acutely increase blood flow despite a drop in BP, depending on the body's level of compensation via increased cardiac output.

    1. Although atenolol had no effect on subjective measures of sleep this hydrophilic drug also reduced REM frequency, suggesting that either it has some central effect, or that REM reduction is due to a peripheral 'shielding' effect.

      Alternatively, it could have been nocturnal hypotension that was causing the sleep disruption.

    2. Analysis of the subjective questionnaires showed that recollection of dreaming and awakening in the night was increased by the three lipophilic drugs, propranolol, metoprolol, and pindolol. These results confirm reports in the literature but are contrary to those expected from considering the effects of noradrenaline on sleep. Analysis of physiological records confirmed subjects' reports that waking was increased by the lipophilic drugs. Dreaming (rapid eye movement sleep, REM) was reduced, as predicted from knowledge of the effect of noradrenaline on sleep. Increased awakening leads to an increase in remembered dreaming which explains the otherwise paradoxical results.

      Surprisingly, beta-blockers, unlike alpha-blockers, appear to impair sleep.

    3. These results confirm reports in the literature but are contrary to those expected from considering the effects of noradrenaline on sleep. Analysis of physiological records confirmed subjects' reports that waking was increased by the lipophilic drugs. Dreaming (rapid eye movement sleep, REM) was reduced, as predicted from knowledge of the effect of noradrenaline on sleep. Increased awakening leads to an increase in remembered dreaming which explains the otherwise paradoxical results.

      Surprisingly, beta-blockers, unlike alpha-blockers, appear detrimental to sleep. I would speculate that this could be the result of a shift in autonomic tone, similar to how caffeine tends to lower heart rate.

    1. Furthermore, no significant relationship (correlation coefficient: r < 0.3) was observed between beta 1 receptor occupancies of the drugs and the number of dreams. On the other hand, good relationships (r > 0.95) were observed between central and peripheral beta 2 or central 5-HT receptor occupancies and the number of dreams. These findings suggest that beta 2 and/or 5-HT receptor occupancy is superior to beta 1 receptor occupancy as an index for the sleep disorders.

      This suggests that a beta 2 agonist may be appropriate for sleep.

      Note: they appear to be talking about the number of dreams recalled (due to awakenings) rather than the actual number of dreams.

    1. These results suggest that the combined use of mirtazapine mirtazapine Antagonist at: histamine, 5-HT2a/c, 5-HT3, a2(adrenaline. autoreceptor included) and prazosin may be a potentially effective treatment to attenuate induction and expression of locomotor sensitization to cocaine.

      Presumably, this is just a result of blocking some of the effects of cocaine to begin with.

    1. AbstractHigh dose thyroid hormone has been in use since the 1930s for the treatment of affective disorders. Despite numerous papers showing benefit, the lack of negative trials and its inclusion in multiple treatment guidelines, high dose thyroid has yet to find wide spread use. The major objection to the use of high dose thyroid is the myth that it causes osteoporosis. This paper reviews the literature surrounding the use of high dose thyroid, both in endocrinology and in psychiatry. High dose thyroid does not appear to be a significant risk factor for osteoporosis while other widely employed psychiatric medications do pose a risk. Psychiatrists are uniquely qualified to do the risk-benefit analyses of high dose thyroid for the treatment of the bipolar I, bipolar II and bipolar NOS. Other specialties do not have the requisite knowledge of the risks of alterative medications or of the mortality and morbidity of the bipolar disorders to do a full risk benefit analysis.

      This is all very interesting. It is also true that, in the treatment of depression, there is a relatively low dropout rate due to side effects from treatment with T3 (liothyronine).

      liothyronine (T3) augmentation in the treatment of depression

  10. Jul 2018
    1. Mg Citrate 0.26 ± 0.02 0.32 ± 0.03   0.33 ± 0.04*

      Interestingly, the superiority of magnesium citrate over other forms is most evident in salivary excretion, both acute and chronic. In particular, I had been led to believe that amino acid chelate was superior. Given that these results are consistent superior plasma levels, I take this to be reasonable evidence that the citrate form is superior for a given value of elemental magnesium. In this case, 300mg elemental Mg.

  11. Jun 2018
    1. Studies reported by Nicoloff and colleagues in 1972 calculated a half-life of T3 that varied with thyroid status (8). The mean half-life was 0.63 days in 7 hyperthyroid patients, 1.0 day in 8 euthyroid individuals, and 1.38 days in 9 hypothyroid patients.
  12. May 2018
    1. Two patients complaining of insomnia had sleep-related periodic leg movements (nocturnal myoclonus) on polysomnographic evaluation. Both also complained of cold feet and had abnormal peripheral pulse examinations. Treatment with phenoxybenzamine, alpha-adrenergic blocker, normalized the peripheral pulse responses, reduced the complaint of insomnia, and reduced the sleep related leg movements but resulted in only mild sleep improvements. Peripheral pulse examinations of ten other patients with sleep-related periodic leg movements revealed abnormal responses in four. From these and other results, it is hypothesized that the sympathetic nervous system may mediate the periodicity of sleep related periodic leg movements.
  13. Apr 2018
    1. There was a boy who was born with congenital hypothyroidism and was raised on traditional T3 (Cytomel). He was never treated with a T4-containing medicine, and so essentially never had a molecule of T4 in his body. By age 26 he had developed normally with no problems.

      This is precisely the type of information I was looking for. Wikipedia implied T4 should be taken with long-term T3, but the reasoning was poorly explained. However, I'd like a more official source for this case report.

      This case would also express no rT3 (reverse-T3). Thus, it appears that neither T4 nor rT3 serve any vital functions.

    1. Naloxone alone has a bimodal effect on analgesia: low intravenous doses (1–2 mg) produce analgesia and higher doses (3+ mg) produce hyperalgesia in healthy normal volunteers (Buchsbaum et al. 1977) and in postoperative patients (Levine et al. 1979). Clinical trials showed that intravenous and epidural opioids combined with naloxone could produce greater analgesia than opioids alone (Rawal et al. 1986; Gueneron et al. 1988; Gan et al. 1997); these studies revealed the importance of the ratio of opioid agonist to antagonist in enhancing analgesia, showing ultra-low naloxone doses (ng/kg to pg/kg) are needed for optimal effect.

      Standard LDN is 4.5mg. According to this data, that may be orders of magnitude too high. Nevertheless, LDN has been found effective.

  14. Jan 2018
    1. Our findings indicate that equol diminishes estrogen-dependent tissue responses in apoE-null mice.

      I've not yet found the impact of equol on estrogen alpha and beta. The benefits in epidemiological research suggest it is likely similar to other phytoestrogens; partial antagonist at the alpha receptor and agonist at the beta receptor.

  15. Dec 2017
    1. Vegans had higher testosterone levels than vegetarians and meat-eaters, but this was offset by higher sex hormone binding globulin, and there were no differences between diet groups in free testosterone, androstanediol glucuronide or luteinizing hormone.

      In other words, vegans have higher total, but not free/unbound, testosterone.

    1. Supposedly, Tianeptine, in contrast to other anti-depressants, stimulates release of neurotransmitter dopamine in nucleus Accumbens, that probably determine addictive potential of this drug.

      This potentially explains why tianeptine gives me energy. I've seen several other anecdotal reports as well. However, I've never taken illicit or prescription opioids, so I don't have a proper mode of comparison.

    1. Gender socialization can direct some men to withhold or restrict emotional expression, leaving men with limited ways to express their feelings of emotional pain and psychological distress.

      ... Or not. It's just as likely, if not more likely, to be biological. Unless there has also been a sex-specific bias in autism diagnosis, it could just as easily be argued that men's autistic personalities cause this effect

  16. Nov 2017
    1. Vegans had the highest intakes of fibre, vitamin B1, folate, vitamin C, vitamin E, magnesium and iron, and the lowest intakes of retinol, vitamin B12, vitamin D, calcium and zinc.

      Of note, vegans consume more iron. Since non-heme iron absorption is regulated (i.e. titrated in proportion to stores), this does not mean vegans absorb more iron. Importantly, however, it does translate into no greater risk of anemia for vegans as compared to meat eaters.

  17. Oct 2017
    1. basal testosterone (1.95 ng/ml)

      i.e. 195 ng/dl, or 6.8 nmol/l. This is not extraordinary, as it is roughly the 2.5th percentile of normal testosterone for most ages.

    2. It is concluded that the severe cholesterol deficiency of this patient did not impair the capacity of the testes to synthesize testosterone. However, the LH/hCG receptor or its subsequent message was activated neither in vivo nor in vitro.

      This supports other evidence, such as the fact that vegans, despite their lower cholesterol, have higher total testosterone.

    1. We show that total testosterone peaks [mean (2.5–97.5 percentile)] at 15.4 (7.2–31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5–97.5 percentile)] to 13.0 (6.6–25.3) nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age. However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years. This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism.

      The remaining question is whether those with high testosterone in old age are the same as those with high testosterone in youth. That is to say, does testosterone diverge proportionally from the mean as one grows older, or are there other factors at play?

    1. Beta blockers have long been associated with sleep disturbances such as difficulty falling asleep, staying asleep, and insomnia. They have been shown to reduce the production of melatonin via specific inhibition of beta-1 adrenergic receptors. Melatonin is a hormone secreted by the pineal gland in the brain, and helps in maintaining normal circadian rhythms.6,20-21 People with hypertension already have a lower melatonin production rate than those with normal blood pressure.22

      The question becomes, then, do beta blockers impair sleep when exogenous melatonin is administered concurrently?

    1. A randomized, placebo-controlled, double-blind, cross-over study6 involving 16 patients with insomnia confirmed by polysomnography demonstrated no effects on sleep efficiency after a single 600-mg dose of the valerian extract Sedonium, while multiple doses over 14 days resulted in significant improvement in parameters of slow-wave sleep measured by polysomnography. There was a nonsignificant trend toward reduced subjective sleep latency after the long-term valerian treatment.6

      It appears that valerian may, after all, be beneficial for sleep when taken consistently. Personally, this in combination with the traditional use of valerian, and that valerian is likely harmless, is sufficient to merit use a recommendation (though emphaticism should be kept to a minimum). Additionally, the cases of contraindication (mentioned in another paragraph) could significantly enhance the magnitude of these results for those whom it worked. Those to whom it is contraindicated can self-select out of using valerian. In the context of a study, the remaining subjects should be re-randomized. For general application, valerian should be recommended to everyone, arming them with the information that it may be useless or detrimental for some people.