Elize
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It differs from person to person. Night time doses keep me awake and give me restless legs
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Kenneth Blanchard On Optimal Hypothyroidism Treatment
- Thread starter Collden
- Start date
Of T4? Or T4/T3 mix? I've been taking T4 at night a few days, doesn't seem to disturb my sleep but also noted less, or slower effects when taken too close to dinner.
Elize
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Both T4 and T3 . I have Synthroid and Mylan Pharma T3.. T3 in my case is a Histamine liberator and activate Mast Cells. Why I tolerate small doses only.
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@Collden I thought that Dr Blanchard used to recommend the T4 to be taken 3 to 5 hours before bedtime. So everything here will be related to the time you are taking your dinner and the time you are going to bed. If all of the previous conditions match then you are in the ideal scenario initially described by Dr Blanchard: both optimal TSH suppression and sleep benefits. I found that a liquid T4 might be greatly superior to tablets and gel caps for optimum absorption with meal. In France, we have a liquid T4 product made by SERB (5mcg/drop) and a product called Tsoludose made by IBSA.
I lick the drops directly from a spoon, just at the end of my evening meal.
As for his recommendation for people with no sleep problem, I think that he often had a preference for taking the drug with food as to prevent the interactions between the synthetic hormone and its direct contact with the walls of the empty stomach.
If there is no problem with weight gain, food cravings or if the time of taking the drug is dictated by any medical reasons or food interactions then obviously the T4 can and must be taken before any food intake.
I lick the drops directly from a spoon, just at the end of my evening meal.
As for his recommendation for people with no sleep problem, I think that he often had a preference for taking the drug with food as to prevent the interactions between the synthetic hormone and its direct contact with the walls of the empty stomach.
If there is no problem with weight gain, food cravings or if the time of taking the drug is dictated by any medical reasons or food interactions then obviously the T4 can and must be taken before any food intake.
Compounding pharmacies are the way to go.
Dr Blanchard said that he used a ME4 binding resin with Avicell (microcrystalline cellulose) as a filler for his slow-release T3 formula.
You may find this website useful to search for compounding pharmacists in your region: www.iacprx.org
Elize
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- Joined
- Jan 25, 2016
- Messages
- 918
.
Thanks am aware of compounding. The problem is the microcrystalline cellulose. Foods cellulose and fillers in medications unfortunately liberate histamine and they can only use microcrystalline to compound slow release T3. Tried that before. Got severe hives and rashes. Taking the minute dose of T3 works better for me now.
Thanks am aware of compounding. The problem is the microcrystalline cellulose. Foods cellulose and fillers in medications unfortunately liberate histamine and they can only use microcrystalline to compound slow release T3. Tried that before. Got severe hives and rashes. Taking the minute dose of T3 works better for me now.
Sorry, I didn’t correctly interpret your question in the first place.
I thought that you were looking for a way to get a slow release T3 and what you are looking for is a slow release formula w/o fillers and food cellulose.
I can’t speak for compounding pharmacies in the US but the compounding pharmacy (In Italy) that I used to order my NDT from was able to switch from various fillers (including rice flour, lactose ect....) on specific request.
If you can’t get specific compounding for specific health conditions then the US compounding pharmacies are no more than useless.
I thought that you were looking for a way to get a slow release T3 and what you are looking for is a slow release formula w/o fillers and food cellulose.
I can’t speak for compounding pharmacies in the US but the compounding pharmacy (In Italy) that I used to order my NDT from was able to switch from various fillers (including rice flour, lactose ect....) on specific request.
If you can’t get specific compounding for specific health conditions then the US compounding pharmacies are no more than useless.
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Elize
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The compounder up the road from me used cellulose or pork gelatin. The cellulose used differs from batch to batch as it depends on what the buyers gets. In South Africa and Hong Kong I had injections. The US can't get such treatment
Amazoniac
Member
This is a good point, props for always questioning everything. Time-release formulations would allow you to get to a desired range with minimum imbalances (contrary to loading doses), but the proposed half-life of T3 is indeed confusing.
The best approach will depend on where is the weakness.
Part of the bloody decay is masked by baseline levels, but there's still activity. Below, they tested on subjects that couldn't maintain them and were relying on supplementation.
- (7.5) Pharmacokinetics in Drug Delivery | Elements of Chemical Reaction Engineering
The convention is k(OD), where 'O' is the compartment of origin and 'D' for destination. Since they're dealing with two compartments, it's k12 and k21.
The convention is k(OD), where 'O' is the compartment of origin and 'D' for destination. Since they're dealing with two compartments, it's k12 and k21.
- Pharmacokinetics of Liothyronine in Patients Undergoing Thyroid Hormone Therapy Withdrawal
"Previous characterization of LT3 PK has been performed by radioactive iodine tracer dilutions, mostly in healthy volunteers or in patients previously treated with LT4 (16,17,20). The models used to predict these data are required to make broad assumptions given the peripheral conversion of T4 and the residual secretion of endogenous T3, which may have affected the accuracy and precision of the model-derived PK parameters. When used, immunoassays were of first generation with limited sensitivity, further decreasing the accuracy and precision of the data. Finally, most of the studies used a pharmacologic dose of LT3. Recently, a PK study on what was believed to be an extended-release T3 formulation was performed by using a modern immunoassay. The study was conducted in healthy volunteers by using a fixed pharmacological dose of T3 (50 mcg) and indicated a Tmax of 2.5 hours with a Cmax of 422 ng/dL (38). Collectively, these limitations and confounders are likely responsible for the wide range of PK data, with a Tmax reported between 1.5 and 6 hours (20,22), and a half-life between 10 and 24 hours (16,20), respectively (Table 4)."
[38] Single Dose T3 Administration: Kinetics and Effects on Biochemical and Physiologic Parameters
"Our experimental model is unique because the study volunteers were devoid of endogenous thyroid hormone production and exogenous LT4 administration, and at the time of the PK studies had received a weight-based LT3 dose administered on a thrice-daily regimen (13). The PK studies were performed by using a dose that was close to the one commonly used for combination therapy, although higher than the one suggested by the ETA (26). This, coupled with the prolonged observation after the last dose, allowed us to assess terminal elimination and, ultimately, fully characterize the PK of LT3, which is explained as a two-compartment model with an early rapid distribution phase, and a slow elimination phase. Not surprisingly, the PK characteristics of LT3 as tested after withdrawal in a state of profound hypothyroidism are dramatically different from the ones observed at steady state. This expansion of the apparent volume of distribution is probably due to the overall decrease in metabolism and (possibly to a greater extent) to the net increase in availability of saturable binding sites after complete depletion of thyroid hormone."
10-hour intervals is messed up.
"The availability of PK data of LT3 at a low dose has also allowed us to generate a model to predict the changes in serum T3 concentrations and its excursions on various combination therapy modalities. The data indicate that a dose of 9.6 mcg on a twice-daily administration (for a hypothetical hypothyroid patient devoid of endogenous thyroid hormone production weighing 72.5 kg) will result in a rise of the average T3 serum concentration from 93 to 175 ng/dL with <15% of the time outside the range. We acknowledge that this modeling is theoretical, and we did not account for the changes in peripheral conversion of T4 into T3 as a result of LT3 administration. The deiodinase 1 (DIO1) gene is positively regulated by T3 (39), and presumably increased T3 levels would prompt T4 to T3 conversion in the liver and kidney. Conversely, the deiodinase type 2 is inhibited by thyroid hormone (40), and the local production of T3 from this enzyme would presumably decrease. Thus, empirical observations are necessary to validate the estimations obtained from this modeling."
"In conclusion, the data presented in this study demonstrate that the PK of LT3 is best explained by a two-compartment model that is characterized by a rapid distribution phase followed by a prolonged elimination phase. The data provide the rationale for using up to 0.07 mcg/kg twice daily to increase the total T3 levels by 50%, while maintaining the serum concentrations relatively stable with minimal excursions outside the reference range. This, in turn, can provide the basis to design intervention studies that are aimed at characterizing the relationship between modulation of serum T3 levels and end organ effects of thyroid hormone."
[38] Single Dose T3 Administration: Kinetics and Effects on Biochemical and Physiologic Parameters
"The pharmacokinetic parameters for total T3 are shown in table 3. The mean Cmax was 346 ng/dL and the mean time to maximum concentration (Tmax) was 2.5 hours. The mean AUC 0–24 hrs, corrected for baseline, was 1,860 ng.hr/dL. The half-life of the T3 preparation was calculated as 22 hours when the decline in T3 concentration between 2.5 and 94 hours was employed. The Cmax, Tmax, and AUC for T3 were unaffected by weight, height, BMI, and age when either Pearson or Spearman correlation coefficients were calculated (data not shown)."
"The Cmax of 346 ng/dL and Tmax of 2.5 hours for liothyronine documented in our study were both fairly similar to those reported by Watson (Cmax 422 ng/dL; T max 2.5 hours). Our Tmax was also similar to the value of 2.35 hours reported by Coastal Pharmaceuticals in their study of 100 mcg liothyronine (ANDA 90–097) (7)."
"Since blood is an intermediate compartment for distribution of T3 from the gut, the initial decline of blood levels of T3 following achievement of Cmax is partly due to further distribution of T3 to target tissues and hydrophobic sites, such as adipose tissue. The best explanation for the shape and duration of T3 blood levels over time as shown in figure 2a could be represented by multiple release rates from the gut into the blood. Otherwise, a linear loss of T3 from the blood following Cmax, and further distribution to other compartments, would be observed. A similar T3 profile to ours was predicted by DiStefano and colleagues based on oral administration of a single dose of T3 and use of a “two-compartment gut model” (9). This model was based on a study of T3 administration in euthyroid individuals (5)."
"Calculation of T3 half-life in the blood may also be complicated by distribution from the blood into other compartments and re-distribution back into the blood. Thus, the apparent half-life of T3 in the blood depends on the choice of time points for the calculation. For example, an average half-life of 22 hours can be calculated, but a maximum half-life of 71 hours can be calculated from the decline of T3 in the blood between 48 and 72 hours. As stated earlier, this product was thus shown not to have an extended serum half-life compared with the similar 24-hour half-life of currently available T3 preparations."
"Most studies, such as bioequivalence studies, do not typically report thyroid-related laboratory values beyond 24 hours following T3 administration. During the course of our study we continued to collect data for the 24–96 hour period and were able demonstrate that despite the return of T3 concentrations to baseline by 48 hours, the response of TSH lagged behind the normalization of T3 values. The nadir of TSH values coincided with the earliest return of T3 to baseline. TSH values then gradually returned to normal between 48 and 96 hours. Interestingly, the TSH values of 3 volunteers rebounded to above their baseline values."
"Once daily administration of short-acting T3 preparations in hypothyroid individuals would not be predicted to be associated with steady T3 levels based on pharmacokinetic data (16), but based on our data could possibly be associated with steady lowering of TSH levels. Daily dosing of 50 mcg T3 was studied in athyreotic patients and resulted in persistent suppression of TSH levels over a 3-week period (17). However, blood sampling was only performed on a weekly basis, so peaks and troughs in TSH or T3 levels would not have been captured. Dividing T3 doses that averaged approximately 40 mcg daily into three times daily dosing regimens in hypothyroid patients, however, avoided any peaks or troughs in T3 or TSH concentrations within the selected periods of sampling (18)."
"The effects of short-acting T3 preparations on parameters such as vital signs and body weight in hypothyroid patients cannot be predicted from our data in euthyroid volunteers, although increased heart rate might be postulated. The increase in heart rate seen in these participants, however, argues against administration of this dose of T3 as a single dose. Studies using thrice daily administration of T3 in athyreotic patients suggest that there may be hepatic effects and also effects on body weight, without effects on heart rate (19)."
"In summary, based on the present observations of sustained reduction of TSH concentrations beyond 24 hours by a single 50 mcg dose of liothyronine, it is possible that a once per day dosing regimen of liothyronine could result in stable lowering of TSH and also stable regulation of other T3 regulated gene products, even without achievement of steadily maintained serum levels of T3."
"The Cmax of 346 ng/dL and Tmax of 2.5 hours for liothyronine documented in our study were both fairly similar to those reported by Watson (Cmax 422 ng/dL; T max 2.5 hours). Our Tmax was also similar to the value of 2.35 hours reported by Coastal Pharmaceuticals in their study of 100 mcg liothyronine (ANDA 90–097) (7)."
"Since blood is an intermediate compartment for distribution of T3 from the gut, the initial decline of blood levels of T3 following achievement of Cmax is partly due to further distribution of T3 to target tissues and hydrophobic sites, such as adipose tissue. The best explanation for the shape and duration of T3 blood levels over time as shown in figure 2a could be represented by multiple release rates from the gut into the blood. Otherwise, a linear loss of T3 from the blood following Cmax, and further distribution to other compartments, would be observed. A similar T3 profile to ours was predicted by DiStefano and colleagues based on oral administration of a single dose of T3 and use of a “two-compartment gut model” (9). This model was based on a study of T3 administration in euthyroid individuals (5)."
"Calculation of T3 half-life in the blood may also be complicated by distribution from the blood into other compartments and re-distribution back into the blood. Thus, the apparent half-life of T3 in the blood depends on the choice of time points for the calculation. For example, an average half-life of 22 hours can be calculated, but a maximum half-life of 71 hours can be calculated from the decline of T3 in the blood between 48 and 72 hours. As stated earlier, this product was thus shown not to have an extended serum half-life compared with the similar 24-hour half-life of currently available T3 preparations."
"Most studies, such as bioequivalence studies, do not typically report thyroid-related laboratory values beyond 24 hours following T3 administration. During the course of our study we continued to collect data for the 24–96 hour period and were able demonstrate that despite the return of T3 concentrations to baseline by 48 hours, the response of TSH lagged behind the normalization of T3 values. The nadir of TSH values coincided with the earliest return of T3 to baseline. TSH values then gradually returned to normal between 48 and 96 hours. Interestingly, the TSH values of 3 volunteers rebounded to above their baseline values."
"Once daily administration of short-acting T3 preparations in hypothyroid individuals would not be predicted to be associated with steady T3 levels based on pharmacokinetic data (16), but based on our data could possibly be associated with steady lowering of TSH levels. Daily dosing of 50 mcg T3 was studied in athyreotic patients and resulted in persistent suppression of TSH levels over a 3-week period (17). However, blood sampling was only performed on a weekly basis, so peaks and troughs in TSH or T3 levels would not have been captured. Dividing T3 doses that averaged approximately 40 mcg daily into three times daily dosing regimens in hypothyroid patients, however, avoided any peaks or troughs in T3 or TSH concentrations within the selected periods of sampling (18)."
"The effects of short-acting T3 preparations on parameters such as vital signs and body weight in hypothyroid patients cannot be predicted from our data in euthyroid volunteers, although increased heart rate might be postulated. The increase in heart rate seen in these participants, however, argues against administration of this dose of T3 as a single dose. Studies using thrice daily administration of T3 in athyreotic patients suggest that there may be hepatic effects and also effects on body weight, without effects on heart rate (19)."
"In summary, based on the present observations of sustained reduction of TSH concentrations beyond 24 hours by a single 50 mcg dose of liothyronine, it is possible that a once per day dosing regimen of liothyronine could result in stable lowering of TSH and also stable regulation of other T3 regulated gene products, even without achievement of steadily maintained serum levels of T3."
"Our experimental model is unique because the study volunteers were devoid of endogenous thyroid hormone production and exogenous LT4 administration, and at the time of the PK studies had received a weight-based LT3 dose administered on a thrice-daily regimen (13). The PK studies were performed by using a dose that was close to the one commonly used for combination therapy, although higher than the one suggested by the ETA (26). This, coupled with the prolonged observation after the last dose, allowed us to assess terminal elimination and, ultimately, fully characterize the PK of LT3, which is explained as a two-compartment model with an early rapid distribution phase, and a slow elimination phase. Not surprisingly, the PK characteristics of LT3 as tested after withdrawal in a state of profound hypothyroidism are dramatically different from the ones observed at steady state. This expansion of the apparent volume of distribution is probably due to the overall decrease in metabolism and (possibly to a greater extent) to the net increase in availability of saturable binding sites after complete depletion of thyroid hormone."
10-hour intervals is messed up.
"The availability of PK data of LT3 at a low dose has also allowed us to generate a model to predict the changes in serum T3 concentrations and its excursions on various combination therapy modalities. The data indicate that a dose of 9.6 mcg on a twice-daily administration (for a hypothetical hypothyroid patient devoid of endogenous thyroid hormone production weighing 72.5 kg) will result in a rise of the average T3 serum concentration from 93 to 175 ng/dL with <15% of the time outside the range. We acknowledge that this modeling is theoretical, and we did not account for the changes in peripheral conversion of T4 into T3 as a result of LT3 administration. The deiodinase 1 (DIO1) gene is positively regulated by T3 (39), and presumably increased T3 levels would prompt T4 to T3 conversion in the liver and kidney. Conversely, the deiodinase type 2 is inhibited by thyroid hormone (40), and the local production of T3 from this enzyme would presumably decrease. Thus, empirical observations are necessary to validate the estimations obtained from this modeling."
"In conclusion, the data presented in this study demonstrate that the PK of LT3 is best explained by a two-compartment model that is characterized by a rapid distribution phase followed by a prolonged elimination phase. The data provide the rationale for using up to 0.07 mcg/kg twice daily to increase the total T3 levels by 50%, while maintaining the serum concentrations relatively stable with minimal excursions outside the reference range. This, in turn, can provide the basis to design intervention studies that are aimed at characterizing the relationship between modulation of serum T3 levels and end organ effects of thyroid hormone."
- Management of hypothyroidism with combination thyroxine (T4) and triiodothyronine (T3) hormone replacement in clinical practice: a review of suggested guidance
"[..]the majority of circulating T3 comes from peripheral conversion of T4 to T3 and not secretion of T3 from the thyroid [8], hence a T4:T3 secretion ratio of approximately 14:1 appears average in humans, suggesting only a small role for secreted T3."
"Studies using both older [59,60,61] and newer [62] thyroid hormone assays have suggested a diurnal rhythm of free T3 and TSH in healthy subjects with no thyroid disease. These studies suggest a peak of T3 at around 4 am with a nadir between 3 to 5 pm; this appears to lag behind TSH levels by about 90 mins [62]. Given its long half-life it is not surprising that in most studies free T4 levels remain very stable throughout the day. Despite a statistically measurable diurnal variation in T3 the actual difference in T3 levels is low (11.2%) and the levels are effectively stable over a 24 h period. It would appear reasonable to mimic these levels if trying to appropriately replace thyroid hormones, particularly as there are few biomarkers which reliably suggest complete thyroid hormone replacement. However, currently this is limited by formulations of T3 which are available (Table 2 for a non-exhaustive list). In many countries, the 20µg table of liothyronine is the only available making accurate dosing very difficult. This is reflected in the combination T4/T3 trials which were not uniform in their method of replacing LT4 with T3, either using a 10:1 or 5:1 LT4:LT3 ratio, or replacing an amount of LT4 with from a fifth to a whole dose of LT3."
"Studies looking at the pharmacology of LT3 replacement all show a significant peak of serum T3 2–4 h after dose and wearing off after 12 h in those on a single daily dose, these include hypothyroid patients on combination therapy [63] (Fig. 1), LT3 monotherapy [64, 65], and even euthyroid subjects taking LT3 only [66]. The profiles are very different to those in patient with normal endogenous thyroid function, and depending on the dose of LT3 the peak level is often above the reference range, and/or the serum TSH is raised/suppressed compared to T4 treatment [67]. Figure 1 suggests that to sample the peak serum T3 level a test taken 2–4 h after ingestion of the T3 would be appropriate."
"To truly mimic the normal production of T3 patients would have to split the dose of T3 and take it two or three times a day, however, the large dose size of the available products may preclude this in patients with a lower requirement for thyroid hormone. Comparison of the figures from Saravanan et al. [63] and Russell et al. [62] would suggest that to mimic serum T3 levels in euthyroid individuals the LT3 dose should be split with the second dose given approximately 8 h after the first. This may prevent the insomnia reported by some patients when they take LT3 prior to bed which is presumably secondary to a serum T3 peak whilst trying to sleep. What effect this will have on the steady state of the drug is unclear as there are no studies looking at serum levels in multiple daily dosing, and even the half-life of T3 is debated with a wide range of opinions."
"Saravanan et al. did not find any difference in cardiovascular parameters (pulse rate and blood pressure) between their groups on T4/T3 and T4 only despite the clear peak in T3 levels at approximately 4 h. This interesting finding reminds us that serum hormone levels do not necessarily reflect action in tissues due to the presence of thyroid hormone transporters and deiodinases in different tissues which may influence the effect of these hormones in individual tissues [69]. Furthermore, most actions of thyroid hormone take several hours to have effect as they require the synthesis of new mRNA and protein."
"Wiersinga et al. in their review suggest 3 different methods for calculating appropriate dosages for combination T4/T3 therapy [6]. These are based on the assumptions that persisting symptoms are due to LT4 monotherapy being unable to deliver normal serum and tissue T4 and T3 levels in humans as shown in rats [17] and that mimicking the normal thyroid secretion of T4 and T3 will correct this [76]. The methods are based on using the dose of LT4 which gives the target TSH in the patient, then replacing a small amount of T4 with T3 using a 3:1 equivalence ratio derived from a study in thyroidectomized patients [77] to give the appropriate ratio. The three methods give a final dose T4:T3 ratio between 13:1 and 20:1, much closer to normal human thyroid secretion [8] but in generally lower than those used in the T4/T3 studies, in some cases significantly lower. Furthermore, many of the studies had variable ratios due to a fixed substitution (eg. 10µg T3 for 50µg T4). This dose ratio is also significantly lower than that of animal thyroid extracts in which the T4:T3 ratio is generally around 4:1 (see later). Note also however that for a patient previously on 100µg of T4 a day the T3 dose from these methods is between 4 and 6µg a day which with most current formulations would be difficult to deliver in a split dose."
"Studies using both older [59,60,61] and newer [62] thyroid hormone assays have suggested a diurnal rhythm of free T3 and TSH in healthy subjects with no thyroid disease. These studies suggest a peak of T3 at around 4 am with a nadir between 3 to 5 pm; this appears to lag behind TSH levels by about 90 mins [62]. Given its long half-life it is not surprising that in most studies free T4 levels remain very stable throughout the day. Despite a statistically measurable diurnal variation in T3 the actual difference in T3 levels is low (11.2%) and the levels are effectively stable over a 24 h period. It would appear reasonable to mimic these levels if trying to appropriately replace thyroid hormones, particularly as there are few biomarkers which reliably suggest complete thyroid hormone replacement. However, currently this is limited by formulations of T3 which are available (Table 2 for a non-exhaustive list). In many countries, the 20µg table of liothyronine is the only available making accurate dosing very difficult. This is reflected in the combination T4/T3 trials which were not uniform in their method of replacing LT4 with T3, either using a 10:1 or 5:1 LT4:LT3 ratio, or replacing an amount of LT4 with from a fifth to a whole dose of LT3."
"Studies looking at the pharmacology of LT3 replacement all show a significant peak of serum T3 2–4 h after dose and wearing off after 12 h in those on a single daily dose, these include hypothyroid patients on combination therapy [63] (Fig. 1), LT3 monotherapy [64, 65], and even euthyroid subjects taking LT3 only [66]. The profiles are very different to those in patient with normal endogenous thyroid function, and depending on the dose of LT3 the peak level is often above the reference range, and/or the serum TSH is raised/suppressed compared to T4 treatment [67]. Figure 1 suggests that to sample the peak serum T3 level a test taken 2–4 h after ingestion of the T3 would be appropriate."
"To truly mimic the normal production of T3 patients would have to split the dose of T3 and take it two or three times a day, however, the large dose size of the available products may preclude this in patients with a lower requirement for thyroid hormone. Comparison of the figures from Saravanan et al. [63] and Russell et al. [62] would suggest that to mimic serum T3 levels in euthyroid individuals the LT3 dose should be split with the second dose given approximately 8 h after the first. This may prevent the insomnia reported by some patients when they take LT3 prior to bed which is presumably secondary to a serum T3 peak whilst trying to sleep. What effect this will have on the steady state of the drug is unclear as there are no studies looking at serum levels in multiple daily dosing, and even the half-life of T3 is debated with a wide range of opinions."
"Saravanan et al. did not find any difference in cardiovascular parameters (pulse rate and blood pressure) between their groups on T4/T3 and T4 only despite the clear peak in T3 levels at approximately 4 h. This interesting finding reminds us that serum hormone levels do not necessarily reflect action in tissues due to the presence of thyroid hormone transporters and deiodinases in different tissues which may influence the effect of these hormones in individual tissues [69]. Furthermore, most actions of thyroid hormone take several hours to have effect as they require the synthesis of new mRNA and protein."
"Wiersinga et al. in their review suggest 3 different methods for calculating appropriate dosages for combination T4/T3 therapy [6]. These are based on the assumptions that persisting symptoms are due to LT4 monotherapy being unable to deliver normal serum and tissue T4 and T3 levels in humans as shown in rats [17] and that mimicking the normal thyroid secretion of T4 and T3 will correct this [76]. The methods are based on using the dose of LT4 which gives the target TSH in the patient, then replacing a small amount of T4 with T3 using a 3:1 equivalence ratio derived from a study in thyroidectomized patients [77] to give the appropriate ratio. The three methods give a final dose T4:T3 ratio between 13:1 and 20:1, much closer to normal human thyroid secretion [8] but in generally lower than those used in the T4/T3 studies, in some cases significantly lower. Furthermore, many of the studies had variable ratios due to a fixed substitution (eg. 10µg T3 for 50µg T4). This dose ratio is also significantly lower than that of animal thyroid extracts in which the T4:T3 ratio is generally around 4:1 (see later). Note also however that for a patient previously on 100µg of T4 a day the T3 dose from these methods is between 4 and 6µg a day which with most current formulations would be difficult to deliver in a split dose."
- Combination Thyroid Hormone Replacement; Knowns and Unknowns
- Liothyronine and Desiccated Thyroid Extract in the Treatment of Hypothyroidism
- T4+T3 combination therapy: any progress?
- Thyroxine Supplementation And The Length Needed For Stabilization Of Effects
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I personally have been experimenting with taking my t4/t3 combo in divided doses throughout the day with foods as opposed to a big dose at night like Ray and Danny talk about. I find the dose is too high at once if I do it that way.
What is TYROMAX???
Dosing is done per kg. So 1.8mcg per kg of body weight. Thats the guidance on the NHS in the UK
Dr Blanchard is not with us anymore, but his books are great.
I take T4 only, but have tried every thyroid protcol going over the years 2008-2015. Now i take T4 only at bedtime.
I find T4 works much better if taken at bedtime. I dont have any sleep issues and i just feel it fits in with when we naturally make our own T4.
TSH peaks in the nighttime, this stimulates the body to produce the T4 for the next day. This also has a knock on effect on cortsol production. T4 and cortisol work together. Low thyroid patients often record low cortisol production in the morning, when really it should be at its highest.
So giving T4 at bedtime means you are working with your circadian rhythm.
When i used T3 with the T4 i found less was much more effective. So i would use 2.5mcg approx in the morning.
My hormone journey has been a long one and in the last year i have started testosterone treatment as well. I now realise testosterone is an important factor in getting thyroid to work well. I am doing better than ever in my life and am now aged 48.
The OP has good thyroid figures, but a high TSH. How old are you ? I assume you dont feel that well, hence you are looking to try some T4.
The thyroid journey is a long descent. I mean the thyroid starts to stutter along time before it really shows up with really bad symptoms. Lots of young people dont realise they have a thyroid issue, and instead get diagnosed with mental health problems. It happened to me aged 21 and it wasnt until i was 36 that i started to look under the thyroid bonnet.
When the tsh starts to climb it can indicate the thyroid is starting to struggle and so it ramps up conversion. Hence you get good FT3 no's and FT4 is ok as well. But going forward in time the thyroid struggles even more and TSH will go higher, but maybe conversion isnt as good and you get more symptoms.
I take T4 only, but have tried every thyroid protcol going over the years 2008-2015. Now i take T4 only at bedtime.
I find T4 works much better if taken at bedtime. I dont have any sleep issues and i just feel it fits in with when we naturally make our own T4.
TSH peaks in the nighttime, this stimulates the body to produce the T4 for the next day. This also has a knock on effect on cortsol production. T4 and cortisol work together. Low thyroid patients often record low cortisol production in the morning, when really it should be at its highest.
So giving T4 at bedtime means you are working with your circadian rhythm.
When i used T3 with the T4 i found less was much more effective. So i would use 2.5mcg approx in the morning.
My hormone journey has been a long one and in the last year i have started testosterone treatment as well. I now realise testosterone is an important factor in getting thyroid to work well. I am doing better than ever in my life and am now aged 48.
The OP has good thyroid figures, but a high TSH. How old are you ? I assume you dont feel that well, hence you are looking to try some T4.
The thyroid journey is a long descent. I mean the thyroid starts to stutter along time before it really shows up with really bad symptoms. Lots of young people dont realise they have a thyroid issue, and instead get diagnosed with mental health problems. It happened to me aged 21 and it wasnt until i was 36 that i started to look under the thyroid bonnet.
When the tsh starts to climb it can indicate the thyroid is starting to struggle and so it ramps up conversion. Hence you get good FT3 no's and FT4 is ok as well. But going forward in time the thyroid struggles even more and TSH will go higher, but maybe conversion isnt as good and you get more symptoms.
Do you take your T4 with food?
Interesting, may be this is why Ray recommends taking the t3/t4 combo at night and some t3 during the day. (I personally do well with the combo)
Of course it is also that T4 is necessary to buffer T3 during the long hours of sleep.
Glad you've found what works for you. The only problem with a T3/T4 combo is that you have to break up the dose so that T3 in any given doses is well below 10mcg to prevent rT3
no but I have done.
food with t4 makes no difference to me.
ive just found bedtime dosing is much better for overall health
Thanks for your input, appreciate it! I'm 34 and suspect I've been hypothyroid since at least age 17. I also take levo around bedtime and haven't noticed any sleep problems, the only time I had insomnia was once when I took it in the late afternoon.
I've been taking 25 mcg levo for 2 weeks now and although I expected no less, its been a lot of ups and downs to so far. First week I noticed mostly increased energy but also some digestive problems and heightened anxiety. Second week was both better and worse than the first, on the one hand I had some weird inflammatory pains moving around in different body parts like gut, chest, lower back and groin. I also passed at least one kidney stone which was a first, also been feeling more afternoon sleepiness and began taking afternoon naps.
On the other hand I also started to have periods now in the second week where I feel extremely good with a calm, stable energy like I haven't felt in years. Like I'll go out for a stroll and can just enjoy slowly walking around, taking in the scenery and relish the fresh air for an hour or more. I never noticed until I started to have those moments how chronically agitated and restless I've always been in the past, like whenever I went out for walks I was always rushing and never enjoyed it much. I also I noticed yesterday that my ability to focus intensively for a long time seems to have improved, was doing a difficult work task and almost felt like I was going into a flow-like state, the more difficult it became the more I enjoyed the struggle.
Average pulse seems to have increased from about 70 to 80, but temps still pretty much the same.
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@Amazoniac
many thanks for those studies, seems to confirm how t3 is used by bodybuilders for example
also the bit about t3 having an effect on weight etc even without increase of heart rate or other obvious effects is interesting
many thanks for those studies, seems to confirm how t3 is used by bodybuilders for example
also the bit about t3 having an effect on weight etc even without increase of heart rate or other obvious effects is interesting
Elize
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So giving T4 at bedtime means you are working with your circadian rhythm
What time is bedtime?
Mine is 10 pm but my next dose is 5:30 am then feel over stimulated when I take a bedtime dose. I also became very hypo when I tried the evening dose with no daytime dose
What time is bedtime?
Mine is 10 pm but my next dose is 5:30 am then feel over stimulated when I take a bedtime dose. I also became very hypo when I tried the evening dose with no daytime dose
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