Guest guest Posted January 10, 2011 Report Share Posted January 10, 2011 Jay, You wrote: > Iv been trying to find information on the biochemistry of the bodys use > of t4. Particularly on how long it takes for a tablet taken to be broken > down and used. I'm interested in finding out what effects it's uptake > and speed. The manufacturers of Synthroid and Armour used to have good dosing guidelines on the web, but they took them down, perhaps for legal reasons. There are a number of technical papers on your questions. I would suggest Google Scholar, if you really want the details. The gist of it is that only about 80% of T4 is absorbed under the best of circumstances. Most of the absorption takes place in the small intestine, so it takes about an hour for this to happen. Any food, including coffee, within this hour, will interfere to some extent with absorption. I have seen studies in dogs, mice and rats, and they all have about the same absorption schedule. A number of people on this list recommend sublingual dosing, since this avoids the stomach, but I have not seen any real literature confirming the effectiveness of this method. When I tried it, I found the sweet taste escaped my tongue, which means at least some of the T4 was still absorbed in the digestive track. So, I would recommend you still avoid food for awhile, even if you can hold it under your tongue. Once your T4 is absorbed, most of it is stored in serum by chemical binding to thyroidglobulin or albumin. About 0.5% of T4 and T3 remains free of this binding and can penetrate into cells. As a result, T4 has a biological half life of 6-7 days. It is slightly longer if you are hypoT; shorter if hyperT. Sex hormones affect the binding, so this is probably what you are experiencing with the menstrual cycle. The issue with endurance exercise, is that most of us have a limited capacity for T4-T3 conversion. It is sufficient for resting or moderate exercise, but we run low on T3 with prolonged heavy exercise. I hit a wall after just a few hours of yard work and have to sit until I recover. I have long suspected that a little T3 right before exercise would increase endurance, but I have not been able to test this. Here is a summary of postings to this list over the years. I had to take out most of the links we had collected, because they are no longer active. Answers to Frequently Asked Questions INTRODUCTION Most of us got here from one of four causes: (1) an autoimmune attack on the thyroid gland and its hormones, a condition called Hashimoto's thyroiditis; (2) surgical removal or radioactive destruction of the thyroid gland for a medical reason such as goiter or cancer; (3) an idiopathic (don't know what causes it) familial pattern, in which the thyroid simply stops working; or (4) an endocrine or protein binding malfunction involving other hormones, that results in some sort of imbalance or conversion insufficiency. You can find the basics in the following link, although it pushes Armour pretty exclusively: http://www.stopthethyroidmadness.com/causes-of-hypo/ We share a common medical condition, eventually affecting up to about 10% of all women, although a lesser percentage of men. If you are in one of the first three categories, clearly indicated as hypothyroid by tests, your doctor probably gave you a prescription for a synthetic T4 replacement and told you to come back in 4-8 weeks for more testing. That process is called titration. If your doctor is conservative (the 8-week variety, which is recommended if you are over 50, a child, or have a cardiac problem), he probably gave you a low starting dose, in which case you won't notice much relief for months, when the dosage finally gets close to optimum. In between, you may have temporary improvement after each dosage increase that will fade as your system adjusts. Eventually, you are likely to feel normal again, that is, if you are one of the lucky majority. Many on the list, though, are here because they weren't as lucky. If your doctor is cautious, allowing your levels to stabilize and checking the side effects before increasing the dose, you might want to show up a little early. The recommended interval is a minimum of six weeks. However, if you are young and otherwise healthy, there is no reason not to push that a bit. The sooner you get to full replacement and get it stabilized, the sooner you feel normal again. The incremental increases only help briefly and then seem to fall off until the next increase. The latest prescribing guidelines for healthy patients under 50 tell doctors to go immediately to a " full replacement dose " and titrate from there. That gets you feeling better much more quickly than the older approach. Gursoy A, et. al. " Which thyroid-stimulating hormone level should be sought in hypothyroid patients under L-thyroxine replacement therapy? " Int J Clin Pract. 2006 Jun;60(6):655-9 Traditionally, practitioners have, for most patients, had their own particular approaches to thyroid hormone replacement that fall into 5 categories. 1. Minimum Medication / High-Normal TSH Some practitioners have preferred to take the most conservative approach, providing the lowest possible dose of thyroid medication, and targeting the top end of the normal range for a patient's TSH level. Their justification has been a concern over the effects of a lower TSH on bone density, as well as concerns that medication might have negative effects on the heart. This approach itself has been controversial however, because there is contradictory evidence as to whether patients medicated to the lower normal range face an increased risk of osteoporosis. It's also been shown that thyroid medication is safe for most patients, and dosage should be increased slowly and monitored carefully for cardiac implications in only the elderly and people with a history of preexisting heart conditions. 2. Medication to Mid-Normal Range Many practitioners have as their objective to provide enough thyroid hormone replacement for a patient's TSH level to end up somewhere in the middle of the " normal range " -- and again, most often, using the older, broader normal range of approximately 0.5 to 5.0 to 6.0. This is considered a " safe " strategy for the physician, as conventional medicine says that hypothyroidism is fully " treated " when the patient is euthyroid (has a normal TSH level). 3. Medication to the 1.0 to 2.0 Range Some practitioners -- including more of the integrative and holistic practitioners, have focused on a TSH level of between 1.0 and 2.0 as the target range. This target has typically been based not on definitive research, but more on clinical experience over time noting at which TSH level the majority of their patients typically report feeling their best. 4. Suppression of TSH to 0.0 or Nearly Undetectable Levels TSH suppression, where higher doses of medication are given to suppress the thyroid's ability to produce any, or most, thyroid hormone is a strategy used with thyroid cancer survivors. Suppression prevents any remnant thyroid tissue from becoming active, and can help prevent cancer recurrence in many patients, and is often recommended by practitioners managing thyroid cancer patients. This approach is considered an important part of the ongoing treatment for thyroid cancer survivors. 5. Medication to Eliminate Symptoms Some practitioners -- mainly from the holistic, alternative or integrative community -- believe that the TSH levels are irrelevant in managing a patient. They may occasionally test the TSH, but their target is resolution of thyroid symptoms, and they will change the dosage of thyroid hormone medication based on a patient's self-reported symptoms, as well as clinical signs including pulse rate, blood pressure, and observable thyroid symptoms such as reflexes, goiter size, eye irritation, and swelling in the face and extremities. This group also tends to include alternative medications and supplements, such as iodine or kelp. IMPLICATIONS FOR PATIENTS With the publication of this new research, there is now scientific justification for doctors to avoid undermedicating patients to high-normal or mid-range TSH levels, and instead, target a level of 2.0 or less, in order to ensure that their patients are receiving optimal care. In late 2002, the National Academy of Clinical Biochemistry (NACB) issued new guidelines for the diagnosis and monitoring of thyroid disease. In the guidelines, the NACB reported that the current TSH reference range -- which usually runs from approximately 0.5 to 5.5 -- may be too wide and actually may include people with thyroid disease. When more sensitive screening was done, which excluded people with thyroid disease, 95 percent of the population tested actually had a TSH level between 0.4 and 2.5. The NACB guidelines led to a recommendation in January 2003 by the American Association of Clinical Endocrinologists (AACE), calling for doctors to " consider treatment for patients who test outside the boundaries of a narrower margin based on a target TSH level of 0.3 to 3.0. " You will probably be on the medication for the rest of your life. The few cases of restored thyroid function I have read about sound like mild partial impairment which stops. Hashimoto's can sometimes do that, as can endocrine malfunctions. Most of the time, everyone that reaches the full replacement dose seems to stay there. Autoimmune conditions can stop and go into either temporary or longer lasting remission. However, the more usual progression is cyclic recurrence, once they have been triggered. In the case of the thyroid, this usually results in permanent loss of function. Other systems are sometimes more resilient. Nobody knows the cause for the immune system to attack the body it is supposed to protect, although this is a very active field of research today. The big distinction of Hashimoto's from the other causes is that thyroid function can go up and down again, alternating hyperthyroid with hypothyroid under the same dosage, until the gland is finally, permanently destroyed. This means the gland stops functioning entirely, stops collecting iodine and producing the T4 and T3 from it that you need. There is also a small reduction in organ size, the only sort of weight loss associated with hypoT. To me a goiter sounds worse, because it results in disfigurement. Once you get your dosage stabilized, you should feel as well as ever, with a couple of caveats. For example, I've noticed an intolerance to heavy exercise, which seems to use up the T3 faster than usual. My system can't keep up for more than about three hours of work, then I become a vegetable for a short period. Several of us on the list call this " hitting the wall. " It is much like what a marathoner runs into when the liver's supply of glucose runs out. Either that or I've just become lazy with age. Really, you can still exercise, but you have to pace yourself. Where before you could " party all night " and pay the piper later, now you tend to pay up front. Body temperature can be a good indicator of metabolism. HypoT folks feel cold because they are cold. Other symptoms can be important indicators, and you should memorize the list of both hypo-T and hyper-T symptoms, just in case. However, if you expect a comment with more content than " That's too bad, " we would also like to see your blood test results. These should include the reference ranges for each test as reported by your lab. HOW TO USE THIS LIST Don't be shy about sharing information. Most of us have done these tests over and over for years. They don't indicate your IQ or anything really personal. They just give clues on what is causing your condition. Also, these are YOUR test results. You have a right to ask for a copy from your doctor or to ask that the lab send a second copy directly to you. I used to ask for a test myself at least every six months, but now I have transitioned to yearly tests, since I have had no symptoms for a long time. My mother went several years before checking her dosage. It nearly killed her once, when they changed the formulation of Synthroid and didn't tell the doctors. THE TESTS A summary of the various tests you may be asked to take: http://vitamvas.tripod.com/lab.html For most of us, increasing the available T4 by taking a synthetic replacement adequately supports the FT3 level. If it doesn't, you could have poor conversion from T4 to T3. Or, you could have excessive binding of both T4 and T3, so the free components are too low. Another possible problem is that antibodies are making your other tests invalid, indicating within the normal range when they are actually outside. One possible solution for all of these is to drive TSH lower than the reference range, or to increase T4 to higher than its reference range. You can do that with either more T4 or by adding T3 to the mix. Again, the reference ranges are valid for initial screening and perhaps for initial titration. After that, interpretations vary, depending on the physician, many of whom do not believe the published lab guidelines. Two major professional groups have issued recommendations about LOWERING the reference ranges for people on the medications. RECOMMENDATIONS Here are the recommendations of the American Society of Endocrinologists and the National Academy of Clinical Biochemists. You might want to share these with your doctor: http://www.nacb.org/lmpg/thyroid_lmpg_pub.stm http://thyroid.about.com/gi/dynamic/offsite.htm?zi=1/XJ & sdn=thyroid & zu=http%3A%2\ F%2Fwww.nacb.org%2Flmpg%2Fthyroid_LMPG_PDF.stm We seem to agree there is a list of foods to avoid, especially if you have at least some thyroid function left. This includes goitrogen foods: http://www.ithyroid.com/goitrogens.htm . I personally eat many of the goitrogens, particularly nuts and raw broccoli, but I have no thyroid function left, nothing left to lose. I still avoid soy, because it apparently goes after thyroxine in serum. I have not noticed any effect from the other goitrogens, since I am on a full replacement dose of thyroxine. I also try to minimize consumption of fluoride. This is another bad actor that is toxic to both an active thyroid gland and thyroid hormones in the blood. Black tea is particularly rich in fluoride, so the only tea I have any more is green tea, and that is pretty rare, coffee being an essential nutrient, at least to me. Herbal teas are not a problem for fluoride. The amount in city water supplies is a concern. Check with your public water company. Although some on the list recommend taking large iodine supplements in addition to the replacement medications, iodine can be toxic to some people, and it has especially bad effects for those with Hashimoto's. It seems to stimulate the antibody attack. Canada's federal health agency issued a warning in 2003 to stay away from kelp, because you might get as much as 4 mg per day by following the directions. Some on the list are taking more than ten times that amount daily. http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/2003/2003_27_e.html Here are some other reports of experimental evidence that iodine supplements aggravate Hashimoto's: Effect of Iodine Restriction on Thyroid Function in Patients With Primary Hypothyroidism. Kanji Kasagi, Masahiro Iwata, Takashi Misaki, Junji Konishi Thyroid 13(6):561-567, 2003. Control of efficiency and results, and adverse effects of excess iodine administration on thyroid function. Koutras A. , Ann Endocrinol (Paris) 57: 463-469, 1996. Chronic autoimmune thyroiditis. Dayan CM, s GH., N Engl J Med 335: 99-107, 1996. Ironically, levothyroxine (T4) itself is an iodine supplement with four iodine atoms in each molecule. I personally would not take iodine (e.g. kelp) unless I had clear evidence of a deficiency. That could be the case for someone with untreated symptoms, or someone not taking hormone replacements, which, in fact, are a concentrated form of iodine. If you think lack of iodine is your problem or that overdosing with it might help, here is the home site of a supplier that some of our listers recommend. Again, this approach is controversial. I don't recommend it myself. http://www.optimox.com/ As to what TO eat, most of us are fighting weight problems. HypoT also puts us at risk of high-cholesterol induced cardiac and stroke and type II diabetes. Diet is probably where the widest range of controversy lies. Many of us have tried the extremely low carbohydrate diets and lost some weight. However, I found that after about 10 months, even the extreme induction form of the diet no longer worked. I think my metabolism had simply adapted. It just took longer than it takes to adapt to a low fat diet. OTOH, hypothyroidism seems to make us particularly susceptible to the effects of high glycemic index foods. So, I still try to minimize sugars and simple or refined starches along with saturated and especially trans fats. We have had a couple of testimonials for coconut oil, but it did absolutely nothing for me. Some on the list will give you a long list of supplements they swear by. I think some of us could stock a health food store with what is in their medicine cabinets. However, some things seem to be on everyone's list. The first is selenium, since it helps with T4-T3 conversion. As with iodine, though, too much selenium is reputed to be toxic and increases your risk of diabetes at about 200 mcg per day. Make sure you aren't getting it from multiple sources. Another supplement that is frequently mentioned is vitamin B-12. For me it helps with energy level if taken intermittently. Too often, and I get jittery, can't sleep, and feel rather wiped out and uncomfortable. In summary, diet won't help much with the primary symptoms unless the hormone levels are properly balanced. For most of us, that means getting the dosage or combination of replacement hormones right. Once that is fixed, the main concern is choosing a " healthy diet " that controls the weight gain. However, we have lots of conflicting opinions on what that means. Calcium carbonate has been shown in several well reviewed tests to interfere with T4 absorption when taken up to three hours after the T4. However, the form of calcium in milk should not do this. It is not carbonate. Iron is another nutrient with this interference capability. Calcium carbonate is in a lot of other medications and supplements as a binder. You should not take any food within an hour after or two hours before your T4, longer for iron, calcium, or fiber. Don't take these anywhere near the same time as your T4. Most of us take the hormone first thing in the morning and other medications after breakfast or in the evening. Fiber is not nearly as bad as calcium carbonate or iron. These will affect absorption even after three hours. I would also suggest waiting for the dosage to settle before starting a low carb diet. That shuts down the intestines independent of thyroid status. The two together could be a real problem. One final possibility is that a lot of the non-dairy creamers have soy in them. Soy will also interfere long after you take the Synthroid. It is also possible that iodide added to salt could aggravate autoimmune thyroiditis, actually making your T3 lower. However, this is usually a slower, longer term effect. Another caution is that a gross excess of iodide can burn the thyroid. Again, this is usually a longer term effect, not something that would affect a selected afternoon and then go away. It would also take a fairly large slug of iodide, much more than is available in table salt. Some people experience side effects from one medication or another. In addition to the following ingredients, Abbott Laboratories is now advising list members that the .05 and .075 mg tablets have 2.9 mg. of sulfites per pill. This is more than enough to adversely effect people sensitive to sulfites. We do not know whether other thyroid medications might have sulfites, which are commonly included with colorings to stabilize them. Here are the Synthroid and generic levothyroxine inert ingredients: Acacia, confectioner's sugar (contains cornstarch), lactose, magnesium stearate, povidone, and talc. No sulfites. The following are the color additives by tablet strength: 25 mcg: FD & C yellow No. 6; 50 mcg: None; 75 mcg: FD & C red No. 40, FD & C blue No. 2; 88 mcg: FD & C blue No. 1, FD & C yellow No. 6, D & C yellow No. 10; 100 mcg: D & C yellow No.10, FD & C yellow No. 6; 112 mcg: D & C red No. 27 & 30; 125 mcg: FD & C yellow No. 6, FD & C red No. 40, FD & C blue No. 1; 150 mcg: FD & C blue No. 2; 175 mcg: FD & C blue No. 1, D & C red No. 27 & 30; 200 mcg: FD & C red No. 40; 300 mcg: D & C yellow No. 10, FD & C yellow No. 6, FD & C blue No. 1. Levoxyl inert ingredients: Microcrystalline cellulose, croscarmellose sodium and magnesium stearate. The following are the coloring additives per tablet strength: (mcg) 25 FD & C Yellow No. 6 Aluminum Lake; 50 None; 75 FD & C Blue No. 1 Aluminum Lake, D & C Red No. 30 Aluminum Lake; 88 FD & C Yellow No. 6 Aluminum Lake, FD & C Blue No. 1 Aluminum Lake, D & C Yellow No. 10 Aluminum Lake; 100 FD & C Yellow No. 6 Aluminum Lake, D & C Yellow No. 10 Aluminum Lake; 112 FD & C Yellow No. 6 Aluminum Lake, FD & C Red No. 40 Aluminum Lake, D & C Red No. 30 Aluminum Lake; 125 FD & C Red No. 40 Aluminum Lake, D & C Yellow No. 10 Aluminum Lake; 137 FD & C Blue No. 1 Aluminum Lake; 150 FD & C Blue No. 1 Aluminum Lake, D & C Red No. 30 Aluminum Lake; 175 FD & C Blue No. 1 Aluminum Lake, D & C Yellow No. 10 Aluminum Lake; 200 D & C Red No. 30 Aluminum Lake, D & C Yellow No. 10 Aluminum Lake; 300 FD & C Yellow No. 6 Aluminum Lake, FD & C Blue No. 1 Aluminum Lake, D & C Yellow No. 10 Aluminum Lake So what is the difference? The big one is lactose in Synthroid and its generics. Some people are intolerable to even a tiny amount of this ingredient. The second big difference is that Synthroid uses dyes for coloring, while Levoxyl has a combination of dyes and lakes. Some of the inert ingredients also contain sulfites. If you are sensitive to sulfur, you may need to choose a dosage with a different coloring. A dye is a distinct chemical material, which exhibits coloring power when dissolved. The lakes are insoluble in nearly all solvents, and therefore do not require sulfites to stabilize them. The term is derived from the early medieval Latin lacca to indicate a combination of pigment with products of the lac insect (Kerria lacca). The lac was imported into Europe from India, and it yielded both red dyestuff and, as a by-product, shellac (shell-lac) and lacquer (lac-quer). Until the 18th century, lake indicated red pigments only. Aluminum lakes are produced by the absorption of a water soluble dye onto a hydrated aluminum substrate. The food product is colored either by dispersion of the lake or by coating onto the surface. " Subclinical " means that a set of indicator symptoms are not confirmed by chemical tests. Before T3 and T4 assays became widely available, the main or only test used was TSH. Thus, at one time, subclinical meant symptoms with a high normal, or slightly above normal, TSH. With other tests and other protocols for each test, the accepted definition has necessarily changed. One major issue with a subclinical diagnosis is whether the tests you had are reliable or relevant. Free T3 is the one that really controls the metabolic symptoms, so a normal Total T4 or Total T3 test may not be completely meaningful, particularly if conversion to T3 is messed up or if too large a fraction of T3 is bound by albumin and globulin. Three proteins in the blood chemically attach to thyroxine, rendering it unable to convert (T4 to T3) or play its role in maintaining metabolism. Fortunately, this binding is temporary, and the thyroxine will spontaneously detach in short order. However, at any given time, about 99% of the T4 and T3 in the blood is tied up with these proteins. Only the tiny fraction left FREE is able to contribute to metabolism and health, which is why it is important to measure FT3 (Free 3,5,3’-triiodothyronine) when you are medicated but still having problems. FT4 can be used to estimate FT3 from total T3, since the percentage of binding is very close to the same. The dominant binding protein is in the globulin family, called thyroxine binding globulin. Although it is present in the lowest concentration of the three, it has the highest affinity and therefore ties up the most T4 and T3. The second is a type of albumin, sometimes called pre-albumin. It ties up about a third of your hormone. A tiny amount is also caught by a third type of protein, transthyretin. Because thyroxine binding globulin is dominant, the binding process is often just called globulin binding. Obviously, globulin binding serves as a control valve, a throttle, on your medicine. It prevents T4 from easily converting to T3, since both need to be in the free form. It creates a reservoir of T4, which is one reason why T4 has a biological half life of nearly a week. If the throttle is too tightly closed, the excess binding results in too little FT3, even though total T4 may be fine. There is too much in the reservoir and not enough getting to your cells. One possible indication of this situation is when Total T4 is fluctuating, but the free fractions only change a little. Another big issue is the effect of antibodies, which may or may not change the other readings. If you had no antibodies detected, this is less likely, unless you are in a very early stage of thyroid deterioration. If so, a small supplementation in either or both T4 and T3 might help with symptoms or their anticipated progression. Just watch for hyperT symptoms. That would tell you to back off the dosage. Again, welcome aboard, and I hope these comments help. If you object to any of the " standard model " information I included, please concatenate some rebuttal posts and web pages, and I'll formulate a two sided FAQ message that we can continue to post every so often for new members. Chuck Quote Link to comment Share on other sites More sharing options...
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