Thanks Velha, I did recall somebody on WD taking much higher doses of L-Carnitine. I'm on a bit of a food-based supplement kick, but I'll try the L-Carnitine again at higher dose at some point.
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B-12 - The Hidden Story
- Thread starter Cort
- Start date
Thanks Velha, I did recall somebody on WD taking much higher doses of L-Carnitine. I'm on a bit of a food-based supplement kick, but I'll try the L-Carnitine again at higher dose at some point.
K
_Kim_
Guest
Velha, could you clarify which product you upped your dosage on? The L-carnitine or the ALA? I'm guessing it was the L-carnitine, because you'd have to be taking a ton of ALA pills to get to 4-5g.
How much are you taking? I had a noticeable improvement going from 800mcg to 1600mcg, and again to 2400mcg. Maybe not a surprise since I have very little folate in my diet, but my folates were in range on my methylation panel. When I started eating gluten-free I cutout my major sources of B1, B2, B3, and folate. Digestion issues got much better, fatigue got much worse.
Freddd
Senior Member
- Messages
- 5,184
- Location
- Salt Lake City
Hi Brenda,
The confusion of Hashimoto's and hypothyroidism is understandable when technical papers say "We studied 10 postmenopausal women with Hashimoto's hypothyroidism treated with varying doses of L-thyroxine replacement." http://www.liebertonline.com/doi/abs/10.1089/thy.1996.6.75
Google Scholar has over 15,000 such references. Google has over 1,500,000 such references.
I am clear now on the differences of the active phase:
Hashimoto's typically involves a slow but steady destruction of the gland that eventually results in the thyroid's inability to produce sufficient thyroid hormone -- the condition known as hypothyroidism. Along the way, however, there can be periods where the thyroid sputters back to life, even causing temporary hyperthyroidism, then a return to hypothyroidism. This cycling back and forth between hypothyroidism and hyperthyroidism is characteristic of Hashimoto's disease. So, for example, periods of anxiety/insomnia/diarrhea/weight loss may be followed by periods of depression/fatigue/constipation/weight gain. In some cases, the onset of Hashimoto's and elevation of antibodies will be accompanied by a variety of symptoms, including anxiety, difficulty sleeping, fatigue, weight changes, depression, hair loss, muscle/joint aches and pains, and fertility problems, among others.
http://thyroid.about.com/cs/hypothyroidism/a/hashivshypo.htm
Post active phase, after the damge is done "In Hashimoto's, antibodies react against proteins in the thyroid gland, causing gradual destruction of the gland itself, and making the gland unable to produce the thyroid hormones the body needs. "
In the end it produces hypothyroidism which is where the confusion, if any appears to be.
very bad reaction and mine was so bad that I was suicidal for a few days
In all the thousands of people I have read reports from or talked to directly this appears to be a unique reaction to presumably mb12. It does not appear in any of the side effects in package inserts of prescription forms of methylb12. Normally b12 deficiency causes depression and taking mb12 can relieve that, often very quickly. In antidepressant literature however, there are such warnings that the antidepressant can actually result in a period of increased suicidal tendencies for unknown reasons early in use before the antidepressant effect starts. Perhaps that is what occurred here. It is certainly not a common reaction to using an OTC sublingual vitamin sublingually.
http://en.wikipedia.org/wiki/Herxheimer_reaction
The Herxheimer reaction (also known as Jarisch-Herxheimer or Herx) occurs when large quantities of toxins are released into the body as bacteria (typically Spirochetal bacteria) die, due to antibiotic treatment or rapid detoxification.
Typically the death of these bacteria and the associated release of endotoxins occurs faster than the body can remove the toxins via the natural detoxification process performed by the kidneys and liver. It is manifested by fever, chills, headache, myalgia (muscle pain), and exacerbation of skin lesions. Duration in syphilis is normally only a few hours but can be much longer, up to months or years, for other diseases, especially Lyme Disease. The intensity of the reaction reflects the intensity of inflammation present.
The Herxheimer reaction has shown an increase in inflammatory cytokines during the period of exacerbation, including tumor necrosis factor alpha, interleukin-6 and interleukin-8.[1][2]
The reaction is also seen in other diseases, such as borreliosis (Lyme disease[3][4] and tick-borne relapsing fever[5]), bartonellosis, brucellosis, typhoid fever, Myalgic Encephalomyelitis, and trichinellosis, Q fever, and cat scratch disease.[6][7]
So methylb12 causes such a massive improvement in immune funtioning immediately that it causes a Herx reaction? That appears to be what you are saying. It is not an antibiotic and does not kill bacteria. However b12 deficiency certainly does cause immune system malfuntioning and taking it appears to allow the the immune system to start funtioning normaly again almost immediately, though that is not a proven effect and not what I would have expected. If it is Lyme disease you have for instance and b12 kills the Lyme causing bacteria so quickly and effectively I would be inclined to let my doctor know about the tremendously effective treatment for Lyme. It would constitute a breakthrough treatment that needs to be studied. It's not a claim I have ever seen before. If this is not what you are claiming, what are you claiming?
What dose of mb12 did you actually take? A 1000mcg used sublingually once? twice? How many absorbed estimated MCGs are we actually talking about here?
If a couple of hundred or even a couple of thousand absorbed mcgs of mb12 produced these huge effects in you, all I can think is that it demonstrates how severely damaged your body was in many ways by severe and prolonged b12 deficiency. Mine certainly was. Good luck and good health.
Hi, Brenda.
Can you explain the difference please?
***I think this difference arises from the heterogeneity of the CFS population. As you know, CFS is defined by a set of symptoms, and the diagnosis is made by exclusion of other known medical conditions. With this type of case definition, we end up with quite a variety in the people who are diagnosed with CFS. So when small numbers of patients are selected for clinical studies, there can be significant differences found between the groups due to the heterogeneity of the overall population and the resulting statistical variation.
No-one is questioning this. I have been using Jarrow b12 for years for my endocrine system, whichis another reason why I question what Fredd is saying. It was only when I took a massive dose, not the 200 to 400 mics mentioned that I had adverse effects. It is the amount that we have taken that we are questioning. I had a normal blood test result and took b12 for quite sometime before I took the huge dose that Fredd advises. I could not have been deficient.
***I can't speak for freddd, but I will address this from the point of view of the Glutathione Depletion--Methylation Cycle Block hypothesis that I have proposed to explain the etiology, pathogenesis and pathophysiology of CFS. According to this hypothesis, the problem with B12 in CFS is that glutathione has become depleted, leaving the B12 unprotected at a certain stage in its processing inside the cells. As a result, one can have a blood serum B12 test that comes out in the normal range, but still not be able to use B12 functionally in the cells to carry out its jobs. It has been found in autism, and we have also found in CFS, that it is necessary to raise the dosage of B12, and to take it together with one or more reduced forms of folate, in order to overcome this functional blockage and restore the methylation cycle and the glutathione levels to normal. This is apparently necessary to overcome the loss of B12 to reactions with toxins, which take place when it is unprotected. I originally encouraged PWCS just to elevate glutathione directly, but this did not turn out to be a successful longterm treatment. It was only when I learned of the success in autism that I realiized that the methylation cycle block must be treated to allow glutathione to come up on a permanent basis.
***With regard to the conventional blood serum B12 test, it is meaningful in cases in which the people are actually deficient in B12, and have been for an extended time. However, it is not very meaningful in CFS, where the issue is usually not lack of normal amounts of B12, but rather is the lack of proper B12 function. A better test in CFS is the urine methylmalonic acid test. This test will show whether enough adenosyl B12 is being made in the cells, because its lack will cause methylmalonic acid to rise. Usually if there is not enough adenosyl B12 being made, then there is also not enough methyl B12 being made, because they share the part of the pathway that involves protection of B12 by glutathione, through the formation of glutahionylcobalamin. An exception is the small number of people who have an inborn error of metabolism that affects only the formation of adenosyl B12, but this is a fairly rare genetic disorder.
***Normally, most of the B12 in the blood is carried by haptocorrin, and this part of the B12 is not accessible to cells other than liver cells. A smaller part is normally carried by transcobalamin. If a conventional serum B12 measurement is made, it does not distinguish between these two parts, and that is another problem in interpreting the results of this type of measurement.
***With regard to having adverse effects from larger dosages of B12 (together with reduced forms of folate), I think it is important to try to determine how adverse the effects are. The Simplified Treatment Approach that I have proposed is somewhat different from the protocol freddd has suggested, but when people first started using it 3 years ago, there were a small number of them who indeed had rather severe adverse effects. I have posted these in the past on this forum. This is the reason I insist that people should be working with their physicians while on this treatment. In some cases, the people involved had other comorbid conditions that were apparently responsible for the adverse effects, including autonomous multinodular goiter and autoimmune diseases. For the majority of people, who did not have such comorbidities, there were usually some unpleasant symptoms, which I believe are associated with die-off of pathogens and mobilization of toxins into the bloodstream. These last for differing lengths of time, presumably depending on the body burdens of infections and toxins that the person has accumulated.
***freddd and I seem to have different philosophies in our approach to these symptoms. My view is that it is best to lower the dosages of the supplements to levels that make the detox and die-off symptoms tolerable. It will take time to clear these out of the body. I wish it were faster, but times of at least two years do not seem to be unusual for someone who has been ill for an extended period of time. I do not have proof that this approach is better in the long run than "pushing through" the symptoms by continuing with the high dosages. It just seems to me that going more slowly is a wiser way to proceed at our current state of knowledge. Also, I think people are more likely to stick with the treatment if they do it at a level where the symptoms are tolerable. If a person stops the treatment because it is intolerable, there is no chance that the treatment will help them. If they continue with it, success is not guaranteed, but at least there will be the opportunity to see if the treatment will in fact help them.
In direct contradiction of both of these studies Fredd claims
Well this opinion just shows us how little Fredd knows about hypothyroidism and Hashimotos.
***Again, I think it's important to keep in mind the heterogeneity of the populations we are dealing with. I focus particularly on CFS, and the numbers I have given apply to CFS. freddd's treatment approach applies to a much broader population, including not only those with CFS, but also those who have any of a wide variety of problems in their B12 biochemistry. These can include B12 deficiency in the diet (such as in pure vegans), hypochlorhydria, lack of secretion of intrinsic factor or inability to recognize intrinsic factor in the ileum (pernicious anemia), intestinal disease such as Crohn's disease or celiac disease that interfere with the ability to absorb B12 bound to intrinsic factor, surgery that has removed the terminal ileum, transcobalamin deficiency, and any of several inborn errors of metabolism that affect one or more of the B12 processing enzymes in the cells. So when freddd cites prevalences, I think he is basing them on a broader population.
***The reason freddd's approach applies to this wider range of disorders is that he uses large dosages of the final, coenzyme forms of B12, and he applies them sublingually or by injection. This bypasses all of the B12 absorption, transport and processing pathways, and delivers the final forms of B12 directly to the cells. In the treatment I have proposed, the form of B12 is hydroxocobalamin, and this must be converted by the cells into the coenzyme forms. So this treatment does not bypass the function of the cells in regulating the amounts of the coenzyme forms that are produced.
I have no problem with anyone sharing what helped them and answering questions but I do have a very big problem with anyone who is not medically qualified and who displays a lack of understanding about Hashimotos to the extent that he confuses it with hypothyroidism, and makes the previous statement and when a growing number of desperate people try his protocol and have a reaction that is beyond detoxing or starting up or anything else (does he think that after years of this we do not know what a Herx is?) and he tells us to KEEP GOING instead of at that point saying I AM NOT MEDICALLY QUALIFIED TO ADVISE YOU IF YOU ARE HAVING SUCH A BAD REACTION YOU MUST SPEAK TO SOMEONE ELSE .
This is in my opinion VERY DANGEROUS.
***Again, I can't speak for freddd, and I have described my philosophy about this above.
We are being expected to accept that the two people here who are agreeing with each other that cannot be dangerous, know more on the subject than we sufferers do due to their understanding of the views of certain researchers yet the forums which have been mentioned for Hashi sufferers contain warnings about taking b12 supplements slowly. There is a lot of disagrement in the endocrinal world and we sufferers often have to go it alone and listen to our own bodies. So now we have two people telling us who have had a very bad reaction and mine was so bad that I was suicidal for a few days and I have been ill for a very long time with mercury poisoning and Lyme disease a combination that is hard to beat in terms of suffering, and the reaction to the b12 was more than I could take or had ever experienced before.
***I'm very sorry about the reaction you had to the treatment you tried. I wish we had a great deal more research completed, so that we would know exactly what the optimum treatment would be for each person. Unfortunately, we are still in the research stage with CFS, and we are having to feel our way with whatever information we can find. And having Lyme disease on top of it makes it very challenging.
All I ask is that when another person like us comes along and reacts like we have that they be told by Fredd that he cannot advise rather than what he is doing encouraging them to go on and telling them that what their body is saying most strongly, that their adrenals and thyroid cannot take the strain, is incorrect instead of overiding their concerns.
***Again, I can't answer for freddd.
The continuation of this issue which has been going on for quite some time, is causing me serious concerns about what is going on here. The fact that Fredd is actually encouraging people to continue instead of allowing them to do so without any outward pressure with NO MEDICAL QUALIFICATIONS regarding a condition which must be handled with extreme care, is what is being addressed but not emphasised enough.[/QUOTE]
***I think I've expressed my suggestions about how to respond to symptoms above. Again, my position is that a person needs to be working with a physician while on the treatment I have suggested, so that if serious adverse affects arise, they can be properly dealt with immediately. With regard to determining whether a reaction to the treatment is severe enough that the treatment should be stopped completely, I suggest consulting with a physician about that. If the symptoms appear to be due to detox and/or die-off, then I suggest that the person, together with their physician, decide whether proceeding at lower dosages would be advisable.
***I want to emphasize that I am a researcher, not a clinician. My focus is to try to understand the biochemical mechanism of CFS. The hypothesis I have proposed gives guidance for developing treatment, but it does not lead us directly to the optimum treatment, and I can't claim that the treatment I have suggested is the very best approach. I extracted it (with the help of a person who has CFS and is on the Yasko treatment) from the full treatment program that Amy Yasko, Ph.D., N.D. uses primarily for autism. I hope that in the future we can learn more about how to optimize the treatment. A small number of physicians who specialize in treating Lyme disease have incorporated testing for the methylation cycle block and treating it if it is found. However, this is only part of their treatment for Lyme disease.
***I also want to emphasize that I favor testing prior to deciding whether to undergo methylation cycle block treatment, using the methylation pathways panel offered by Vitamin Diagnostics, Inc. in the U.S., and by the European Laboratory of Nutrients in the Netherlands. Running this test will indicate whether a person has the biochemical abnormality that the treatment is designed to correct, and it will also provide baseline values for a number of parameters, which can be used to gauge the progress of the treatment. Evaluating whether the treatment is helpful based on symptoms can be difficult initially, because of the symptoms that I believe are due to detox and die-off of pathogens. So having lab-measured numbers can tell you whether progress is being made or not, until the symptom picture clears up, which may take some time.
***I hope this is helpful, and I hope you will be able to find an effective and tolerable way to treat your illness.
***Best regards,
***Rich
Can you explain the difference please?
***I think this difference arises from the heterogeneity of the CFS population. As you know, CFS is defined by a set of symptoms, and the diagnosis is made by exclusion of other known medical conditions. With this type of case definition, we end up with quite a variety in the people who are diagnosed with CFS. So when small numbers of patients are selected for clinical studies, there can be significant differences found between the groups due to the heterogeneity of the overall population and the resulting statistical variation.
No-one is questioning this. I have been using Jarrow b12 for years for my endocrine system, whichis another reason why I question what Fredd is saying. It was only when I took a massive dose, not the 200 to 400 mics mentioned that I had adverse effects. It is the amount that we have taken that we are questioning. I had a normal blood test result and took b12 for quite sometime before I took the huge dose that Fredd advises. I could not have been deficient.
***I can't speak for freddd, but I will address this from the point of view of the Glutathione Depletion--Methylation Cycle Block hypothesis that I have proposed to explain the etiology, pathogenesis and pathophysiology of CFS. According to this hypothesis, the problem with B12 in CFS is that glutathione has become depleted, leaving the B12 unprotected at a certain stage in its processing inside the cells. As a result, one can have a blood serum B12 test that comes out in the normal range, but still not be able to use B12 functionally in the cells to carry out its jobs. It has been found in autism, and we have also found in CFS, that it is necessary to raise the dosage of B12, and to take it together with one or more reduced forms of folate, in order to overcome this functional blockage and restore the methylation cycle and the glutathione levels to normal. This is apparently necessary to overcome the loss of B12 to reactions with toxins, which take place when it is unprotected. I originally encouraged PWCS just to elevate glutathione directly, but this did not turn out to be a successful longterm treatment. It was only when I learned of the success in autism that I realiized that the methylation cycle block must be treated to allow glutathione to come up on a permanent basis.
***With regard to the conventional blood serum B12 test, it is meaningful in cases in which the people are actually deficient in B12, and have been for an extended time. However, it is not very meaningful in CFS, where the issue is usually not lack of normal amounts of B12, but rather is the lack of proper B12 function. A better test in CFS is the urine methylmalonic acid test. This test will show whether enough adenosyl B12 is being made in the cells, because its lack will cause methylmalonic acid to rise. Usually if there is not enough adenosyl B12 being made, then there is also not enough methyl B12 being made, because they share the part of the pathway that involves protection of B12 by glutathione, through the formation of glutahionylcobalamin. An exception is the small number of people who have an inborn error of metabolism that affects only the formation of adenosyl B12, but this is a fairly rare genetic disorder.
***Normally, most of the B12 in the blood is carried by haptocorrin, and this part of the B12 is not accessible to cells other than liver cells. A smaller part is normally carried by transcobalamin. If a conventional serum B12 measurement is made, it does not distinguish between these two parts, and that is another problem in interpreting the results of this type of measurement.
***With regard to having adverse effects from larger dosages of B12 (together with reduced forms of folate), I think it is important to try to determine how adverse the effects are. The Simplified Treatment Approach that I have proposed is somewhat different from the protocol freddd has suggested, but when people first started using it 3 years ago, there were a small number of them who indeed had rather severe adverse effects. I have posted these in the past on this forum. This is the reason I insist that people should be working with their physicians while on this treatment. In some cases, the people involved had other comorbid conditions that were apparently responsible for the adverse effects, including autonomous multinodular goiter and autoimmune diseases. For the majority of people, who did not have such comorbidities, there were usually some unpleasant symptoms, which I believe are associated with die-off of pathogens and mobilization of toxins into the bloodstream. These last for differing lengths of time, presumably depending on the body burdens of infections and toxins that the person has accumulated.
***freddd and I seem to have different philosophies in our approach to these symptoms. My view is that it is best to lower the dosages of the supplements to levels that make the detox and die-off symptoms tolerable. It will take time to clear these out of the body. I wish it were faster, but times of at least two years do not seem to be unusual for someone who has been ill for an extended period of time. I do not have proof that this approach is better in the long run than "pushing through" the symptoms by continuing with the high dosages. It just seems to me that going more slowly is a wiser way to proceed at our current state of knowledge. Also, I think people are more likely to stick with the treatment if they do it at a level where the symptoms are tolerable. If a person stops the treatment because it is intolerable, there is no chance that the treatment will help them. If they continue with it, success is not guaranteed, but at least there will be the opportunity to see if the treatment will in fact help them.
In direct contradiction of both of these studies Fredd claims
Well this opinion just shows us how little Fredd knows about hypothyroidism and Hashimotos.
***Again, I think it's important to keep in mind the heterogeneity of the populations we are dealing with. I focus particularly on CFS, and the numbers I have given apply to CFS. freddd's treatment approach applies to a much broader population, including not only those with CFS, but also those who have any of a wide variety of problems in their B12 biochemistry. These can include B12 deficiency in the diet (such as in pure vegans), hypochlorhydria, lack of secretion of intrinsic factor or inability to recognize intrinsic factor in the ileum (pernicious anemia), intestinal disease such as Crohn's disease or celiac disease that interfere with the ability to absorb B12 bound to intrinsic factor, surgery that has removed the terminal ileum, transcobalamin deficiency, and any of several inborn errors of metabolism that affect one or more of the B12 processing enzymes in the cells. So when freddd cites prevalences, I think he is basing them on a broader population.
***The reason freddd's approach applies to this wider range of disorders is that he uses large dosages of the final, coenzyme forms of B12, and he applies them sublingually or by injection. This bypasses all of the B12 absorption, transport and processing pathways, and delivers the final forms of B12 directly to the cells. In the treatment I have proposed, the form of B12 is hydroxocobalamin, and this must be converted by the cells into the coenzyme forms. So this treatment does not bypass the function of the cells in regulating the amounts of the coenzyme forms that are produced.
I have no problem with anyone sharing what helped them and answering questions but I do have a very big problem with anyone who is not medically qualified and who displays a lack of understanding about Hashimotos to the extent that he confuses it with hypothyroidism, and makes the previous statement and when a growing number of desperate people try his protocol and have a reaction that is beyond detoxing or starting up or anything else (does he think that after years of this we do not know what a Herx is?) and he tells us to KEEP GOING instead of at that point saying I AM NOT MEDICALLY QUALIFIED TO ADVISE YOU IF YOU ARE HAVING SUCH A BAD REACTION YOU MUST SPEAK TO SOMEONE ELSE .
This is in my opinion VERY DANGEROUS.
***Again, I can't speak for freddd, and I have described my philosophy about this above.
We are being expected to accept that the two people here who are agreeing with each other that cannot be dangerous, know more on the subject than we sufferers do due to their understanding of the views of certain researchers yet the forums which have been mentioned for Hashi sufferers contain warnings about taking b12 supplements slowly. There is a lot of disagrement in the endocrinal world and we sufferers often have to go it alone and listen to our own bodies. So now we have two people telling us who have had a very bad reaction and mine was so bad that I was suicidal for a few days and I have been ill for a very long time with mercury poisoning and Lyme disease a combination that is hard to beat in terms of suffering, and the reaction to the b12 was more than I could take or had ever experienced before.
***I'm very sorry about the reaction you had to the treatment you tried. I wish we had a great deal more research completed, so that we would know exactly what the optimum treatment would be for each person. Unfortunately, we are still in the research stage with CFS, and we are having to feel our way with whatever information we can find. And having Lyme disease on top of it makes it very challenging.
All I ask is that when another person like us comes along and reacts like we have that they be told by Fredd that he cannot advise rather than what he is doing encouraging them to go on and telling them that what their body is saying most strongly, that their adrenals and thyroid cannot take the strain, is incorrect instead of overiding their concerns.
***Again, I can't answer for freddd.
The continuation of this issue which has been going on for quite some time, is causing me serious concerns about what is going on here. The fact that Fredd is actually encouraging people to continue instead of allowing them to do so without any outward pressure with NO MEDICAL QUALIFICATIONS regarding a condition which must be handled with extreme care, is what is being addressed but not emphasised enough.[/QUOTE]
***I think I've expressed my suggestions about how to respond to symptoms above. Again, my position is that a person needs to be working with a physician while on the treatment I have suggested, so that if serious adverse affects arise, they can be properly dealt with immediately. With regard to determining whether a reaction to the treatment is severe enough that the treatment should be stopped completely, I suggest consulting with a physician about that. If the symptoms appear to be due to detox and/or die-off, then I suggest that the person, together with their physician, decide whether proceeding at lower dosages would be advisable.
***I want to emphasize that I am a researcher, not a clinician. My focus is to try to understand the biochemical mechanism of CFS. The hypothesis I have proposed gives guidance for developing treatment, but it does not lead us directly to the optimum treatment, and I can't claim that the treatment I have suggested is the very best approach. I extracted it (with the help of a person who has CFS and is on the Yasko treatment) from the full treatment program that Amy Yasko, Ph.D., N.D. uses primarily for autism. I hope that in the future we can learn more about how to optimize the treatment. A small number of physicians who specialize in treating Lyme disease have incorporated testing for the methylation cycle block and treating it if it is found. However, this is only part of their treatment for Lyme disease.
***I also want to emphasize that I favor testing prior to deciding whether to undergo methylation cycle block treatment, using the methylation pathways panel offered by Vitamin Diagnostics, Inc. in the U.S., and by the European Laboratory of Nutrients in the Netherlands. Running this test will indicate whether a person has the biochemical abnormality that the treatment is designed to correct, and it will also provide baseline values for a number of parameters, which can be used to gauge the progress of the treatment. Evaluating whether the treatment is helpful based on symptoms can be difficult initially, because of the symptoms that I believe are due to detox and die-off of pathogens. So having lab-measured numbers can tell you whether progress is being made or not, until the symptom picture clears up, which may take some time.
***I hope this is helpful, and I hope you will be able to find an effective and tolerable way to treat your illness.
***Best regards,
***Rich
Sunday,
Another comment on my experience - when I started the protocol all of my horrible fatigue went away with low doses of adB12, after a while I increased the adB12 and found the fatigue returning (like my cofactors ran out as Freddd suggests). At the higher doses of adB12 I needed to take more carnitine. Also, I'm taking large doses of methylfolate too - I didn't note any particular effect physically when increasing the dose except less mB12 coloring in my urine, so I decided to keep the dose higher for now.
Velha
R
Robin
Guest
re: defence against abuse
lebowski,
Criticism can be valid, both here and in the scientific community. Simply disagreeing is not "trolling" or attacking; and arguing on the scientific merits or pointing out possible adverse reactions is OK.
These are open forums in the context that all points of view are welcome. What critics may not do is attack Freddd personally.
Brenda and everyone, the forum rules have been revised to include this clause:
The messages on the Forums do not constitute medical advice by qualified health professionals. Always consult your physician before trying any user recommended treatments.
OK, again I will leave this thread to your B12 discussion.
lebowski,
Criticism can be valid, both here and in the scientific community. Simply disagreeing is not "trolling" or attacking; and arguing on the scientific merits or pointing out possible adverse reactions is OK.
These are open forums in the context that all points of view are welcome. What critics may not do is attack Freddd personally.
Brenda and everyone, the forum rules have been revised to include this clause:
The messages on the Forums do not constitute medical advice by qualified health professionals. Always consult your physician before trying any user recommended treatments.
OK, again I will leave this thread to your B12 discussion.
Freddd
Senior Member
- Messages
- 5,184
- Location
- Salt Lake City
Hi Brenda,
I am including quotes from Rich to respond to some of the things he left open in regards to me in responding to you.
***I can't speak for freddd, but I will address this from the point of view of the Glutathione Depletion--Methylation Cycle Block hypothesis that I have proposed to explain the etiology, pathogenesis and pathophysiology of CFS. According to this hypothesis, the problem with B12 in CFS is that glutathione has become depleted, leaving the B12 unprotected at a certain stage in its processing inside the cells. As a result, one can have a blood serum B12 test that comes out in the normal range, but still not be able to use B12 functionally in the cells to carry out its jobs. It has been found in autism, and we have also found in CFS, that it is necessary to raise the dosage of B12, and to take it together with one or more reduced forms of folate, in order to overcome this functional blockage and restore the methylation cycle and the glutathione levels to normal. This is apparently necessary to overcome the loss of B12 to reactions with toxins, which take place when it is unprotected. I originally encouraged PWCS just to elevate glutathione directly, but this did not turn out to be a successful longterm treatment. It was only when I learned of the success in autism that I realiized that the methylation cycle block must be treated to allow glutathione to come up on a permanent basis.
It is the amount that we have taken that we are questioning. I had a normal blood test result and took b12 for quite sometime before I took the huge dose that Fredd advises. I could not have been deficient.
I come at this from a much broader base of people with a multitude of manifestations of this lack of active b12s. It may indeed be that their active b12s are not protected from destruction by toxins. Another way to look at it is that there is insufficient b12 to overcome the toxins, and mb12 is a potent detoxifier in sufficient quantity. For it to destroy toxins it needs to be available in excess of the bpound levels.
"Normal" blood tests are NOT predictive of who will respond to active b12s. In one study in which people are selected by symptoms rather than by test results, 63% of the positive responders would have been excluded by test results with the initial average serum cobalamin level over 700pg/ml and some higher than 1500pg/ml, above the usual top end of the "normal" range. Further, the blood test gives no indication of whether a deficiency exists in the cerebral spinal fluid which has been found to exist in CFS/FMS studies. Further the blood tests lumps it all together and does not distinguish between the possiblitlity of specific mb12 and/or adb12 deficiencies in the body. A person can have up to 4 specific deficiencies. The uMMA test can detect a severe deficiency of adb12 and HCY can detect a severe deficiency of mb12 but again neither of these can give a CSF/CNS cobalamin status. I think that I have posted some studioes that show the ineffectiveness of testing, and if I haven't posted them here, I will.
***With regard to the conventional blood serum B12 test, it is meaningful in cases in which the people are actually deficient in B12, and have been for an extended time. However, it is not very meaningful in CFS, where the issue is usually not lack of normal amounts of B12, but rather is the lack of proper B12 function. A better test in CFS is the urine methylmalonic acid test. This test will show whether enough adenosyl B12 is being made in the cells, because its lack will cause methylmalonic acid to rise. Usually if there is not enough adenosyl B12 being made, then there is also not enough methyl B12 being made, because they share the part of the pathway that involves protection of B12 by glutathione, through the formation of glutahionylcobalamin. An exception is the small number of people who have an inborn error of metabolism that affects only the formation of adenosyl B12, but this is a fairly rare genetic disorder.
Due to the widespread results of people, including many on this board, having distinctly different results from adb12 and mb12 I question the actual rarity. Perhaps there is more than one form of the genetic disorder(s) or perhaps the diagnosis of CFS concentrates them. The adb12 appears more effective than mb12 at dealing with severe fatigue, exercise intolerance, muscle rebuilding and repair and a major contributor to eliminating brainfog.
***With regard to having adverse effects from larger dosages of B12 (together with reduced forms of folate), I think it is important to try to determine how adverse the effects are. The Simplified Treatment Approach that I have proposed is somewhat different from the protocol freddd has suggested, but when people first started using it 3 years ago, there were a small number of them who indeed had rather severe adverse effects. I have posted these in the past on this forum. This is the reason I insist that people should be working with their physicians while on this treatment. In some cases, the people involved had other comorbid conditions that were apparently responsible for the adverse effects, including autonomous multinodular goiter and autoimmune diseases. For the majority of people, who did not have such comorbidities, there were usually some unpleasant symptoms, which I believe are associated with die-off of pathogens and mobilization of toxins into the bloodstream. These last for differing lengths of time, presumably depending on the body burdens of infections and toxins that the person has accumulated.
Mb12 has more effects on more things all at the same time than hydroxyb12. Also, it has in studies shown to have a dose proportionate response unlike hydroxyb12 because it is not limited to what can be carried via the usual channels. Based on much personal experince and observation of many others the curve is not linear. The most effect is achieved in the first 250mcg reaching the serum and it falls off after that. A 5000mcg sublingual has only somewhat more noticable effects than a 1000mcg. Going to 25,000mcg makes only a little difference over 5000mcg. In terms of injections, the first 250mcg has a huge effect. 1000mcg has a bit more. 5000mcg doesn't produce a noticable difference by many. There is one additional step when the CNS effects start showing up between 5mg and 7.5mg. Beyond that injections to 25mg make no additional perceivable difference. The falloff of "startup" effects is similar. More doesn't make a linear difference though there may be an intiual noticable threshold once one gets above the bound level. I wish it were easy to find a knowledgable physician. Many don't believe that a sublingual mb12 could have any effect at all and that any perceived effect is placebo. I've been told that over and over. In fact I've been told that injections don't have noticable effects either and must be placebo effect. However, ignorance of b12 and folate aside, I work with my physician with this and have all along. I am tested regularly with what he considers the important tests for montoring my situation. Many people have to take the these vitamins despite their physicians telling them that they are worthless and do nothing.
***freddd and I seem to have different philosophies in our approach to these symptoms. My view is that it is best to lower the dosages of the supplements to levels that make the detox and die-off symptoms tolerable. It will take time to clear these out of the body. I wish it were faster, but times of at least two years do not seem to be unusual for someone who has been ill for an extended period of time. I do not have proof that this approach is better in the long run than "pushing through" the symptoms by continuing with the high dosages. It just seems to me that going more slowly is a wiser way to proceed at our current state of knowledge. Also, I think people are more likely to stick with the treatment if they do it at a level where the symptoms are tolerable. If a person stops the treatment because it is intolerable, there is no chance that the treatment will help them. If they continue with it, success is not guaranteed, but at least there will be the opportunity to see if the treatment will in fact help them.
This is a major difference. With the active b12s and folate, initial startup effects of whatever cause are usually more or less finished in 2-4 months though they may be more intense while occurring. Overall, across the many different manifestations of these deficiencies, a relatively small percentage have startup effects anywhere near as intense as what I had or more so. In other circumstances it has been much more difficult to have enough strartup effects so that the person is sure that anything is happening and the initial form of the protocol reflected the needed to produce ANY effect within the first month so as to be convincing to the person that continuing could be of some help. This may be because of the dose proportionate effect of mb12 and doing more faster. As other cofactors are added in additional startup effects often occur, also of up to several months duration typically. Further, neuropsychiatric healing appears to take several months to start and to have a several month unpleasant period quite independent of what the body is doing.
***Again, I think it's important to keep in mind the heterogeneity of the populations we are dealing with. I focus particularly on CFS, and the numbers I have given apply to CFS. freddd's treatment approach applies to a much broader population, including not only those with CFS, but also those who have any of a wide variety of problems in their B12 biochemistry. These can include B12 deficiency in the diet (such as in pure vegans), hypochlorhydria, lack of secretion of intrinsic factor or inability to recognize intrinsic factor in the ileum (pernicious anemia), intestinal disease such as Crohn's disease or celiac disease that interfere with the ability to absorb B12 bound to intrinsic factor, surgery that has removed the terminal ileum, transcobalamin deficiency, and any of several inborn errors of metabolism that affect one or more of the B12 processing enzymes in the cells. So when freddd cites prevalences, I think he is basing them on a broader population.
Quite so. About one third of people do not respond to the inactive cobalamins. About 20% don't respond to mb12 alone.
***The reason freddd's approach applies to this wider range of disorders is that he uses large dosages of the final, coenzyme forms of B12, and he applies them sublingually or by injection. This bypasses all of the B12 absorption, transport and processing pathways, and delivers the final forms of B12 directly to the cells. In the treatment I have proposed, the form of B12 is hydroxocobalamin, and this must be converted by the cells into the coenzyme forms. So this treatment does not bypass the function of the cells in regulating the amounts of the coenzyme forms that are produced.
I have found that bypassing all of the assumptions about what the body can utilize and transport tremendously increases positive results. I think that there is a whole group of illnesses that concentrates people with one or more of these groups of problems. In treating in this way many complicating symptoms are removed from consideration revealing comorbidities including bacterial overgrowth and parasites as actual causes of the b12 problems. Long frustrating periods of lack of positive results are avoided. By starting things fairly rapidly and then removing those things that don't make a difference much floundering is avoided.
The active b12s usually have such pronounced effects that lab tests are not needed to show that healing is occurring. Further, the interpretation of many tests is corrupted by 50 years of inactive b12s and folate being the norm. Again, this is my opinion. Also, unfortunately, most physicians haven't the foggiest idea of what tests to run in this arenaor how to interpret them. Mostly they are not even aware of the MCV creep upwards so that borderline macrocytotic and lots of multisegmented neutraphils and low platelet etc is the new "normal". They don't use what they have.
And Brenda, I can't "override your concerns" I can only suggest a different interpretation. I have no power. I'm a data analyst used to working with big data sets that may not apply to any specific individual. I can only make predicitions based on the data. So looking at your symptoms the first prediction is that active b12s would have a significant effect and cause significant and intense startup symptoms. Use your doctor for your concerns and to check and see what is dangerous compared to what is uncomfortable. There is a substantial difference. Personally I was willing to tolerate some changes in discomfort as it was already way too much and too miserable. It was bad enough I woke up every day for more than a decade in tears wanting to die and not being so blessed. For me at least it was already maximum bad and intolerable. Changes were just changes and some things got much better very quickly and I still dealing with others.
winston
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Hi Velha508, I would like to know what dose of the B's you are on and if you also need the injections and if so how many a day. I am on my fourth try of this protocol and finally am able to tolerate the B's without nausea. It sounds very intimadating to even think about injections. Hopefully I won't need them. It appears their are many who do the injections. Thanks.
Lena
Lena
Freddd
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Hi Robin,
Consider that probably 90% of the discussion in these forums is alternative medicine and thus outside mainstream; for example if you went to an MD s/he would tell you that there is no evidence for such things as detox or chronic lyme disease.
I think you have hit the nail on the head here. The attitudes of physicians towards certain groups of patients, the "Rodney Dangerfields" of the medical world, makes it almost impossible to get good medical care once we are categorized. I have had the misfortune to be placed in multiple despised categories; chronic pain, FMS,CFS, B12 deficient but not by tests. When some of the prominent b12 deficiency symptoms were assigned to the "conversion disorder" category 60 years before b12 was discovered in any form, and many docs still believe that, they automatically make many of us "Its All In Your Head" cases and effective diagnosis becomes impossible.
I took a friend into an urgent medical care clinic last week. She had a deep infection in her thumb and was having generalized worsening body symptoms. They wanted to blame the symptoms on the morphine she takes despite her being accomodated to morphine for several years and having no post dose reactions of any kind typically and very minor transient ones with a larger dose. Because of the psychological effect on docs chronic pain patients can't get treatment in an ER or urgent care clinic that is worth a bucket of warm spit if pain is a symptom and often even if it isn't. When the docs see I'm on 30mg of injectable b12 a day they think I must be toxic with it and my problems have to be caused by that or the morphine I also take. Or they decide IAIYH and any reasonable treament becomes impossible. In many cases they seem to be out to punish a person in morphine or other pain management drug. In 1995 when I ended up in the hospital ER with a serious gall bladder attack they ignored me for 5 hours until 10mg of oxycodone must be out of my system and threatened to kick me out if I couldn't control my moaning because it was disturbing the patients.
The reason all of us are at a forum like this is that the conventional medical system as presently constituted belittles us, treats us badly, and doesn't treat us effectively. For some reason, they hear the words "detox" or "chronic lyme" or "b12 deficiency" or "pain managment" or other taboo words and turn off their brains instead of trying to understand what is happening despite the use of the forbidden words. Once a doc does that they become useless to us and treat us as if we were committing blasphemy in church.
Some docs don't do this and those who find such a doctor are very lucky. As a plan design consultant I would make substantial changes to the system in order to handle people like us much better. However, many of us are completely excluded from buying insurance because we are uninsurable because of our "imaginary" diseases and problems.
Sunday
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Yay Lena, I'm so glad you're finally getting though this (and WITHOUT nausea, I am envious!). Please keep us posted, I'm interested to hear of any changes.
dmholmes, interesting about the effects of the gluten-free diet. I hadn't thought about that. Right now I'm taking 800mg methylfolate, one tablet. I'm thinking given your and Velha's experience it would make sense for me to up that dose, esp. as I had a pretty strong reaction to it when I started it up.
Velha, thanks for the further info. I know we're all different, but it's very helpful for me to hear of people's experiences; it fleshes out the protocol and gives me ideas of ways to tinker with it, to get it the best it can be for me. I think when I re-order my supplements I might double up on the l-carnitine as well and see how that goes. It would be great if I could get my energy level up, esp. now my brainfog is clearing a bit and I can think what to do.
And in general, I'm happy to report that I feel good today! And since yesterday I spent 20 minutes or so stacking firewood (my nemesis the last time) AND I had a friend in for tea AND I went out to my writer's group, this is really excellent news. In this new stage, it seems to be taking about 2 weeks to get over the last dose-uppage (although that's based on a pretty small sample). Anyway, instead of upping my dosage once again, I think I'm going to stay where I am and give myself a couple of days of actually feeling like a human being, and get some stuff done! Then back on the methylation wagon.
dmholmes, interesting about the effects of the gluten-free diet. I hadn't thought about that. Right now I'm taking 800mg methylfolate, one tablet. I'm thinking given your and Velha's experience it would make sense for me to up that dose, esp. as I had a pretty strong reaction to it when I started it up.
Velha, thanks for the further info. I know we're all different, but it's very helpful for me to hear of people's experiences; it fleshes out the protocol and gives me ideas of ways to tinker with it, to get it the best it can be for me. I think when I re-order my supplements I might double up on the l-carnitine as well and see how that goes. It would be great if I could get my energy level up, esp. now my brainfog is clearing a bit and I can think what to do.
And in general, I'm happy to report that I feel good today! And since yesterday I spent 20 minutes or so stacking firewood (my nemesis the last time) AND I had a friend in for tea AND I went out to my writer's group, this is really excellent news. In this new stage, it seems to be taking about 2 weeks to get over the last dose-uppage (although that's based on a pretty small sample). Anyway, instead of upping my dosage once again, I think I'm going to stay where I am and give myself a couple of days of actually feeling like a human being, and get some stuff done! Then back on the methylation wagon.
Sunday
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B12s for other neuro illnesses
Freddd, could you give me your opinion on whether you think this protocol (or something like it) might be useful for someone with peripheral neuropathies, but not CFS? My brother-in-law has some trouble with this; the neurologists tested him up the wazoo and gave him a multisyllabic five-word name for it, but basically have no clue. I'm wondering if this protocol, or some variant, could help him.
I'm also wondering what your thoughts are on this protocol and ALS. A friend of a friend is in bad trouble with ALS, and I was thinking of advising him to check this out (among a couple of other options), because it seems to me that the neuro aspects and symptoms of ALS might overlap with the CFS/FM B12 deficiency symptoms. Since you have experience with a broader spectrum of B12 deficiencies, I think your opinion would be particularly helpful.
Anyone else wants to pitch in with illuminating comments, please do!
Freddd, could you give me your opinion on whether you think this protocol (or something like it) might be useful for someone with peripheral neuropathies, but not CFS? My brother-in-law has some trouble with this; the neurologists tested him up the wazoo and gave him a multisyllabic five-word name for it, but basically have no clue. I'm wondering if this protocol, or some variant, could help him.
I'm also wondering what your thoughts are on this protocol and ALS. A friend of a friend is in bad trouble with ALS, and I was thinking of advising him to check this out (among a couple of other options), because it seems to me that the neuro aspects and symptoms of ALS might overlap with the CFS/FM B12 deficiency symptoms. Since you have experience with a broader spectrum of B12 deficiencies, I think your opinion would be particularly helpful.
Anyone else wants to pitch in with illuminating comments, please do!
Freddd
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Hi Sunday,
Freddd, could you give me your opinion on whether you think this protocol (or something like it) might be useful for someone with peripheral neuropathies, but not CFS?
I first ran into an early form of this protocol on a peripheral neuropathy forum. I didn't originate it. I organized it and did brand testing and other things in order to produce more consistant results. In other words I debugged it. I certainly do think that it could be helpful. Studies show that mb12 promotes neurological healing regardless of what caused the damage; physical, toxic chemical, diabetes, deficiency, etc. Also, this may indicate that your friend has a mb12 deficiency without an adb12 deficiency, but not necessarily, and not be visible to testing for that reason. More than half of the neuropathies are never attributed to a cause.
I'm also wondering what your thoughts are on this protocol and ALS. A friend of a friend is in bad trouble with ALS, and I was thinking of advising him to check this out (among a couple of other options), because it seems to me that the neuro aspects and symptoms of ALS might overlap with the CFS/FM B12 deficiency symptoms.
The high dose part of all this comes from Japanese research on the effects high dose mb12 on ALS and MS. A site on ALS in general with a lot of active discussion forums is:
http://www.als.net/
http://www.als.net/forum/Default.aspx?g=posts&m=321147񎙻
The second link is to the methylb12 info. Most of it predates my posts and nobody is trying these methods that I can tell. Some people have tried mb12 but mostly in ways that can be predicted to fail.
In the Japanese research several things were evident.
- There was definite functional improvment that lasted for the duration of the study but not long past the discontinuance of high dose b12.
- The studies were of short duration, a few months at best.
- Dosing frequency and sizes were haphazard. They picked one dose and frequency and used it the entire study. Not one of the studies did titrations to find the minimum effective single dose nor to find the optimum dosing frequency for maximum sustained effect.
In this, CNS effectiveness appears to depend heavily upon the batch of b12 involved. Not all mb12 is created equal.
It may not suprise you that when investigating what supplements were used for ALS they included every one of the critical cofactors and basics that we include here. The ONLY thing the people putting out those nutritional protocols had missed were brand or batch differences that we have found so important and method of taking mb12. They also missed the adb12.
juniemarie
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Sunday Bravo! It is uplifting when someone having some success, and I complete agree about how helpful it is in fine tuning our own protocol when people post their experience , as you say it fleshes it out.
Sunday
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Freddd, thanks so much, that's really helpful info.
Junemarie, thank you too! It's nice to have others (who know what it means) marking my progress. I guess the encouragement works both ways around, because I'm also uplifted when I see good reports from someone on this thread.
Junemarie, thank you too! It's nice to have others (who know what it means) marking my progress. I guess the encouragement works both ways around, because I'm also uplifted when I see good reports from someone on this thread.
Rich, are elevated liver enzymes (AST, ALT) directly related to methylation disfunction? I have not come across this in the literature. I have had mildly elevated enzymes for the last 5 years (when the b12 levels were in the process of eroding). ALT roughly 70, and AST at around 50 to 60. For my weight, I was told these levels are unusual. I have been examined very closely by one of the best liver specialists for several years. No signficant problems have been found with the liver itself (very slight fatty liver, but nothing that would cause the inflammation indicated by elevated liver enzymes). My last blood test continues to indicate mildly elevated liver enzymes. I do not drink and am very healthy (other than the b12 deficiency and hypothyroidism).
It would probably be a good idea for me to get the methyl. panel done, although I won't have a pre-b12 protocol snapshot to compare it to.
thanks
Edit:
I SEE YOUR SUBSEQUENT POST AND AM INCLUDING IT HERE AGAIN.
Hi, Janis.
Here's a possible explanation for the low bile production:
Glutathione is used by the liver to produce the fraction of bile that is not associated with bile salts. So if the methylation cycle is overdriven to the point that the flow down the transsulfuration pathway goes very low, as appears to be what happened in your case, then the glutathione production will drop, and lower bile volume would be one consequence of that. High liver enzymes could reflect high oxidative stress in the liver cells, also a consequence of lowering glutathione.
Rich
Rich, other than P5P/B6, what are some of the other supplements (of the top of your head) that could be used to speed up the flow through the transsulfuration pathway?
Hi, DrD.
As you may know, elevated liver enzymes in the blood mean that the liver cells are dying more rapidly than normal. There are many possible causes for this. Since you've had a liver specialist on your case, I'm guessing that the usual causes have been ruled out. If you have CFS, I think it is very likely that you have glutathione depletion and a partial methylation cycle block. If glutathione goes too low in the liver, it can develop oxidative stress, and that is a possible cause of die-off of liver cells. Conventional doctors do not test for this. I do think that the Vitamin Diagnostics methylation pathways panel might be helpful for you. I don't know if you take supplements that are known to be particularly helpful to the liver. Some that are include selenium, B vitamins, alpha lipoic acid, Milk Thistle or silymarin, and N-acetylcysteine. If there is a high body burden of mercury, Dr. David Quig of Doctor's Data Labs has recommended that the N-acetylcysteine dosage be limited to 300 mg per day. Alpha lipoic acid can also move mercury around, so care should be taken with that one if mercury is abundant, too.
Best regards,
Rich
As you may know, elevated liver enzymes in the blood mean that the liver cells are dying more rapidly than normal. There are many possible causes for this. Since you've had a liver specialist on your case, I'm guessing that the usual causes have been ruled out. If you have CFS, I think it is very likely that you have glutathione depletion and a partial methylation cycle block. If glutathione goes too low in the liver, it can develop oxidative stress, and that is a possible cause of die-off of liver cells. Conventional doctors do not test for this. I do think that the Vitamin Diagnostics methylation pathways panel might be helpful for you. I don't know if you take supplements that are known to be particularly helpful to the liver. Some that are include selenium, B vitamins, alpha lipoic acid, Milk Thistle or silymarin, and N-acetylcysteine. If there is a high body burden of mercury, Dr. David Quig of Doctor's Data Labs has recommended that the N-acetylcysteine dosage be limited to 300 mg per day. Alpha lipoic acid can also move mercury around, so care should be taken with that one if mercury is abundant, too.
Best regards,
Rich
hi Rich, Yes every conceivable liver test has been run (copper, Wilson's, even some very very rare disorders). I am taking many of the Freddd protocol supplements right now. I don't have CFS, but had a major b12 deficiency crash that put me down several months back. I am doing much better on the Freddd protocol (inlcuding methyl injections). The liver doc is stumped. (has been for the last 4 years). I am on all the b vitamins in accordance w/ the protocol. I also started SAM-e which is supposed to help the liver as well. I was on Milk Thistle for a long time several years back, but it did not lower the AST or ALT. Also, someone mentioned fish oil causing inflammation. We are not sure, but large doses of fish oil appear to raise my ALT and AST enzymes for some reason. I will look into the selenium and ALA. thanks
Edit: Rich, if i get teh Vitamin Diags methyl pathw. panel done, could i forward the results to you as well. I don't think my General Practitioner would understand what to do with the results, frankly speaking.....