Thiamine

For years I have read about thiamine, and thiamine deficiency, in ME. Thiamine deficiency is known to cause many symptoms that are similar to ME. There are a few stories of people improving with taking thiamine injections. Here is one story. There are others, enough to make me wonder more than once over the past few years of the need to check for thiamine deficiency.

In the search for information about hyperacusis I came across this fine article by Melody O'Beau, written, I presume, years ago. In it she relates her experience with a rare metabolic disorder that short-circuits thiamine being taken up and used by the body. It is not so much the amount of thiamine in the blood, but more the "functionality" of thiamine in the body. This functionality is low, presumably the result of a missing enzyme. Melody postulates, in her case, that this is a mitochondrial defect. Coincidentally, a few months ago, Dr. Joseph Brewer handed me a copy of this same article (of which I was aware) but this "reminder" stirred my interest enough to finally pursue the functional thiamine test (for my daughter) suggested in Melody's blog.

This test is call the transketolase test and can be done for $1oo at the King James Medical Laboratory in Westlake, OH (1-800- 437-1404). The lab needs two blood vials, one ambient, one frozen, both shipped overnight. They give two result - one, a baseline blood level of thiamine, and two, a level of the functionality of thiamine under TP provocation. Results over 17% indicate poor functionally of thiamine - and the need to raise thiamine levels, most likely through injections. Results of raising thiamine can be dramatic.

Dr. David Bell writes about this low thiamin functionality in his Lyndonville News.

"Full thiamine deficiency is rare because of generally good nutrition, but some persons have a defect in the enzyme system that uses thiamine and as a result have dysautonomic symptoms. This can be detected with an erythrocyte transketolase index, where thiamine pyrophosphate (TPP) stimulation test greater than 14% demonstrates thiamine deficiency. The illness, caused by an enzyme abnormality, can be effectively treated by giving very high doses of thiamine which bypass the defect."

People with this situation have a difficult time raising thiamine with oral supplements. In this case, they take thiamine injections on a daily or twice weekly schedule. The injections can range from .1 ml to 2ml depending on the patient's particular need, which is determined by trial and error.

Thiamine function deficiency has been postulated to cause fatigue, muscular and sensitivity issues. The following bit of information appears on various sites: "Vitamin B1 (thiamine) deficiency produces optic nerve dysfunction". A noted mitochondrial researcher wrote to me, "The functional thiamine deficiency is an important finding as vitamin B1 is needed to get magnesium into cells. In muscle ATP always works as a complex with magnesium so correcting intracellular magnesium and factors that affect it like thiamine status is important."

From another dysautonomia study can be found this: "In spite of its largely unknown action TTP deficiency may play an important part since it is synthesized in mitochondria, supporting the conclusion that thiamine is an important nutrient where there is mitochondrial disruption."

Thiamine deficiency falls into the realm of something that is clearly identifiable and "something that is treatable". These are categories that escape ME patients except in rare instances - like Hashimoto's thyroiditis.

The internet is quite an amazing place to gather information. In this case the "trip-switch" information was written up quite a number of years ago by a seriously involved Lyme patient. Years later others are able to benefit from her written testimony/experience. I have communicated my appreciation to Melody herself, and noted the usefulness of this article written long ago.

Mitochondria

Recent events have gotten me to focus again on mitochondria and its relation to ME. None of the following is presented as medical advice or guidance. I am not a doctor and I do not want to be one. On the other hand, it is worth noting that those with ME are "on their own" when it

comes to medical diagnosis and treatment. The situation for ME sufferers is worse than the 19th century, when physicians at least would ply their trade.

Dr. Sarah Myhill's website, perhaps the most extensive ME website on the internet, has ample information on the critical role that mitochondria play in ME. It is a great starting point. Another informative article is by Dr. David Bell, and can be found in his Lyndonville News here. Dr Bell, an excellent clinician trying to find answers, has had a long-standing interest in the role of mitochondria in ME.

Various clinicians - Dr Joseph Brewer, Dr Sarah Myhill, Dr Paul Cheney - believe that mitochondrial irregularities play a part - perhaps a very large part - in ME/CFS. You can read an article by Dr. Myhill here. In this article Dr. Myhill outlines how mitochondrial failure plays such a very big role in ME. (Incidentally not everyone has caught on to this idea.)

Dr. Myhill collaborated with Dr. John McLaren Howard and Dr. Norman Booth in an important study published in January 2009. This paper, which can be viewed here, was presented by Dr. Booth at the IACFS conference in Reno, NV in 2009. A short article on these three researchers is available here.

Dr. John McLaren Howard is a real unsung hero in ME research. Dr. Howard co-founded Biolab in London (with Dr. Stephen Davies). Prior to retiring from Biolab a few years ago, Dr. Howard pioneered some very important testing in the area of mitochondria and ME. He has continued to do these tests at Acumen lab in Cornwall. His son Mark continues to work as Manager of Biolab.

Dr Myhill's website gives a good explanation of what Acumen is looking for in their testing.

The test itself is relatively easy to do. I believe my daughter was the first person from the US to do this test, back in 2007. In crude terms the test measures ATP function (the rate at which it is recycled into cells) and the efficiency with which ATP is made from ADP. Further testing looks at various blockages to the transport of ATP and ADP. Here is an example of an ATP results page:

The blood test requires one heparanised and one EDTA tube, shipped ambient via Fedex to Acumen lab in the UK. USA Fedex shipments have to be sent to Acumen labs, c/o Cameras Plus, 17A Gold Street, Tiverton, Devon UK EX16 6QB. The samples have to be shipped "international priority" which will get them to Dr. Howard in 48 hours. They need to be shipped in an insulated pack with the proper paperwork. Fedex will help with the international shipping label. They will not help with the packaging in any way. A triplicate copy of an international waybill needs to be filled out in a specific way, the process of which can also be learned through the Fedex site. If the blood is drawn into the correct tubes, if the shipment is packed according to international Fedex procedures, if the paperwork is filled out properly, the sample will breeze through customs to Acumen labs in a timely fashion. Some care has to be taken in these matters.

The test can be done through Dr. Myhill. She will write a particularized summary that is very useful. She has seen hundreds of these tests and works closely with Dr. Howard.

Rich van Konynenburg's thoughts (always welcome) on mitochondria and ME can be seen on the Phoenix Rising forum. This ME/CFS information site was founded by Cort Johnson. This website provides us all with much needed information and connections - and is an ongoing, necessary resource. Not a day goes by that I do not read it.

The big question is, once the specific mitochondria problems are identified, can these deficiencies be rectified? As with all matters with ME, the proof is in the pudding. It is trial and error - but at least the patient has a target, and a means of measurement and tracking. Many people have been helped by this test and its targeted treatment.

Is it possible that such sharp and diverse minds as Myhill, Cheney, Howard, Booth, Bell, and Brewer can be gathered around a subject - mitochondrial failure - and that there be nothing there? No, I do not think so.

The interesting thing about mitochondria dysfunction or illness in general is that it is viewed as a disease - as opposed to ME, which is viewed as nothing. At the moment there is broad attention being paid to mitochondrial diseases and mitochondrial dysfunction, and this reality opens up an entire area on to which ME might be able to piggyback. One of the greatest hopes for ME patients is that something will slop over from another research area - HIV, cancer, mitochondria, MS, stem cell - and inadvertantly land in the lap of ME.

Several national mitochondrial disease websites can be viewed here and here.

The proposed intervention, tailored by the physician to the particular needs of the patient, revolve around what is know as the "mitochondria cocktail". Dr. Myhill stumbled upon mitochondria support through the research of Dr. Stephen Sinatra, the American metabolic cardiologist. The mitochondrial cocktail consists of various supplements. These include NAD, Co-Q10, d-ribose, carnitine, Idebenone, b2 (riboflavin), b1 (thiamine), creatine, and magnesium and b12 injections. A good webpage that covers some of these supplements is this Medscape article. Each patient's cocktail is particularized - either by a physician or by trial and error. The experienced patient, whether with lyme or ME or both, will be able to tell what works for them, and what doesn't, thus devising their own balanced protocol.

Setting the table

The job of the Patient Advocate is to “remain objective” - and to try to keep the big picture in mind. This is difficult - as CFS/ME is a disease of many small and seemingly disconnected parts. The PA has to juggle and consider all the elements, and to try to not let parts drift off unattended. I have tried to delineate these separate parts of this illness (as I see them) in other blog posts.

The disease of CFS/ME itself is known to fluctuate or “cycle” – often for unknown reasons. The patient can get better or worse without any clear explanation. However, occasionally things can get out of whack for a particular reason. This can be because of slippage and forgetting the maintenance.

Many supplements and drugs are suggested for the treatment of CFS/ME. The Patient Advocate tries to prioritize them. The PA spends a lot of time reading about various medicines and supplements. The PA’s ideas should not be taken as medical advice - as the Patient Advocate has no training in this area.

A few years back Dr. Paul Cheney offered his priorities for treatment. These suggestions were made prior to his more recent treatment modalities, However, all of these suggestions remain in his protocol - except for Nexavir, which has been replaced by a more complicated set of bison cell signalling factors. Dr. Cheney’s “key item” list includes:

Magnesium (non-oral) [SQ or Paste],
Klonopin 0.5 mg,
Hydroxycobalamin (by injection) @ high dose,
Isoprinosine,
Kutapressin (aka Nexavir)

Nancy Klimas also likes Isoprinosine, and looks forward to the results of a phase two trial that will never be forthcoming. She also points out that several supplements have small study track records of showing benefit to CFSers: Omega 3, Co-Q and Vitamin D, among others.

Here are some of the items that this Patient Advocate tries to keep an eye on, items that he feels can make a difference:

1. It is important, early on, to determine if the patient has Hashimoto’s thyroiditis. This autoimmune or viral attack on the thyroid is easy to diagnose – high TSH, high TPO antibodies, goiter, long list of symptoms. Hashimoto’s thyroiditis is eminently treatable, perhaps the most treatable disease in the world with one of the oldest “modern” medications. Treating this illness does take some time, and there is some uncertainty to doing it properly. Treatment includes dietary changes, supplements (Iodine, selenium) and thyroid hormone, either synthetic or natural. Treatment is for life. Benefit comes within 3-24 months on being stabilized on thyroid hormone at the correct dosage.

2. It is necessary to support the adrenals during thyroid hormone supplementation, particularly at the beginning. There are various ways to support the adrenals. These include low dose hydrocortisol, adaptogens, live cell therapy, salt and water, licorice and so forth. A poorly functioning or under functioning thyroid drags down the adrenals, so thyroid and adrenal problems go hand in hand. Taking thyroid hormone to stabilize the thyroid also stresses the adrenals - so attention has to be paid to support of the adrenal glands.

3. Magnesium is key to over 400 regulations in the body. Hence its importance. Magnesium is often low in CFS/ME patients. It is difficult to raise magnesium with oral supplements, although some oral supplements are better than others – magnesium glycinate, for instance, is more absorbable. Dr. John McClaren Howard’s testing at Acumen can determine if the patient has magnesium deficiency, thus precipitating low production of ATP in the mitochondria. Once the magnesium deficiency is realized, it can be treated. Dr. Myhill says that magnesium can be raised with daily (or every other day) low- dose (0.5 cc) sub-Q magnesium injections. Over time, magnesium levels can be raised and benefit derived from doing this. Taurine or lidocaine can be included in the injection to make it less painful. More than likely the injections have to be continued on a maintenance basis to keep the magnesium from depleting again. There seems to be something endemic to CFS regarding magnesium depletion, as if the disease itself precipitates a lowering of intracellular magnesium. Many drugs or supplements can also cause depletion of magnesium. The possibility of antibiotics or antivirals acting as a magnesium drain is very real. Magnesium has to be considered on an ongoing basis as long as the patient has the disease. It is not like you treat a little and then “get beyond” the supplementation. This is true of many things – co-Q. b12, carnitine, glutathione, omega 3, for instance, all need support.

4. It is important to keep an eye on Iron levels. Iron also tends to be low in CFS/ME patients. Low iron has a host of symptoms, many of which mimic low magnesium. Low iron is associated with a host of symptoms including photophobia, sleep irregularities, RLS, and muscle pain. Low iron can be difficult to raise. Supplements do not seem to raise iron easily - and it often takes a long time. Iron cream, a prescription item from Hopewell Pharmacy in NJ, is more effective in raising iron over time. Regular blood levels of iron and ferritin need to be measured in order to determine levels - and the effect of various forms of supplementation. Often iron injections are necessary to raise iron. Low ferritin is associated with thyroid dysfunction and balancing the thyroid function necessitates getting ferritin levels up into the mid-normal range.

5. Vitamin D is another element that is predictably low in CFS/ME patients. Again no one knows why this is. Vitamin D can be supplemented and the number can be raised over time. Often this involves daily supplement in the low thousands of I.E. Ten minutes daily in the summer sun can raise stores of vitamin D and it is important to build the vitamin D in this way if it is possible.

6. Nexavir is a cell signaling factor or peptide from pig’s liver. It is believed to be an immune shifter and to work in good percentage of patients. It comes in an injectable form or a gel, applied once a day. Patients complain about the smell of the gel but it is nothing. Doctors as diverse as Cheney, Guyer, de Meirleir, Enlander and Levine will prescribe Nexavir. Nexavir needs to be taken for six months or longer to determine effect. Nexavir is very expensive and is not covered by insurance.

7. My most recent favorite supplement is curcumin. Many small studies have been made of this Indian spice and the supplement has a modest but growing track record of lowering cholesterol, increasing good cholesterol and cutting inflammation, especially in the eyes. There are two curcurmin supplements that contend with one another for being the best or most absorbable – Meriva and nutravine longvida.

Through supplementation the patient can raise their vitamin D, iron, magnesium and fix their thyroid. Raising each of these items has to be seen in the larger context of strengthening the immune system. Improvement is often subliminal and not immediately obvious. In addition it is possible to raise b12 through sublingual or injection, carnitine, and co-Q-10, equally important in various instances as the above numbered items. More problematic is the raising of the anti-oxidant glutathione, which needs a more sophisticated set of supplements proposed by Rich van Konynenburg, information of which is readily available on the internet. (I need to write an entry on methylation supplementation and the glutathione blockage, which is so important as a treatment modality) Supplementation to increase gut ecology is also dicey and everyone is on their own in this complex nightmare to regulate the gut and make it work correctly – although again there are some broad parameters that can be learnt by the neophyte like myself.