DR. LUTHER LINDNER'S RESEARCH
Posted: Sat Nov 06, 2004 8:11 am
In researching pathogens and MS I stumbled upon some research done by a Dr. Luther Lindner from Texas A&M university. It was pretty old so I decided to email him to see if he was still working on it. The following is his reply followed by a link to his patent.
I am indeed working on some bacteria that may play a role in MS. I want
to strongly caution you, however, that at this point in time, I can't
prove that the bacteria I am working on cause MS or anything else. More
important, the bacteria in question can't be cleared from the human
bloodstream with available antibiotics, and sometimes we see the
antibiotics actually stimulate their growth, which is a strange but real
phenomenon that is not good. Because the response to antibiotics can't
be predicted at this point, I do not recommend trying them. There are
some nutritional measures, however, which are fairly safe which may
help.
I have attached a document with some information about what I have been
working on.
INFORMATION DOCUMENT FOR RESEARCH ON NEW BACTERIUM
This is written in response to requests for information about our research in relation to multiple sclerosis, the chronic fatigue syndrome and related disorders. I am a physician (pathologist) associated with a research and development and diagnostics firm currently located in Bryan, Texas. I am also on the faculty of the College of Medicine, Texas A&M University Health Science Center, but my work on these systems has no connection with the University. The firm has been undergoing a corporate reorganization. Its current designation is Pathobiotek, Inc, a subsidiary of ATNG, Inc. We have been studying newly recognized microorganisms, one group of which is the one of interest here.
The microorganisms are a group of peculiar bacteria. They were discovered essentially by accident in blood samples. As our research has developed, there is no longer any question that they are real. Our research has classed the major group of bacteria as unique strains of closely related species of Methylobacterium with notably different growth requirements than the usual strains of these species. They are present in the bloodstream in all of the population, including normal persons. Some persons carry more than one species. They may be acquired prior to birth, although new strains might be acquired later. They are generally present in higher numbers in persons who are symptomatic. Their distribution throughout the body has not yet been studied. We have at least a partial understanding of the mechanisms that allow them to survive in the bloodstream. We have recently made major advances in understanding what they require nutritionally to survive and grow.
There is no proof that they cause either of these diseases or any other disease, but in persons who have been treated with appropriate regimens, a reduction in these bacteria is typically associated with clinical improvement and an increase corresponds with increased symptoms. Although this could be a secondary effect, the observation that treatments that directly reduce their levels produce improvement suggests that it is not. It is presumed that the symptoms require not only the presence of the bacteria, but also some sort of immune or inflammatory reaction against them to produce disease that is not present in asymptomatic individuals, but this is not proven. Individual strains of bacteria may be important. It is possible that an immune reaction is triggered by exposure to other organisms or chemicals and may require genetic susceptibility. It is also possible that the growth of this bacterium may be affected by other organisms.
We know that there is at least one additional bacterium in the bloodstream, but it is not yet definitively identified, and we know nothing of its potential association with disease.
We are not treating any patients ourselves. Our primary interest is in improving the culture system, developing diagnostic reagents and understanding the characteristics of the organisms and whether and how they cause disease. Assuming that the organism can be confirmed as the cause of these and/or other diseases, the long-term goal of the research is to study the immune response to these bacteria and to develop better treatments by finding better drugs, a more effective nutritional regime, and / or developing an effective vaccine. We have tried EXPERIMENTAL long-term antibiotic treatment regimens that have shown benefit in some patients, using standard FDA-approved antibiotics. An Australian physician, Dr. William Maitland, treated a large series of patients and reported a little better success than we had. These regimens will not work adequately with the majority of patients due to the extreme antibiotic resistance of these bacteria, and they are NOT RECOMMENDED at this time for reasons detailed below. We saw good responses in at least 20% of MS patients with a sometimes marked improvement in function. Chronic fatigue patients are more likely to show a short-term response; again only about 20% achieved a long-term relatively complete response. None of the available antibiotic treatments are free of hazards and many of these drugs are expensive.
A good result on antibiotic regimens is definitely not equivalent to cure. The bacteria cannot be completely eliminated with available drugs. Some CFS patients have remained asymptomatic after treatment, however, and some MS patients have sustained a clinical remission while on antibiotics that has apparently allowed major healing with a marked improvement in their function. How long that improvement can be sustained and whether or not treatment can be repeated in the future is unknown. Nutritional adjustments and avoidance of certain drugs and nutrients that stimulate growth of the bacteria can also provide improvement or at least a reduction in disease activity.
We strongly advise against treatment with antibiotic regimens without culture monitoring of the number of organisms and with antibiotic sensitivity testing. We have found that antibiotics can actually STIMULATE bacterial growth and make the patient WORSE and that this can usually be predicted by sensitivity testing. This is related to modulation of cell wall pumps. Antibiotics also have inherent risks, particularly when used long-term. Sensitivity testing is NOT available at this time. We discontinued it due to the limitations of the present culture system and the difficulty and expense involved in creating a system that will meet CLIA requirements with the present technology. We hope to eventually have specific identification and quantification of the bacteria and sensitivity testing available, using molecular technology that will fully meet CLIA requirements, either through ourselves or through license to a reference laboratory. Until these systems are available, ANTIBIOTIC TREATMENT IS NOT RECOMMENDED DUE TO THE RISKS OF BLIND TREATMENT!
In the interim, patients may still derive benefit from nutritional adjustments, which may do nearly as much good as the antibiotics over the long term. We have learned a lot about the basic nutritional requirements of the bacterium, although we still have a lot to learn. This information allows the growth of the bacteria to be manipulated within limits. Most of what we have found to be true about the optimum nutritional regimen with regard to this bacterium is good nutrition anyway. Our present nutritional recommendations are detailed in the attached document. There is no single convenient source for the recommended nutrients at this time. We are currently arranging for a company to market supplements with our recommended ingredients in the very near future.
Our laboratory is located at 3729 East 29th St., Bryan, Texas 77802 There currently is no phone service as the lab is only manned intermittently. Corporate e-mail should be directed to patho@chartermi.net. Our website is being redeveloped. I am only at the lab part of the time and my e-mail is not through them at this time, so inquiries directed to me should go to my office at Texas A&M or to my home. My office phone there is (979) 845-7260, E-mail lindner@tamu.edu. My home address is 2507 Merrimac Ct., College Station, TX 77845, phone is (979) 693-3940, fax (979) 693-2658.
Although we cannot provide any feedback to patients on the results at this time, we would like to receive blood samples from a limited number of selected patients for our research, particularly from patients with well-defined diagnoses who will send repeated specimens with feedback on changes in their clinical status that we can correlate with our assays. If you would be willing to provide specimens, contact me.
A nonprofit research foundation exists for the sole purpose of supporting our research. Donations may be submitted care of Pathobiotek if you choose, but are not specifically requested. The foundation name is the Lindner Research Foundation.
Copyright Luther E. Lindner M.D., Ph.D. 1995-03. This document may be copied and shared with others. Version 11-28-03.
Soli deo gloria.
NUTRITION AND LIFESTYLE SUGGESTIONS IN RELATION TO OUR BACTERIUM
Copyright Luther E. Lindner M.D., 1995-03. All rights reserved. This document may be copied and shared with others. Version 1-25-03.
Methylobacterium sps. are present in the bloodstream in all "normal" persons and in increased levels in persons with nonspecific symptoms or a number of active clinical disorders including the chronic fatigue and immune dysfunction syndrome (CFIDS), fibromyalgia, and several autoimmune disorders such as multiple sclerosis, lupus erythematosis, and rheumatoid arthritis. There is no direct evidence that the bacteria are the cause of these disorders, and the causation may be complex, but individual patients with these problems who have shown a reduction in their bacterial counts on an appropriate regimen have also had a significant improvement in their symptoms. It may be possible to partially control the level of the bacteria by nutritional measures. Some patients are actually made worse by antibiotic treatment. They can also be made worse by inappropriate diet and certain other factors.
Persons who are ill should attempt to maintain good nutrition in general. High dose vitamins make many patients feel better. We have recently found that there is a danger to taking increased amounts of certain vitamins, especially nicotinic acid (niacin, vitamin B-3), which can significantly stimulate bacterial growth. Replacing other grains in the diet with corn may reduce the body's levels of nicotinic acid. Because niacin and several other components of multivitamin capsules appear to stimulate bacterial growth and to be needed by them, the use of comprehensive multivitamin preparations is strongly discouraged. Vitamin C and possibly vitamin E are desirable, however large doses of vitamin C may affect antibiotic sensitivity. Vitamins A and D do not appear to have any effect, pro or con. Very large doses of certain of the B vitamins, vitamins A, C, D and E can be toxic, so there is a limit to how much of any of the vitamins should be taken. Some patients have reported improvement in symptoms from vitamin B-12 injections; these are usually administered by a physician. Apparently a similar effect can be achieved with high dose oral B-12, on the order of 200-1000 micrograms per day. Recent experiments suggest there may be a legitimate rationale for a B-12 effect. A specific metabolite produces some growth stimulation, and its level can be reduced by increased B-12. Folic acid also appears to directly inhibit bacterial growth. B-6, B-12 and folic acid may be particularly important in persons using cysteine (cystine) supplements or with a high cysteine intake(see below).
One physician specializing in CFIDS has observed that lecithin supplements appear to be beneficial. We have found that choline, which is a component of lecithin, is relatively strongly inhibitory to growth of our bacteria. I recommend supplementation with either choline or lecithin, with soy lecithin possibly a preferred source.
The CFIDS literature suggests that there may be improvement from injections of magnesium sulfate and oral zinc supplements. In culture increased levels of magnesium have little effect on the growth of the bacteria. Presumably the reported effects of magnesium are due to a secondary effect on symptoms. I cannot recommend these injections at this time, although they do no harm. You could consider supplementation with oral magnesium, but be careful with the dose, especially if it is not taken in combination with calcium. Magnesium compounds are laxatives at oral doses over a few hundred milligrams at a time.
Our studies indicate that the growth of these bacteria is stimulated by compounds of copper, manganese, tin, iron and possibly other metals. You should avoid mineral supplements containing these minerals as well as foods that are high in them. It is likely that copper, manganese and iron are the most important of these.
We have repeatedly noted that both stress in general and inflammatory processes in particular stimulate the growth of the bacteria. Inflammation results in the release of several copper and manganese-containing enzymes from white blood cells and raises blood copper levels. Inflammation, stress, and certain hormones all elevate blood levels of copper, mostly bound to a specific protein. I suggest a reduced intake of foods high in copper, particularly shrimp, lobster, crab, crayfish, and liver. If you have copper pipes consider bottled water for drinking and cooking. Manganese and iron may be harder to avoid. Absolute avoidance of these foods is not indicated, first because at least some of these minerals is necessary for health and second because there may be an easier way to deal with the problem. Dental amalgam could be a source of some of these minerals, although it is unlikely that it plays a major role with most patients.
I strongly recommend an increased intake of zinc. Zinc suppresses the growth of these bacteria in culture and increased zinc intake competes with the other minerals that we have noted as a problem, resulting in less absorption, increased excretion, and less availability within the body. Zinc also has a beneficial effect on the immune system in general. The recommended amount is 25-35 mg. a day of zinc as zinc sulfate or an equivalent zinc compound for the average adult. Amounts over 50 mg. can lead to overdosage. Overdosage will produce anemia and weakness because excessive reduction of available copper interferes with the body's ability to make enzymes that supply the bulk of the energy to all the cells in the body and interferes with the incorporation of iron into the hemoglobin in red blood cells that carries oxygen throughout the body. Because of the problems with possible overdosage, I recommend periodically monitoring the iron levels in the blood and/or the blood counts.
I also recommend monitoring the iron level because of the possibility that iron stimulates bacterial growth. The best test for total body iron stores is the serum ferritin, but it is possible that this is not the best test for whatever the active form of iron for the bacteria is, most likely the free iron. We recommend keeping the level at the lower end of the normal range. If it is in midrange or above, I recommend donating blood periodically to reduce body iron stores.
Another trace metal that has been suggested as beneficial in the CFIDS literature is chromium. Our testing shows no inhibition of bacterial growth by this, and possibly stimulation with some strains, so any beneficial effect is indirect, but we have confirmed symptomatic benefit in some patients. Chromium is known to be needed for insulin activity, through mechanisms that aren't fully clear. Many CFIDS patients have sugar cravings and fatigue increasing several hours after eating. Chromium antagonizes this. Since increased zinc will probably antagonize absorbtion of chromium, some chromium supplementation along with it is probably needed. I recommend 100-200 micrograms per day. Chromium may also reduce the risk of arteriosclerosis. There is a risk to excessive chromium supplementation so these levels are probably maximum.
These metals are probably acting as cofactors in critical biochemical reactions needed by the bacterium. Certain metals are probably acting as oxidants, oxidizing as yet unidentified compounds. This raises the possibility that high levels of antioxidant compounds may be of help. The known major antioxidant materials in the diet are vitamin C, vitamin E, carotenoids and selenium, as well as a variety of sulfur-containing compounds and bioflavonoids, including so-called pyncnogenols and proanthocyanins. We do not yet have solid data on the possible effect of these, but since they are good in the diet for other reasons, supplementation with this class of compounds is recommended.
We have encountered a few patients with elevated porphyrin levels. It is unclear whether this is common, but elevated metal levels, especially iron, can elevate prophyrins. Elevated porphyrins can be toxic.
Another mineral that may be beneficial is boron, in the form of borates. It definitely inhibits bacterial growth in culture. A recommended dosage is not yet established.
The CFIDS literature suggests that certain sulfur-containing compounds may be beneficial. Garlic in particular has been mentioned. The compound that gives garlic its aroma (stink?) is one of these sulfur-containing compounds. These compounds react with several metals within the body, including copper, and therefore may be complementing zinc. This doesn't get rid of the copper, but ties it up temporarily. The garlic powders and oils that have been deodorized may lack some sulfur compounds and may be useless. Onions and other relatives of garlic may have some of the same benefits. I have seen two patients who apparently converted from antibotic resistance to slight sensitivity while taking large doses of garlic.
Experiments on the effect of sulfhydryl reagents suggest other sulphur compounds may have value, but also suggest that sulfhydryl compounds may sometimes be bad. The best data we have is on the effect of l-cysteine (cystine), an amino acid that is one of the basic building blocks of proteins. Cysteine usually stimulates bacterial growth in culture, but this can be converted to growth inhibition in the presence of certain other compounds.
Another set of sulfur-containing compounds that is sometimes recommended in CFIDS is DMSO (dimethylsulfoxide) and the closely related compound MSM (methyl sulfonylmethane or dimethylsulfone). These have anti-inflammatory properties. Commercial DMSO always contains some MSM. We have found that these interact with our bacteria in an unpredictable fashion, and under some conditions they may stimulate growth, so they ae not recommended at this time.
We have observed in culture that the chemical which makes peppers hot can stimulate bacterial growth. Peppers should be used in moderation.
The CFIDS literature suggests that taurine may be beneficial. In the testing to date, taurine has no effect on cultures. In the body cysteine is converted to taurine. Taurine could be affecting the breakdown of cysteine.
Various herbs and other nutritional remedies have been recommended by various persons without a scientific basis. Limited testing done to date has not shown most herbs to be beneficial. I have, however, noted a few individuals taking complex mixtures of herbs that have shown marked improvement both in their levels of bacteria and in their symptoms, so there undoubtedly exist nutritional supplements of this sort that are benficial. Pycnogenol preparations, especially Isotonix OPC-3 (see www.marketamericaUSA.com for local distributor) are probably helpful. Another supplement that may be effective that is also reasonably priced is The Missing Link from Designing Health, Inc., (805) 257-1705. A complex regimen from Sunrider International (the Sunpack)is the most effective that I have seen to date. producing significant reductions in bacterial levels and symptoms, but it is expensive (about $200 / month) and it is unclear what most of the components do. A distributor in Houston, who will ship, is Janet Snell at 281-870-1092. It has recently been suggested that turmeric root or its main active component curcumin may be beneficial. This is known to have strong anti-inflammatory effects and may also have a direct effect on the bacteria. Other herbs that reportedly have an anti-inflammatory effect include comfrey, feverfew, and fenugreek. Since the herbs are very complex materials, they may contain compounds that are hazardous at high doses or in chronic use. Recommended doses are not established.
It is now possible to predict many chemicals, including drugs, that will stimulate or inhibit bacterial growth. Many of the herbal preparations contain large amounts of complex phenolic compunds and their conjugates which are predicted to inhibit growth.
As previously discussed, we have observed that the growth of the bacterium is somehow tied to the inflammatory process. Isolates of the bacteria from patients who have been stressed, are more ill, or who have active inflammatory processes going on show not only greater numbers of organisms, but also their organisms have a greater growth potential in culture which subsides over time. Something the bacteria have acquired in the patient is required for the growth process. I initially related this to release of metal-containing enzymes during inflammation, and that may be part of the process, but our data suggests at least one other cause. Apparently the growth of the bacteria is affected by the availability of derivatives of unsaturated fatty acids that are produced as part of inflammation. Unfortunately, at this time we aren't sure which of these derivatives is the critical one that produces most of the growth stimulation.
The critical material(s) are presumably derived from an unsaturated fatty acid known as arachidonic acid that is released as one of the primary reactions in the inflammatory process. Arachidonic acid is a normal and necessary component of the body that can be derived from the diet directly or synthesized in the body from other unsaturated omega-6 fatty acids. Many anti-inflammatory drugs such as aspirin and its relatives block the conversion of arachidonic acid to compounds that are effective mediators of inflammation. Unfortunately, these drugs block some of the possible conversions but not all, and administration of most drugs in this class to patients has not produced much effect on the bacteria or the symptoms of the patients, so presumably they are not blocking the critical pathway(s) of conversion. Nizoral blocks another pathway. Steroids partially block the release of free arachidonic acid. Steroids have been used for a long time in the treatment of various "autoimmune" disorders including lupus erythematosis, rheumatoid arthritis, and multiple sclerosis, all of which may be related to our bacterium. They are not a cure-all, since there are many complications associated with their use and they don't block the conversions completely. It is possible that the beneficial effect of the steroids in these processes is directly related to suppression of growth of the bacteria, rather than just their effects in suppressing inflammation.
Nonsteroidal anti-inflammatory drugs may partially block this process and their use at a moderate level should be considered, taking into consideration the risks of long-term use. Other things can be done to affect this. The first is to control any treatable inflammatory processes that exist in the body and to control infection and inflammation in general, no matter what the source. This includes a general control of stress. CFIDS and MS patients have known for a long time that physical or mental stress or illness makes their disease worse. They have also noted a relationship of their symptoms to dental infections, sinus infections and similar problems. If necessary, the lifestyle should be adjusted and other medical and dental problems should be cleaned up. Extreme exercise and injuries should be avoided. It is suggested by some sources that food allergies may be present and be providing an inflammatory stimulus in some patients. Testing for food allergies and elimination of offending foods is suggested.
Another dietary maneuver that can be tried is to adjust the amount of arachidonic acid that is available to be released in the body by adjusting the dietary intake of fatty acids. Fat intake in general should be reduced, and particularly the intake of most cooking oils and margarines. Completely avoiding unsaturated fatty acids will have bad consequences. The type of unsaturated fatty acids that are consumed, however, will affect the amount of arachidonic acid available in the body. There is reason to believe that the omega-3 fatty acids that are available in marine fish and some other seafoods are desirable and they can replace much of the arachidonic acid in the body. Nuts and nut oils also tend to contain non-omega-6 fatty acids and are also a good source of fats. Reduction of meat in the diet and replacement of much of it with marine fish is recommended. This may have health benefits unrelated to our bacterium, such as reduced arteriosclerosis. Oil of primrose, flaxseed oil, borage oil and nuts are recommended sources of these. Walnuts, almonds, and macdamia nuts appear to be particularly good nuts. Most of the available vegetable oils contain mostly omega-6 fatty acids which are the precursors of arachidonic acid. Most processed foods contain these and they should be reduced in the diet. Canola oil and olive oil may have a more neutral effect and are the recommended cooking oils. We have not studied the effects of this kind of competition in the laboratory, so I have no direct evidence that it will work, but it does seem to help some patients. This requires a major adjustment in the diet. Simple supplementation with commercial fish oil capsules, for instance, without removing the dietary omega-6 fatty acids, requires very large intakes (20-40 g./day) to significantly alter the overall body composition of unsaturated fatty acids, and the high fat intake is not good. With a carefully controlled diet, however, there is reason to believe that practical intakes (5-6000 mg./day) may be helpful.
Several physicians have reported that supplementation with lecithin (soy is the recommended source), which contains certain fatty acids and other components, may be beneficial. The mechanism suggested for this benefit is probably not correct, but we have seen that a component of lecithin known as choline is inhibitory to the bacteria. Recommended doses are not yet available.
The CFIDS literature suggests that supplementation with carnitine helps some patients. It has no direct effect in our cultures. Carnitine plays a role in the metabolism of fatty acids, so it may afect the availability of arachidonic acid. I do not recommend carnitine supplements until we have studied this, although it is a normal and harmless dietary component in reasonable levels. The CFIDS literature also suggests that Q10 (ubiquinone) may have some value. This also doesn't have a direct effect on the bacterium, but may again be helpful in lowering the production of active arachidonate derivatives.
Some data suggests that a component of milk promotes the growth of the bacterium. We don't know what that component might be or whether the effect we see in culture also happens in the patient. It is prudent to limit the intake of milk and milk products until more is known.
A recent observation is that some currently unidentified component present in fruit juices stimulates bacterial growth in culture. Since juices are digested prior to absorbtion, it is unclear at this time whether fruit juices will also stimulate levels in the patient. Until data is obtained, it is suggested that fruits and fruit juices be consumed in limited amounts. Citrus fruit may be less of a problem.
Excessive light exposure may promote growth of the bacteria, so sun exposure should be controlled.
At this time a large portion of the patients tested are resistant to the available antibiotics. In general, these patients have higher levels of bacteria and their bacteria show greater growth potential in culture. Nutritional manipulation to slow the growth of bacteria based on selective vitamin supplementation with folic acid, vitamin B-12 and vitamin B-6 (optimum amounts not known), choline or lecithin (optimum amounts not known), zinc 25-50 mg/day, chromium 100-200 mcg/day, garlic (?), appropriate sources of non- omega-6 unsaturated fatty acids (at least 5g (5000mg) per day), elimination of undesirable foods, particularly those containing high levels of copper and omega-6 unsaturated fatty acids, a reduction of iron levels and possibly herbal supplements may convert some of these untreatable patients into responders or at least reduce the severity of their clinical problems. We are currently experimenting with a supplement regimen based on these recomendations, which appears to produce symptomatic improvement in at least some patients. If the regimen proves to be generally helpful, we will try to find someone who will make it available commercially.
the following is a link to his patent that I looked up.
http://patft.uspto.gov/netacgi/nph-Pars ... =6,255,467
I am indeed working on some bacteria that may play a role in MS. I want
to strongly caution you, however, that at this point in time, I can't
prove that the bacteria I am working on cause MS or anything else. More
important, the bacteria in question can't be cleared from the human
bloodstream with available antibiotics, and sometimes we see the
antibiotics actually stimulate their growth, which is a strange but real
phenomenon that is not good. Because the response to antibiotics can't
be predicted at this point, I do not recommend trying them. There are
some nutritional measures, however, which are fairly safe which may
help.
I have attached a document with some information about what I have been
working on.
INFORMATION DOCUMENT FOR RESEARCH ON NEW BACTERIUM
This is written in response to requests for information about our research in relation to multiple sclerosis, the chronic fatigue syndrome and related disorders. I am a physician (pathologist) associated with a research and development and diagnostics firm currently located in Bryan, Texas. I am also on the faculty of the College of Medicine, Texas A&M University Health Science Center, but my work on these systems has no connection with the University. The firm has been undergoing a corporate reorganization. Its current designation is Pathobiotek, Inc, a subsidiary of ATNG, Inc. We have been studying newly recognized microorganisms, one group of which is the one of interest here.
The microorganisms are a group of peculiar bacteria. They were discovered essentially by accident in blood samples. As our research has developed, there is no longer any question that they are real. Our research has classed the major group of bacteria as unique strains of closely related species of Methylobacterium with notably different growth requirements than the usual strains of these species. They are present in the bloodstream in all of the population, including normal persons. Some persons carry more than one species. They may be acquired prior to birth, although new strains might be acquired later. They are generally present in higher numbers in persons who are symptomatic. Their distribution throughout the body has not yet been studied. We have at least a partial understanding of the mechanisms that allow them to survive in the bloodstream. We have recently made major advances in understanding what they require nutritionally to survive and grow.
There is no proof that they cause either of these diseases or any other disease, but in persons who have been treated with appropriate regimens, a reduction in these bacteria is typically associated with clinical improvement and an increase corresponds with increased symptoms. Although this could be a secondary effect, the observation that treatments that directly reduce their levels produce improvement suggests that it is not. It is presumed that the symptoms require not only the presence of the bacteria, but also some sort of immune or inflammatory reaction against them to produce disease that is not present in asymptomatic individuals, but this is not proven. Individual strains of bacteria may be important. It is possible that an immune reaction is triggered by exposure to other organisms or chemicals and may require genetic susceptibility. It is also possible that the growth of this bacterium may be affected by other organisms.
We know that there is at least one additional bacterium in the bloodstream, but it is not yet definitively identified, and we know nothing of its potential association with disease.
We are not treating any patients ourselves. Our primary interest is in improving the culture system, developing diagnostic reagents and understanding the characteristics of the organisms and whether and how they cause disease. Assuming that the organism can be confirmed as the cause of these and/or other diseases, the long-term goal of the research is to study the immune response to these bacteria and to develop better treatments by finding better drugs, a more effective nutritional regime, and / or developing an effective vaccine. We have tried EXPERIMENTAL long-term antibiotic treatment regimens that have shown benefit in some patients, using standard FDA-approved antibiotics. An Australian physician, Dr. William Maitland, treated a large series of patients and reported a little better success than we had. These regimens will not work adequately with the majority of patients due to the extreme antibiotic resistance of these bacteria, and they are NOT RECOMMENDED at this time for reasons detailed below. We saw good responses in at least 20% of MS patients with a sometimes marked improvement in function. Chronic fatigue patients are more likely to show a short-term response; again only about 20% achieved a long-term relatively complete response. None of the available antibiotic treatments are free of hazards and many of these drugs are expensive.
A good result on antibiotic regimens is definitely not equivalent to cure. The bacteria cannot be completely eliminated with available drugs. Some CFS patients have remained asymptomatic after treatment, however, and some MS patients have sustained a clinical remission while on antibiotics that has apparently allowed major healing with a marked improvement in their function. How long that improvement can be sustained and whether or not treatment can be repeated in the future is unknown. Nutritional adjustments and avoidance of certain drugs and nutrients that stimulate growth of the bacteria can also provide improvement or at least a reduction in disease activity.
We strongly advise against treatment with antibiotic regimens without culture monitoring of the number of organisms and with antibiotic sensitivity testing. We have found that antibiotics can actually STIMULATE bacterial growth and make the patient WORSE and that this can usually be predicted by sensitivity testing. This is related to modulation of cell wall pumps. Antibiotics also have inherent risks, particularly when used long-term. Sensitivity testing is NOT available at this time. We discontinued it due to the limitations of the present culture system and the difficulty and expense involved in creating a system that will meet CLIA requirements with the present technology. We hope to eventually have specific identification and quantification of the bacteria and sensitivity testing available, using molecular technology that will fully meet CLIA requirements, either through ourselves or through license to a reference laboratory. Until these systems are available, ANTIBIOTIC TREATMENT IS NOT RECOMMENDED DUE TO THE RISKS OF BLIND TREATMENT!
In the interim, patients may still derive benefit from nutritional adjustments, which may do nearly as much good as the antibiotics over the long term. We have learned a lot about the basic nutritional requirements of the bacterium, although we still have a lot to learn. This information allows the growth of the bacteria to be manipulated within limits. Most of what we have found to be true about the optimum nutritional regimen with regard to this bacterium is good nutrition anyway. Our present nutritional recommendations are detailed in the attached document. There is no single convenient source for the recommended nutrients at this time. We are currently arranging for a company to market supplements with our recommended ingredients in the very near future.
Our laboratory is located at 3729 East 29th St., Bryan, Texas 77802 There currently is no phone service as the lab is only manned intermittently. Corporate e-mail should be directed to patho@chartermi.net. Our website is being redeveloped. I am only at the lab part of the time and my e-mail is not through them at this time, so inquiries directed to me should go to my office at Texas A&M or to my home. My office phone there is (979) 845-7260, E-mail lindner@tamu.edu. My home address is 2507 Merrimac Ct., College Station, TX 77845, phone is (979) 693-3940, fax (979) 693-2658.
Although we cannot provide any feedback to patients on the results at this time, we would like to receive blood samples from a limited number of selected patients for our research, particularly from patients with well-defined diagnoses who will send repeated specimens with feedback on changes in their clinical status that we can correlate with our assays. If you would be willing to provide specimens, contact me.
A nonprofit research foundation exists for the sole purpose of supporting our research. Donations may be submitted care of Pathobiotek if you choose, but are not specifically requested. The foundation name is the Lindner Research Foundation.
Copyright Luther E. Lindner M.D., Ph.D. 1995-03. This document may be copied and shared with others. Version 11-28-03.
Soli deo gloria.
NUTRITION AND LIFESTYLE SUGGESTIONS IN RELATION TO OUR BACTERIUM
Copyright Luther E. Lindner M.D., 1995-03. All rights reserved. This document may be copied and shared with others. Version 1-25-03.
Methylobacterium sps. are present in the bloodstream in all "normal" persons and in increased levels in persons with nonspecific symptoms or a number of active clinical disorders including the chronic fatigue and immune dysfunction syndrome (CFIDS), fibromyalgia, and several autoimmune disorders such as multiple sclerosis, lupus erythematosis, and rheumatoid arthritis. There is no direct evidence that the bacteria are the cause of these disorders, and the causation may be complex, but individual patients with these problems who have shown a reduction in their bacterial counts on an appropriate regimen have also had a significant improvement in their symptoms. It may be possible to partially control the level of the bacteria by nutritional measures. Some patients are actually made worse by antibiotic treatment. They can also be made worse by inappropriate diet and certain other factors.
Persons who are ill should attempt to maintain good nutrition in general. High dose vitamins make many patients feel better. We have recently found that there is a danger to taking increased amounts of certain vitamins, especially nicotinic acid (niacin, vitamin B-3), which can significantly stimulate bacterial growth. Replacing other grains in the diet with corn may reduce the body's levels of nicotinic acid. Because niacin and several other components of multivitamin capsules appear to stimulate bacterial growth and to be needed by them, the use of comprehensive multivitamin preparations is strongly discouraged. Vitamin C and possibly vitamin E are desirable, however large doses of vitamin C may affect antibiotic sensitivity. Vitamins A and D do not appear to have any effect, pro or con. Very large doses of certain of the B vitamins, vitamins A, C, D and E can be toxic, so there is a limit to how much of any of the vitamins should be taken. Some patients have reported improvement in symptoms from vitamin B-12 injections; these are usually administered by a physician. Apparently a similar effect can be achieved with high dose oral B-12, on the order of 200-1000 micrograms per day. Recent experiments suggest there may be a legitimate rationale for a B-12 effect. A specific metabolite produces some growth stimulation, and its level can be reduced by increased B-12. Folic acid also appears to directly inhibit bacterial growth. B-6, B-12 and folic acid may be particularly important in persons using cysteine (cystine) supplements or with a high cysteine intake(see below).
One physician specializing in CFIDS has observed that lecithin supplements appear to be beneficial. We have found that choline, which is a component of lecithin, is relatively strongly inhibitory to growth of our bacteria. I recommend supplementation with either choline or lecithin, with soy lecithin possibly a preferred source.
The CFIDS literature suggests that there may be improvement from injections of magnesium sulfate and oral zinc supplements. In culture increased levels of magnesium have little effect on the growth of the bacteria. Presumably the reported effects of magnesium are due to a secondary effect on symptoms. I cannot recommend these injections at this time, although they do no harm. You could consider supplementation with oral magnesium, but be careful with the dose, especially if it is not taken in combination with calcium. Magnesium compounds are laxatives at oral doses over a few hundred milligrams at a time.
Our studies indicate that the growth of these bacteria is stimulated by compounds of copper, manganese, tin, iron and possibly other metals. You should avoid mineral supplements containing these minerals as well as foods that are high in them. It is likely that copper, manganese and iron are the most important of these.
We have repeatedly noted that both stress in general and inflammatory processes in particular stimulate the growth of the bacteria. Inflammation results in the release of several copper and manganese-containing enzymes from white blood cells and raises blood copper levels. Inflammation, stress, and certain hormones all elevate blood levels of copper, mostly bound to a specific protein. I suggest a reduced intake of foods high in copper, particularly shrimp, lobster, crab, crayfish, and liver. If you have copper pipes consider bottled water for drinking and cooking. Manganese and iron may be harder to avoid. Absolute avoidance of these foods is not indicated, first because at least some of these minerals is necessary for health and second because there may be an easier way to deal with the problem. Dental amalgam could be a source of some of these minerals, although it is unlikely that it plays a major role with most patients.
I strongly recommend an increased intake of zinc. Zinc suppresses the growth of these bacteria in culture and increased zinc intake competes with the other minerals that we have noted as a problem, resulting in less absorption, increased excretion, and less availability within the body. Zinc also has a beneficial effect on the immune system in general. The recommended amount is 25-35 mg. a day of zinc as zinc sulfate or an equivalent zinc compound for the average adult. Amounts over 50 mg. can lead to overdosage. Overdosage will produce anemia and weakness because excessive reduction of available copper interferes with the body's ability to make enzymes that supply the bulk of the energy to all the cells in the body and interferes with the incorporation of iron into the hemoglobin in red blood cells that carries oxygen throughout the body. Because of the problems with possible overdosage, I recommend periodically monitoring the iron levels in the blood and/or the blood counts.
I also recommend monitoring the iron level because of the possibility that iron stimulates bacterial growth. The best test for total body iron stores is the serum ferritin, but it is possible that this is not the best test for whatever the active form of iron for the bacteria is, most likely the free iron. We recommend keeping the level at the lower end of the normal range. If it is in midrange or above, I recommend donating blood periodically to reduce body iron stores.
Another trace metal that has been suggested as beneficial in the CFIDS literature is chromium. Our testing shows no inhibition of bacterial growth by this, and possibly stimulation with some strains, so any beneficial effect is indirect, but we have confirmed symptomatic benefit in some patients. Chromium is known to be needed for insulin activity, through mechanisms that aren't fully clear. Many CFIDS patients have sugar cravings and fatigue increasing several hours after eating. Chromium antagonizes this. Since increased zinc will probably antagonize absorbtion of chromium, some chromium supplementation along with it is probably needed. I recommend 100-200 micrograms per day. Chromium may also reduce the risk of arteriosclerosis. There is a risk to excessive chromium supplementation so these levels are probably maximum.
These metals are probably acting as cofactors in critical biochemical reactions needed by the bacterium. Certain metals are probably acting as oxidants, oxidizing as yet unidentified compounds. This raises the possibility that high levels of antioxidant compounds may be of help. The known major antioxidant materials in the diet are vitamin C, vitamin E, carotenoids and selenium, as well as a variety of sulfur-containing compounds and bioflavonoids, including so-called pyncnogenols and proanthocyanins. We do not yet have solid data on the possible effect of these, but since they are good in the diet for other reasons, supplementation with this class of compounds is recommended.
We have encountered a few patients with elevated porphyrin levels. It is unclear whether this is common, but elevated metal levels, especially iron, can elevate prophyrins. Elevated porphyrins can be toxic.
Another mineral that may be beneficial is boron, in the form of borates. It definitely inhibits bacterial growth in culture. A recommended dosage is not yet established.
The CFIDS literature suggests that certain sulfur-containing compounds may be beneficial. Garlic in particular has been mentioned. The compound that gives garlic its aroma (stink?) is one of these sulfur-containing compounds. These compounds react with several metals within the body, including copper, and therefore may be complementing zinc. This doesn't get rid of the copper, but ties it up temporarily. The garlic powders and oils that have been deodorized may lack some sulfur compounds and may be useless. Onions and other relatives of garlic may have some of the same benefits. I have seen two patients who apparently converted from antibotic resistance to slight sensitivity while taking large doses of garlic.
Experiments on the effect of sulfhydryl reagents suggest other sulphur compounds may have value, but also suggest that sulfhydryl compounds may sometimes be bad. The best data we have is on the effect of l-cysteine (cystine), an amino acid that is one of the basic building blocks of proteins. Cysteine usually stimulates bacterial growth in culture, but this can be converted to growth inhibition in the presence of certain other compounds.
Another set of sulfur-containing compounds that is sometimes recommended in CFIDS is DMSO (dimethylsulfoxide) and the closely related compound MSM (methyl sulfonylmethane or dimethylsulfone). These have anti-inflammatory properties. Commercial DMSO always contains some MSM. We have found that these interact with our bacteria in an unpredictable fashion, and under some conditions they may stimulate growth, so they ae not recommended at this time.
We have observed in culture that the chemical which makes peppers hot can stimulate bacterial growth. Peppers should be used in moderation.
The CFIDS literature suggests that taurine may be beneficial. In the testing to date, taurine has no effect on cultures. In the body cysteine is converted to taurine. Taurine could be affecting the breakdown of cysteine.
Various herbs and other nutritional remedies have been recommended by various persons without a scientific basis. Limited testing done to date has not shown most herbs to be beneficial. I have, however, noted a few individuals taking complex mixtures of herbs that have shown marked improvement both in their levels of bacteria and in their symptoms, so there undoubtedly exist nutritional supplements of this sort that are benficial. Pycnogenol preparations, especially Isotonix OPC-3 (see www.marketamericaUSA.com for local distributor) are probably helpful. Another supplement that may be effective that is also reasonably priced is The Missing Link from Designing Health, Inc., (805) 257-1705. A complex regimen from Sunrider International (the Sunpack)is the most effective that I have seen to date. producing significant reductions in bacterial levels and symptoms, but it is expensive (about $200 / month) and it is unclear what most of the components do. A distributor in Houston, who will ship, is Janet Snell at 281-870-1092. It has recently been suggested that turmeric root or its main active component curcumin may be beneficial. This is known to have strong anti-inflammatory effects and may also have a direct effect on the bacteria. Other herbs that reportedly have an anti-inflammatory effect include comfrey, feverfew, and fenugreek. Since the herbs are very complex materials, they may contain compounds that are hazardous at high doses or in chronic use. Recommended doses are not established.
It is now possible to predict many chemicals, including drugs, that will stimulate or inhibit bacterial growth. Many of the herbal preparations contain large amounts of complex phenolic compunds and their conjugates which are predicted to inhibit growth.
As previously discussed, we have observed that the growth of the bacterium is somehow tied to the inflammatory process. Isolates of the bacteria from patients who have been stressed, are more ill, or who have active inflammatory processes going on show not only greater numbers of organisms, but also their organisms have a greater growth potential in culture which subsides over time. Something the bacteria have acquired in the patient is required for the growth process. I initially related this to release of metal-containing enzymes during inflammation, and that may be part of the process, but our data suggests at least one other cause. Apparently the growth of the bacteria is affected by the availability of derivatives of unsaturated fatty acids that are produced as part of inflammation. Unfortunately, at this time we aren't sure which of these derivatives is the critical one that produces most of the growth stimulation.
The critical material(s) are presumably derived from an unsaturated fatty acid known as arachidonic acid that is released as one of the primary reactions in the inflammatory process. Arachidonic acid is a normal and necessary component of the body that can be derived from the diet directly or synthesized in the body from other unsaturated omega-6 fatty acids. Many anti-inflammatory drugs such as aspirin and its relatives block the conversion of arachidonic acid to compounds that are effective mediators of inflammation. Unfortunately, these drugs block some of the possible conversions but not all, and administration of most drugs in this class to patients has not produced much effect on the bacteria or the symptoms of the patients, so presumably they are not blocking the critical pathway(s) of conversion. Nizoral blocks another pathway. Steroids partially block the release of free arachidonic acid. Steroids have been used for a long time in the treatment of various "autoimmune" disorders including lupus erythematosis, rheumatoid arthritis, and multiple sclerosis, all of which may be related to our bacterium. They are not a cure-all, since there are many complications associated with their use and they don't block the conversions completely. It is possible that the beneficial effect of the steroids in these processes is directly related to suppression of growth of the bacteria, rather than just their effects in suppressing inflammation.
Nonsteroidal anti-inflammatory drugs may partially block this process and their use at a moderate level should be considered, taking into consideration the risks of long-term use. Other things can be done to affect this. The first is to control any treatable inflammatory processes that exist in the body and to control infection and inflammation in general, no matter what the source. This includes a general control of stress. CFIDS and MS patients have known for a long time that physical or mental stress or illness makes their disease worse. They have also noted a relationship of their symptoms to dental infections, sinus infections and similar problems. If necessary, the lifestyle should be adjusted and other medical and dental problems should be cleaned up. Extreme exercise and injuries should be avoided. It is suggested by some sources that food allergies may be present and be providing an inflammatory stimulus in some patients. Testing for food allergies and elimination of offending foods is suggested.
Another dietary maneuver that can be tried is to adjust the amount of arachidonic acid that is available to be released in the body by adjusting the dietary intake of fatty acids. Fat intake in general should be reduced, and particularly the intake of most cooking oils and margarines. Completely avoiding unsaturated fatty acids will have bad consequences. The type of unsaturated fatty acids that are consumed, however, will affect the amount of arachidonic acid available in the body. There is reason to believe that the omega-3 fatty acids that are available in marine fish and some other seafoods are desirable and they can replace much of the arachidonic acid in the body. Nuts and nut oils also tend to contain non-omega-6 fatty acids and are also a good source of fats. Reduction of meat in the diet and replacement of much of it with marine fish is recommended. This may have health benefits unrelated to our bacterium, such as reduced arteriosclerosis. Oil of primrose, flaxseed oil, borage oil and nuts are recommended sources of these. Walnuts, almonds, and macdamia nuts appear to be particularly good nuts. Most of the available vegetable oils contain mostly omega-6 fatty acids which are the precursors of arachidonic acid. Most processed foods contain these and they should be reduced in the diet. Canola oil and olive oil may have a more neutral effect and are the recommended cooking oils. We have not studied the effects of this kind of competition in the laboratory, so I have no direct evidence that it will work, but it does seem to help some patients. This requires a major adjustment in the diet. Simple supplementation with commercial fish oil capsules, for instance, without removing the dietary omega-6 fatty acids, requires very large intakes (20-40 g./day) to significantly alter the overall body composition of unsaturated fatty acids, and the high fat intake is not good. With a carefully controlled diet, however, there is reason to believe that practical intakes (5-6000 mg./day) may be helpful.
Several physicians have reported that supplementation with lecithin (soy is the recommended source), which contains certain fatty acids and other components, may be beneficial. The mechanism suggested for this benefit is probably not correct, but we have seen that a component of lecithin known as choline is inhibitory to the bacteria. Recommended doses are not yet available.
The CFIDS literature suggests that supplementation with carnitine helps some patients. It has no direct effect in our cultures. Carnitine plays a role in the metabolism of fatty acids, so it may afect the availability of arachidonic acid. I do not recommend carnitine supplements until we have studied this, although it is a normal and harmless dietary component in reasonable levels. The CFIDS literature also suggests that Q10 (ubiquinone) may have some value. This also doesn't have a direct effect on the bacterium, but may again be helpful in lowering the production of active arachidonate derivatives.
Some data suggests that a component of milk promotes the growth of the bacterium. We don't know what that component might be or whether the effect we see in culture also happens in the patient. It is prudent to limit the intake of milk and milk products until more is known.
A recent observation is that some currently unidentified component present in fruit juices stimulates bacterial growth in culture. Since juices are digested prior to absorbtion, it is unclear at this time whether fruit juices will also stimulate levels in the patient. Until data is obtained, it is suggested that fruits and fruit juices be consumed in limited amounts. Citrus fruit may be less of a problem.
Excessive light exposure may promote growth of the bacteria, so sun exposure should be controlled.
At this time a large portion of the patients tested are resistant to the available antibiotics. In general, these patients have higher levels of bacteria and their bacteria show greater growth potential in culture. Nutritional manipulation to slow the growth of bacteria based on selective vitamin supplementation with folic acid, vitamin B-12 and vitamin B-6 (optimum amounts not known), choline or lecithin (optimum amounts not known), zinc 25-50 mg/day, chromium 100-200 mcg/day, garlic (?), appropriate sources of non- omega-6 unsaturated fatty acids (at least 5g (5000mg) per day), elimination of undesirable foods, particularly those containing high levels of copper and omega-6 unsaturated fatty acids, a reduction of iron levels and possibly herbal supplements may convert some of these untreatable patients into responders or at least reduce the severity of their clinical problems. We are currently experimenting with a supplement regimen based on these recomendations, which appears to produce symptomatic improvement in at least some patients. If the regimen proves to be generally helpful, we will try to find someone who will make it available commercially.
the following is a link to his patent that I looked up.
http://patft.uspto.gov/netacgi/nph-Pars ... =6,255,467
