CISRA’s Synergy Health Newsletter

Issue 10. Carbohydrate, Chlorogenic Acid and Benicar Sensitivity (2007, with Feb. 2010 update)

Carbohydrate, Chlorogenic Acid and Benicar Sensitivity
in Relationship to the Marshall Protocol:
Preliminary Observations and Links to Theories of Chronic Disease

by J. C. Waterhouse, Ph.D.

Short Summary: A diet is proposed that appears to reduce allergic or sensitivity/intolerance reactions in certain susceptible people and help eliminate treatment-resistant bacteria by reducing an immunosuppressive class of substances (vitamin D receptor blockers). The diet consists of reducing consumption of a number of foods/beverages containing chlorogenic acid and closely related substances and reducing consumption of starches and certain sugars and fibers. The reasons that this diet is not suitable for certain people are given, along with the reasons this diet may help some people have greater success on the Marshall Protocol. Clinical observations, experiments and scientific studies are described that support this approach and link it to several theories of chronic disease.

Feb. 2010 Update: The update consists of information on Epsom salts as an approach to lowering chlorogenic acid sensitivity and a less allergenic brand of enzyme (Enzymedica’s Carbgest). In addition, some changes and additions have been made to the list of foods with chlorogenic acid.

Note on Translational Medicine: This article shows how insights from sophisticated, molecular modeling methods may help the chronically ill reduce symptoms and progress in bacterial killing, especially in cases of increased food/medication sensitivity/intolerance. This work arises from the understanding developed by Trevor Marshall, Ph.D., of the pathogenesis of a number of chronic inflammatory diseases (eg., sarcoidoisis, rheumatoid arthritis, fibromyalgia, chronic Lyme disease and others). This understanding has been incorporated into the Marshall Protocol (MP). The MP involves an antibacterial approach, which relies heavily on immune modulation to kill treatment resistant bacteria (cell wall deficient bacterial forms and bacteria in biofilms). These findings are an example of how clinical observations, when combined with the precise mechanistic knowledge gained from molecular modeling, can lead to useful revelations about treatment.

Detailed Summary

The observations described below, suggest certain substances found in food, like chlorogenic acid (CGA), that are able to bind to the vitamin D receptor (VDR), appear to cause allergic or sensitivity/intolerance reactions in a small percentage of people. In highly susceptible people, CGA appears to be particularly effective at stimulating these immune sensitivity/intolerance reactions (through cross-reactions) to vitamin D, vitamin A, genistein, certain medications (e.g., Benicar), carnosic acid and a substance produced by bacteria that feed on certain carbohydrates (starch and certain sugars and fibers). CGA occurs in a diverse array of foods and beverages and is particularly high in coffee, tea, apples, soft drinks, prunes, lemon peel and pomegranate, among others. Sensitivity may manifest as negative and/or addictive reactions to various foods, supplements and medications.

As mentioned above, what all these cross-reacting substances appear to have in common is the ability to bind to the vitamin D receptor (VDR). The acronym is introduced here, VBS (VDR binding substance), to mean any substance that can bind to the vitamin D receptor, either blocking or activating it.

The fact that VBSs are all able to bind to the VDR means that at least some portion of the molecules are very similar. And VBSs appear to be similar enough in structure to cause immune sensitivity cross-reactions. Cross-reactions are well-known phenomena in allergy and immunology and are due to the similarity of structure of particular portions of sometimes diverse types of molecules. If the shapes of certain portions of the molecules are similar enough, patients may find increased sensitivity to one molecule increases sensitivity to the other similar molecules and thus causes the cross-reactions mentioned above.

The biological role of VBSs in binding to the vitamin D receptor is also very important. We now know that VDR binding substances can be important due to the vital role of the VDR in helping the innate immune system protect us from infection. In fact, blocking of the VDR by certain VBSs appears to be responsible for many chronic and autoimmune diseases (1, 2, 3, 6, Issue 10. A Short Introduction to the Marshall Protocol), while activation of the VDR by other VBSs can help us to heal.

Molecular modeling indicates that chlorogenic acid blocks the VDR. Thus, reducing CGA will increase VDR activation, resulting in greater immune activation and bacterial killing (6). Molecular modeling and clinical evidence shows that 1,25D (the active form of vitamin D) and Benicar activate the VDR, while high levels of 25D, carnosic acid, capnine and CGA block the VDR.

The bacterial killing enhanced by an active VDR is a desirable goal, but may increase symptoms due to the immune system reaction that occurs when the immune system attacks the bacteria and cleans up toxins and cellular debris. This immune system reaction increases inflammatory cytokines (e.g., IFN gamma, TNF alpha), which can increase pain, fatigue and a diverse array of other symptoms (a.k.a. Jarisch-Herxheimer, “Herx” or immunopathology reactions). The reaction to bacterial killing can become intolerable and even life-threatening if not controlled properly (see “Cautions – Updated“).

So, VBSs have significance in two different ways. They can be a source of sensitivity reactions in a small minority of people, who thus may need to avoid them with a low VBS diet. And their ability to bind the VDR, means they can play an important role in the ability of the innate immune system to kill pathogenic microbes. How to deal with the multiple effects of VBSs (in sensitivity reactions and in VDR activation) is discussed in detail in the sections on practical implications (Sections C, D, E).

This article first presents additional background on the new observations on CGA and VBS sensitivity (Section A, below) and then discusses the relationship of VBSs to several theories of chronic disease (Section B). As mentioned above, there appears to be at least one type of bacteria that inhabits the intestines of some chronically ill people that is able to produce a VDR binding substance (VBS). Some experiments are described that suggest that it is species in the bacterial family, Enterobacteriaceae, that produce this VBS in the intestines. Though not all bacteria in this family produce VBSs, the Enterobacteriaceae include pathogenic forms of Escherichia coli, which have been linked to Crohn’s disease. It also includes Klebsiella pneumoniae, a common pathogen that has been linked to ankylosing spondylitis and other rheumatic diseases. Also in this family, are bacterial species linked to various diseases in the genera, Shigella, Salmonella, Yersinia, Proteus, Enterobacter and Citrobacter.

The production of a VBS by intestinal pathogens, as proposed here, provides support for Marshall’s explanation of many chronic inflammatory diseases (1, 2, 3, 4, 5, 6). The VBS production by these and other pathogens could inhibit innate immune system function and thus allow bacteria to cause these chronic conditions. Reversing this VDR blockage, as in the Marshall Protocol (MP), is therefore seen as key to treatment success. Molecular modeling and clinical research that support this view are discussed.

Other topics discussed in Section B include how VBSs and the MP may relate to new revelations in the journal, Nature, about how particular bacteria in the intestines may promote obesity. The role of the optimal diet predicted by evolutionary medicine (low in sugar and starches) is also discussed, as well as the potential role of VBSs in the Specific Carbohydrate Diet approach to treating certain intestinal diseases (e.g., Crohn’s disease, ulcerative colitis, irritable bowel syndrome).

Practical implications are discussed in detail in Section C, D and E, including the types of foods to be reduced in a low VBS diet, the ability of some probiotics to lower VBS production, the potential utility of enzymes (e.g., No Fenol), and the rare circumstances in which a break from Benicar might be appropriate for those on the MP.

Suggestions are also made about how people in various situations might apply this information to help determine what diet would be best for them, since individual needs will differ (see Section D and “Cautions – Updated“). A low VBS diet is not appropriate for everyone, particularly those who are having very intense immunopathology reactions due to bacterial killing. Section F provides the details about CGA/VBS levels in various foods, supplements and medications.

The multiple effects of various VBSs are not always easy to distinguish. However, one can tell that one is likely to have an immune sensitivity to a substance if one experiences a reaction in less than 10 -15 minutes (short cut test can be useful, see: Testing for Food/Chemical Reactions before doing any testing). This is a test that may help one to distinguish a sensitivity reaction from other responses. Changes in the intensity of bacterial die-off reactions that involve the VDR would take longer to occur.

Note: The findings presented here are not a part of the Marshall Protocol at this time, just preliminary observations until more data is gathered. The current position of the MP website is that one should try to avoid consuming excessive amounts of chlorogenic acid on the Marshall Protocol, primarily through drinking too much coffee, and to avoid too much genistein from soy products. The reason discussed on the MP site is the possibility that chlorogenic acid will block the VDR and interfere with the ability of the immune system to kill bacteria. It should be remembered that most people do not have a problem with a sensitivity to Benicar or chlorogenic acid and do not need to avoid the foods discussed here. The MP website also suggests a low carbohydrate diet, but not of the specific type or for the specific reasons discussed here.

Note to MP patients – this information is aimed primarily at a small minority of individuals who have had difficulties and most people do not need to be concerned about the issues discussed here.

Caution on the Use of the Marshall Protocol: The power of the antibiotics used on the Marshall Protocol is so greatly enhanced by the immune system modulation of the MP that patients may have serious or even life threatening reactions if they do not start at low enough antibiotic dosages and do not proceed according to the guidelines (see Autoimmunity Research Foundation – Phase One Guidelines and Issue 10. A Short Introduction to the Marshall Protocol). Health Care providers are responsible for the use of this information. Neither the Autoimmunity Research Foundation nor the author assumes responsibility for the use or misuse of this protocol.

Advice to the Reader: This article is meant for doctors and health professionals as well as patients, so it contains practical suggestions, along with more technical material and some may choose to skip or skim some sections.

Before changing one’s diet, one should read Sections D and E and Cautions – Updated, and consult a health professional, because what is suggested for one person may be the opposite of what would be beneficial to another due to differing individual situations. These are preliminary observations and it is suggested that you watch the website for updates.

Section A. Background

Chlorogenic Acid Allergy/Sensitivity/Intolerance (CGA)

The Marshall Protocol (MP) is a treatment that combines immune modulation with very low dosages of pulsed antibiotics to kill treatment-resistant bacteria. These cell wall deficient (CWD) and biofilm bacteria are seen as the cause of many autoimmune and chronic diseases (See Issue 10. A Short Introduction to the Marshall Protocol)

I have experienced a number of improvements in my own long-standing chronic Lyme disease/chronic fatigue syndrome/fibromyalgia/irritable bowel syndrome in the more than two years I have been on the MP. In the last six months, I have made a number of observations with regard to food/chemical sensitivities/intolerances and the MP. In this section, I will give a history of how I made these observations and will also describe how they have led me to some preliminary conclusions about the role of chlorogenic acid (CGA) and related substances in allergy/sensitivity/intolerance, including their effects on the ability of the body to kill treatment-resistant bacteria.

I have discussed in previous articles (e.g., Marshall Protocol — Talk Transcript), how my food sensitivities were severe and extensive over many years, and how this initially remained unchanged on the MP. After about two years, however, my food reactions began to lessen, presumably due to the progress I have made in lowering my bacterial load and improving my immune function through the MP. I began to tolerate a number of foods I did not tolerate before. And those foods I did react to, caused fewer and milder symptoms. So, I began widening my diet and testing my reactions to many different foods (See Issue 10. Detecting Food Allergies/Sensitivities/Intolerances: Beyond the Pulse Test).

Interestingly, after I began trying some new foods, I found that a few began to cause a much greater increase in certain symptoms than I expected, including a high pulse increase. It turned out that these foods were all high in CGA. For example, I became highly sensitive to apples, coffee, tea, melon, prunes, which all have high levels of CGA. I also discovered that as I widened my diet, I was becoming much more sensitive to anything containing vitamin D, vitamin A, carnosic acid, genistein and certain medications and supplements.

One medication I became more sensitive to was Benicar, the medication that is an integral part of the Marshall Protocol. This was indicated by a variety of symptoms and a pulse increase of over 20 beats per minute, which began 1- 2 minutes after chewing even 2 mg of Benicar and allowing it to remain in my mouth for a few minutes ( Issue 10. Detecting Food Allergies/Sensitivities/Intolerances: Beyond the Pulse Test and Cautions – Updated). The reaction was most reliable when I was fasting, and when it was at least 6 to 7 hours after last taking Benicar. The very high degree of reactivity to Benicar only began after consuming foods high in chlorogenic acid.

Fortunately, around the time I was having these reactions, Dr. Marshall used molecular modeling (6) to identify chlorogenic acid as a substance that could bind to the vitamin D receptor (VDR). It became clear that all the substances I had suddenly become sensitive to contained VDR binding substances (VBSs) that he had previously identified.

Apparently, aside from its effects on the VDR, CGA can also be a potent source of allergy/sensitivity/intolerance responses. The increase in sensitivity to Benicar that occurred following the increase in CGA now made sense because it became clear that these substances cross-react due to their similarity in structure revealed by molecular modeling research (2, 3, 4, 6).

Cross-Reactions, Allergy, Immune Sensitivities/Intolerances (non IgE), Haptens, Bacteria

It seems appropriate to give a little background on cross-reactions and some related topics. Cross-reaction means that the structures of the molecules are similar enough that the immune system regards them as nearly the same. Consuming one to the point of becoming sensitive to it, causes one to also become sensitive to the other cross-reacting substances. It appears that foods with a large amount of chlorogenic acid are particularly potent at stimulating this type of sensitivity reaction.

My emphasis is not on the classical Type I allergy (IgE mediated), but on reactions that involve another mechanism, such as a Type II, III or IV sensitivity responses (7). Partly this is because both blood tests and intradermal testing has indicated these are the types of reactions I experience, but also because these types of reactions are often harder to detect and therefore overlooked, despite being common and important (see Issue 5 Food Sensitivity Article).

I currently have data on another patient who had a similar experience as mine. He had begun consuming more CGA while on the MP and had a similar pattern of sensitivities develop, which then declined with a dietary change similar to the one I describe here.

In my research, I found that chlorogenic acid is recognized as a potent allergen for some people (8) and it is included on one of the ALCAT food/chemical intolerance test panels (www.ALCAT.com). It should be noted that substances may be quite different chemically, but have a particular area of their molecule that is very similar and thus can have the same effect upon a receptor or immune cell and thus cause similar sensitivity reactions.

Also, it is now recognized that even very small molecules, and even substances like metals, can bind with a large molecule and create what are called haptens. Recently, it has been shown that nickel allergy can occur when a nickel ion bonds to a lipopolysaccharide from a bacteria to form a hapten, thus showing a possible link between nickel sensitivity and bacterial infection (9). These haptens can stimulate immune allergy/sensitivity reactions, even though the original small molecule could not.

I had become mildly sensitive to Benicar previously and took a break from it in the first year of the MP. But the sensitivity declined and I went back on it. Now, I realize that dietary factors can affect this tendency toward Benicar sensitivity.

Vitamin D, Supplements and Sun Exposure

As mentioned above, when I included high CGA foods in my diet, I also become very sensitive to foods with vitamin D in them. Vitamin D binds the vitamin D receptor, so is similar in structure to the other VBSs, like CGA, and thus cross-reacts with them. As a result, based on my reactions, I have also learned that many supplements probably do have either hidden vitamin D in them, or other substances, like CGA. For instance, I tested one high quality fish oil supplement whose manufacturer claimed the vitamin D had been removed and my level of reaction indicated it still had significant levels of vitamin D and/or vitamin A, though it was likely that much of it had been removed.

I had similar reactions with most supplements, even a number of high quality, expensive ones. I think this is due to very small amounts of vitamin D or A contaminating the supplement or due to small amounts of CGA or carnosic acid that is extracted along with the nutrient, from the plant product that is used to make the supplement (Section F).

My reaction to sun exposure also greatly increased during this period of CGA sensitivity due to vitamin D production that occurs in the sun. The reaction occurred within 2-3 minutes of exposure of even a very small area of unprotected skin. Patients on the MP have sun reactions for a variety of reasons, including increased bacterial killing and hormonal reactions. However, my observations indicate that for some people, whose reaction occurs almost immediately (within the first 10-15 minutes), the reaction may be at least partly due to a sensitivity to vitamin D (Section M. “Methods”).

When I changed my diet to reduce VBSs, my short-term sun reaction was also reduced. This supports the view that the dramatic effect of sun exposure on my pulse and other symptoms was similar in nature to my VBS sensitivity and that the ability to bind the VDR was what all my very reactive substances had in common. The same changes in sun reaction intensity were confirmed in another patient who made the same dietary changes.

Role of Carbohydrates – Pathogenic Bacteria and the Innate Immune System

For several weeks, as I avoided the CGA and vitamin D containing foods, and took a break from Benicar, my sensitivities declined gradually. Then I decided to stop eating oats and was surprised to find my reactivity declined even more, even though oats do not contain CGA. Then, when I reduced my consumption of grains altogether, by reducing my white rice consumption to about 2/3 cup per meal, there was an even more dramatic decline in my sensitivity to chlorogenic acid, vitamin D, Benicar and other similar substances.

Soon after this diet change, I was able to resume Benicar and tolerate sun exposure much better. Even after I resumed the Benicar, my sensitivities to these substances has continued to decline on the low starch and low chlorogenic acid diet. The same reduction in sensitivity/intolerance was confirmed to occur in two other people, who made similar changes.

Based on these observations, I have hypothesized that certain bacteria in the intestines that feed on starch and certain sugars and fibers can produce a substance similar to CGA. This substance is another VBS that also stimulates cross-reactions with other substances that bind the VDR. Reducing the sugars/starches/fibers that feed these bacteria thus decreases the sensitivities to all VBSs, including CGA, vitamin D and Benicar, due to their cross-reactivity.

As discussed previously, the VDR is an important regulator of the immune system and its activation has profound effects on innate immunity. Thus, besides inducing sensitivity reactions in a small percentage of people, some VBSs activate the VDR (eg. 1,25D and Benicar) and some block the VDR (e.g., 25D and chlorogenic acid). The exact details of their structure determine how tightly they will bind to it and whether they will activate the VDR or block it. If they bind to it without activating it, they can prevent other substances from activating it and thus block it. If they activate it, a series of processes will begin that fulfill the function of the VDR. Activation of the VDR results in facilitation of the activity of certain immune cells (macrophages) and the production of anti microbial peptides that kill bacteria, viruses and fungi.

Thus, besides the relevance to CGA and other sensitivities, the production of a VDR binding substance (VBS) by certain starch-feeding bacteria would be expected to have consequences for bacterial killing.

These consequences have, in fact, been observed. In addition to my own repeated experiments (see below and Section M. “Methods”), several other people on the Marshall Protocol have noted increases in bacterial die-off reactions when they lower starchy carbohydrates in their diet. This provides more support for the hypothesis that a VBS is produced by certain intestinal bacteria and that it blocks the VDR.

And as might be expected, some people who have experienced excessive bacterial die-off reaction have found that consuming carbohydrates or high CGA foods or beverages has relieved their symptoms related to the bacterial killing. My findings indicate that this is because there is a VBS produced by the starch-feeding bacteria in their intestines that is able to block the VDR and thus block the innate immune system’s attack against the bacteria. However, as discussed below, there is evidence that not all people have this effect from starch consumption, probably due to differences in the particular bacteria in the intestines of different individuals.

Section B. Relationships to Theories of Chronic Inflammatory Disease

Identifying the VBS-Producing Bacteria

In my preliminary investigations, I compared the effects of oral doses of different antibiotics that are known to kill different types of bacteria, in order to see how they affected the ability of starch reduction to alter bacterial killing intensity (for those interested in more details see Section M. Methods). If pretreatment with a particular antibiotic led to elimination of the effect of reducing starch, then I knew that antibiotic was able to kill the VBS-producing bacteria. In other words, the antibiotic had already killed most of the bacteria that starch reduction would have reduced and so there would be no further effect from reducing starches in my experiment.

I tested 5 different MP antibiotics and Bactrim was the most powerful in its ability to kill the VBS-producers. Clindamycin had no impact and the other three were in between (Demeclocycline was second best). I used information in the literature about which antibiotics are best at killing which types of bacteria. The fact that Bactrim, but not Clindamycin, kills Enterobacteriaceae suggests that the bacteria that produce the VBS in my experiments may be pathogenic forms of this family. The Enterobacteriaceae include a number of potential pathogens: Klebsiella pneumoniae, many pathogenic strains of Escherichia coli, and pathogenic species of Salmonella, Shigella, Yersinia, Proteus, Enterobacter and Citrobacter.

Klebsiella was the first genus of bacteria in this family that I considered. It is a bacteria that has been detected in my colon in the past and was linked to episodes of diarrhea. Klebsiella pneumoniae has been linked to rheumatic diseases such as ankylosing spondylitis and other rheumatic diseases. Antibodies to Klebsiella have also been found to be higher in Crohn’s Disease (10). Overgrowth of Klebsiella in the intestines has been linked to diarrhea, so patients who have had diarrhea as a symptom may be somewhat more likely to have them in their intestines and notice the effect of variations in carbohydrate consumption.

For another example supporting the role of the family Enterobacteriaceae, a recent study (11) has shown that some pathogenic forms of E. coli, are likely to be responsible for infecting damaged areas of the colon in inflammatory bowel disease. This is also consistent with other studies implicating pathogenic E. coli in Crohn’s disease (e.g., 12, 13). A diet which eliminates starch and sugar and related substances, the Specific Carbohydrate Diet, has also been used to treat these diseases, as discussed below.

Other members of this family, Shigella, Yersinia and Salmonella are also pathogens capable of causing acute illness and reactive arthritis. Several strains of Enterobacter are causes of infection in immunocompromised patients. Particularly common infection sites are respiratory and urinary tracts. There are also pathogens in the genera Proteus and Citrobacter capable of producing serious illness.

Of course, not all species in the Enterobacteriaceae family produce a VBS. For instance, my experiments showed that Lactobacteria spp do not produce a VBS. This is in agreement with the beneficial effects reported from use of Lactobacteria spp and non-pathogenic E. coli as probiotics.

As mentioned previously, my experience so far indicates that not everyone with chronic inflammatory disease is affected by lowering starch consumption. This agrees with the hypothesis that it is only certain potentially pathogenic species that produce a VBS in the intestine and that these species are not present in everyone. My observations also indicate that although intestinal VBS production is most likely in people who have had significant gastrointestinal symptoms, this is not a necessary precondition for being affected by these intestinal bacteria.

Linkage to Marshall’s Pathogenesis of Chronic Inflammatory Disease

The production of a VDR-blocking substance by these bacteria, as proposed here, fits in well with the pathogenesis of chronic inflammatory diseases developed by Marshall (1, 2, 3, 6). The VBS production by these pathogens could inhibit innate immune system function and thus play a role in the pathogenesis of these chronic conditions. The discovery through molecular modeling (14, 15), that capnine, a substance produce by a type of bacteria found in biofilms (gliding bacteria, Lysobacter), can also block the VDR, is an indication that VBSs can be produced by bacteria and thus supports Marshall’s theory.

A recent study confirmed a role for a deficient innate immune system response in Crohn’s disease. The authors proposed that this is a constitutional, probably genetic weakness that leads to bacteria breaching of the mucosal barrier and granuloma formation (16, 17). However, the alternative discussed here is that VBS production from intestinal and other bacteria is the source of this defective innate immune response.

It may be noted that a variety of different bacterial species have been linked to inflammatory bowel disease. This is similar to the situation in other chronic diseases, like sarcoidosis, arthritis and multiple sclerosis (18, 19, 20). Many researchers spend years testing for the presence of certain pathogens and trying to link particular species to particular diseases (18). However there seems to be a lack of significant progress using this approach.

A different, less species-focused, polymicrobial approach underlies the Marshall Protocol and pathogenesis. An immune defect is recognized and linked to bacteria and environmental factors. It is taken for granted that the infection involves many species, many of which are unknown at present and most of which are very hard to reliably detect with commonly used methods.

The MP approach is to correct the immune defect to the degree possible and treat with low, pulsed doses of several antibiotics, in particular combinations, and in a particular sequence, to cover the maximum number of bacterial species. Eventually, the bacterial load allows the immune system to normalize and the rest of the bacteria and other pathogens can then be eliminated by a fully functioning innate immune system. The protocol must be done carefully and in stages, since many patients have built up very large bacterial loads and require careful management to avoid excessive immunopathology reactions (see Cautions on the Use of the Marshall Protocol).

This approach has been receiving increasing support from several lines of research. There is new evidence that treatment-resistant biofilm bacteria may respond better to pulsed doses of antibiotics (21), the approach used by the MP. Multiple antibiotics are increasingly being used and immune modulation is also an approach being used more frequently. Although cell wall deficient bacteria that can hide in host cells and evade detection and eradication have been pushed to the background for decades, recent studies continue to indicate that they are important (22, 23, 24).

Marshall’s work ties in with the findings presented here. Marshall proposed that an effective strategy for a bacterial species to produce chronic disease would be to disable the VDR, which is the key to innate immunity. The VDR has many functions, including allowing macrophages to function optimally and the production of anti microbial peptides (3, 6, 24).

The discovery of capnine’s ability to block the VDR (14) provides proof of the concept that some bacteria may use blockage of the VDR as a strategy against the host’s immune system, and Marshall predicted that other species would be found that also use this strategy. The observations and experiments discussed here provide clinical evidence in support of this view by indicating that another VDR-blocking substance is produced in the intestines probably by pathogenic species of the family Enterobacteriaceae. This is compatible with past epidemiological evidence, as discussed above. It seems likely that even more bacteria will eventually be found that use this effective strategy of producing a substance that blocks the VDR to block innate immunity.

Relationship to Evolutionary Medicine and Homo Sapiens Optimal Diet

It has been increasingly argued that the healthiest diet for humans is the diet that was eaten during the longest period of our evolution, which was prior to agriculture. One of the foremost experts on the “Paleo Diet” (26), is Loren Cordain, who has researched and written on this subject for many years. Although not all experts agree on every aspect of the diet that was consumed by our ancient ancestors (e.g., what was the percentage of meat consumed vs. vegetables), they all agree that grains, sugar and legumes were not consumed to any significant degree by ancient, pre-agricultural man.

Cordain and others have noted that there was a decline in health, indicated by examination of skeletal evidence, after agriculture took hold. Agriculture permitted large civilizations to develop through grain cultivation, but Cordain argues that the widespread switch to cereal grains has been a two-edged sword, and he has even linked it to diseases like multiple sclerosis, autism and schizophrenia (27). Perhaps if grain and sugar consumption contribute to such diseases, it is through being better able to support intestinal bacteria that are able to produce VBSs that block the innate immune system and facilitate chronic bacterial infection.

Another problem that has been increasingly linked to over consumption of starch and sugars is obesity. Many diet books that focus on lowering carbohydrate consumption focus primarily on the effects of carbohydrates on insulin. Many conclude that obesity is another problem linked to consuming a diet that evolution did not prepare us for.

However, there is another theory that focuses on bacteria’s role in obesity that also relates to starch/sugar consumption. It has recently been found that the ratio of Firmicutes to Bacterioidetes in the gut is greater in people who are overweight and decreases when they lose weight (28). Although the ratio declines regardless of whether the weight loss diet is low carbohydrate or low fat, the ratio declines much more steeply and quickly if the diet is low carbohydrate (28).

It turns out that Firmicutes are more abundant in vegetarians (29), the elderly, and especially elderly hospitalized patients (30). Along with more Firmicutes, hospitalized patients also had more Enterobacteriaceae (30). Although research continues on the significance of the abundance of Firmicutes, its greater abundance in the obese and elderly and/or ill people suggests that an overabundance of Firmicutes is not desirable.

So, it appears that a diet high in cereal grains and sugar is not natural for humans and contributes to the development of many modern chronic diseases. But rather than blaming all the negative effects on insulin, an alternative hypothesis is that our consumption of this high starch/sugar diet leads to a higher percentage of Firmicutes and Enterobacteriaceae as we age. Whether more Firmicutes tends to promote more pathogenic Enterobacteriaceae or they both contribute equally to pathogen load is unknown.

But one result of Enterobacteriaceae and possibly other pathogenic bacteria becoming established may be the production of one or more VBSs that block the VDR, thus blocking innate immunity. Together with other factors, such as excess vitamin D supplementation, which can also block the VDR, the high starch/sugar diet could help contribute to the load of bacteria that invades other parts of the body and causes chronic disease.

The gastrointestinal tract is only one of the routes through which infections are acquired. And, in fact, the pancreas may also become infected with cell wall deficient bacteria and perhaps contribute to the development of diabetes and insulin resistance as well. But the continued consumption of sugar and starch may contribute significantly by adding even more VBS to the amount of VBS produced by bacteria that infect other areas (e.g., lungs, joints, urinary tract).

Relationship of Low VBS Diet to Specific Carbohydrate Diet to Treat Inflammatory Bowel Disease

A diet that eliminates sugar, cereal grains, certain fibers and starchy vegetables also has a history in the treatment of inflammatory bowel disease and has recently been named the Specific Carbohydrate Diet. The diet suggested in this article to lower VBSs has many similarities to the SCD in terms of the types of starches, fibers and sugars that should be minimized (31).

The main difference between the diets is that the SCD completely prohibits the foods that stimulate the bacterial VBS production, whereas in a low VBS diet, it is just suggested to reduce them. The SCD also allows consumption of a number of foods that are high in CGA (e.g., apples, peanuts, coffee, tea) and these would have to be avoided if one is very sensitive to VBSs. Lactobacteria spp, that can help replace the pathogenic bacteria are also used extensively on the SCD (and may be useful sometimes on a low VBS diet, see below).

Elaine Gottschall in her book on the SCD, Breaking the Vicious Cycle (31), proposes a circular causation process that begins with damage to the small intestinal surface, which leads to impaired digestion of disaccharides (like table sugar and starch), which then leads to malabsorption of disaccharides. The malabsorbed disaccharides then provide food that fuels bacterial overgrowth, which then increases bacterial by-products and mucus production, which then completes the cycle by leading to more damage to the small intestinal surface etc…

Marshall’s pathogenesis, supported by my observations, identifies a likely source of the small intestinal damage that initiates the cycle: pathogenic bacteria that are able to gain a foothold by producing a substance, a VBS, that blocks the innate immune system’s ability to eradicate them.

Thus, the SCD may not simply work by reducing the vicious cycle Gottschall describes. Instead, when most successful, the SCD may work by reducing the food in the intestinal lumen that the pathogenic bacteria use to fuel production of VBSs, which block the innate immune system. By lowering VBS production, the SCD may enable an increase in function of the innate immune system, which will help eliminate bacteria that are damaging the intestinal lining.

There are several characteristics of patient responses to the SCD that support this view. The long period of time that many patients seem to need to be on the SCD seems to exceed the length of time that would be needed to heal the intestines, which is the explanation used for patients having success in achieving remission while on the SCD. Exacerbations are reported by people on the SCD and this may be due to periods in which the innate immune system has been producing too strong a bacterial die-off reaction, as is frequently observed in these diseases when bacterial killing is occurring (6). During these periods, patients sometimes need to go back on steroids or other immunosuppressants.

The fact that some foods with a high CGA level are used on the SCD (apples, peanuts) may allow some patients to reduce the bacterial die-off reactions to a more tolerable level without realizing they are doing so. These CGA/VBS foods and beverages would succeed in partially blocking the VDR and thus keeping the level of immunopathology reaction at a moderate level. However, the CGA consumption may also produce severe CGA/VBS allergies/sensitivities in some people and this probably plays a role in why so many people on the SCD have to alter the diet based on their individual reactions.

For many people, the Specific Carbohydrate Diet does not seem to work or only works partially. This may be due, in part, to the difficulty of adequately balancing bacterial killing (affected by CGA/VBS level), with the problems of sensitivities to VBSs and other foods. Perhaps the identification of the cross-reacting VBSs presented here will help those on the SCD find the best diet to allow long term healing as well as short term symptom relief. But it seems likely that in most cases, the infection is systemic and has progressed far enough that complete eradication of the CWD and biofilm bacteria will be needed through an approach like the Marshall Protocol. Of course, more data will be needed to determine whether this view is correct.

(Note: I should clarify that I distinguish between the bacteria in the lumen, which can increase in numbers greatly from hour to hour due to diet, from those bacterial pathogens that have invaded the intestinal wall and other tissues. It is my view that the latter probably require a protocol, such as the MP, to have a significant beneficial effect.)

Section C. Applying Information About VBSs

Low VBS Diet

A diet that reduces VDR (vitamin D receptor) binding substances (VBSs) involves reducing high chlorogenic acid (CGA) foods and foods that stimulate production of VBSs by bacteria in the intestinal tract in some people (see previous sections). All disaccharides and polysaccharides need to be limited, including cereal grains, starches and most sugars. Sugars that are permitted are glucose, fructose and galactose.

Certain soluble fibers that feed the bacteria also should be minimized (e.g., psyllium, acacia fiber, guar gum, xanthan gum, Metamucil and FOS, fructoligosaccharides, inulin, Nutraflora, found in probiotics and yogurt). If one has a problem with constipation without these fibers, increased consumption of high fiber fruits and vegetables and/or extra magnesium may be useful. See Section F for a discussion of which supplements and foods are best for a low VBS diet.

Most dried beans (e.g., chickpeas, kidney beans) are to be reduced on a low VBS diet, although lentils, white (navy) beans and split peas apparently can be used if they are soaked overnight and the water is discarded before cooking. Potatoes, yams, milk, table sugar, corn syrup and similar added sugars are to be reduced, but fruit sugar (fructose) and honey can be consumed in moderation. However, some people will need to keep some of these other sugar and carbohydrates low for other reasons (e.g., diabetes, yeast overgrowth or obesity).

Meats, fruits, vegetables, cheese, yogurt, eggs and nuts are fine and do not need to be limited unless they are high in CGA or one has an allergy/sensitivity/intolerance to them independently of the VBS issue (with regard to nuts, see other articles in this newsletter Issue 10. Almond and Walnut Sensitivity and Issue 10. Lysine, Arginine and Viral Infections).

Initially, if one is very sensitive, one might need to reduce other VBS sources in the diet (vitamin D, vitamin A, carnosic acid, see Section F). Most herbal supplements will probably need to be reduced or eliminated, at least temporarily.

If one wants to be very thorough, the information on the Specific Carbohydrate Diet will be useful (31), since items it says to avoid are probably generally those that should be reduced on the low VBS diet. If one has extreme VBS sensitivity or has inflammatory bowel disease or severe diarrhea, one might want to be more strict and try avoiding all the foods on the list of “SCD Illegal foods” (31).

However, one should see the section on “Different Approaches for Different Situations” in Section D and the Cautions – Updated, below, before making any changes. This is because some people may have too strong a bacterial die-off reaction if the VBSs are too low. And it should be kept in mind that some of the foods and beverages that are allowed by the SCD must be reduced to be on a low VBS diet and that this will be particularly important if one has a very strong CGA sensitivity (e.g., apple, peanut, coffee, tea. see Section F).

Probiotics

Probiotics are used extensively in the Specific Carbohydrate Diet and have frequently been recommended for diseases involving the intestines and occasionally other conditions. There are a variety of theories about how they work, but the theory that best fits the observations presented here is that they are able to temporarily replace harmful bacteria, which in this case means VBS producing bacteria. By lowering the VBS production, this may have effects on sensitivity reactions and VDR activation, as discussed previously.

Many different probiotics are recommended by different practitioners. Here, the focus is on finding those without added ingredients that might stimulate the pathogenic bacteria (i.e., FOS, inulin, fructooligosaccarides, psyllium) as well as minimizing allergenic ingredients. Sensitivity to the organisms themselves can also occur, and so for that reason, some may not tolerate them (for ways to test for sensitivity, see Issue 10. Detecting Food Allergies/Sensitivities/Intolerances: Beyond the Pulse Test).

The SCD recommends consuming homemade yogurt to obtain the probiotic Lactobacteria organisms (homemade, because it allows it to be fermented long enough to remove all lactose). For a low VBS diet, the only suggestion for yogurt is to find one with live culture and with minimal added fiber and sugar. Increasingly, that has become harder to do. For many, it may not matter, but it is preferable to try to find yogurt without FOS, inulin, fructooligosaccarides, pectin, Nutraflora, guar gum and other gums. In order to minimize sugar, it is preferable to buy a plain yogurt and add fruit and/or honey to sweeten it. (Note: one brand I found recently that was suitable in June 2007 was Straus Family Creamery Plain yogurt, but watch for changes in ingredients).

If one wants to use a probiotic in capsule form, there are several products approved by the SCD. There are Kirkman Lab’s Lactobacteria acidophilus and GI Prohealth has a Lactobacteria and a Saccharomyces product (34). Cellulose is the preferred filler. For the SCD, it has been recommended to start with no more than 3 billion organisms daily and to not exceed 9 billion.

The only probiotic organisms approved by the SCD are: Lactobacteria acidophilus, Lactobacteria bulgaricus and Streptomyces thermophilus. Although these probiotic bacteria are the species usually recommended for the SCD, Saccharomyces is also allowed. If other probiotic products do not work well enough for one on a low VBS diet, some may choose to try the SCD-approved brands instead.

In my own experiments, I have tried the Lyo – San Lactobacteria, Nutrition Now’s PB8 and Jarrow’s Saccharomyces boulardii (a yeast), which are not SCD approved brands (34). I have found them all to be relatively low in allergens and my rather limited testing suggests they are able to temporarily replace most of the VBS-producing bacteria.

I have found for maximum effect in lowering VBS, some probiotic should be taken with every meal, especially with any meals with rice or other starchy foods. Since Saccharomyces boulardii is a form of yeast, one should avoid combining this probiotic yeast with No Fenol or similar enzyme products (see below), which may break down its cell wall. The other probiotics should be taken at least 2 hours apart from any antibiotic.

Adding a probiotic to a low VBS meal does further decrease the VBS production according to my experience. This indicates that diet alone does not completely eliminate the VBS production, but only reduces it. I have not found the effect of the probiotics to last overnight, so bedtime or early morning doses might sometimes be helpful (1/4 –1/3 of a capsule contents might be used sometimes). One should take it with at least a glass of water. It can be taken with or without food.

It should be remembered that although probiotics are allowed on the MP, they are not a required part of it, nor are they required for a low VBS diet. Not all patients are affected by starches in the same way, or experience an effect on their bacterial killing, as described at the end of Section B. This is because not everyone will have the VBS-producing bacteria in their intestines. So, for some, just lowering CGA consumption will be all that will be involved if they wish to try a low VBS diet.

Enzymes that May Help in a Low VBS Diet (e.g., No Fenol)

No Fenol (32) contains enzymes (e.g., xylanase, cellulase) that break down polysaccharides. They also appear to break down phenolics, like CGA and salicylate, as well. In place of or in addition to reducing/avoiding the VBSs and sugars/starches/fibers, one might try using No Fenol or an enzyme product with the same or similar ingredients at the same high levels.

(Feb. 2010 Update: I have evidence to indicate that Enzymedica brand’s Carbgest is more hypoallergenic than Houston Lab’s No Fenol and it should work as well, so now suggest using the former product instead. It also may be good to begin with a small amount (either 1/16th or 1/8th capsule per meal) to minimize the adjustment reaction that may occur due to bacterial/yeast die off and/or withdrawal from allergens. One can gradually increase it as needed. It may be needed only temporarily in some cases.)

No Fenol may cause a yeast die-off reaction initially and diet adjustment is probably better, but my observations indicate that it does break down the chlorogenic acid and reduce the production of the VBS by bacteria. Thus, if one wants to reduce sensitivity or increase bacterial die-off as described below, the VBS/carbohydrate reduction diet might be replaced by simply adding one or two capsules of No Fenol per meal to one’s higher starch and higher CGA diet.

Another possibility would be to use No Fenol only at meals when one is splurging and eating extra carbohydrate/sugar sources and/or CGA sources on special occasions. I have limited experience with using it, but one may refer to for experiences of others with various health problems (33)

Or No Fenol might be used in addition to a low starch, low CGA diet. One capsule with each meal or snack and a partial capsule for a very small snack should be adequate in most cases. I have found that adding No Fenol to a meal without any starch/sugar is able to further reduce VBS levels beyond the reduction achievable with a no starch/sugar meal.

No Fenol can be sprinkled on food, since it is fairly tasteless. Most people will prefer to get the capsules or powder, since the chewable type has substances that may be allergenic for some people (e.g., salicylates).

Enzyme use is discouraged on the Marshall Protocol unless truly necessary. So, it would probably be best for those on the MP to use other means first and only use No Fenol or other enzymes to the extent necessary.

The Importance of Detecting Non VBS Food Sensitivities/Intolerances

It is also very helpful to be aware of other foods that are not well tolerated due to one’s particular sensitivities that are unrelated to VBS content. Exposure to any reactive foods can exacerbate many symptoms. It also tends to increase the overall sensitivity level, disrupts/irritates/inflames the intestinal lining and perpetuates a so-called “leaky gut.”

These food reactions also can result in more poorly digested food passing through the intestines, providing food for bacteria, such as the Enterobacteriaceae, thus increasing the VBS exposure indirectly. So, for people who are very sick and/or are prone to gastrointestinal symptoms, it can be helpful to identify and minimize any foods one reacts to. One should be aware that many people might have food sensitivities/intolerances they are unaware of because they are hidden, delayed or chronic/addictive (non-IgE).

Many people have tried one or two food allergy/sensitivity lab tests or elimination diets and have failed to benefit and conclude they can get no further benefit from trying to manipulate their diets. However, it is often helpful to reconsider this issue. The variable, hidden and sometimes pervasive nature of the food sensitivities may make it particularly helpful to use new methods and approaches that are very seldom encountered, but are presented elsewhere on this site in (Issue 10. Detecting Food Allergies/Sensitivities/Intolerances: Beyond the Pulse Test).

It is sometimes very hard to give up foods that one is sensitive to because they sometimes act as stimulants and might even seem to relieve depression, anxiety etc. through this stimulant effect. Randolph et al identified different mental and physical states associated with these reactions, ranging from mild to severe levels of impairment (35). One may not need to eliminate the reactive foods entirely, but if one identifies them, one can keep exposures within limits and avoid unforeseen or overly intense reactions.

I have found that a low level of consumption of reactive foods that give a mild stimulant effect may even be useful at times, when kept in bounds, in order to help deal with neurological symptoms during bacterial die-off reactions (e.g., mild depression or “spaciness”). It must be remembered, however, that there will be ups and downs associated with withdrawal reactions at times (35). If one knows that it is a withdrawal reaction, it is much easier to cope with. On the whole, one must weigh the positive against the negative through trying different diets and rotation patterns to arrive at the diet that is best for one at one’s particular stage in the healing process.

Fortunately, for those on the Marshall Protocol, it appears that food, pollen and chemical allergies/sensitivities/intolerances disappear as the MP helps the immune system to normalize by reducing the bacterial load. And evidence so far suggests that a low VBS diet also helps.

Section D. Different Approaches for Different Situations

1. VBS sensitivity OR not enough bacterial killing (Jarisch-Herxheimer or “Herx”)– might benefit from low VBS diet: If one has sensitivity reactions to many foods, especially to high CGA foods such as tea, coffee, peanuts, apples and prunes, this may indicate a low VBS diet would be helpful. The sensitivity may present either through increased symptoms related to the diet, or by a craving/addictive response to the food. If one is prone to craving starchy foods, this might indicate that a low VBS diet should be considered. Also, occasionally a low VBS diet might be appropriate if one is having difficulty tolerating Benicar due to a sensitivity reaction (see below for help in determining if a sensitivity reaction is what is occurring – it usually is not). Do not stop Benicar without your doctor’s consent and unless you know that you can tolerate stopping it. It turns out it is usually preferable to continue it, as discussed further below. Another circumstance where a low VBS diet might be used is when one is not killing enough bacteria while on the MP. A low VBS diet might help in the activation of the VDR and allow bacterial killing to proceed.

2. Too much bacterial die-off reaction – might benefit from a higher VBS diet. If one is having excessive bacterial die-off reactions on the MP and one is having trouble keeping the reactions in check, one might increase the consumption of starchy food and certain fibers and CGA sources – the opposite of a low VBS diet. If used in this way, one might need to stay at a fairly constant level of consumption of these items. But even if one has the goal of raising VBS, it is probably not a good idea to consume much sugar for a variety of reasons (see Section E, below).

3. One has no VBS sensitivity or need to alter bacterial killing – might just be aware of the potential effects: It may be helpful to be aware of the potential for variations in CGA, starch/sugar/fiber and probiotic intake to affect symptoms, so that one does not misinterpret symptom changes that might be due to diet and assume they are due to other causes. For instance, if one were to unexpectedly have a particularly strong bacterial die-off reaction and realize that one had eaten a salad and fruit instead of the usual dish of pasta, one might discover that the increased reaction was really due to reduced blockage of the VDR due to the low starch lunch. One then might find that eating a starchy meal might reduce the excessive bacterial die-off reaction. Thus, by being aware of these effects, one would have gained the benefit of reducing symptoms and avoided the mistaken conclusion that a change was needed in medication dosage. Similarly, if one had an increase in immunopathology reaction to bacterial killing (“Herx”) after eating yogurt, it might be linked to the live probiotic culture’s effect on VBS levels.

4. If one is intolerant of CGA/VBSs and is experiencing an excessive or intolerable reaction to bacterial die-off –other measures may be needed. Somewhat of a difficulty exists for those who try to reduce CGA and similar VBSs due to their sensitivity to them, but will tend to have too strong a reaction due to activation of their innate immune system and the resulting bacterial die-off reaction if they do so. In most cases, the solution that one can use when on the Marshall Protocol is to slow the symptoms resulting from the Jarisch-Herxheimer reaction by altering the antibiotic dosage to reduce the rate of killing. In some cases, where the various methods of reducing the bacterial die-off reaction do not work or when one is not on the MP, the only solution may be using a steroid, like dexamethasone, to temporarily slow the rate of bacterial killing to a tolerable level. Patients on the MP can find out more about immunopathology reactions to bacterial killing and the variety of methods for slowing them here: “My immune system response / symptoms are too strong. What should I do?” and Marshall Protocol — Easy Finder, where one can search for the term “immunopathology.”

When Symptoms Increase from Benicar: Why a Break is Seldom the Answer

As discussed previously, Benicar is able to activate the VDR, which then activates innate immunity, often causing bacterial die-off reactions. It also has a variety of hormonal adjustment effects that may increase symptoms (6). At the same time, Benicar has many palliative effects noticed by many patients, some of which are described in the scientific literature (36, 37, 38, 39, 40, 41, 42).

In nearly half the cases, the palliative effects dominate and the patient feels better taking 40 mg Benicar every 6 or 8 hours. In the other half of the cases, the patient feels worse or no better taking the Benicar in the short term, generally because the bacterial die-off reactions dominate. But in either case, palliative effects are occurring and long term benefit is derived from bacterial killing (see A Short Introduction to the Marshall Protocol).

Despite all the above, occasionally it appears someone may need to take a break from Benicar due to a sensitivity reaction. For instance, if one experiences a sore mouth within 10-15 minutes of taking Benicar or chewing on it and allowing it to remain in one’s mouth (e.g., for more details, see: Issue 10. Detecting Food Allergies/Sensitivities/Intolerances: Beyond the Pulse Test) or if one experiences a large pulse increase 20-30 minutes after swallowing it, this may indicate a sensitivity. Reactions that take longer to occur are much more likely to be related to bacterial killing or hormonal adjustment, and in those cases a break is not needed, and actually an increase in Benicar will often be beneficial.

For most people, though, even if they suspect mild to moderate Benicar sensitivity, it seems probable that changing to a low VBS diet, would be enough to eliminate the Benicar sensitivity without needing to stop Benicar. In any case, one should consult one’s doctor regarding any medication changes.

If it does become necessary to stop Benicar, it seems likely, based on my observations, that going on a low VBS diet would usually allow resumption of the Benicar after a fairly short period of time. The time needed for a break would probably depend on the level of sensitivity and the level of VBS reduction, but I estimate that 1 to 8 weeks would be the typical range. Sublingual testing of Benicar may be helpful before resuming (see above).

Some patients who have had trouble on the MP in the past, or suspect they might in the future, may try following the low VBS diet and overall food sensitivity reduction methods recommended here for one to several months before taking Benicar. This might help them have greater success in tolerating Benicar and thus have better success with the MP.

A separate, but related issue is that some people believe Benicar’s modest blood pressure lowering effect is too much on top of their already low blood pressure. Usually low blood pressure responses on the Marshall Protocol are related to bacterial killing, but I have found that low blood pressure can be exacerbated by extensive food sensitivity reactions.

I found that my very low blood pressure normalized when I reduced my food sensitivities before I began the MP (it went from approximately 86/56 to 105/65). I have not had a significant problem with my blood pressure on the MP, and it may be that reducing food sensitivities dramatically, as I did, would help others with low blood pressure issues (see Issue 10. Detecting Food Allergies/Sensitivities/Intolerances: Beyond the Pulse Test).

Section E. Summary of Options for Lowering VBSs

Below is a summary of the options for lowering VBSs. In two patients, the sensitivity improved greatly with only the first option. But it took more than two months. The sensitivity would probably have decreased more rapidly by making a larger reduction of starchy food or by using two or more of the following options. Some experiments with combinations of these approaches indicate the effects are additive.

Put briefly, the options are (also see Section C, above):
1. Dietary: Reduce the amount of starchy foods, fiber supplements and sugar. Instead consume low CGA fruits, vegetables, nuts, vegetable oil and animal products (see Section F for CGA levels).
2. Probiotic Lactobacteria supplements may be taken with every meal, especially with any meals with rice or other starch/sugar/fiber. Saccharomyces boulardii (a species of yeast) also seemed to be effective. Yogurt with live Lactobacteria may be used, as discussed above.
3. Enzyme – No Fenol (33) or a similar enzyme combination that is able to break down polysaccharides and phenolic substances (like chlorogenic acid) as described above.
4. Feb. 2010 Update — Epsom salts
It appears that increasing sulfate by using Epsom salts (magnesium sulfate) may decrease CGA/VBS sensitivity in some people by aiding metabolism/detoxification of phenolic substances. For those on the Marshall Protocol, it is probably better to keep the water lukewarm so as not to provoke too much immunopathology (aka Jarisch-Herxheimer reaction or “herx”). For those who have not used them before, it may be better to start with a small amount and build up the amount (e.g., from 1/4 cup to 2 cups), since occasionally there are adjustment reactions, such as a feeling of being “hyper”. Many find they produce a relaxing effect and find them helpful in reducing symptoms or decreasing food reactions either immediately or over 1-3 weeks. An alternative is to apply a concentrated solution of Epsom salts to part of the body, also starting with a small area and then gradually increasing (e.g., starting with one ankle and increasing to both ankles and calves.) See http://www.enzymestuff.com/epsomsalts.htm and http://mpkb.org/doku.php/home:othertreatments:baths for more on this subject. Note: Excessive use of magnesium-containing products, like Epsom salts, can lead to diarrhea. Those with poor kidney function should be careful to avoid overuse of Epsom salts and other supplements containing magnesium, in order to avoid hypermagnesemia.

Patients with a problem with VBS sensitivity will probably need to stay on a low VBS diet for 1-6 months. But experience so far suggests that if starch/sugar/fiber levels are kept fairly low, patients are eventually able to tolerate more of the moderate and higher level CGA/VBS foods at least every now and then. This should be even more likely if they are on the Marshall Protocol. In my own case, since I have been on the low VBS diet for several months, I am now able to eat most foods without a problem as long as I minimize those highest in CGA and keep my starchy food consumption at a low to moderate level.

High VBS diet?

If the short-term goal is to reduce bacterial killing and one is not too sensitive to VBSs (as in situation # 2 in part D, above), then one might try a higher VBS diet. However, it is always advisable to consult a health professional who is familiar with your particular situation before making significant changes in diet, supplements or medications. For some people, for instance, a high starch/sugar diet would be advised against (e.g., diabetes, insulin resistance or yeast overgrowth problems). If you can not eat starches for these reasons, other alternatives for a high VBS diet are available, such as CGA consumption (e.g. Decaffeinated tea or coffee) or use of certain fibers (e.g., psyllium).

However, a higher VBS diet is probably best used as a temporary measure to slow or moderate immune system reactions from bacterial killing. Although, this is still only a hypothesis and needs further confirmation, it would seem that a lower VBS diet is preferable in the long run, when tolerated. For instance, when one has been on the MP for a while and the bacterial load is reduced enough, someone who originally seemed to need a higher level of starch in their diet may find that reducing the level of starch helps them feel better and facilitates bacterial killing and immune function. There are indications that it may have other long-term health benefits as well (see Section B).


Cautions – Updated:
Marshall Protocol, Food Testing, Withdrawal Reactions, Other Dietary Considerations – Individual Differences

Caution on the Use of the Marshall Protocol: The power of the antibiotics used on the Marshall Protocol is so greatly enhanced by the immune modulation of the MP that patients may have serious or even life threatening reactions if they do not start at low enough antibiotic dosages and do not proceed according to the guidelines (see Autoimmunity Research Foundation – Phase One Guidelines and A Short Introduction to the Marshall Protocol). Health Care providers are responsible for the use of this information. Neither the Autoimmunity Research Foundation nor the author assumes responsibility for the use or misuse of this protocol.

Caution on Testing for Food Reactions: Anyone who has a tendency to anaphylactic reactions (severe reactions in which tissues swell and wheezing may occur–it can be fatal without timely emergency treatment) should avoid any at-home testing or only test foods that one is already eating and it’s known won’t cause a serious reaction. Remember that reactions often increase when one has eliminated the food for a few days and then is exposed to it (“unmasking,” see Issue 8 Food Allergy Article).

So, be even more cautious if you have not stopped or started the food before or have a history of asthma or wheezing. If you have ever have had an anaphylactic reaction, you should consult your doctor about having injectable epinephrine and other needed medications on hand and know the instructions for their use while on the way to the emergency room, in case of accidental exposures. Peanuts and shellfish are two of the worst offenders when it comes to anaphylactic reactions to foods and it may only take a very small quantity in those who are susceptible to anaphylaxis. Once again, do not try any at-home testing that puts you at any risk of an anaphylactic reaction. If you have any doubts or further questions, discuss the issue with a knowledgeable doctor who is familiar with your health situation.

Additional Caution on Reactions to Diet Change and Withdrawal Reactions: Some people may become very symptomatic due to withdrawal reactions (usually lasting 3-7 days) when reducing reactive substances. Common withdrawal symptoms include diarrhea and/or constipation, sleep disturbances, nausea, cravings, loss of appetite, depression, anxiety, headaches and other pains. If one has a strong sensitivity to Benicar, for instance, one might experience a withdrawal reaction like this if one stops it (however, one might also experience an increase in symptoms through loss of the palliative effect, see: Section E).

For the sickest people and those who have been consuming a very reactive food or beverage consistently for a long time, it may help to make the withdrawal reaction more tolerable if one reduces it gradually. Perhaps the most cautious way to do this is to first stop any source of spikes in the level of a reactive substance. For example, say one has a sensitivity to chlorogenic acid. In this case, one could leave in the constant sources (e.g., daily cups of coffee or tea, or other daily fruit from the moderate CGA category). The items one might eliminate first would be the apple one has once a week, or the pomegranate juice or peanuts one consumes now and then. Once the “spikes” have been removed, then one can gradually replace higher CGA foods with lower level ones, doing this a little at a time or gradually reducing an item like coffee, over a period of several weeks.

Some people may have enhanced immunopathology (Jarisch-Herxheimer or “Herx”) reaction if they reduce carbohydrates and CGA foods, so this should be borne in mind (see Section C, D, E. Practical Implications). One might be wise to make dietary changes only when one is not already “Herxing” too strongly in order to avoid symptoms that are too intense. For some options for reducing reactions to bacterial killing for those on the Marshall Protocol, see “My immune system response / symptoms are too strong. What should I do?”

Cautions Regarding Other Dietary Considerations: There may be many considerations with regard to the optimal diet that are particular to the individual. For example, diabetics and those with yeast overgrowth problems may have to cut back on fruit and honey, while others may not be able to tolerate much potassium or protein due to kidney disease. A few people may experience symptoms of hypoglycemia or pseudohypoglycemia (including anxiety/panic attack, headaches, sleep disturbances and other symptoms) if they consume too many carbohydrates, even including non VBS sources, like fruit and honey (see Hypoglycemia and Low Carbohydrate Diet Tips. Some foods may also cause allergy/sensitivity/intolerance independently of VBSs (see Issue 10. Detecting Food Allergies/Sensitivities/Intolerances: Beyond the Pulse Test). In addition, a large consumption of nuts may cause an imbalance in the arginine to lysine ratio, which may be a problem for those with Herpes family virus infections (cold sores, shingles, EBV, CMV, see Issue 10. Lysine, Arginine and Viral Infections). To be sure to take into account one’s individual needs one should consult one’s physician or health professional regarding any changes in treatment and any significant changes in medication, supplements or diet.

Health Care providers are responsible for the use of this information. Neither the Autoimmunity Research Foundation nor the author assumes responsibility for the use or misuse of this protocol.

Section F. Sources of Chlorogenic Acid and Similar VBSs in the Diet (See Cautions – Updated before making dietary changes).

As discussed in previous sections of this article, preliminary observations suggest it may be important for susceptible people to eat a diet that results in a lower exposure to VDR binding substances (VBSs) in order to be able to follow the Marshall Protocol (MP). Below, are lists of foods and supplements that my experience indicates are high in chlorogenic acid or other similar, cross-reacting substances (Section M. Methods). But it should be remembered that most people do not need to avoid these foods or go on a low VBS diet to do the MP and that this is not currently a part of the MP.

If one uses this low VBS diet, involving lower chlorogenic acid (CGA) and lowering of starch and certain sugars and fibers, it may increase bacterial killing and the associated immunopathology symptoms (see Section D and ( Cautions – Updated). So patients should only try a low VBS diet if they are already killing bacteria at a mild or moderate level or if they can compensate for a potential increase in bacterial die-off reaction by decreasing their antibiotic dosages or by using other appropriate medication adjustments (see “My immune system response / symptoms are too strong. What should I do?”).

As discussed in Section C, an example of a low VBS diet would be a limited amount of white rice or other grain (no more than 1/3-3/4 cup per meal), nuts, fruits, non starchy vegetables and meats, poultry, dairy products and eggs (preferably egg whites).

As for fiber sources, fruits and vegetables provide abundant fiber. Many people who have VBS sensitivity will need to avoid types of fiber sometimes used to feed probiotic organisms. This is because in susceptible people, FOS and certain soluble fiber sources (guar gum, xanthan gum, and FOS, fructoligosaccharides, inulin, Nutraflora, found in probiotics and yogurt) also feed the VBS-producing bacteria that occur in some people.

Some may prefer to use low fiber grains. When comparing grains, I have found that the same amount of a high fiber grain (e.g., quinoa or oats) results in at least twice as much VBS production as a very low fiber grain, like white rice. I also found that just one capsule of psyllium husk fiber produced as large an effect on VBS production as a whole cup of white rice (for problems with constipation, see section on supplements below).

To follow a low VBS diet, one should minimize the use of foods and beverages in the moderately high and high CGA categories. Those with severe sensitivities may want to emphasize consumption of foods in the very low and no CGA categories. Some people might choose to completely eliminate grains and sugar and go on a Specific Carbohydrate Diet (see Section C, D, E. Practical Implications) if they want to see if they will benefit from increased strictness or if they have an inflammatory bowel disease.

One should also consider one’s other food intolerances, since some people do not tolerate various foods for reasons other than their effect on VBSs. As mentioned earlier, diabetics and those with yeast overgrowth problems may have to cut back on fruit and honey, while others may not be able to tolerate much potassium or protein. One should consult one’s physician or health professional, regarding any changes in treatment and any significant changes in diet, supplements or medications.

Contains High Chlorogenic Acid (or other cross-reacting VBS)

The top nine seem to be the most potent sources and priority should be given to avoiding them, if one wants to avoid chlorogenic acid (listed in approximate order of decreasing potency)

coffee (decaffeinated or regular)
lemon peel
peanut
tea, both black and green, decaffeinated and regular (probably herbal teas also)
apple
pomegranate
prunes (and plums)
blackberries
soft drinks (e.g., Coke, 7up, Dr. Pepper, Root Beer, both diet and regular)

citrus: orange, lemon, lime, grapefruit
banana
currants
mango-nectarine (this is one fruit and reacts differently from a nectarine or mango)
raspberries
melon (watermelon, cantaloupe, honeydew)
shrimp, clam, tuna (probably all seafood)
smoked ham
ground buffalo
chicken skin
New Zealand, grassfed lamb
okra
potato
eggplant
strawberry
apricots
figs
dates
pistachios
macadamia nuts
sunflower seeds and oil
avocado,
canned bean sprouts,
canned water chestnuts
plantain
dark green lettuce and probably other dark leafy greens
spinach
cooked broccoli (in raw broccoli, it appears the chlorogenic is not bioavailable, so raw broccoli appears to be O.K. The broccoli stalks also seem to be less reactive than the florets)
cauliflower
parsnips
cucumber
celery
cabbage
rutabaga
tomato
Now brand gelatin capsules
Now brand cellulose capsules
Brewer’s yeast
vinegar (distilled white)
cayenne pepper
paprika
onions
lemon juice
pectin (this gets added to some things and is generally from apples)
green chiliNote: The last 10 should not be as much of a problem since they are not usually consumed in as large quantities

Moderate Chlorogenic Acid (approximately in order from highest to lowest levels)
organic lean pork, barley, rye, red cabbage, unsoaked fortified rice, cooked sweet potato, buckwheat, yellow summer squash, cocoa powder (pure chocolate), pineapple, mung beans, kidney beans, soy products, tofu, lentils, turkey, fat from pork from supermarket, chicken dark meat without skin, cherries, nectarine, artichoke,
pumpkin, iceberg lettuce, dried papaya, red grapes, black grapes, cranberries (canned), fat from non organic ground beef, hemp oil, coconut oil, cottonseed oil lip balm

Low Chlorogenic Acid
Brazil nuts, walnuts, green beans, very lean beef, very lean pork from Ralph’s supermarket, pears (cooked –from fruit cup), green peas, split peas (soak overnight in water and throw out water), asparagus, beets, millet, filberts (hazelnuts), granulated sugar (derived from beets), almond oil, raw broccoli (the stalks are lower in CGA than the florets)

Very Low Chlorogenic
soaked Brazil nuts, cashews, almonds, pecans, raw carob powder, Canola oil, safflower oil, walnut oil, carrots, mango, blueberries, peaches, olive oil

Essentially No Chlorogenic acid (however, see below regarding starch/sugar/fiber)
rice, wheat, corn, quinoa, other grains and grain based products (with exceptions of millet and buckwheat), tapioca, dairy products, cane sugar, Splenda, vanilla extract, raisins (from Thompson’s green grapes, this is the usual type for raisins), green grapes, honey, barley malt sweetener, meats and poultry (except turkey).

Note on Starch/Sugar/Fiber Content and Foods Not Mentioned: For most people, a low VBS diet should also limit or reduce grains, starchy foods and certain sugars and fibers, see above and Section C, D, E. Those foods not mentioned have not been tested yet and probably should be avoided when minimizing VBSs.

Spices and Herbs: Carnosic acid

Another substance that can bind the VDR is found in rosemary and sage. Most spices and herbs apparently have carnosic acid or CGA according to my testing. However, if used in small amounts they should be O.K. for most people. Very sensitive people may need to avoid them at first. (Note: Also see Supplement discussion, below)

Vitamin D in Foods

I became so sensitive to vitamin D for a while due to it cross-reacting with chlorogenic acid, that I also found it necessary to be careful about certain animal products due to their vitamin D content. Besides the well-known sources of vitamin D, fish, shellfish, egg yolks, liver, and fortified foods (e.g., milk, cereal etc..), those foods with the most vitamin D in the U.S. were actually the organic and “natural” meats, especially the fatty portion. I don’t know if that will be the case in other countries. All dairy products, even without any added A or D and even non-fat dairy products seem to have some vitamin D. Chicken breast, beef, lamb and pork from the supermarket (not advertised as “organic” or “natural”) had the least vitamin D, particularly if fat was avoided. Avocado, sunflower seeds and oil and mushrooms were quite reactive, apparently from their vitamin D content, though they may also contain CGA. However, once a low VBS diet is used for a while, the vitamin D content of meat and dairy products is of much less concern. The same was true of vitamin A, which was initially quite reactive. For other sources of vitamin D, see: Foods with vitamin D at: http://marshallprotocol.com/forum2/2434.html. Feb. 2010 Update – it is possible that my testing confounded chlorogenic acid or a similar substance that may have been stored in the fat of animals rather than vitamin D. Or there may have been multiple VBSs may have been present.

Supplements

Most supplements reacted in a similar way to VBSs, with very few exceptions and thus probably contain vitamin D, carnosic acid, chlorogenic acid, genistein or something that causes a similar reaction. Of course, I could only test a fairly limited number of all the supplement products that are available.

Of the one’s I tested, I found these to be the least reactive: Solgar’s chelated products, such as zinc, boron, calcium, magnesium and Solgar’s vitamin K, chromium picolinate, CoQ10 and lysine, Natrol Ester C, Solaray Food Carotene, Twin Labs B-50 (vitamin B complex) and Twin Labs No Flush Niacin. I did not find any non reactive vitamin E. I decided to use just a few drops of Unique E (AC Grace Co.) every day, even though it was slightly reactive.

Carnosic Acid has been found to block the VDR according to molecular modeling research (6). It is abundant in rosemary and sage as well as some other herbs. Rosemary extract is increasingly being used and should be watched for, if avoiding VBSs.

Genistein, a soy isoflavone has also been found to bind with and interfere with the VDR and thus is also a VBS (6). So, soy products may need to be reduced and soy isoflavone products should be considered to be high in VBS as well.

My testing confirms that one especially needs to avoid ingredients like rosemary extract, soybean oil, alfalfa, malic acid and FOS/inulin. Fiber supplements should also be avoided, as discussed above. However, cellulose used in supplements is usually well tolerated, if kept at low levels. In general, it is best to avoid as many unnecessary ingredients as possible to minimize VBSs.

As for magnesium, I found that Solgar’s Chelated Magnesium was one of the best. But when I was most sensitive to CGA, I found Twin Lab’s Magnesium Caps (magnesium oxide) to be the least reactive. It is not as well absorbed as the chelated magnesium, however, but may be fine temporarily, when sensitivity is highest. Too much will cause diarrhea and sometimes it may be useful to divide a single 400-mg capsule into half and take 200 mg in the morning and 200 mg in the evening. Or one might take 400 mg in the morning and 200-mg in the evening. One can buy extra empty gelatin capsules or empty half the contents into water or onto food. It is helpful to adjust the amount to just the right level that will help with constipation, but not lead to gas production or diarrhea.
If one has a problem with constipation, one option that works for many people is to consume more magnesium, but you should consult your doctor with regard to your own circumstances. I have found Solgar Chelated Magnesium and Twin Labs Magnesium Caps to work well in my own case (see above).

In my experiments, I found that Milk of Magnesia promotes VBS production, as indicated by the level of bacterial die-off reaction two hours after taking it. Apparently, the high alkalinity of the Milk of Magnesia (magnesium hydroxide) is favorable to the growth of the VBS-producing bacteria. This was confirmed by additional tests, in which I found that other relatively alkaline substances also had the same effect of reducing bacterial die-off reactions within two hours (calcium and magnesium carbonate, citrate and baking soda). In contrast, relatively non alkaline forms of the minerals did not have this effect (magnesium oxide and chelated calcium and magnesium).

Supplement use is generally discouraged on the MP, unless truly necessary for a documented deficiency or intolerable symptoms – and then, usually only to RDA levels. When tablets exceed the RDA level, as some of those mentioned above do, one may take them on alternate days or divide/chop them into smaller pieces. When possible, dietary sources of nutrients are preferred. The above observations on the widespread presence of VBSs in supplements support this recommendation.

Medications

According to my testing, many commonly used medications appear to contain VBSs, but it is not necessary to avoid them, according to my experience, since they are generally taken in small amounts, unlike foods. For many of these, Dr. Marshall’s research provides support for this cross-reaction, since the molecular modeling shows they can bind the VDR (e.g., hormones, steroids, opiates). Antibiotics, aspirin and NSAIDS did not cause a reaction, however some brands of NSAIDS have a starch base, which may be reactive for very sensitive people, if it is derived from potato. As has been mentioned, some people may develop a sensitivity to Benicar, but it would probably only be very rarely that a patient might benefit from stopping Benicar due to a sensitivity (see Section D). I also found that I reacted to all the capsules in which medications came in, presumably due to their dyes (since I did not react to clear gelatin capsules used for supplements). If it is all right with one’s doctor and/or pharmacist, one can transfer contents of medications that comes in capsules into clear gelatin capsules (can be purchased at health food stores). But be sure all of the contents are transferred.

Note: These are preliminary observations and not a part of the MP at the time of this writing.

Current Marshall Protocol Recommendations

It is recommended that one not consume excessive amounts of chlorogenic acid on the Marshall Protocol (e.g., in coffee), and to avoid too much genistein, an isoflavone found in soy products. The reason discussed on the Marshall Protocol site is not related to sensitivity to CGA, as discussed here. Instead, avoidance is recommended due to its ability to bind to the vitamin D receptor, which might reduce the immune function and associated bacterial killing that has been enhanced by the protocol. A low carbohydrate diet of some kind is recommended on the MP. However, it is left to the patient to determine whether or not to use a low carbohydrate diet and if so, exactly what type of diet it should be. What I discuss in this article are preliminary observations and not currently part of the MP.

Note: Health Care providers are responsible for the use of this information. Neither the Autoimmunity Research Foundation nor the author assumes responsibility for the use or misuse of this protocol.

Section M. Methods

Sensitivity Reactions

The general methods I used that led me to connect sensitivity reactions to chlorogenic acid (CGA) containing foods and to other VDR binding substances (VBSs) is described in a general manner in Section A. However, I will include some additional details here for those who are interested.

Testing for CGA – I used short cut testing to estimate the relative CGA content as described in Issue 10. Detecting Food Allergies/Sensitivities/Intolerances: Beyond the Pulse Test . I obtained information on the relative amount of CGA or related VBS in a food primarily based on testing my own reactions of pulse and symptom response. For a number of the foods, additional pulse tests were performed on two other people and showed similar results. The relative levels of CGA were determined based on how long and how much of the food was required to reach a reaction threshold. If the CGA was at a low concentration in the food, it took a longer time and a larger amount of the food to cause a reaction and the food was rated as lower in CGA.

My conclusions that the reactions I identified were due to CGA or another VBS are based on the following:
1. Reactions were generally consistent with reports in the literature as to the levels of CGA in the higher CGA foods,
2. Reactions required larger amounts of foods to elicit a reaction for the moderate CGA foods,
3. Only foods that had high CGA were able to cause such a strong pulse and symptom reactions at that time,
4. Reactions to CGA containing foods did not fluctuate from day to day based on whether I ate a particular food, but had a slow pattern of decline over more than two months, as I became less sensitive to CGA and then dropped rapidly after I reduced the large VBS source related to consumption to oats, rice and other grains.

It also may be helpful to describe the contrasting, more usual situation, for those interested. On a number of occasions, as I have very frequently over many years, I did become sensitive to a food due to a component other than CGA. I would test a food with a short cut test and not have any reaction. Then I would eat the food for several days and I would become sensitive to it. This would be clear due to symptoms that increased over the time I was eating the food and then withdrawal reactions after I stopped the food. It would be confirmed when I tested a tiny amount of the food after having stopped it for approximately 24 hours.

In cases like these, I could tell this was not a CGA reaction, because the pulse reaction was smaller and because, a few days before, I had not reacted to it and fluctuations in reaction level like this, on a short term basis, were not being found with CGA foods. Also, I could still distinguish the CGA reaction to that particular food. If I tested a larger amount of that same food over a longer period, I would eventually reach a point where the pulse would increase 30 beats per minute, far beyond the level of reaction to the non CGA component of the foods. This was clearly the CGA reaction due to the large increase and the need for a large amount of the food to elicit it (in this example, the food did not have a very high CGA concentration). After a few days the reaction that occurred to the small amount of the food (due to a high concentration component, e.g., a protein) would decline, as I avoided the food. However, the CGA reaction, that was a larger reaction and that required a much larger amount of the food would stay the same.

In most cases, my sensitivity based on the short cut pulse test declines within a few days or weeks after stopping a food I react to. The only exceptions are when I am still being exposed to the food or another food it is cross-reacting with. So, the fact that there was such a gradual decline in my sensitivity to CGA and other VBSs over several months gave me the time to test many foods because my sensitivity remained high. The decline became much more rapid when I discovered that bacteria feeding on starches and certain sugars and fibers were producing a VBS. Soon after that discovery, my testing method was not very useful, due to a rapid drop in my CGA/VBS sensitivity level, when I reduced the starches in my diet. I soon found that I had to test 50,000 IU of vitamin A to get a reaction, whereas before 10 IU caused a 30 beat per minute pulse increase. Initially, just smelling peanut butter caused a large pulse reaction, while later it took much more peanut butter to cause even a small pulse increase. Finally, the only item I could usefully test was tea, since I could make it extremely concentrated.

Sun Reaction

Here I will discuss the evidence in support of my hypothesis that the reactions to sun exposure I discussed were due to vitamin D production in the skin and its conversion to 1,25D (facilitated by the high inflammatory cytokines). The reaction I experienced included feeling shaky, weak and tired, along with a large pulse increase beginning within the first two minutes (30 beats per minute or more).

The hypothesis is supported by the fact that zinc oxide sunscreen (most others do not work) and ketoconazole cream prevented any pulse or symptom increase. Zinc oxide-containing sunscreen (usually the micronized, “invisible” type zinc is used) has been one of the only types of sunscreens that MP patients have found to stop or reduce sun exposure symptoms. It appears to be able to produce an effective barrier to the sun, somewhat similar to wearing clothes to cover up. Ketoconazole cream is also effective for many MP patients, since it has been shown to be able to enzymatically block the conversion of 25D to 1,25D in the skin (25).

In my experiments, I found that when a small amount of unprotected skin was exposed (e.g., four square inches), my pulse would go up more than 30 beats per minute within three minutes.

Gradually, over the period of reduction in VBS sensitivity, the sun sensitivity declined in a manner that paralleled the decline in reactions to CGA in food. And then, there was a more abrupt decline in sensitivity to sun, when I reduced oats and rice, and thus reduced the bacterial VBS source.

The reactions at first only required exposing four square inches of skin that was unprotected by clothing, zinc oxide or Ketoconazole cream for two minutes. Over time, it began to take 5 or 10 minutes of exposing a whole forearm to react and then eventually, after the low starch diet was initiated, it took 40 minutes of exposing arms and legs to get a pulse reaction.

The same general patterns occurred in another patient who had a similar experience of increasing CGA foods and developing increased sensitivity to the sun, that then declined in a nearly identical manner with the lower VBS diet.

Testing Effects of VBSs on Bacterial Killing

After my sensitivities had declined to such a degree that most short cut pulse testing was not useful, my attention turned to the effect of VBSs on bacterial killing and the associated “die-off” reaction (Jarisch-Herxheimer reaction or immunopathology). I was not focused on this aspect until I read the reports of some patients on the MP who had changed their CGA or starchy food consumption and reported effects on their bacterial die-off symptoms.

It was fortunate that over the last two years, through careful observations and records, I developed a way to very reliably quantify my most noticeable and rapidly occurring symptom related to bacterial killing. This is the effect on my muscle function when walking. The more immunopathology (inflammation associated with bacterial killing), the greater effect on my gait and the sooner this effect occurs.

When the effect is strongest, when I try to take long strides, I am unable to do so normally because of weakness and contraction in certain muscles. When the effect is at a more moderate level, I can walk normally for a while and then at a certain point, my gait becomes irregular and I feel weaker and am forced to limp.

Physiologically, this may be due to a deficiency in ATP (adenosine 5′-triphosphate) production that may be correlated with the degree of inflammation associated with bacterial killing (immunopathology). Lower ATP (the energy currency of the body) in the muscle fibers would lead to a weak feeling and irregularity in the gait. Low ATP may also cause contractions in certain muscle fibers.

Regardless of the mechanism, this change in my gait invariably occurs after Benicar increases VDR function and the production of antimicrobial peptides (our body’s own antibiotics) or after taking any of the MP antibiotic combinations. It begins after about 1 hour and reaches a peak at three to four hours and then generally stays at that peak for 8 hours or more and then gradually declines over several days.

The way of quantifying the reaction that has worked reliably for me, when in the moderate reaction range, is to count the number of paces taken before the gait is affected. My muscles take about 10 minutes to recover between tests. So, if I rest for at least that long, I can repeat the test and I find the same result. On many occasions, I did the test without recalling what the expected result would be (or even having an expected result in mind). But the results were always consistent with the observations and preliminary conclusions I have presented in this article.

So, for all of the conclusions I made with regard to effects of VBS on bacterial killing, I was able to set up experiments in which I took an amount of MP antibiotic and Benicar so that I could expect (based on past experience) that my bacterial killing reaction would be constant for at least a 10 hour period. I would carefully control my diet during the time of the experiment and then would add factors to see how they would affect the reaction. For example, after obtaining a stable reaction for a few hours, I would introduce another factor, such as a CGA-containing food (eg., tea) and note the effect on the number of paces after three hours. Then on another occasion, I would introduce the same amount of tea, combined with No Fenol to see what the combined effect would be.

Or I would eat ½ cup rice along with chicken at one meal and count the paces I could take before my muscles were affected. Then at the next meal, I would consume the same foods, while only making one alteration, for instance adding a probiotic. Over many weeks, I gathered the data I have presented. In many cases, however, I mention data reported by other people on the MP website or elsewhere. Although data from other patients is usually less detailed, it has supported the general conclusions I have presented.

References

(Links to: Dr. Marshall’s papers and presentations)

(1) Marshall TG, Marshall FE, Sarcoidosis succumbs to antibiotics – implications for autoimmune disease. Autoimmun Rev 2004; 3(4):295-300.
(2) Marshall TG, VDR Nuclear Receptor Competence is the Key to Recovery from Chronic Inflammatory and Autoimmune Disease, Presentation at Days of Molecular Medicine Conference-Inflammation in Chronic Disease, Karolinska Institut, Stockholm, Sweden, 2006.
(3) Marshall TG, A New Approach to Treating Intraphagocytic CWD Bacterial Pathogens in Sarcoidosis, CFS, Lyme and other Inflammatory Diseases, Presentation at American Academy of Environmental Medicine Conference, 2006.
(4) Marshall TG, Molecular genomics offers new insight into the exact mechanism of action of common drugs – ARBs, Statins, and Corticosteroids. FDA CDER Visiting Professor presentation, FDA Biosciences Library, Accession QH447.M27 2006.
(5) Marshall TG, Are statins analogs of vitamin D? Correspondence to Grimes, DS. Lancet 2006; 368:1234.
(6) for study site with links to many published studies, progress reports and additional MP information, see: www.marshallprotocol.com, Phase One Guidelines, Recovery Transcripts, 2006 Conference, Links to Patient Reports — Improvements and Conference DVDs available from www.AutoimmunityResearch.org.
(7) Brostoff, J. and S.J. Challacombe, eds. 1987. Food Allergy and Intolerance. Balliere Tindall. Eastbourne, England.
(8) Bariana DS, Krupey J, Scarpati LM, Freedman SO, Sehon AH. Chlorogenic Acid: Further Evidence for its Antigenic and Allergenic Activity. Nature 207, 1155 – 1157 Sept;1965.
(9) Sato N, Kinbara M, Kuroishi T, Kimura K, Iwakura Y, Ohtsu H, Sugawara S, Endo Y.Lipopolysaccharide promotes and augments metal allergies in mice, dependent on innate immunity and histidine decarboxylase. Clin. Exp. Allergy, 37 . 743 – 751 (2007).
(10) O’Mahony S, Anderson N, Nuki G, Ferguson A.Systemic and mucosal antibodies to Klebsiella in patients with ankylosing spondylitis and Crohn’s disease. Ann Rheum Dis. 1992 Dec;51(12):1296-300.
(11) Baumgart M et al. (2007). “Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn’s disease involving the ileum.” ISME J. http://dx.doi.org/10.1038/ismej.2007.52 (accessed August 11, 2007).
(12) Rolhion N, Darfeuille-Michaud A. Adherent-invasive Escherichia coli in inflammatory bowel disease. Inflamm Bowel Dis. 2007 May 2;
(13) Glasser AL, Boudeau J, Barnich N, Perruchot MH, Colombel JF, Darfeuille-Michaud A. Adherent invasive Escherichia coli strains from patients with Crohn’s disease survive and replicate within macrophages without inducing host cell death. Infect Immun. 2001 Sep;69(9):5529-37.
(14) Marshall, TG. Bacterial capnine blocks transcription of human antimicrobial peptides. 2007. July 11-13. Metagenomics Conference. University of California at San Diego. http://autoimmunityresearch.org/abstracts/metagenomics2007-handout.pdf
(15) Dempsey KE, Riggio MP, Lennon A, Hannah VE, Ramage G, Allan D, Bagg J.Identification of bacteria on the surface of clinically infected and non-infected prosthetic hip joints removed during revision arthroplasties by 16S rRNA gene sequencing and by microbiological culture. Arthritis Res Ther. 2007 May 14;9(3).
(16) Marks DJ, Harbord MW, MacAllister R, Rahman FZ, Young J, Al-Lazikani B, Lees W, Novelli M, Bloom S, Segal AW. Defective acute inflammation in Crohn’s disease: a clinical investigation. Lancet. 2006 Feb 25;367(9511):668-78.
(17) Müller CA, Autenrieth IB, Peschel A. Innate defenses of the intestinal epithelial barrier. Cell Mol Life Sci. 2005 Jun;62(12):1297-307.
(18) Onwuamaegbu ME, Belcher RA, Soare C, Cell wall-deficient bacteria as a cause of infections: a review of the clinical significance. J Int Med Res 2005; 33(1):1-20. Free full text at: http://www.jimronline.net/content/html/fullhtm.asp?ArticleID=545.
(19) Waterhouse JC, Marshall TG, Fenter B, Mangin M, Blaney G, Vitamin D Metabolism in Chronic Disease. In Vitamin D: New Research, Nova Science Publishers, NY, 2006. http://winmlm.neostrada.pl/vitamindbook/vitamindnewresearch.pdf
(20) Waterhouse JC, Vitamins D in Chronic Disease. Recovery from Chronic Disease Conference, Autoimmunity Research Foundation, Los Angeles, 2006, Vitamin D in Chronic Disease. 2006 Conference Presentation
(21) Lewis K, Persister cells, dormancy and infectious disease. Nature Reviews – Microbiology. 2007; 5:48-56.
(22) Mattman, Lida, Ph.D., Cell Wall Deficient Forms: Stealth Pathogens, CRC Press, Boca Raton, 2000.
(23) MacDonald AB, Spirochetal cyst forms in neurodegenerative disorders,…hiding in plain sight. Med Hypotheses 2006; 67(4):819-32.
(24) Brahmachary M et al., Computational promoter analysis of mouse, rat and human antimicrobial peptide-coding genes. BMC Bioinformatics 2006, 7(Suppl 5):S8 doi:10.1186/1471-2105-7-S5-S8.
(25) Lehmann B, Sauter W, Knuschke P, Dressler S, Meurer M. Demonstration of UVB-induced synthesis of 1 alpha,25-dihydroxyvitamin D3 (calcitriol) in human skin by microdialysis. 2003. Arch Dermatol Res. 2003 Apr;295(1):24-8.
(26) Cordain L. The Paleo Diet. 2002. John Wiley & Sons. Hoboken, New Jersey.
(27) Cordain L. Cereal Grains: Humanity’s Double Edged Sword, World Review of Nutrition and Dietetics 84 1999:19-73.
(28) Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006 Dec 21;444(7122):1022-3
(29) Hayashi H, Sakamoto M, Benno Y. Fecal microbial diversity in a strict vegetarian as determined by molecular analysis and cultivation. Microbiol Immunol. 2002;46(12):819-31.
(30) Bartosch S, Fite A, Macfarlane GT, McMurdo ME. Characterization of bacterial communities in feces from healthy elderly volunteers and hospitalized elderly patients by using real-time PCR and effects of antibiotic treatment on the fecal microbiota. Appl Environ Microbiol. 2004 Jun;70(6):3575-81.
(31) Gottschall E. Breaking the Vicious Cycle. Intestinal Health Through Diet. 2004. Kirkton Press. Ontario, Canada. http://scdiet.org and Lists of SCD “Legal” and “Illegal” Foods.
(32) No Fenol Houston Nutraceuticals , phone: (866) 757-8627.
(33) Enzymes – Information on No Fenol and Similar Enzymes
(34) Kirkman Lab’s Lactobacteria acidophilus ( (800) 245-8282 ), GI Prohealth’s Lactobacteria and Saccharomyces product are probiotics permitted on the SCD. Lyo – San Lactobacteria, Nutrition Now’s PB8 and Jarrow’s Saccharomyces boulardii are others I found helpful in reducing VBS production.
(35) Randolph TG., M.D. and Ralph W. Moss, Ph.D. 1989. An Alternative Approach to Allergies. Bantam, New York.
(36) Dandona P, Kumar V, Aljada A, Ghanim H, Syed T, Hofmayer D, Mohanty P, Tripathy D, Garg R, Angiotensin II receptor blocker valsartan suppresses reactive oxygen species generation in leukocytes, nuclear factor-kappa B, in mononuclear cells of normal subjects: evidence of an antiinflammatory action. J Clin Endocr Metab 2003; 88(9):4496-501.
(37) Tronvik E, Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA. 2003; 289(1):65-9.
(38) Kurikawa N, Suga M, Kuroda S, Yamada K, Ishikawa H. An angiotensin II type 1 receptor antagonist, olmesartan medoxomil, improves experimental liver fibrosis by suppression of proliferation and collagen synthesis in activated hepatic stellate cells. Br J Pharmacol 2003; 139(6):1085-94.
(39) Fan YY, Augmentation of intrarenal angiotensin II levels in uninephrectomized aldosterone/salt-treated hypertensive rats; renoprotective effects of an ultrahigh dose of olmesartan. Hypertens Res 2006; (3):169-78.
(40) Okada K, Olmesartan medoxomil, an angiotensin II receptor blocker ameliorates insulin resistance and decreases triglyceride production in fructose-fed rats. Hypertens Res 2004; 27(4):293-9.
(41) Seko Y, Effect of the angiotensin II receptor blocker olmesartan on the development of murine acute myocarditis caused by coxsackievirus B3. Clin Sci (Lond. 2006; 110(3):379-86.
(42) De Cavanagh EM, Piotrkowski B, Basso N, Stella I, Inserra F, Ferder L, Fraga CG, Enalapril and losartan attenuate mitochondrial dysfunction in aged rats. FASEB J 2003; 17(9):1096-8.

 

Written by synergyhn

October 22, 2008 at 4:00 pm

Follow

Get every new post delivered to your Inbox.

%d bloggers like this: