HISTORY OF IMMUNOMETABOLIC REMEDIES

            With the introduction of the new Syntrion remedies into the American market, there are now 3 lines of immunometabolic remedies available, each from a different manufacturer in Germany, and each having distinctly different qualities and clinical applications.

Although referred to as isopathics and not immunometabolics, the initial remedies in this class introduced to the US were those manufactured by the Sanum-Kehlbeck company. These remedies most closely conform to the traditional production methods developed by Gunther Enderlein and his compatriots in the 1920s.  Indeed, the company still adheres to some of the terminology and espouses a clinical model largely unchanged from the time of Enderlein. Remedies in this product line are manufactured using cultures of various fungi and bacteria. The exact manufacturing process is a proprietary secret, but the remedies are prepared using a method that carefully rinses away the interior of the cell and any metabolic products found in the culture medium, essentially harvesting the cell wall. This preparation is then put into various homeopathic dilutions and sold as tablets, capsules, suppositories, drops, and drops in unit-dose ampules.

The Sanum remedies can be used to induce biological effects in clinical practice, and are often favored by those practitioners who wish to induce an exuberant cytokine response to strongly modulate the immune response.  It is easy to see how they can do so, in that immunology textbooks abound with information about cytokine responses that can be induced by bacterial lipopolysaccharide, found in the cell wall.  We used these remedies with success in clinical practice for years, but found that, with certain remedies, care is needed so as not to overly upregulate a systemic inflammatory response while trying to clean up various latent infections and toxic foci from the body.

A second manufacturer is SanPharma, a family-owned company. For one year, Syntrion founder Ronald Ullmann served as president of SanPharma, during which time he introduced several changes that represented major modernization steps in the production of these microbial remedies. Ullmanns research led him to believe that the beneficial biological effects of the remedies come from metabolites produced by the organisms, but that the pro-inflammatory side effects come from the cell wall fragments present in the remedies. He then changed production methods to exclude cell wall fragments and include only metabolic products from the microbes. The result was the new generation of SanPharma remedies, which enabled us to get the desirable effects in our clinical practice with far fewer adverse reactions. Eventually, we discontinued using the Sanum-Kehlbeck remedies, and switched to using the SanPharma line, and in doing so our clinical successes improved. Specifically, we found that we could now safely induce a downregulation of systemic inflammation while at the same time reducing immune hyper-reactivity and also taking the immune system out of anergy.

A recent article written by Gitte Jensen, Ph.D. and published in the peer-reviewed Journal of Alternative and Complementary Medicine supports our clinical findings. In the article, Dr. Jensen presents her research on the SanPharma fungal remedies and points out that the SanPharma remedy Notatum which we considered anti-inflammatory reduced the baseline of COX-2 enzymes in vitro. 

Finally, after making key improvements to the SanPharma line, Ronald Ullmann left the SanPharma company to continue his research into the possibilities of microbial-based remedies. His research involved studying the effects of specific microbial metabolites on various human cell lines including immune system cells. He developed a way of harvesting specific microbial metabolites, and preparing specific homeopathic preparations of these materials. In other words, rather than making a remedy that contains all of the metabolic products from s particular organism, he learned to tune the effect of the remedies by harvesting only specific metabolites that were shown to be beneficial. The result is the new Syntrion line of microbial remedies.

SYNTRION IMMUNOMETABOLIC REMEDIES

Syntrion remedies are derived from specific metabolites of various fungal organisms, which are harvested and prepared in a D4 homeopathic preparation. They are available in the form of tablets and lotions. 

The products that will be introduced to the US market in summer 2006 are SyAllgen, SyCircue, SyImmune and SyRegule tablets, and SyAllgen, SyCircue, SyImmune and SyFungin lotions. An lotion called SyDerm that Syntrion developed to repair connective tissue and prevent the premature aging of the skin will also be introduced later this year.

DOSAGE AND FREQUENCY

Most patient protocols will involve the use of both the tablets and the lotion.  The tablet is taken by dissolving in the mouth, at least a few minutes away from food, 3 times per day, or more often for very acute situations.  This gives a systemic effect.  It also gives information to the immune system as can only be accomplished by passing through the mucosa.  The mucosal administration seems to modulate immune system effects in the gut and upper respiratory system.

The lotion is applied to the appropriate body area twice per day.  Unless otherwise determined by the specific application, use about 1/8 teaspoon per dose.  The lotion focuses the effect of the remedy in the region of the body that you desire to target.  It also has a systemic effect associated with its transdermal application.  Different information is given to the immune system with a transdermal lotion versus a tablet dissolved in the mouth.  Transdermal application seems to have a systemic effect that favors the lungs and nervous system.

In our initial trials with these remedies, both the tablet and the lotion are used.  In fact, we often find that neither the tablets or the lotion test as effective by electrodermal screening, while the combination of both tests extremely effective.  Other times, just one form or the other will be used successfully.  This probably pertains to which type of information the immune system needs to have the needed response.  The use of the tablets and lotion combined gives the most complete effect.

While we have not given these remedies to enough children to know for sure whether the dosage recommendations should be altered for them, it appears so far that the response is more related to frequency of administration than dosage of administration.  Therefore, for now, we are recommending that children be dosed the same as adults.

SYALLGEN

SyAllgen is one of the two remedies that will be used at the onset of a case management.  It is used first because it tends to be non-provoking, and sets the scene for major beneficial changes in the biological terrain.

SyAllgen is made from metabolites harvested from Penicillium frequentans.  Unlike the remedy Quentans from SanPharma, this remedy is used to downregulate allergic tendencies as well as other types of immunological hyper-reactivity.

Most of the pilot studies done on SyAllgen have been with allergies such as food sensitivities and hay fever.  In our own practice, we have been encouraged and excited about the degree to which SyAllgen seems to stabilize the allergic patient.  Some symptomatic relief is seen within a few hours to a few days of starting SyAllgen.  But what is more exciting is that the overall reactivity tends to decrease significantly within about 3 weeks, resulting in lowered systemic inflammation, better musculoskeletal stability, and a lowering of the systemic toxic load in patients taking this remedy.

Pilot studies done in Germany with SyAllgen lotion showed a very good and immediate response in shavers itch, insect bites and atopic dermatitis.  We have used it for sunburn, and find that it reduces the uncomfortable itching, but not the redness. 

We have also used it in bee stings.  It doesnt do much for the acute initial sting.  A drop of peppermint oil on the sting will take care of the acute pain immediately.  (Do not place peppermint oil near eyes or other sensitive orifices.)  The SyAllgen will then take care of the delayed histamine reaction that occurs in the hours to days following the sting.  We do not yet know if prolonged treatment with SyAllgen will reduce the severity of the reaction to bee stings in highly allergic people who are required to carry an epi-pen to treat anaphylaxis.  However, it does a good job of reducing the severity of other types of allergic reactions, so this application would be a worthwhile one to try.

In vitro studies on immune system cell lines done in Germany showed that SyAllgen prevents the over-induction of immune system activity that occurs when immune system cells are exposed to various toxins.  This implies that SyAllgen may be the remedy of choice for reducing the TH1 overstimulation in autoimmune conditions.  We have not had enough time with this remedy to determine to what extent this is true, but have found it to be very good for reducing systemic inflammatory upregulation.

The reduction in systemic inflammation is partially, but not completely, related to its ability to downregulate COX-2.  All of the Syntrion are COX-2 downregulators, but their effects are not just related to COX-2.

Regarding the mechanism of reducing allergic sensitivity, SyAllgen was found to reduce mast cell motility and histamine release.

Thus, think of SyAllgen for immune system hyper-reactivity, whether it be TH1 or TH2 fixation.  This makes SyAllgen a major first remedy to use in the beginning of a case management.  When applicable, SyAllgen will be used as the initial remedy in the majority of cases, for a duration of 6 weeks to 3 months.

SyAllgen combines well with SyRegule/SyFungin or SyImmune, but initial treatment with SyAllgen alone is usually necessary.  We have not yet seen cases where SyAllgen and SyCircue are used systemically at the same time, unless the SyCircue is being used topically for a local condition.

SyAllgen combines well with any of the PEKANA remedies. If being used for basic anti-inflammatory and terrain regulation purposes, the Basic Detox Kit would commonly be chosen to use with SyAllgen. If hay fever is being treated, ProAller and Ricura may be the PEKANA remedies of choice.  To target the effects of SyAllgen to the gut, combining with Apo-Stom works quite nicely. In later stages of treatment, where key toxins are being liberated from deep tissue foci, the addition of SyAllgen prevents many of the reactions that are attributed to the movement of the toxins inducing a cytokine response.

To summarize, SyAllgen will be used for 3 purposes:

1. Reduction of systemic inflammation and immune system hyper-reactivity at the onset of a case management.
2. Any time allergic symptoms are present.
3. Later in case management when key toxins are being liberated while toxic foci are being cleansed, to prevent adverse reactions.

Nutritional products that should be used with SyAllgen include the usual anti-inflammatory products, such as omega 3 fatty acids, B vitamins such as B12 and folate to support homocysteine transmethylation, and anti-oxidants, especially flavenoids like quercitin.

SYCIRCUE

SyCircue is prepared from metabolites harvested from Mucor racemosis.  Research done at Syntrion using umbilical cells determined that certain metabolites of Mucor have an effect on endothelial cell differentiation. In the presence of inflammation and of certain toxins, the endothelial cells will partially de-differentiate, and new cells will be prevented from fully differentiating. This partial de-differentiation causes all kinds of mischief in the circulatory beds. Communication between the bloodstream and the matrix is compromised. The result is that toxins do not drain well from the matrix, and nutrients and regulating molecules do not reach the tissues properly. The use of SyCircue provides the signals that force a full endothelial differentiation, thus clearing up all sorts of circulatory problems.

In clinical practice, we constantly see cases where a toxic load or an upregulation of systemic inflammation will create a regulatory blockade. Our experience with SyCircue suggest that this blockade may be due in large part to this pro-inflammatory endothelial partial de-differentiation. Use of SyCircue resolves this issue in a manner which does not tend to be provoking. In fact, it appears that the addition of SyCircue to a program of PEKANA remedies that has created some symptomatic aggravation is much more likely to quell the adverse symptoms of toxin download than it is to cause further aggravation. 

Having just said that, our opinion may be colored by the fact that we always add adequate drainage medicines to a protocol that uses immunometabolic remedies.  It is possible that the outpouring of toxic waste that has been trapped in the matrix, as occurs when SyCircue is used, would cause adverse symptoms if not properly buffered with Pekana remedies.  The fact that we have not seen any adverse responses with SyCircue could be either that the SyCircue has enough anti-inflammatory effects in its own right, or that we have so far been fortunate enough to always have chosen the appropriate Pekana medicines with the SyCircue.

This means that SyCircue is often the first remedy used in a case management, or the second remedy after treatment with SyAllgen.  Any time that the correct PEKANA remedies have been chosen, but are not creating as much clinical change as you would expect, consider adding SyCircue. The resolution of the circulatory regulatory blockade just might put the progression of the case right on track.  Similarly, if the first Syntrion remedy given was SyAllgen, but not much clinical improvement occurred, This means that the actual correct first remedy was either SyCircue or SyRegule.

Some interesting pilot studies have been done in Germany on SyCircue. One involved a number of glaucoma patients. They were given 1 tablet of SyCircue orally 3 times per day and instructed to rub the SyCircue lotion into the periorbital tissue 2 times per day. Follow-up in 4 weeks showed normal intra-ocular pressure in all test subjects.

Studies on bruising showed improved healing time with use of the lotion.

Another study on decubitus ulcers showed good improvement, which was further improved when SyCircue and SyImmune were used together.

We find the SyCircue effective for simple muscular soreness. Muscular pain from over-exertion seems to respond very quickly to SyCircue. In this application, SyCircue and Inflamyar seem to enhance each other's effects.  An effective use of the two remedies is to massage Inflamyar into sore muscles, then choose a few spots where the tissue stays indurated and painful despite the Inflamyar application, and massage a dollop of SyCircue into these spots.

In my practice, I do lots of Chinese cupping therapy. Regions on the back corresponding to visceral blood stasis that do not resolve with cupping tend to respond to a combination of cupping and bleeding. When SyCircue is used as the lubricant for cupping therapy, the bleeding is usually not needed.

Another anecdote from our practice is the use of SyCircue in 2 patients experiencing unresolved extreme ankle soreness for 2 or more weeks following a deep vein thrombosis episode.  Application of the SyCircue resolved much of that pain within 2 days.

Some interesting patterns have been seen in combining SyCircue with Pekana and SanPharma remedies.  Sometimes a fairly large dose of Pekana drainage medicine is needed in the first 2-4 weeks of using SyCircue.  An example might be Itires taken ¾ teaspoon per dose, or Opsonat taken 25 or 30 drops per dose, or Toxex taken 25 drops per dose.  Use extreme caution and monitor closely if larger than average doses of potentially provoking remedies are being given.  But, we have given these larger doses with SyCircue in a few dozen cases now without incident. 

One explanation for this might be that the larger doses of drainage are needed to download the regulatory blockade that has been preventing the matrix from discharging its load of toxins into the bloodstream for elimination, and this blockade was caused by circulatory problems at the level of the vascular-matrix interface.  SyCircue resolves the vascular problem and restores the ability of the matrix to detoxify properly.

Another interesting pattern is the combining of a SyCircue program with frequent doses of Cereus or Firmus.  Some patients have required as much as 5 doses per week of  one of these bacterial remedies, which would normally be too provoking for most patients.

So, now we have 2 remedies that can be used as the first remedy in a new case. Choose SyAllgen if there are symptoms of allergy or autoimmune inflammation. Choose SyCircue if there are signs of circulatory blockade. Signs of circulatory blockade would be soreness and induration in tissues, darkened coloration, presence of spider veins, etc.  It does not seem appropriate to use both of these medicines simultaneously.

Once the patient has used one of these 2 remedies for long enough to give significant improvement, they can move on to either SyImmune or SyRegule/SyFungin if indicated.

SYIMMUNE

SyImmune is prepared from metabolites harvested from Penicillium notatum.  Metabolites were chosen that enhance the immune system's response to all kinds of microbial infections. The majority of the research has been done with viral infections, but the remedy is not limited in application to viruses.

In an acute infection, non-specific immune responses that involve inflammatory upregulation do their best to contain the infection until an antibody response can be generated.  In the lag time between the onset of the infection and development of the full adaptive immune response, the patient can feel very sick due to cytokine upregulation, which produces fever, aches, malaise, etc.  Use of  SyImmune collapses the time needed for the development of the adaptive immune response.  The result is that the patient develops immunity to the pathogen in less time, and the infection resolves more quickly.

In cell line experiments, communication between CD4 cells and macrophages was seen to improve. Antigen recognition of Candida was increased. Modulation of various interleukins was studied, with strong effects on IL-1 found.

Some of the most dramatic pilot studies were with herpes lesions. Application of SyImmune directly to the skin lesions gave a favorable response even in herpes sores that were unresponsive to Valtrex.

Similarly, the SyImmune lotion has been used with plantar warts.  We do not yet have experience regarding venereal warts.

In early sore throat, we have seen good response to applying the lotion to the cervical lymph nodes.  In fact, we have seen several cases where an early sore throat of mild to moderate severity, complete with low-grade fever, was cleared up in about 20 minutes after one application of the SyImmune lotion.  This represents a better-than-average response to this remedy.

Another German pilot study showed more rapid recovery from influenza in a protocol where 1 tablet was given per hour up to 6/day until improvement noted, then dosage was reduced to 1 tablet every 2 hours, then to 3/day. Another study was done on ear infections using the same oral dosing as for flu, but adding the topical lotion applied 2 times per day to cervical lymph nodes and behind the ears.

It would seem that SyImmune is for upregulating the immune response against microbial infection, and for taking the immune system out of an anergic state.  However, this is accomplished without upregulating the inflammatory response.

Complementary to this is SyAllgen, which downregulates an over-stimulated immune system.  In combination, these two medicines can be used together to restore dynamic immune system regulation.  We have seen several cases respond well to a combination of SyAllgen and SyImmune, using one tablet of each 3 times per day and a dab of each lotion on the cervical lymphatics twice per day, in patients with chronic infections and chronic inflammation. Some of these patients seem to be able to start both medicines right away, and another subset of patients seem to need to start with the SyAllgen alone for 2 weeks before adding the SyImmune.

SYREGULE/SYFUNGIN

These medicines are made from metabolites harvested from a Candida specie. The tablet form of the medicine is called SyRegule, and the lotion form is called SyFungin.  These remedies are for eliminating fungal infection of the skin or systemic fungal infections.  Unlike the SanPharma medicine Candida, which has no direct anti-fungal effects, but instead regulates the terrain and reduces immunological overload, the Syntrion medicines actually have an anti-fungal effect.  This is noticeable as the induction of true Herxheimer reactions in patients with a moderate to high level of fungal load.

SyFungin, as the name suggests, is for skin fungal infections.  We have found it to be effective in all sorts of fungal skin rashes, such as athlete's foot.  In Germany, tests have shown it to be effective in athlete's foot, diaper rash and other minor skin fungal infections.  It is also effective in nail-bed fungal infections, but topical use only is not adequate, as shown by a return of the toe-nail fungus when the lotion is discontinued.

The tablets are named for their ability to regulate the fungal terrain in a gut dysbiosis.  These have been used successfully in Germany for irritable bowel syndrome and gut mucosal irritations. 

We have found it more effective to use both the tablets and the lotion together.  However, this combination is powerful enough in effect that it can be provoking in nature.  Usually, SyRegule/SyFungin will not be provoking if the patient is first prepared with SyAllgen, SyCircue, or SyImmune, and drainage is added to the program. 

A Herxheimer reaction refers to the malaise that results from the immune system's reaction to breakdown products of microbes that are being destroyed through the action of a medicine.  These microbial products (and here we are referring to the pathogenic microbe, not the microbes from which the remedy is produced) will themselves cause a cytokine response to be initiated. This cytokine response can result in inflammation and even fever.  Thus, even though the Syntrion remedies are all anti-inflammatory in nature, if they cause the destruction of a heavy enough load of microbes, or if they cause enough serious toxins to be released from the matrix, the result can be an increase of the inflammatory response in the patient.  The severity of this cytokine response depends on:

1. the degree of encumbrance of the matrix.
2. the number of unregulated pro-inflammatory influences in the patient's physiology including omega 3 to omega 6 levels in the cell membranes, homocysteine and insulin levels, anti-oxidant status, status of the liver detoxification and whether the gut is in a eubiotic or dysbiotic state.
3. whether appropriate Pekana drainage medicines have been included in the patient's protocol.
4. whether the Syntrion remedies have been used in the appropriate sequence.

Usually, any problems with Herxheimer reactions will pass within several hours,
and the patient will be better for having the microbial load removed.  If the reaction does not subside overnight, or if it is too severe for the comfort level of the patient, then either:

1. add or change drainage remedies used
2. reduce frequency of administration of the provoking medicine, switching initially to the use of just the tablets, or
3. stop the potentially provoking medicine, and switch to one of the preparatory remedies. In the case of an overly exuberant reaction to SyRegule/SyFungin, the preparatory remedies would be SyAllgen or SyCircue.

A Herxheimer reaction is different than a "download".  A download is just the
release of toxic products from the matrix, and can always be managed by selecting appropriate Pekana medicines or adjusting their dosage.  A Herxheimer reaction relates to the release of toxic microbial products caused by the destruction of a microbe that has been infecting the body.
           
The most common drainage medicines used with SyRegule/SyFungin are Mucan and Supren, closely followed by Psy-Stabil.  There seems to be a close relationship between adrenal stress, sympathetic nervous system overdrive, and chronic fungal infection.  For this reason, a true eradication of chronic fungal infection can require attention to biochemical neurotransmitter abnormalities and psycho-social factors creating undue anxiety and disproportionate existential hopelessness.

Patients that do not tolerate the SyRegule/SyFungin, or who are overly distressed by Herxheimer reactions, should stop these medicines and use the SyAllgen instead (or possibly SyCircue) for 2 to 6 weeks to prepare them for the changes induced by breaking up of the fungal terrain.

One interesting fact to ponder is that fungal infections avoid destruction by the immune system by producing chemicals that induce a TH2 upregulation.  In other words, they induce an allergic state in order to downregulate the immune response that would kill them.  Any time that an allergic patient is treated with good drainage medicines and avoidance of food allergens and allergy-reducing flavenoids, if you do not see good clinical change within 1 month, this should be taken as circumstantial evidence of fungal infection.  These patients will need to be treated with a combination of SyAllgen and SyRegule/SyFungin in order to defeat this strategy whereby the fungal infection evades the immune response.  Syntrion is currently conducting studies to see to what extent this synergy is measurable.

Most patients who have chronic illness have some degree of fungal overgrowth as a component of their systemic load of toxicity and infection.  SyRegule and SyFungin offer another tool in clearing up this factor of contributory burden.

SEQUENCING AND COMBINING SYNTRION REMEDIES

As discussed above, certain of the Syntrion remedies are best used initially, and the others later.  The better the patient's overall state of health, the more you can just select whatever remedy fits the symptom picture, and it will work well without adverse effects.  However, for patients with a heavily burdened terrain, it is best to start with SyAllgen or SyCircue, and when these have initiated improvement, you can then go after the load of infection with SyImmune or SyRegule/SyFungin.

SyAllgen tends to combine well with SyImmune or SyRegule.  We have not yet seen cases where other combinations tested as being appropriate using kinesiology or electrodermal screening to make that determination.

While there will undoubtedly be cases where either the tablets or the lotion work well alone, they generally are used in combination.  If only one form is used, it is much more common to use the lotion only versus the tablet only.  When testing these medicines for effectiveness by kinesiology or electrodermal screening, it is not uncommon to see neither the tablets nor the lotion being effective, but the combination of the two testing as effective when combined.

CONCLUSIONS

The applications of these remedies discussed in this article are based on initial impressions from the medicines given to relatively small populations of patients. The early results and feedback, as well as re-exam on follow-up appointments are sufficient to cause great excitement. What we do not yet know are the fine points about remedies combinations with each other, with SanPharma and with PEKANA remedies. We are still actively discovering the subtleties that come with years of experience with a set of remedies. For that reason, please keep an open mind that our findings may change to some extent, and know that we will continue to publish updates about the practical aspects of working with the Syntrion remedies.

Technical and hard scientific information about specific effects being observed in the cell line experiments will continue to be published in the USA by BioResource. The small pilot studies in Germany are leading to larger studies as various clinics are understanding the potential that these medicines have, and subjecting the Syntrion remedies to scrutiny on larger groups of patients.

Meanwhile, we have already experienced enhanced clinical success, and so we offer our initial impressions to you.