S.I.B.O.: Paradigm Shift from

Bacterial Infection to Gender Specific Hormonal Dysregulation

Abstract:

In the past 20 years, a gastro-intestinal complex has emerged that has been tentatively linked to

Small Intestinal Bacterial Overgrowth (SIBO). The symptoms of constipation, bloating, and

distress even to the level of cachexia have been presumed to be from bacterial overgrowth of

methane producing Achaea bacteria including Methanobacteriales oralis and

Methanobacteriales smithii. However, the SIBO symptom complex that was initially reported to

be responsive to rifaximin and neomycin antibiotic therapy has subsequently become more and

resistant leaving both patients and treating physicians in a quandary.

The author was asked to consult on 18 patients whom had disruptive gastrointestinal symptoms,

positive SIBO breath test and repeated failure to respond to courses of antibiotic therapy -

primarily rifaximin. The initial evaluation showed that almost all male and female patients were

found to have endocrine, autoimmune and bioavailable free testosterone abnormalities. The

abnormalities of bioavailable free testosterone were measured as the Free Androgen Index (FAI)

and consisted of low serum total testosterone (TT) and increased Sex Hormone Binding Globulin

(SHBG). Hormonal supplementation with anabolic steroids was initiated by protocol. Both men

and women received weekly nandrolone injections and stanozolol. Men in addition receive

testosterone in the injections. The therapeutic goal was to increase the Free Androgen Index to

the ideal range by gender described by Anderson in 1972. The autoimmune serum laboratory

and Heidelberg testing were found unexpectedly to have a very frequent occurrence of rare

gastrointestinal autoimmune disease (pernicious anemia), hyperchlorhydria and autoimmune

gastritis. The serum endocrine laboratory testing found a high incidence of endocrine

dysfunction including hypothyroidism, Hashimoto’s thyroiditis, menopause, male

hypogonadism, adrenal fatigue and low levels of vitamin D3. Concurrent with diagnoses found

in the laboratory assessment, the endocrine, autoimmune and vitamin deficiencies were treated

and corrected.

Twelve of the 15 patients followed for one-year had greater than 75% improvement of symptoms

with anabolic therapy for a minimum of 4 months. The therapeutic goal of raising the total

testosterone divided by the sex hormone binding globulin (SHBG) ratio, the Free Androgen

Index was confirmed within 4 months of anabolic treatments. Diet restriction and supplements

were continued by the naturopathic physician who continued to treated the hyperchlorhydria,

digestion, constipation and SIBO complaints. At the end of 12-months, not one of the 12 patients

remained on rifaximin or any other antibiotic, anti-fungal or anti-helminth agent. Five of the 12

had discontinued the anabolic protocol and remained symptom-free.

Androgen therapy corrected anemia, added weight to those with low BMIs, improved their sense

of well-being, improved muscle mass, strength and libido. For the most part, side effects were

limited to hirsutism which was usually minimized with spirolactone therapy.

Of the original 18, 3 patients were excluded either having not yet completed four months of

anabolic therapy or being lost to follow up. Of the remaining 15, three did not reach the Quality

of Life threshold set by the investigators of 75 percent reported improvement. One discontinued

therapy after one month due to side effects, one had anatomical defects of the pyloric sphincter,

and one was too cachexic to respond adequately. The former did find greater than 50%

improvement at times within the treatment course.

As the relief of symptoms is the focus of treatment, it seems prudent for physicians to begin to

include the evaluation and correction of autoimmune and hormonal disruption as an integral part

of the initial evaluation and subsequent treatment of these antibiotic resistant SIBO patients.

With the increasing failures of multiple and expensive antibiotic treatments for SIBO, this study

demonstrated a paradigm shift that seems warranted: from singularly focusing on treatment of a

breath test to a comprehensive treatment program that includes correction of serum measurement

of autoimmune and hormonal disruption.

Background Information:

The work of Pimentel1 in identifying Archaea bacteria as a cause of inflammatory bowel

syndrome-constipation(IBS-C) in SIBO parallels the work of Barry Marshall, M.D. who linked

the presence of H. pylori to peptic ulcers. However, bacterial resistance for H. pylori has

developed at a rapid pace that it is leaving more than 30% of H. pylori patients worldwide

resistant to standard antibiotic therapy.2,3 Similar concerns of antibiotic resistance have been

voiced to explain the failure of rifaximin and neomycin for SIBO infections as a variety of other

antibiotics, including ciprofloxin, ampicillin, metronidazole, gentamycin, chlortetracycline, and

trimethoprim/ sulfamerazine and polymyxin have been added to SIBO treatment with only fair

results.4-5 Pimentel4 states even the indications for antibiotic use are only “fair.” Other physicians

doubt the treatment and the established breathe tests altogether. Thompson6 stated that there are

no long-term studies of rifaximin that extend over 10 weeks. Chan7 stated that “Rifaximin does

not improve patients' reporting of gastrointestinal symptoms and hydrogen breath tests do not

reliably identify who will respond to antibiotic therapy.”

As Bures8 stated in the World Journal of Gastroenterology, “Therapy for SIBO must be complex,

addressing all causes, symptoms and complications, and fully individualized. It should include

treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective

antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to

SIBO.”

As antibiotic treatments for both H. pylori and SIBO are increasingly becoming ineffective, other

factors must be addressed that affect the host microbiota ecosystem if effective treatments will be

offered to SIBO patients. Since endocrine dysfunctional and autoimmune states are frequently

seen with SIBO patients, the author raised the question, “could the endocrine and autoimmune

dysfunction be a contributing cause of SIBO?”

The author hypothesized that should the findings of endocrine and autoimmune dysregulation be

apparent in the data collected, then correction of these endocrine and autoimmune disease states

might also improve the signs and symptoms of the SIBO infection in susceptible individuals--

thereby offering a new direction for treatment and understanding the contributing causes to this

disorder.

Method:

The referring physician identified 18 SIBO patients whom had failed treatment with not only

recurrent trials of various antibiotic regimens including rifaximin/ neomycin, but also

naturopathic and vitamin/mineral supplementation. They reported having their Quality of Life

interrupted by their gastrointestinal disease symptoms. Eight of the 18 had to discontinue their

fulltime employment due to SIBO. Five were retired or unemployed. Supplements used during

the 12-month review were listed. (Table I). Three of the 18 patients were eliminated from this

review because the anabolic therapy had not been in place for 4 months, their records were

incomplete or they were lost to follow up.

Fifteen patients were included. Each was interviewed separately by the second author who also

independently reviewed their charts, laboratory tests and conducted a personal telephone

interview. The SIBO LABORATORY CHECK LIST includes pertinent gastrointestinal and

autoimmune testing. (Table II). Rare gastrointestinal disorders of hyperchlorhydria, anatomical

disruption of the pyloric sphincter, pernicious anemia and chronic autoimmune atrophic gastritis

(CAAG) were identified by utilizing the Heidelberg test, autoimmune and serum assays pertinent

to the gastrointestinal tract. As hyperchlorhydria, hypochlorhydria, pernicious anemia and

chronic autoimmune atrophic gastritis were discovered, naturopathic and medical therapies were

begun. This occurred often weeks after stabilization of hormones had occurred with the anabolic

therapy protocol. Esophageal-Diagnostic Gastroscopy (EDG) was ordered in select individuals.

Concurrently, the HORMONAL LABORATORY CHECK LIST included those laboratory tests

pertinent to the endocrine system: serum assays of pituitary, thyroid, adrenal, pancreatic, gonadal

function and Vitamin D3 25-OH were evaluated. (Table III). SHBG and calculated Free

Androgen Index (FAI) was added as it addresses bioavailability of gonadal hormones. Normal

FAI ranges by gender was taken from Burke and Anderson9. IGF-1 range was taken from RM

Bennett.10 Therapeutic range was considered normal if it exceeded the mid-range. The range and

mid-point of these serum assay values by gender and age from Quest Diagnostic Reference

Laboratories appear next. (Table III). The full set of laboratory tests, medications and treatment

course are listed in the SPREAD SHEET including 1) occurrence of autoimmune diseases, 2)

ocurrences of medical diseases, 3) laboratory tests, and 4) medical treatments. The information

was recorded from the initial assessment and as recorded at the 12-month follow up. (Table IV).

In these resistant SIBO patients, the summary of their concurrent medical diagnoses, doses and

forms of medications prescribed, benefits and side-effects are listed at 12-months. (Table V). If

the patient had discontinued the anabolic protocol, the laboratory tests of testosterone, SHBG

and FAI were listed when the patient was on therapy. Hormone therapy included ICD 10

Diagnosis, doses and frequency of prescription medications, intramuscular injections of

testosterone (men), nandrolone (men and women), stanozolol (men and women) and

methylcobalamin were noted (Table V.) Estradiol replacement by cream or patch was

selectively prescribed to women with menopausal or vaginal complaints (Table V). The table

listing previously prescribed antibiotic medications that potentially disrupted the microflora of

the GI tract in SIBO resistant patients are noted. (Table VI)

Results:

Naturopathic and over-the-counter medications remained in use in 9 patients of the 15 patients in

the 12-month study. Twelve of the 15 previous antibiotic- SIBO failures reported greater than

75% improvement during the follow up year with this multiple discipline approach to treatments.

The unexpected high frequent occurrence of auto-immune and hormonal disease treatment in this

population of 15 patients appears summarized herein. (Table VI.)

Based on prior experience, the women patients were titrated from 10mg to 20mg of nandrolone

intramuscular injection weekly. Forty mg was the maximum tolerated. Stanozolol was given as

10mg to 20mg in a weekly injection or 25mg weekly or bimonthly depending on the serum

assays of total testosterone and SHBG. Rarely was 25mg of stanozolol prescribed twice per

week. The medications were adjusted to maximize the biomarker, FAI and the patient’s response

to treatment. In only one patient was the medication temporarily discontinued probably due to

her underlying medical problem of biliary cholangitis.

Men were titrated from 40mg to a maximum of 80mg nandrolone in the weekly intramuscular

injections. The stanozolol injection was given as 10mg to 20mg in a weekly injection or an oral

capsule of 25mg weekly, twice weekly to rarely bimonthly depending on the serum assays of

both total testosterone and SHBG the components of the key biomarker, FAI.

The goal of endocrine therapy was to reduce the thyroid antibodies, TSH, FSH and LH while

increasing the DHEA-s, morning cortisol, baseline Vitamin D3 and IGF-1. The goal of anabolic

therapy was to raise the total testosterone, lower the SHBG, and raise the FAI. All patients were

followed closely for changes in blood pressure, weight, heart palpitations, fluid retention, breast

tenderness, any side-effects and hirsutism.

Failures of Therapy:

One 74-year old cachexic male made some significant albeit temporary improvement after

suffering from SIBO related diseases for more than 20 years and reported a 50 to 70 percent

improvement in quality of life. The combination therapies with human growth hormone (hGH)

increased his weight by 15 pounds, reduced his gastrointestinal symptoms but, he remained

cachexic. As he continued to self-doctor his medications, he lost weight off the nandrolone/

testosterone/ stanozolol protocol and his overall course of therapy was not considered fully

successful by the author’s standards.

One premenopausal woman showed pyloric dysfunction on the Heidelberg test and a normal

EGD except with antral gastritis. She failed to improve on any and all therapies and was deemed

a failure.

One cachexic woman discontinued the therapy after one month. She failed to gain weight or find

relief of her symptoms as she was resistant to all naturopathic and prescription medications. She

was in the group eliminated from the study.

One adult female patient showed moderate improvement on anabolic therapy, but then developed

tan stools and upper abdominal pain. She was treated as a case of primary biliary cholangitis

with clinical pernicious anemia with 5000mcg of methyl-cobalamin daily with dramatic clinical

improvement. She had periods of very good control on a combination of hormonal, naturopathic

and methylcobalamin medications, hormonal stability was difficult to establish. Improvement

was noted at greater than 50 and as high as 75 percent. Her improvement and course on

hormonal therapy is ongoing. She and her husband consider her a great success so she is, for the

purpose of this study, not included with the three failures listed above.

Discussion:

Are Antibiotic Therapies Bound to Fail?

Based on molecular subtyping and antimicrobial susceptibilities of diarrheal patients in China11,

it is expected that more of the gastrointestinal microbiome will become resistant quickly as

antibiotic resistance spreads. Antibiotic resistance to Campylobacter coli was noted in nalidrixic

acid (100%), ciprofloxacin (100%), levofloxin (99%), tetracycline (94%), metronidazole (93%),

erythromycin (61%), streptomycin (72%), gentamicin (59%), ampicillin (50%), and

chloramphenicol (29%). Multidrug resistance was detected in 108 of 109 Campylobacter coli

isolates.

Eamonn Quigley, M.D., outgoing president of the American College of Gastroenterology and

Professor of Medicine and Human Physiology at the National University of Ireland in Cork

stated “we’re seeing more resistance to some of the more conventional therapies in term of H.

pylori eradiation.” “This is of concern for both “patient acceptance of treatment regimens” and

the cost and some of the drugs are quite new.”12

Expect antibiotic resistance in the treatment of SIBO to increase likewise. Already, it is being

seen in neomycin therapy. Although unlikely for rifaximin, prospective data are needed.”11

The Existence of Autoimmunity

There are a number of autoimmune diseases that have been found to have a higher incidence of

SIBO than in control populations. There are three groupings of autoimmune diseases that are

diagnosed by serum assay and associated with SIBO. They are:

1) Autoimmune disease in the gastrointestinal tract: pernicious anemia with anti-parietal

cell antibodies and with anti-intrinsic factor antibodies. Chronic Autoimmune Atrophic

Gastritis (CAAG) may have some of the same antibodies in addition to elevated gastrin

serum levels.

2) Organ specific autoimmune diseases such as Hashimoto’s thyroiditis with anti-parietal

and anti-intrinsic factor antibodies, that may coexist with any other autoimmune diseases

and have other tissue specific auto-antibodies, and

3) Systematic autoimmune diseases such as rheumatoid arthritis and lupus that may be

associated with other either or both autoimmune diseases previously listed (with or

without anti-parietal and anti-intrinsic factor antibodies). They may have general

inflammatory markers such as sedimentation rate, C-reactive protein and general

autoimmune test such as Anti-nuclear antibodies (ANA), anti-streptolysin O (ASO) ,

antibodies to angiotensin-converting enzyme (ACE), and Rheumatoid Factor (RF).

The serum assays and clinical data from these 18 chart reviewed patients are representative

of all three.

Firstly, autoimmune diseases of the gastrointestinal tract are well recognized. Pernicious anemia

is an autoimmune disease that destroys the parietal cells. Deficiency of intrinsic factor, presence

of intrinsic factor blocking and binding antibodies, and anti-parietal cell antibodies can be found

in both pernicious anemia and chronic autoimmune atrophic gastritis (CAAG). Clinically,

intrinsic factor is essential for vitamin B12 absorption and severe deficiency leads to

megaloblastic anemia and the potential for neurological consequences. CAAG patients have

abnormal gastrin and chromogranin A (CgA). Treatment of both conditions is by intramuscular

injections of cobalamin (B12) and iron to treat respectively B12 and iron deficiency anemia.

There are inconsistencies of serum diagnostic testing and treatment. The bioidentical forms of

B12 treatment available as methyl-, hydroxy- and adenosyl- cobalamin are preferred over

cyanocobalamin14. Recommended dosages of B12 in clinical treatment vary widely from oral to

intramuscular as shown in the literature.

There is proven coexistence of chronic autoimmune atrophic gastritis (CAAG) and

hyperparathyroidism (PHPT). Since CAAG is four times more frequent in autoimmune

hyperparathyroidism (PHPT) than in the general population, and the occurrence of PHPT is

three-fold greater in CAAG than in the general population, the author and others suggests “a

potential role for autoimmunity.”15

While the autoimmune disease of the gastrointestinal tract consistently show anti-parietal

antibodies and anti-intrinsic factors, these antibodies are present in endocrine and autoimmune

diseases outside of the gastrointestinal tract. Such diseases include primary hyperparathyroidism

(PHPT)12, Type I diabetes14-17, latent autoimmune diabetes18, autoimmune thyroid disease19-20,

vitiligo21-22, celiac7,20, recurrent aphthous stomatitis23, pangastritis24, lupus25 and multiple

sclerosis26.

Secondly, these endocrine and autoimmune states, such as diabetes, have comorbidity with other

autoimmune disease states. Type I diabetes characterized by the autoimmune loss of insulin-

producing pancreatic β cells exhibit an increased risk of other autoimmune disorders such as

autoimmune thyroid disease(AT), Addison’s disease, autoimmune gastritis, coeliac disease and

vitiligo.27-28 Vitiligo patients and their relatives have increased frequency of anti-thyroid

microsomal, anti-parietal cell and anti-adrenal autoantibodies. This highlights the strong genetic

contribution.29

These autoimmune organ diseases respond to individual therapy: insulin replacement for

diabetes, thyroid replacement for autoimmune thyroid disease and anti-inflammatory

medications for lupus. Treatment of one of the individual diseases does not improve the other

autoimmune medical conditions.

Thirdly, not only do these endocrine and autoimmune disease states have higher incidence of

comorbidity with other endocrine -autoimmune states (previously called Polyglandular

autoimmune syndrome type II (PSAS Type II))30 but, the diseases are systemic: rheumatoid

arthritis, Sjögren syndrome, and systemic lupus erythematosus for example. Fallahi19 found all

three types of autoimmune disorders could exist in the same population. He suggested that

patients with AT who remain unwell, or who develop new non-specific symptoms (despite

adequate treatment) should be screened for other autoimmune disorders.19 Vrkljan suggested that

the diseases (pernicious anemia, primary hypothyroidism, and Addison’s disease) “share the

same etiological factors but also overlap in pathophysiology and clinical characteristics… favors

older classifications of APS which consolidate all endocrine and other organ specific

autoimmune diseases into one category.”31 Wielosz32 instituted immunosuppressive therapy in

autoimmune polyglandular syndrome which reduced the symptoms of connective tissue disease.

Zampetti18 made an association missing from all previously referenced articles on the

interrelationship of 1) autoimmune disease of the gastrointestinal tract, 2) autoimmune disease of

specific organs and 3) systemic autoimmune disease. He referenced the word gender.

Gender Specific Medicine or Molecular Mimicry?

It has been hypothesized that “functional disorders such as irritable bowel syndrome, chronic

fatigue syndrome and anorexia nervosa are caused by auto-antibodies to neuronal proteins

induced by molecular mimicry with microbial antigens.” For 40 years, some have hypothesized

that pooled immunoglobulin and elimination of the bacteria from the microbial flora that express

the cross-reacting antigens should be possible.33-34

The literature repeatedly demonstrates that treating the autoimmune disease, whether it be

pernicious anemia35 or hypothyroidism36, can clear the SIBO. Clearing the SIBO does not

improve the underlying autoimmune disease nor do antibiotics offer any consistent, long-term

solution.

Why then put the bacteria first? Is it not logical that the underlying autoimmune state changes the

bacterial flora?

The immunology of these previously listed diseases that have a comorbid association with SIBO

has been recognized for 40 years.37 Stockbruegger38 stated that “the bacterial overgrowth in

pernicious anemia may be facilitated by altered immunological conditions” rather than the

molecular mimicry hypothesis that bacteria are causative.

The objective data from Stockbruegger38 and Ngo39 offer an alternative hypothesis to the cause

of autoimmunity that rejects molecular mimicry. They hypothesize that the overlap of bacterial

overgrowth and autoimmune disease is dependent on:

1) altered immune conditions38 and

2) gender,38 genetics and

3) exposure to external factors (i.e., hormones) and the subsequence response to such factors

might influence susceptibility to autoimmune disease.39

The altered immune conditions in these patients has been extensively noted by Ngo at

macrophage, T cells, cytokines, interleukins and natural killer cell levels.39 He notes that the

differences in immunology function can depend on the gender and age of the individual. The

gender of the host dictates the basic normal levels of Gender Specific Hormones.

SIBO, certain autoimmune diseases such as pernicious anemia, autoimmune thyroiditis, and

systemic diseases such as lupus, rheumatoid arthritis and multiple sclerosis share a gender

predilection of female: male of 3:1 or greater. This 3:1 ratio only persists during the reproductive

years; 15 to 50 years of age. This gender deferential is not pronounced in either the pediatric or

elderly population.

Prior Knowledge

Before beginning this retrospective chart review, Lichten40 hypothesized that the failure in these

SIBO patients was due to Wolbachia. Wolbachia bacteria exist within microfilaria (host

nematode). The Wolbachia is necessary for the life cycle of microfilaria because Wolbachia

introjects a second X chromosome. Without the second chromosome, the microfilaria becomes

male and dies; only the XX chromosome female reproduces. The author hypothesized that the

increasing estrogenic milieu caused by the changing exposure to xeno-estrogens in hormonal

contraception, environmental disrupting chemicals (EDCs) and persistent organic

pesticides(POP) was shifting the balance to producing more microfilaria females. The most

effective previous treatment was referenced to be doxycycline and albendazole.

Therefore, in the treatment of these patients, a number were treated with albendazole and

doxycycline per protocol.41 GI distress was noted in greater than 50 percent and only one was

able to continue therapy for the required 3 months. Her improvement on the anabolic protocol

continued independent of starting and stopping the Wolbachia protocol. Reference to the wide

range of prescription medications previously used to disrupt the GI flora in this population

appear in Table VI.

Lichten42 published a report in 1991 on the treatment of 141 premenstrual women with menstrual

migraine. He addressed the presumed hormonal cause of migraine by prescribing danazol, an

anabolic steroid, to lower the estradiol luteal surge, raise the testosterone level and lower the Sex

Hormone Binding Globulin(SHBG). In 67 of 81 patients followed for one year, dramatic relief of

the signs and symptoms of migraine were documented. Migraine is now considered an auto-

immune-mediated disease with 3 times higher anti-phospholipid antibodies, anti-cardiolipid and

anti-β2-glycoprotein I antibodies.43

Lichten44 offered proof of a novel medical protocol to treat extensive stage IV endometriosis that

in this case report prevented hemicolectomy. The patient remains pain-free after 8 years after

initiating and continuing weekly nandrolone and stanozolol injections.45 Endometriosis is now

considered an auto-immune disease46 with the sensitivity of 6 biomarkers (anti-TMOD3b-

autoAb, anti-TMOD3c-autoAb, anti-TMOD3d-autoAb, anti-TPM3a-autoAb, anti-TPM3c-

autoAb, and anti-TPM3d-autoAb) higher at the specificity of ≥80% for diagnosis of rAFS stage I

to II endometriosis as well as ultrasound-negative endometriosis. Endometriosis is also

statistically associated with autoimmune Graves’ Disease.47

Lichten48 and James Sowers in an unpublished IRB in 1999 documented that parenteral

testosterone lowered insulin requirements in brittle diabetic men by 50%. Kapoor49 and

Vonhueler50 subsequently reported that testosterone reduced hemoglobin A1c on average by 2%

in long-term studies lasting up to 52-weeks. Diabetes Type I (insulin requiring) and Type II

(adult onset) are both considered autoimmune diseases.

Lichten51 in a yet unpublished case report combined testosterone, nandrolone and stanozolol to

reverse a case of Crohn’s disease scheduled for hemicolectomy and ileocecal pouch in an 18-

year old Caucasian male who had experienced a 100-pound weight loss. Testosterone therapy in

Germany and Syria for up to 7 years was effective at dramatically reducing the Crohn’s Disease

Activity Index and C-reactive protein.52

Nassser52 clearly summarized why these observations can be made about testosterone and why

they clinically applied to its first derivative, nandrolone: “Low serum testosterone is associated

with an increase in inflammatory factors, while testosterone administration reduces them. There

is evidence for an immunomodulatory effect of testosterone on differentiation of regulatory T

cells.”52

CONCLUSIONS:

This retrospective chart review analysis is the first to document the utilization of anabolic

steroids in a rifaximin- antibiotic resistant SIBO population. This data supports the findings that

the altered immune serum laboratory findings associated with SIBO and comorbid autoimmune

diseases can be influenced by Gender Specific Hormones. Treatment with anabolic steroids that

are Gender Specific can improve the signs, symptoms and autoimmune markers of autoimmune

diseases including potentially Crohn’s and Inflammatory Bowel Disease (IBD).

Together, this retrospective chart review, prior knowledge and previous publications offers

observational proof that Gender Specific Anabolic Hormones can be an effective and supportive

treatment regimen of SIBO, IBD and autoimmune diseases. The Free Androgen Index (FAI) may

prove to be a key reproducible biomarker for diagnosis, recovery and follow up improvement of

not only resistant cases of SIBO but also select autoimmune disease states.

It is clear that the anabolic therapy protocol applied herein was directed at normalizing Gender

Specific Hormones levels to that of a young adult. The effect of gender on autoimmune function

is well known.53 What about its effect on autoimmune antibodies? Nandrolone and testosterone

both have direct effects on natural killer cells (NK)54, interleukins, thymus serum factor and IL-1

production mediated by macrophages. This may explain why nandrolone was effective in these

autoimmune cases, not dissimilar to the attempt by Wielosz32 to use azathioprine to treat

autoimmune polyglandular syndrome.

There is further loss of support for the hypothesis of molecular mimicry as a subset of these

patients treated with medications that disrupt microbiota of the gastrointestinal tract were

ineffective in improving SIBO complaints. (Table VI).

Gender Specific Hormones of antibiotic resistant SIBO appears to offer an effective treatment

and the FAI offers a biomarker of disease and potential for follow up of recovery.

Conclusions:

Gender Specific Medicine may offer effective treatment for both antibiotic failure in SIBO

patients and for supporting the underlying autoimmune disease. The ability to increase the FAI

bio-marker value strongly correlated with improvement in the patient’s symptoms in this chart

review. The authors feel that there is strong support that the paradigm shift of medical

investigation and treatment of SIBO alone and autoimmune diseases in general needs to be

expanded to include Gender Specific Medicine hormonal evaluations, anabolic therapy and the

potential use of the FAI as these disease states progress and during potential recovery.

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TABLE I. NUTRACEUTICALS and SUPPLEMENTS

Pepto-Bismol™

Alka-Selzer™ Gold (sodium bicarbonate)

Bilex™

Ox bile

Digestive Enzymes

Aygestin™ 23 Colloidal Silver

Aloe Vera

Olive Leaf Extract

Mastic gum

Betaine hydrochloric acid

Allimed™

Neem Plus™

Vitamin B12

Vitamin B6

Vitamin D

Boron/ Boric Acid

Probiotic

Proton Pump Inhibitors

TABLE II. SIBO LABORATORY CHECK LIST

□ SIBO Breath Test (Lactulose Breath Test)

□ IBS serum check of the migrating motor complex

□ CdT

□ Vinculin

□ Pernicious Anemia Serum Antibodies and B12 levels

□ Intrinsic Factor

□ Intrinsic Factor Blocking Antibody

□ Intrinsic Factor Binding Antibody

□ B12 (cobalamin) serum assay

□ Chronic Autoimmune Atrophic Gastritis

□ Gastrin serum assay

□ Gastric Cancer Screen (optional)

□ Pepsinogen II

□ Heidelberg Test of Gastric ‘pH’ at baseline and sodium bicarbonate challenge

□ Esophageal-gastro-duodenoscopy (EDG)

□ Celiac Disease

□ IgA-transglutaminase (IgA-TTG)

□ deaminated gliadin (IgG-DGL)

□ Demographics

□ Height □ Weight □ BMI

□ Birth Year □ Environmental Toxin Exposure

□ Smoker □ Alcohol

□ Medications

□ Proton Pump Inhibitors

□ Thyroxine

TABLE III. HORMONAL LABORATORY CHECK LIST

Disease State Laboratory Test Range Women Men

□ Complete Blood Count

□ Metabolic panel

□ Auto-immunity Profile

□ Sedimentation rate

□ Anti-nuclear antibody

□ C- reactive protein

□ Hypothalamic

□ hypovitaminosis D Vitamin D3 25-OH > 60 > 60

□ hyperparathyroidism Parathyroid Hormone

□ Thyroid

□ hypothyroidism Thyroid Stimulating Hormone < 2.

□ Total triiodothyronine

□ Free T3 (triiodothyronine)

□ Free Thyroxine (T4)

□ Reverse T3 (triiodothyronine)

□ Thyroid Antibodies

□ Thyroid Peroxidase Antibodies

□ Adrenal

□ Dehydroandosterone-sulfate

□ Cortisol AM

□ Cortisol PM

□ Pancreas

□ Hemoglobin A1c

□ Fasting insulin

TABLE III. HORMONAL LABORATORY CHECK LIST -part 2

□ Ovarian Hormones

□ Total Estradiol

□ Total Testosterone

□ Progesterone

□ Sex Hormone Binding Globulin

□ Free Androgen Index- calculated 0.01.

□ Pituitary

□ hypopituitarism Insulin Like Growth Factor-1 >200 >225

□ menopause Follicle Stimulating Hormone <20

Luteinizing Hormone <20

□ Testes Hormones

□ Total Estradiol

□ Total Testosterone

□ Sex Hormone Binding Globulin

□ Free Androgen Index-calculated > 0.075.

□ hypogonadism Follicle Stimulating Hormone < 3.5

Luteinizing Hormone < 2.0

□ Prolactin

TABLE IV.

Full data set SKEMATIC EXCEL CHART

TABLE V.

The Number of Patients with laboratory findings, autoimmune diseases, medical diseases, medical treatments at initial evaluation and at 12-month follow up

TABLE VI.

3 cases of pernicious anemia treated with high dosages of methyl-cobalamin (B12) between

1000mcg and 5000mcg daily. [SB,____, ____, _____, ____, ____, ____, ____}. [____, _____]

3 cases of undiagnosed hypothyroid disease . [SB,____, ____, _____, ], one case of Grave’s

disease [CJ},and 3 cases of previously diagnosed Hashimoto’s thyroiditis [,_____, _____, ____]

was diagnosed by TSH, Free T3, Free T4, Reverse T3, thyroid antibodies, thyroid peroxidase

antibodies. Treatment consisted of combining thyroid therapy with thyroxine (T4) with

triiodothyronine (T3).

In the 15 patients followed for 12-months, all 3 men and 10 of 12 women showed 3 to 10-fold

elevation of the SHBG associated with abnormally low FAI based on the ideal range on

Anderson. The women were treated with nandrolone and stanozolol by weekly intramuscul.ar

injections. When the patients complained of painful injections, they were shifted to oral

stanozolol starting at one capsule weekly

The 3 men with low FAI had evidence of hypogonadism/ low testosterone (male) defined by

elevated serum assays FSH/ LH. Testosterone was added to the previously described nandrolone

and stanozolol for men.

Of the 12 women, 3 cases of menopause (female) were identified as these 3 had elevated serum

assays of FSH/LH and low serum total estradiol. When menopausal symptoms were still present

after initiating nandrolone, they were treated with add back estradiol topical or transdermal

patches.

There were 6 cases of hypopituitarism defined by IGF-1 below ideal range of RM Bennett MD

for fibromyalgia. Five patients were prescribed human growth hormone (hGH) after having good

but incomplete relief with anabolic therapy. Three found the medication beneficial and

continued the therapy. Two men and one woman returned to full employment. The remaining

individual was the 74-year old cachexic male considered a failure of therapy although some

improvements over all were noted. The remaining female individual discontinued the medication

due to cost. An L-arginine stimulation test was ordered for each of the patients continuing

therapy.

One presumed case of primary biliary cholangitis was seen by the author’s request at a major

University Teaching Hospital in Boston. The patient’s right upper quadrant pain dissipated on

5000mcg of methylcolbamin intramuscularly every day and subsequently redued to 5000mg

every other day. The tan stools remained but therapeutic treatment with ox bile, methylcolbamin

and anabolic therapy dramatically improved her quality of life.

Two patients had positive findings of Antinuclear Antibody (ANA) titers of 1:160 that fluctuated

to 1:80 on anabolic treatment. This was considered normal range variation, but, the presence of

positive ANA was noted in the findings of autoimmune disease states in 2 of these 18 patients.

TABLE VI.

PRESCRIPTION AGENTS THAT DISRUPT THE MICROFLORA OF THE GI TRACT

Class Individual agent Number of Pubmed.com references

Number of Patients in study on meds

Number of trials

Aminoglycosides Neomycin 24 Cepaholsporins- 1st Cefalexin 1 Cephalosporins- 2nd Cefprozil 1 Cephalosporins- 3rd Ceftriaxone 5 Glycopeptides Vancomycin 33 Lincosamindes Cleocin 18 Macrolides Biaxin 6 Monobactams Aztreonam 4 Nitrofurans Nitrofurantoin 0 Xazolidinones Linezolid 1 Penicillins Amoxicillin 23 Penicillin Combination

Amoxicillin/ clavulanate

5 Augmentin

Quinolones Ciproflaxacin 28 Sulfonamides Trimethoprim-

Sslfamethoxazole 7 Bactrim

Tetracyclines Doxycycline 9 Drugs against mycobacteria

Rifampicin 110

Steptomycin 8 Others Chloramphenicol 6 Metromidazole 73 Nitazoanide 1 Antifungal Fluconazole 13 Antiparasitic Albendazole 0