Research

The following is a collection of…

a) Research studies we are interested in performing and fundraising for
b) Completed studies that are interesting to read and apply towards models of patient diagnosis and treatment
e) Pharmaceutical Drug treatment options

One Great Gut Research Interests:

  • Synbiotics(probiotics and prebiotics)
  • Gut illness and Co-Administration of  Ayurvedic herbs with Next Generation synbiotics
  • Ayurvedic herb-based Fecal Microbial Transplant protocols
  • Gut illness and cannabis
  • Pet allergies / histamine intolerance and gut microbes
  • Exploration into the effects of Fluoride on the Microbiome and Gut Illnesses
  • Entheogen research to target the gut brain axis
  • Low residue diet and sustained prolonged health of the GI Intestinal track
  • Exploration into effects of wheat on  gut permeability and blood-brain barrier permeability
  • Microbiomics
  • Indigenous/Aboriginal/Native human strain microbiomics
  • Endogenous human strain microbiomics
  • Enteric Nervous System(ENS) and Gut Health
  • Stress and Gut Health
  • Polyvagal Theory (Vagus Nerve) and Gut/Brain Axis
  • Tap Water / Fluoride and Gut Health
  • Gut Health and Nervousness
  • Mucosal lining / endothelial cells research
  • Effect of GMOs, Glyphosate, environmental toxins on gut health
  • Sig A, gut function
  • Appendicitis and diverticulitis
  • Galt(Gut-associated lymphoid tissue) System
  • Chronic Infection / Chronic Parasitology (Macroscopic)
  • Meta Analysis, Meta Review of current digestion health research

Noteworthy Completed Studies:

The American journal of gastroenterology “Low-dose naltrexone therapy improves active Crohn’s disease.”  102.4 (2007): 820-828. Smith, Jill P., et al.

Journal of clinical gastroenterology – “Safety and tolerability of low dose naltrexone therapy in children with moderate to severe crohn’s disease: a pilot study.”  47.4 (2013): 339. Smith, Jill P., et al.

The Central European Journal of Medicine – Wiener klinische Wochenschrift – A retrospective, case-control study on traditional environmental risk factors in inflammatory bowel disease in Vukovar-Srijem County, north-eastern Croatia, 2010. – Epub – 2015

Review on Antimicrobial Resistance – Tackling drug-resistance infections globally

UK Prime Minister commissioned review on Antimicrobial Resistance Chaired by Jim O’Neill – December 2014

mBio – American Society for Microbiology – Acinetobacter baumannii Coordinates Urea Metabolism with Metal Import To Resist Host-Mediated Metal Limitation – September 2016

Science Magazine – Antibiotic use and its consequences for the normal microbiome – April 2016

Diabetes Metabolism Research and Reviews – Steroid-induced diabetes: a clinical and molecular approach to understanding and treatment – 2014

Hypercortisolism and insulin resistance: comparative effects of prednisone, hydrocortisone, and dexamethasone on insulin binding of human erythrocytes. – 1982

Experimental and Toxicologic Pathology – Journal – Elsevier – Effect of genetically modified corn(GMO) on the jejunal mucosa of adult male albino rat – 2016
r
ef: Blog

Pharmacology – Cannabis Finds Its Way into Treatment of Crohn’s Disease – December 2013

PLOS One  – Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis – Dec 2011

Frontiers in Microbiology – Gut Microbiota: The Brain Peacekeeper – March 2016

Molecular Metabolism – Gut Microbiota and Glucometabolic Alterations in Response to Recurrent Partial Sleep Deprivation in Normal-weight Young Individuals – October 2016

BioMed Central – BMC Gastroenterology – Increasing rate of inflammatory bowel disease: a 12-year retrospective study in NingXia, China – 2015

Cell Reports – The Gut Microbiota Modulates Energy Metabolism in the Hibernating Brown Bear Ursus arctos –  February 2016

Environmental Health Perspectives  – Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to Methylmercury or Vaccines Containing Thimerosal – 2005

Alimentary Pharmacology & Therapeutics – Randomised clinical trial: yoga vs written self-care advice for ulcerative colitis – March 2017 – H. Cramer, M. Schäfer, M. Schöls, J. Köcke, S. Elsenbruch, R. Lauche, H. Engler, G. Dobos, J. Langhorst

Clinical Gastroenterology and Hepatology – Cannabis induces a clinical response in patients with Crohn’s disease: a prospective placebo-controlled study – October 2013

JAMA – Association of Proton Pump Inhibitors With Risk of Dementia – February 2016

Clinics – São Paulo, Brazil – The Role of Fecal Calprotectin in Investigating Inflammatory Bowel Diseases – May 2009

Nature – Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer – February 2016

World Journal of Pediatrics – Springer – Effect of gluten free diet on gastrointestinal and behavioral indices for children with autism spectrum disorders: a randomized clinical trial – 2016

Nature – Diet-induced extinctions in the gut microbiota compound over generations – January 2016

Danish Cancer Society Research Center – Profermin is efficacious in patients with active ulcerative colitis–a randomized controlled trial – Krag A1, Munkholm P, Israelsen H, von Ryberg B, Andersen KK, Bendtsen F. – 2013

World Journal of Gastroenterology – Safety and efficacy of Profermin® to induce remission in ulcerative colitis – Krag A1, Israelsen H, von Ryberg B, Andersen KK, Bendtsen F. – 2012

Diet: Journal of Pediatric Gastroenterology and Nutrition – Nutritional therapy in pediatric Crohn disease: the specific carbohydrate diet – 2014

Diet: Gastroenterology & Endoscopy news – Popular IBD Diet Associated With Increased Microbial Diversity – 2014

Association For Psychological Science – The Science Behind Secrets

Cannabis and Cannabinoid research – Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid – 2016

Phytochemistry – The International Journal of Plant Chemistry, Plant Biochemistry and Molecular Biology. – Truffles contain endocannabinoid metabolic enzymes and anandamide – February 2015

Diet: UMass Center for Clinical and Translational Science Research Retreat – Pilot Testing a Novel Treatment for Inflammatory Bowel Disease – 2011

British Pharmacology Society – Evaluation of new therapies for inflammatory bowel disease – 2003

Australian Dental Journal – Doxycycline-induced staining of permanent adult dentition – December 2005

The Journal Of Clinical Investigation – Effects Of Suggestion And Conditioning On The Action Of Chemical Agents In Human Subjects – The Pharmacology of Placebos – January 1950

Therapeutic Advances In Psychopharmacology – Antidepressive, anxiolytic, and anti addictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years – 2016

Current Psychiatry Reports –  Is depression an inflammatory disorder? – 2011 –  Full manuscript

World Journal Of Gastroenterology – Presence of phthalates in gastrointestinal medications: Is there a hidden danger? – 2013

PLOS ONE – Placebos Without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome -2010

Science Translational Medicine – Altered Placebo and Drug Labeling Changes the Outcome of Episodic Migraine Attacks – Jan 2014

The New England Journal Of Medicine – A controlled trial of arthroscopic surgery for osteoarthritis of the knee. – July 2002

Journal Of The American Medical Association – The Powerful Placebo – December 1955

Sage Journals – Aluminum as an adjuvant in Crohn’s disease induction – A Lerner – 2012

Prime International Journal Of Aesthetic And Anti-Ageing Medicine – Evaluating thermotherapy using the amethyst Bio-belt and the infrared
negative ion amethyst BioMat
– 2013 – Dr. George Grant

Evaluating the reduction of cancer pain using the infra-red negative ions amethyst BioMat in 12 subjects over 6 months – Dr. George Grant

Cochrane IBD Group – Biofeedback for treatment of irritable bowel syndrome – January 2017

Inflammatory Bowel Diseases – Fecal Microbiota Transplantation is Safe and Efficacious for Recurrent or Refractory Clostridium difficile Infection in Patients with Inflammatory Bowel Disease – October 2016

American Society for Microbiology – Bacteriome and Mycobiome Interactions Underscore Microbial Dysbiosis in Familial Crohn’s Disease – September 2016

World Journal Of Gastroenterology –  Rectal administration of d-alpha tocopherol for active ulcerative colitis: A preliminary report – 2008

The Journal of Nutrition – Absorption of Topically Applied Vitamins: Two Figures – 1956

Inflammatory Bowel Diseases
– Knowledge, Attitudes, and Beliefs Regarding the Role of Nutrition in IBD Among Patients and Providers – October 2016 – Conclusions: Significant gaps in knowledge relating to nutrition in IBD seem to exist. Targeted educational initiatives and improved access to nutritional experts are warranted. In addition, a standardized process for the assessment of malnutrition among patients with IBD should be developed.

Physiol Rev. 2011 Jan;91(1):151-75. doi: 10.1152/physrev.00003.2008.
Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer.

Science – Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy – November 2015 – Our data suggest that manipulating the microbiota may modulate cancer immunotherapy.

PLoS One – Mothers Secretor Status Affects Development of Children’s Microbiota Composition and Function: A Pilot Study – Sept 2016 – Conclusion: Child and mothers’ secretor status have an impact on children’s’ microbiota composition at 2 to 3 years of age.

National Institute for Health Care Management – The Concentration of Health Care Spending – 2012

The Surgeon General’s report on nutrition and health – 1988

Thanks to Dr.  Alan Goldhamer, Dr. Michael Klaper MD, Jennifer Marano Dr. Permutter MD and our Medical and Scientific Advisory Committee for their contributions

Noteworthy Articles and Surveys:
The Pros and Cons to Colonoscopies by Dr. Mercola

State of health of unvaccinated children by Andreas Bachmair in Germany

Serious Adverse Drug Events Reported to the Food and Drug Administration, 1998-2005 – Sept 10, 20017 – Thomas J. Moore, AB; Michael R. Cohen, RPh, MS, ScD; Curt D. Furberg, MD, PhD
Per this study: Infliximab(Remicade) is the seventh most dangerous drug resulting in 1228 deaths for the selected time period. ENBREL® (etanercept)‎ is ranked tenth, with 1034 reported deaths. Infliximab(Remicade) is ranked 3rd for causes of Disability or other serious outcome with 8320 cases.

Drug Treatment Options

 

  • Aminosalicylates: Oral 5-ASAs include balsalazide (Colazal), olsalazine (DiPentum), mesalamine (Asacol and Pentasa), and sulfasalazine (Azulfidine). Rectal 5-ASA treatments include mesalamine enemas (Rowasa) and suppositories (Canasa)
  • Corticosteroids: Prednisone, Budesonide (Endocort & Uceris)
  • Immunomodulators: Azathioprine [Imuran], 6-MP [Purinethol], Methotrexate, Infliximab [Remicade]
  • Antibiotics: Metronidazole [Flagyl], Ciprofloxacin [Cipro]
  • Biologic therapies: Adalimumab, Certolizumab, Pegol, Infliximab, and Natalizumab.

Humira by AbbVie  – $15 Billion in Sales in 2015. Top selling prescription drug in the world , for years, according to data from IMS Health. Lower cost drug biotech drug Amjevita will be available soon, available for severe psoriasis, Crohn’s diseases and a half-dozen additional conditions.

Aminosalicylates:
These include aspirin-like compounds that contain 5-aminosalicylic acid (5-ASA). These drugs are given orally or rectally. They do not suppress the immune system but decrease inflammation at the wall of the intestine itself, and are used to help heal both in the short- and long-term. They are used to treat mild-to-moderate episodes of IBD. They also are sometimes used to prevent relapses. They do have extensive side effects.

Aminosalicylates have anti-inflammatory effects on the mucosa lining the organs of the GI tract. They also inhibit the function and production of immune system cells. Several aminosalicylates are available for the treatment of Crohn’s disease. Oral 5-ASAs include balsalazide (Colazal), olsalazine (DiPentum), mesalamine (Asacol and Pentasa), and sulfasalazine (Azulfidine). Rectal 5-ASA treatments include mesalamine enemas (Rowasa) and suppositories (Canasa).

 

Corticosteroids:

  • Corticosteroids are a class of anti-inflammatory drug that are used mainly for treatment of moderate to severe flares of Crohn’s Disease. They are used more sparingly because now there are effective treatments with fewer side-effects. The side effects of corticosteroids include Cushing’s syndrome, mania, insomnia, hypertension, high blood glucose, osteoporosis, and avascular necrosis of long bones. These should not be confused with the anabolic steroids used to enhance athletic performance.
  • The most commonly prescribed oral steroid is prednisone, which is typically dosed at 0.5 mg/kg to achieve remission. Intravenous steroids are used in cases where oral steroids are not effective, or where oral steroids cannot be taken.
  • These are administered in the hospital setting. Because corticosteroids reduce the ability to fight infection, extreme caution must be used to make sure that there is no active infection, particularly an intra-abdominal abscess before the initiation of steroids.
  • Uceris releases the budesonide throughout the colon for Ulcerative Colitis. Also, the coating used is different. Uceris begins to dissolve as it enters the transverse and descending colon the area where colitis is usually most active. It is formulated with a matrix called as MMX, that exclusively dissolves in large intestine. It not advised to ever crush the pills ever as they will dissolve in the stomach in stead of making it’s way down to the large intestine. There are precautions to pay attention to when using Uceris.
  • Budesonide is an oral corticosteroid with limited absorption and high level of first-pass metabolism, meaning that less quantities of steroid enter into the bloodstream. It has been shown to be useful in the treatment of mild-to-moderate Crohn’s disease and for maintenance of remission in Crohn’s disease. Formulated as Entocort, budesonide is released in the ileum and right colon, and is therefore has a topical effect against disease in that area.
  • Budesonide is also useful when used in combination with antibiotics for active Crohn’s disease.
  • Steroid enemas can also be used for disease of the lower colon and rectum, in order to treat symptoms. Hydrocortisone and budesonide liquid and foam enemas are being marketed for these reasons.

 

Immunomodulators:

This class of medications modifies the body immune system so that it cannot cause on-going inflammation. Immunomodulators are typically used in people where aminosalicylates and corticosteroids have not been effective, or have only been partially effective.

They may be useful in reducing or eliminating reliance on corticosteroids. They also may be effective in maintaining remission in people who have not responded to other medications given for this purpose. Immunomodulators may take up to three months to begin working.

  • Immunomodulators are drugs that weaken or suppress the immune system.
  • While the immune system protects the body from harmful bacteria, viruses, and other invaders, activation of the immune system results in inflammation.
  • Immunomodulating drugs decrease tissue inflammation by reducing the population of activated immune cells or interfering with the production of proteins that summon the immune cells to an organ.

Some of these drugs used to treat Crohn’s disease include 6-mercaptopurine (6-MP or Purinethol), azathioprine (Imuran or Azasan), methotrexate and cyclosporine. Immunomodulator therapy has been shown to be more effective than steroids in maintaining remission. Remission may be achieved in over 60 percent of patients.

The drugs 6-MP and azathioprine (Purinethol and Imuran) are related molecules given orally for Crohn’s disease of the small intestine and colon. They are quite effective in treating Crohn’s disease but have a slow onset of effect (two to four months).

Because of this, they are often given along with a corticosteroid, with the intention of gradually decreasing the steroid dose as the 6-MP or azathioprine takes effect. Azathioprine rapidly gets metabolized in the blood to 6-MP. 6-MP in turn is metabolized in immune cells to the active compound 6-thioguanine (6-TG). It is the 6-TG that results in elimination of chronically activated immune cells. 6-TG can suppress the bone marrow, requiring close monitoring of the blood while on therapy.

 

  • Some people are genetically susceptible to bone marrow suppression with only small doses of azathioprine or 6-MP. They lack the normal enzyme (called TPMT) which rapidly detoxifies 6-TG. In addition, both can have a bad effect on the liver and pancreas. 6-MP and azathioprine also increase the risk of lymphoma and skin cancer, and with bone marrow suppression they also increase the risk of serious infections.

Methotrexate (Rheumatrex) is an alternative to 6-MP or azathioprine. It is typically given using an intramuscular or subcutaneous injection once a week. It is only effective in about 40% of patients with Crohn’s disease who do not respond to steroids. Methotrexate is known to cause interstitial pneumonitis, which often presents as a cough and difficulty breathing.

Crohns sufferers need to be monitored for bone marrow suppression. Methotrexate can cause liver damage, especially in patients treated long-term and in those who use alcohol or have pre-existing liver disease. Cyclosporine (Sandimmune and Neoral), are also used to suppress organ rejection after a transplant. They are used in patients whose illness did not respond to steroid drugs particularly in fistulizing Crohn’s disease. However, cyclosporine has a number of serious and uncomfortable side effects, including fever, rash, nausea, low white cell count, kidney failure, and hepatitis. Inflammation of the pancreas, or pancreatitis, may occur in 3 to 15 percent of patients on the drug. It is generally used as a last resort when other immunomodulators or anti-Tumor Necrosis Factor Alpha medications are not effective.

Antibiotics
Antibiotics have a modest effect on Crohn’s disease, with greater evidence in clinical trials than the 5-ASA medications. There is evidence to show that antibiotics are more effective in Crohn’s colitis than Crohn’s ileitis. Antibiotics are particularly used to treat perianal disease, which includes fistulas, and in all abscesses associated with Crohn’s disease.

The most commonly used antibiotic is metronidazole (Flagyl), an antibiotic also prescribed for treating parasites and vaginal infections. It is used for Crohn’s patients who have anal fistulas. Metronidazole interacts badly with alcohol, so people taking the drug should refrain from drinking. There are severe side effects. Chronic use at high doses has been associated with permanent nerve damage. The drug must be stopped if people experience numbness or tingling in their fingertips, toes, or other extremities.

Ciprofloxacin (Cipro), another antibiotic, is commonly used in treating mild to moderate Crohn’s disease. It is sometimes prescribed in combination with metronidazole for Crohn’s disease, particularly for abscesses and anal disease. They are also used for post-surgical problems such as pouchitis.
Biologic therapies:
These therapies are genetically engineered to target very specific molecules involved in the inflammatory process. The newest class of therapy to be used in IBD, these includeadalimumab, certolizumab pegol, infliximab, and natalizumab. These are not drugs, but proteins (antibodies) that target the action of certain other proteins that cause inflammation. These medications are indicated for people with moderately to severely active disease who have not responded well to conventional therapy.

They also are effective for reducing fistulas. (Fistulas, which may occur with Crohns disease, are small tunnels connecting one loop of intestine to another or two organs in the body that are usually not connected.) Biologics may be an effective strategy for reducing steroid use, as well as for maintaining remission.

There are many substances found in nature, such as herbs, foods, and vitamins, that are considered biologically-based practice. Unlike pharmaceutical products, natural remedies are not regulated by the FDA.

Side Effects

Sulfasalazine [Azulfadine]

Common Side Effects

  • abdominal or stomach pain or upset
  • diarrhea
  • loss of appetite
  • nausea or vomiting
  • aching of joints
  • headache (continuing)
  • itching
  • increased sensitivity of skin to sunlight
  • skin rash

Less Common or Rare

  • aching of joints and muscles
  • back, leg, or stomach pains
  • bloody diarrhea
  • bluish fingernails, lips, or skin; chest pain
  • cough
  • difficult breathing
  • difficulty in swallowing
  • fever, chills, or sore throat
  • general feeling of discomfort or illness
  • loss of appetite
  • pale skin
  • redness, blistering, peeling, or loosening of skin
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • yellow eyes or skin

Mesalamine [Asacol, Pentasa, Mesasal, Salofalk]

Common Side Effects

  • abdominal or stomach cramps or pain (mild)
  • diarrhea (mild)
  • dizziness; headache (mild)
  • runny or stuffy nose or sneezing

Less Frequent or Rare

  • acne
  • back or joint pain
  • gas or flatulence
  • indigestion
  • loss of appetite
  • loss of hair

Less Common

  • abdominal or stomach cramps or pain (severe)
  • bloody diarrhea
  • fever
  • headache (severe)
  • skin rash and itching

Rare

  • anxiety
  • back or stomach pain (severe)
  • blue or pale skin
  • chest pain, possibly moving to the left arm, neck, or shoulder
  • chills
  • fast heartbeat
  • nausea or vomiting
  • shortness of breath
  • swelling of the stomach
  • unusual tiredness or weakness
  • yellow eyes or skin

5-ASA Drugs – [Dipentum]

People allergic to aspirin should avoid 5-ASA compounds because they are similar chemically to aspirin.

Common Side Effects

  • headache and malaise (a vague feeling of illness)
  • cramps and gas
  • watery diarrhea

Uncommon Side Effects

  • hair loss
  • skin rash

Rare Side Effects

The rare side effects of 5-ASA affect fewer than 1 percent of people who take these drugs, but these side effects are potentially very serious.

  • inflammation of the lung (pneumonitis)
  • inflammation of the tissue surrounding the heart (pericarditis)
  • inflammation of the pancreas (pancreatitis)
  • a paradoxical worsening of inflammation of the colon (colitis)
  • inflammation of the kidney (nephritis)
  • a fall in the number of platelets – thrombocytopenia; leading to bleeding

Rare instances of worsening of diarrhea, cramps, & abdominal pain that may be accompanied by fever, rash and malaise may occur. This reaction is thought to be an allergy to the 5-ASA compound.

5-aminosalicylates and pregnancy

The safety of the 5-ASA drugs during pregnancy and breastfeeding is still being studied. Preliminary studies suggest that they are safe when taken during pregnancy and that women should continue taking these drugs during pregnancy.

Corticosteroids: Prednisone and Methylprednisolone

Very Common Side Effects

  • Weight gain. At first water retention only, then increase in body fat
  • increase in appetite
  • exacerbation of heart trouble or swelling in the legs
  • mood swings/personality changes
  • Nervousness/irritability/depression
  • difficulty in sleeping
  • increased susceptibility to infections

Common Side Effects

  • Mild weakness in the muscles of arms or legs
  • Blurred vision
  • Hair growth: both thinning and excessive growth
  • Easy bruising of the skin
  • Slow healing of cuts and wounds
  • Acne
  • Round face
  • Slowed growth in children and adolescents
  • Osteoporosis (loss of bone calcium), especially in:
    • women
    • people with chronic kidney disease
    • history of osteoporosis in the family
    • people who smoke
    • people who are not physically active

Occasional Side Effects

  • High blood pressure
  • Elevated blood sugar
  • Red or purple stretch marks on the skin
  • Stomach irritation or stomach ulcers, especially when also taking aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs)

Less Common Side Effects

  • Blurred vision from cataracts
  • Glaucoma
  • Fractures due to osteoporosis, most often in the hip and spine
  • Osteonecrosis, a serious and painful condition that occurs most often in the hip or shoulder when the bone is deprived of circulation
  • Severe weakness of the muscles (myopathy)
  • Psychosis, which is a severe disturbance of thinking
  • Serious infections due to suppression of the immune system

Immune modifiers:
Azathioprine [Imuran], 6-MP [Purinethol], Methotrexate, Infliximab [Remicade]

 

Azathioprine [Imuran]

Common Side Effects:

  • loss of appetite
  • nausea or vomiting

Less Common:

  • Skin rash
  • Cough, hoarseness
  • fever or chills
  • lower back or side pain
  • painful or difficult urination
  • unusual tiredness, weakness
  • Black, tarry stools
  • blood in urine or stools
  • pinpoint red spots on skin
  • unusual bleeding or bruising

Rare

  • fast heartbeat
  • fever (sudden)
  • muscle or joint pain
  • nausea, vomiting, and diarrhea (severe)
  • redness or blisters on skin
  • shortness of breath
  • sores in mouth, on lips
  • stomach pain
  • swelling of feet or lower legs
  • feeling of discomfort or illness (sudden)

Side effects of azathioprine and 6-MP also include:

  • increased vulnerability to infections
  • inflammation of the liver (hepatitis) and the pancreas (pancreatitis)
  • bone marrow toxicity (interference with the formation of cells that circulate in the blood)

Patients on long-term, high dose azathioprine to prevent rejection of the kidney after kidney transplantation have an increased risk of developing lymphoma, a malignant disease of lymph cells. There is no evidence at present that long term use of azathioprine or 6-MP, in the lower doses used in Crohn’s disease, increases the risk of lymphoma, leukemia or other malignancies.

Remicade

Remicade is a monoclonal antibody. It is used to treat Crohn’s disease in patients who have not been helped by other medicines and also in patients who have a type of Crohn’s disease in which fistulas form. It is also used to treat rheumatoid arthritis.

Warning about Remicade

In deciding to use a medicine, the risks of using the medicine must be weighed against the good it will do. The following are important considerations:

  • Allergies: It is important to identify any unusual or allergic reaction to Remicade or to rodents (such as rats or mice). Mouse cells are used in the preparation of Remicade. Also any allergic reactions to any other substances, such as foods, preservatives, or dyes.
  • Pregnancy: Studies have not been done in either humans or animals. It is not known if Remicade causes harmful effects in the fetus.
  • Breast-feeding: It is not known whether Remicade passes into breast milk. Because there may be harmful effects in the nursing baby, it may be necessary for you to stop breast-feeding during treatment.
  • Children: Studies on this medicine have been done only in adult patients, and there is no specific information comparing use of Remicade in children with use in other age groups.
  • Older adults: There is no specific information comparing use of Remicade in the elderly with use in other age groups. However, older adults generally get more infections than do younger adults, and it is not known if Remicade may affect the number of infections that senior citizens get.
  • Other medical problems: The presence of other medical problems may affect the use of Remicade especially:
    • Heart disease: Remicade is not recommended for those with congestive heart failure
    • Infection: Remicade is not recommended for patients with an active infection.
    • Inactive tuberculosis infection: Should be treated before starting Remicade therapy

Precautions Considering Remicade

  • It is important to have a tuberculin skin test to ensure that there is no inactive tuberculosis infection, as this could worsen while on Remicade therapy.
  • It is also important to have a heart check-up if you have existing heart disease and decide to take Remicade as this could worsen while on Remicade therapy

Side Effects of Remicade

Remicade may cause:

More Common Remicade symptoms

  • chest pain
  • fever
  • chills
  • itching
  • hives
  • flushing of face
  • troubled breathing within a few hours after taking it
  • abdominal pain
  • cough
  • dizziness
  • fainting
  • headache
  • muscle pain
  • nasal congestion
  • nausea
  • runny nose
  • shortness of breath
  • sneezing
  • sore throat
  • tightness in chest
  • unusual tiredness or weakness
  • vomiting
  • wheezing

Less Common Remicade Side Effects

  • back pain
  • bloody or cloudy urine
  • cracks in skin at the corners of mouth
  • diarrhea; difficult or painful urination
  • frequent urge to urinate
  • high blood pressure
  • low blood pressure
  • pain
  • pain or tenderness around eyes and cheekbones
  • skin rash
  • soreness or irritation of mouth or tongue
  • soreness or redness around fingernails or toenails
  • vaginal burning or itching and discharge
  • white patches in mouth and/or on tongue

Rare Side Effects

  • abscess (swollen, red, tender area of infection containing pus)
  • back or side pain
  • black, tarry stools
  • blood in urine or stools
  • bone or joint pain
  • constipation
  • falls
  • feeling of fullness
  • general feeling of illness
  • hernia (bulge of tissue through the wall of the abdomen)
  • infection
  • irregular or pounding heartbeat
  • pain in rectum
  • pain spreading from the abdomen to the left shoulder
  • pinpoint red spots on skin
  • stomach pain (severe)
  • swollen or painful glands
  • tendon injury, unusual bleeding or bruising
  • weight loss (unusual); yellow skin and eyes

The majority of the patients who responded to a first infusion of Remicade/infliximab developed recurrence of their disease within three months.

Response to infliximab after repeated infusions sometimes is lost if the patient starts to develop antibodies to the infliximab (which attach to the infliximab and prevent it from working).

TNF-alpha is an important protein for defending the body against infections. Infliximab, like immuno-modulators, increases the risk for infection. One case of salmonella colitis and several cases of pneumonia have been reported with the use of infliximab. There also have been cases of TB reported after the use of infliximab.

Because infliximab is partly a mouse protein, it may induce an immune reaction when given to humans, especially with repeated infusions.

In addition to the side effects that occur while the infusion is being given, patients often develop a “delayed allergic reaction” that occurs 7-10 days after receiving the Infliximab. This type of reaction may cause flu-like symptoms with fever, joint pain and swelling, and a worsening of Crohn’s disease symptoms. It can be serious, and if it occurs, a physician should be contacted.

Although Infliximab is only FDA approved for a single infusion at this time, be aware that repeated infusions are likely to be required once Remicade therapy has been initiated.

Rare cases of nerve inflammation like inflammation of the nerve of the eye, has been reported with the use of infliximab.

Infliximab can aggravate and cause the spread of an existing infection. It must not be given to those with pneumonia, urinary tract infections or a localized collection of pus (i.e., abscess).

It now is recommended that people be tested for TB prior to receiving infliximab. People who previously had TB should inform their physician of this before they receive infliximab.

Infliximab can promote intestinal scarring which is part of the process of healing and, thus can worsen strictures which are the narrowed areas of the intestine caused by inflammation and subsequent scaring and lead to intestinal obstruction.

Remicade can cause partial healing/closure of anal fistulae. This interferes with the drainage of fluid through the fistulae, and may result in collections of fluid in which bacteria multiply, which can result in abscesses.

The effects infliximab on the fetus are not known.

The long-term safety and effectiveness is not yet known. Caution is warranted in its use.

Infliximab can cause the spread of cancer cells; therefore, it should not be given to patients with cancer.

Adalimumab [Humira]

Common side effect

  • skin reactions at the site of injection – swelling, itching, or redness
  • upper respiratory infections
  • sinusitis
  • nausea

General Side Effects

Increases the risk of infection – it should not be given to patients with pneumonia, urinary tract infection or abscess (i.e. localized collection of pus).

Rare Side Effects

  • lymphoma (cancer of the lymphatic system)
  • nervous system inflammation with symptoms of numbness and tingling
  • vision disturbances
  • weakness in legs
  • symptoms that mimic systemic lupus like skin rash, arthritis, chest pain, or shortness of breath. These lupus-like symptoms resolve after stopping the drug.
  • worsening heart disease such as heart failure
  • severe allergic reactions with rash
  • difficulty breathing
  • severe low blood pressure or shock
  • serious allergic reactions after the fist injection or after many injections

Antibiotics – Flagyl, Cipro

Common Side Effects

Antibiotics destroy both good and bad bacteria. Replacement of good bacteria is essential through Probiotics

Metronidazole and alcohol together can cause severe nausea, vomiting, cramps, flushing, and headache.

Uncommon Side Effects

  • permanent nerve damage (peripheral neuropathy) – numbness and tingling in the fingertips, toes, and other parts of the extremities.
  • nausea
  • headaches
  • loss of appetite
  • a metallic taste
  • a rash

Thank You Dr. Pamela Nathan DHM for this contribution

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