Ulcerative Colitis (UC) Overview

• Ulcerative Colitis (UC) is a disorder causing inflammation and ulcers in the digestive tract's inner lining, which is a type of inflammatory bowel disease (IBD) and an autoimmune process.
• The incidence of UC is rising worldwide.
• UC has a bimodal age distribution and it impacts 20–30 year olds and 50–80 year olds
• Men and women are affected equally by UC.
• The annual direct and indirect costs related to UC in the US are estimated to be $8.1 billion–$14.9 billion.

Types of UC

• Ulcerative proctitis is confined to the rectum, causing rectal bleeding and/or pain.
• Left-sided colitis extends from the rectum to the left side of the colon, resulting in bloody diarrhea, abdominal cramping and pain, and weight loss.
• Pan colitis affects the entire colon, causing bloody diarrhea, abdominal cramping, weight loss, fatigue, and night sweats.
• Fulminant colitis is a rare, severe form affecting the entire colon, causing severe pain, diarrhea, and sometimes dehydration.
• UC can affect areas of the body outside the GI tract, including the skin, eyes, hepatobiliary system, and musculoskeletal system.

Diagnosis of UC

• Classic symptoms of UC include bloody diarrhea (with or without mucus), rectal urgency, tenesmus, and abdominal pain often relieved by defecation.
• Diagnosis involves clinical presentation, endoscopic findings, histology, and ruling out alternative diagnoses.
• It is important to define the extent and severity of inflammation to determine the treatment course and predict prognosis, which is done through ileocolonoscopy with biopsy.
• A pathognomonic sign of UC is continuous colonic inflammation, characterized by erythema, loss of normal vascular pattern, granularity, erosions, friability, bleeding, and ulcerations, with distinct demarcation between inflamed and non-inflamed bowel.

Etiology of UC

• Multifactorial pathogenesis of ulcerative colitis includes genetic predisposition, epithelial barrier defects, environmental factors, dysregulated immune responses, and gut microbial dysbiosis.
• Viral or bacterial infections, poor diet, heredity, allergy, and antibiotic use affecting gut microbiota may contribute to UC
• Treatments to reduce inflammation are administered until the underlying cause is discovered.

Prevention Against UC

• Appendectomy performed for an inflammatory condition is associated with a low risk of subsequent ulcerative colitis.
• Appendectomy is only beneficial before the age of 20.

Treatment of UC

• UC treatment, whether conventional or personalized, modulates immunoinflammatory pathways.
• Modulation involves mechanisms such as PPARγ, Nrf2, NF-kB, macrophages, and Th17/Treg balance regulation.
• Conventional therapies focus on improving quality of life, achieving steroid-free remission, and minimizing cancer risk.
• Treatment choice depends on disease extent, severity, and course. Once remission is achieved, patients continue on medications to maintain it.

Conventional Therapies

• Mesalamines are a first-line therapy for inducing remission in mild-moderate ulcerative colitis and are taken orally, as a suppository, or through an enema.
• If Mesalamines are ineffective, steroids might be tried
• Moderate-severe UC agents include Anti-TNF Agents, anti-integrin agents, anti-interleukin agents, and Janus kinase inhibitors.
• Approved medical therapies for acute severe ulcerative colitis include steroids, infliximab, and cyclosporine
• Colectomy should be considered for patients with acute severe UC who do not respond to Infliximab or cyclosporine
• Emergency surgery is indicated for refractory toxic megacolon, colonic perforation, or severe colorectal bleeding.

Acute Severe Ulcerative Colitis

• Colectomy rates decrease in hospitalized patients with severe ulcerative colitis when treated with infliximab.
• Clinical response is typically seen within two to three days and colectomy rates have been shown to be less in patients treated with cyclosporine.
• Cyclosporine directly inhibits calcineurin (a component of cytokine gene transcription) and downregulates IL-2, IL-3, IL-4, and TNF-alpha.

Possible Side Effects of Conventional Therapies

• Increased risk of infection
• Liver dysfunction
• Bone loss
• Allergic reactions
• Infusion reactions
• Decreased effectiveness of antibodies
• Cost
• Accessibility
• Psychological impact

Personalized Medicine Therapies

• Dietary and nutritional therapies are important for ulcerative colitis patients.
• Hormonal therapies are valuable for ulcerative colitis patients
• Ulcerative colitis is an autoimmune disease so patients may benefit from avoiding gluten, fixing the gut, and starting low-dose naltrexone (LDN).

Dietary Therapies

• Dietary factors such as the spread of the "Western" diet, high in fat and protein, but low in fruits and vegetables, are associated with the rise of inflammatory bowel disease.
• High dietary intakes of total fats, PUFAs, omega-6 fatty acids, and meat increase the risk of Crohn's disease and ulcerative colitis.
• High fiber and fruit intakes decrease Crohn's disease risk, whereas high vegetable intake decreases ulcerative colitis risk.
• It's a good idea to keep a diary of food intake to identify foods that exacerbate symptoms

Foods and Liquids that Can Cause Symptoms

• Spicy foods
• Nuts
• Seeds
• High fiber foods
• Alcohol
• Carbonated beverages
• Artificial Sweeteners

Food Allergies

• Those with ulcerative colitis often exhibit high histamine levels in colon and rectum tissues, so high-histamine foods/drinks and foods/liquids that trigger histamine release should be avoided
• Some patients also have elevated IgE containing cells in the rectal mucosa
• Elevated circulating eosinophil counts can occur during ulcerative colitis exacerbations

High Histamine Foods and Drinks

• Aged cheese
• Shellfish
• Alcohol and other fermented beverages
• Avocados
• Eggplant
• Spinach
• Processed or smoked meats
• Fermented foods and dairy products such as sauerkraut and yogurt
• Dried fruit

Foods and Drinks That Trigger A Histamine Release

• Chocolate
• Alcohol
• Bananas
• Tomatoes
• Wheat germ
• Papaya
• Beans
• Citrus fruits
• Nuts such as cashews, peanuts, and walnuts
• Food dyes and other additives
• One study showed that food allergy was found to be the causative factor in 45% of UC cases - 70% of participants had food allergy as a factor in their disease process.
• Good results were seen in 47% of the patients when allergies were controlled without other therapy.
• Those with ulcerative colitis may do better if gluten-free: instruct patients to go gluten free
• The prevalence of Lactose intolerance can range from 8-59% in UC patients so patients to avoid dairy
• Gut microbiota composition can be critical in inflammatory bowel disease, with recent evidence suggesting a connection between diet and intestinal bacteria

Diet and Intestinal Bacteria

• The composition of the gut microbiota is thought to be a critical environmental factor in the inflammatory bowel disease and there is recent evidence of a connection between diet and intestinal bacteria
• There is evidence that further investigation of the link between diet and the gut microbiome may play a role in the development of inflammatory bowel disease
• Diet and aerobic exercise may play a synergistic role in the prevention, pathogenesis and management of ulcerative colitis

Nutritional and Botanical Therapies

• About 40% of UC patients get relief through natural constituents, which help reduce toxic side effects and maintain clinical remission, such as plant extracts, essential oils, nutraceuticals, and phytochemicals

Botanical Therapies

• Germinated barley foodstuff produces improvement in patients and increases butyrate production.
• Wheatgrass juice contains apigenin with anti-inflammatory/antioxidant effects and may improve ulcerative colitis symptoms.
• Aloe vera may inhibit prostaglandin E2 and IL-8, and improve histological scores.
• Bromelain may serve as an adjunctive therapy for mild ulcerative colitis
• Hericium erinaceus (Lion's Mane) can alleviate symptoms with anti-inflammatory effects.
• Spirulina (Arthrospira Plantensis) supplementation improved quality of life by improving sleep disturbances and stress and
• Moringa oleifera can mitigate inflammatory properties and modulate gut microbiota homeostasis.
• Punica granatum (pomegranate) exhibits anti-colitic properties and may help in alleviating symptoms through inhibiting the NF-kB signaling pathway
• Garlic extract can reduce inflammatory mediators, enzymes, and gene expressions induces by LPS.
• Dandelion root has antioxidant and anti-inflammatory actions and can modulate the gut microbiome, rectify metabolic imbalances, and rejuvenate short-chain fatty acid levels.
• Boswellia serrata was used to treat ulcerative colitis by individuals in Germany

Psyllium, Curcumin and Slippery Elm

• Patients with UC had a reduction in symptoms with psyllium
• All people with chronic ulcerative proctitis may experience an improvement in their disease after supplementing with curcumin.
• Curcumin inhibits the activation of NF-kappa B and and should be taken as 550 mg BID or TID
• Slippery elm has been studied for use as a supplement for irritable bowel disease and has been shown to be effective
• Consuming Licorice may also be helpful
• Green tea contains polyphenols that may help prevent activity and transcription of inflammation

Nutritional Therapies

• Omega-3-fatty acids are helpful because of their anti-inflammatory effect. The dose is 3–15 grams qd
• Check folic acid and B12 levels and supplement when needed
• Check zinc levels and replace accordingly -10-15 mg of zinc per 1 mg of copper is important to maintain in the body
• Diarrhea in UC can cause a loss of electrolytes - the patient may require a Magnesium supplement
• Patients need to be supplemented with Vitamin A or b6 as they tend to be low
• For patients who need Vitamin D supplementation, they must use D3 and not D2 as it has a better effect
• Patients who have gone through surgery should use Phosphatidylcholine to help combat ulcerative colitis
• Butyrate can help patients

Sulfur Containing Compounds

• Sulfur containing compounds have are anti-inflammatory and can help ulcerative colitis.
• N-Acetyl Cysteine
• Sulforaphane Diallyl Trisulfide- can promote mucosal healing within the gut

Polyphenols and Oil Therapies

• Polyphenols or flavonoids possess antioxidant and anti-inflammatory properties and effective against ulcerative colitis.
• Moringa ameliorates the pathological symptoms
• Olive, walnut and flax seed oil alleviates intestinal inflammation and restores intestinal barrier function in Mice

Hormonal Therapies

• Some people may serum DHEA levels. So it is important to measure the DHEA levels in serum and take action from there
• Melatonin may help patients get significant improvement within the gut

Other Therapies

• Cannabinoids show positive effect for patients

Fix The GI Tract Section

• A personalized stool test needs to be completed to treat infections and bacteria as needed
• Prebiotics and Probiotics needs to continue throughout the GI tract, this will bring benefits to the patient
• fecal microbiota transplantation can reduce bowel permeability and increase the production of short-chain fatty acids

LDN - Low Dose Naltrexone

• This has been shown to help patients who have ulcerative colitis.
• LDN is known for been almost as potent Remicade, as it treats ulcerative disease
• LDN has been shown to be effective for patients with ulcerative colitis
• The GI Tract has large number opioid receptors, and the antagonism there could have therapeutic effects in the inflamed mucosa

Case History Notes

• A nutritional test was ordered which revealed that she was still low in B5 and B12.
• Her MVI was continued as was her EPA/DHA. She was started on a B complex twice a day.
• The doctor mentioned that low B vitamins may be due to stress and also due to her OCP.
• A repeat saliva test was ordered to confirm that her cortisol level was improving and that she did not need higher doses of DHEA.