Nutrition News and Views July/August 2013 Vol.17, No.4 For health professionals

URINARY TRACT TISSUES AND ISSUES, Part 1 By Judith A. DeCava, CNC, LNC

Cystitis (also called Urinary Tract Infection or UTI) is an inflammation of the urinary bladder. The lower urinary tract consists of the urethra (the tube that carries urine from the bladder) and the bladder. The upper urinary tract includes the kidneys and ureters (tubes that carry urine from the kidneys to the bladder). Where inflammation occurs determines whether the condition is called cystitis, pyelonephritis or urethritis.

Not everyone with cystitis develops symptoms. But the most common symptoms include a burning sensation or discomfort during urination, more frequent urination, the urge to urinate even when the bladder is not full, urinary incontinence (leakage), pain or pressure in the pelvic area, dark-colored or cloudy or malodorous urine. If not resolved, cystitis can lead to more serious symptoms including blood in the urine, fever, nausea, vomiting, backache in the kidney area, pain in the pubic area, occasional discharge of pus in the urine or from the urethra—signs of pyelonephritis (kidney inflammation) or urethritis (inflammation of the urethra). In most cases Escherichia coli (E.coli) bacteria are involved, although other types of bacteria or yeasts (like Candida) have been found. These bacteria or yeasts do not belong in the urinary tract and are ‘foreign’ to it. The E.coli or other bacteria come from feces; Candida comes from the vagina. They can adversely affect an irritated or compromised urinary tract, particularly if the bacteria are ‘sick’ (having engulfed wastes or toxins). The bacteria from feces make their way through the urethra into the bladder, or rarely, to the kidneys. In men, the ‘sick’ bacteria may stress the prostate. Although the tendency is to blame some microorganism, inflammation of the bladder can occur without ‘infection’ from bacteria foreign to the urinary tract. And, even if there are foreign bacteria or yeasts involved, it does not mean that they cause the problem. A healthy urinary tract flushes out any toxic or foreign substances through the urine. The underlying cause would more likely be an unhealthy urinary tract lining which is more susceptible to insult or irritation from foreign bacteria or yeasts. 1, 2

Cystitis is much more common in women (1 in 5 women will have cystitis during her lifetime). One reason is the female urethra (the tube that carries urine from the bladder) is shorter than a male’s. Also, the urethral opening is near the perineum (region between the vulva and anus) which tends to harbor fecal matter including ‘sick’ bacteria that may contribute to cystitis. In men, the urethra is much longer, making it harder for bacteria to migrate; there is a greater distance between the opening of the urethra and the anus; and prostatic fluid has antibacterial properties. When foreign bacteria, toxins or other substances that don’t belong in the urinary system are not flushed out quickly enough, irritation or injury to the lining of the bladder and urethra can occur. Sexual intercourse (including ‘honeymoon cystitis’), delayed urination after intercourse, use of diaphragms with a spermicide, spermicides alone, oral contraceptives, obesity, incontinence (urinary or fecal), and a history of recent cystitis all increase risk. Intercourse that is rough or frequent can cause irritation or push bacteria up into the bladder. Spermicides induce colonization of E. coli and alter vaginal flora. Exposure to irritants such as perfumed soaps or scented douches can also contribute to the tendency for cystitis. Men experience a higher prevalence of cystitis starting in their mid-50s and 60s when an enlarged prostate and obstruction of the urinary tract are more probable. In older women, reduced estrogen can cause marked changes in the bacteria living in the vagina and the area around the urethral opening as well as weaken the vaginal lining. Estrogens also help maintain the muscle and ligament structures in the pelvic area. Postmenopausal women tend to have lower levels of lactobacillus in particular. This type of healthy bacteria help lower the pH of the vagina, making it less hospitable to ‘sick’ bacteria and thus help prevent their spread to the urinary tract. 3

Generally, there is some tissue weakness or a lack of resistance to stress. Occasionally, kidney or bladder stones, catherization, and anatomical or functional abnormalities can increase risk in both men and women. But usually the lining of the bladder and/or urethra is somehow compromised and not as healthy as it should be. A bladder that has been irritated, has lax tissues, or is affected by reactions to toxins or drugs or food intolerances is more susceptible. Urine that stagnates in the bladder because the tissues have become so weak that the back of the bladder hangs lower than the opening means that the bladder never completely empties and urine sits there. This too can irritate the bladder and lead to inflammation.

Symptoms, a urine dipstick, urine analysis and/or urine culture are usually used for diagnosis. Using a dipstick, however, is not always accurate. The US Preventive Services Task Force does not advise urine testing for people without symptoms. Why? The antibiotic regimen prescribed by many doctors is riskier than no treatment for people with symptomless UTIs. Adverse effects from antibiotics and development of bacterial resistance (from overuse) are reasons given. Medical treatment is almost always a prescription for antibiotics. Yet studies have shown that this does not decrease risk of recurrent UTIs and does increase risk of antibiotic resistance. Antibiotics become less effective with each episode of cystitis and stronger antibiotics are prescribed until they too are no longer effective. Plus the underlying cause is not approached. 4

Most people have heard how cranberry juice can help prevent the recurrence of cystitis. Yet study results have been mixed, evidently depending on the content, quality, additives, and processing methods of the juice. 5, 6, 7 Unsweetened juice—not the types with refined sugars—appears to be best. (Raw honey or pure maple syrup can be added to offset the tartness, if needed.) 8 Cranberries may interfere with the attachment of foreign bacteria to the lining of the urinary tract. 9 One component in cranberries that may do this is d-mannose. Isolated d-mannose has been used to prevent recurring cystitis. But cranberries contain many other ingredients including organic acids, natural fructose, vitamin C complex with flavonoids, anthocyanidins, proanthocyanidins (PACs), catechins, triterpenois, and more. There are indications that many of these can prevent foreign bacteria from sticking to the urinary tract wall. 10 Even though it’s thought that inhibition of adherence of bacteria is the main action of cranberries, the exact mechanism has not been established. A 2012 Cochrane review found a “small trend” towards fewer UTIs in people taking cranberry products compared to placebo or no treatment.” They concluded that “until there are more studies of products containing enough of the active ingredient [emphasis added], measured in a standardized way, cranberry products cannot be recommended for preventing UTIs.” This is the drug mentality, insisting on one measured active ingredient. Different dosages and product types were used in the studies, so a standardized dosage—as a pharmacological agent—was not employed. Another reason for their conclusion is the need for improvements in the design of studies. 11 Some scientists have questioned the validity of the Cochrane group jumping to conclusions. 12 Amy Howell, PhD, who has been researching cranberries for two decades, doesn’t agree with the Cochrane group’s basic dismissal of cranberries and their juice for prevention of cystitis. Her lab “has consistently found that cranberries effectively help prevent bacterial adhesion to bladder cells…They are washed out of the body in the urine stream.” 11 A 2012 review published in The Archives of Medicine, which included 13 clinical trials with 1,616 participants, found that unsweetened cranberry juice was more effective than capsules or tablets—the point is that cranberry juice was effective. It’s possible that some components in the juice are removed when making capsules or tablets, yet there are types that preserve the whole cranberry and are effective. 13 Many experts agree that more and better research is needed. 5, 6 Cranberry juice may prevent cystitis, but so far evidence is lacking to show it can be used to treat cystitis. Cranberries, blueberries, and other foods that may help prevent cystitis recurrence are rich in flavonoids (including anthocyanins and proanthocyanidins) plus contain mannose and a host of other components that may help. 14, 15

D-mannose is a naturally occurring simple sugar contained in cranberries, blueberries, other berries, and other foods. D-mannose adheres to the bladder epithelium and, in essence, interferes with the ability of E.coli or other bacteria that are not normal inhabitants of the urinary tract to adhere there. Then the bacteria or other foreign substances can be flushed out of the bladder with the urine. To date, research on the effects of isolated D-mannose is very limited. Little is known about the safety of long-term use of D-mannose supplements. There are some potential side effects such as bloating. When taken in excess doses, it may stress or damage the kidneys. Foods containing d-mannose (along with all their co-workers) may be the best choice. 16, 17

Lactobacilli bacteria are a normal component of the urinary and genital flora of healthy women. Various strains of Lactobacillus have been found to be helpful in preventing and treating cystitis and other genitourinary problems. In a double-blind trial, L. rhamnosus GR-1 and L. reuteri RC-14 were found to be not quite but nearly as effective as antibiotics for preventing UTI recurrence. 18 Another study involved having women with recurrent cystitis and current cystitis use suppositories containing either a type of Lactobacillus (crispatus) or a placebo. There was a 50% reduction in recurrent cystitis. 19 Lactobacillus acidophilus used in a clinical trial was shown to hinder attachment of ‘sick’ or foreign bacteria to the lining of the urinary tract. Also, the carbon

2 dioxide-producing lactobacilli most commonly found in the normal bladder flora (L. crispatus and L. jensenii) can help keep the bladder in its preferred acidic state. Probiotics can help prevent cystitis but may not relieve the situation when inflammation is already present. 20,21 A review of studies stated that the evidence suggests that probiotics are safe and “may indeed be effective at preventing UTIs in women.” 22,23 Consuming fermented foods such as yogurt, kefir, and others lower the likelihood of recurring UTIs up to 80%. 24

There is some evidence that the risk for cystitis may be altered by dietary influences, modifications, and digestive health. Refined sugars, refined flours, altered oils or fats and other over-processed, chemicalized nonfoods can be irritating to the urinary tract. Frequent consumption of fresh (not canned or bottled) juices, especially berry juices, and fermented milk products containing live probiotics (Lactobacilli) was associated with a decreased risk of recurring UTIs. Consuming fermented milk products three or more times per week was more effective than less than once per week. Increasing garlic and onions in the diet—both of which produce antimicrobial activity against ‘sick’ microorganisms—may also be helpful. These two foods have been shown to inhibit the growth of ‘sick’ E.coli and other ‘sick’ bacteria types. 25, 26, 27

Although focus has been on the connection between bacteria and UTIs, it seems that virtually every woman would, at some time, get some E.coli or other ‘sick’ bacteria in her urinary tract. But not all women get cystitis or recurring cystitis. Thus, the health of the urinary tissues themselves must have a lot to do with this issue. Support to these tissues and to the inflammation and repair process would be imperative for those who have a cystitis tendency. Vitamin C complex has numerous beneficial effects and functions including support to the immune system, proper absorption and utilization of other nutrients, production of many hormones and nerve- conduction substances. It is involved in the production of collagen, the main protein substance in the body, which is involved in wound repair, connective-tissue structures, and more. Vitamin A complex, carotenes, vitamin E complex, and zinc are also supportive to the health of the tissues involved as well as to the immune system. A number of herbs have a history of use for preventing recurrent cystitis and/or in treating it. Uvi-ursi, pipsissewa, Oregon grape root, and goldenseal have been shown to be effective. Mucilage herbs are soothing to the irritated bladder lining, allowing inflammation processes to heal. These include corn silk, marshmallow root, and plantain leaf. Echinacea supports the immune system and inflammation/repair processes. Some herbs act to increase blood flow to the kidneys and thus raise the glomerular filtration rate; dandelion leaf or root, parsley, buchu seed, cough grass root, juniper leaf, lovage root, and birch bark are among these. 14, 27-30

Preventive measures include:  Drinking plenty of filtered or purified water and other healthful fluids to increase urinary output and flush out any substances that do not belong in the urinary tract.  Consume unsweetened cranberry juice (or eat fresh or frozen cranberries). These are very tart.  Consume foods that contain d-mannose or their freshly-made juices—cranberries, blueberries, black or red currants, gooseberries, peaches, apples, green beans, capsicums, cabbage, eggplant, turnips, home-grown ripe tomatoes. The body can produce some mannose. Aloe vera is also a source. Fresh orange juice and pineapple juice may inhibit adherence of bacteria in the urinary tract.  Take a good probiotic supplement that contains Lactobacilli bacteria.  Include plenty of fiber (whole grains, vegetables, fruit, legumes) in your diet as well as fermented dairy products, nuts, seeds, and unrefined oils and other unaltered natural fats.  Avoid consuming common bladder irritants like alcohol, refined sugars, chocolate, artificial sweeteners, carbonated beverages, caffeine, black tea, decaffeinated coffee, vinegar, tomatoes, very spicy foods.  After a bowel movement, women should wipe from front to back (to avoid getting ‘sick’ bacteria or other unwanted substances near or in the urethra.  Women should urinate after sexual activity.  Don’t resist the urge to urinate. Holding it may increase risk particularly if the muscles are weak.  Women should avoid the use of diaphragms and spermicides for contraception; switch to another form of birth control if possible. When menstruating, change sanitary napkins or tampons frequently.  Avoid tight-fitting underwear and clothing. Wear cotton undergarments; synthetics (like nylon) trap heat and moisture. Thongs are so close to the anus it is easy for fecal bacteria/matter to get into the urethra.  Food sensitivities/intolerances can lead to cystitis-type symptoms. An elimination diet may determine if this is the case. 25-28, 31-34 3

The following supplements may be considered for a person with recurring cystitis: Just Before Two Meals: After Two Meals: 1 Renatrophin PMG—chew 1 Cod Liver Oil 2 Echinacea-C—chew 1 Collinsonia Root 1 Chlorophyll Complex 1 Cranberry Complex If there is a history of taking antibiotics, add 1 Pro-Synbiotic after two meals.

If symptoms of cystitis begin, the following may be taken every three waking hours until resolved: 1 Renatrophin PMG 1 Desiccated Spleen 1 Echinacea-C 1 Chlorophyll Complex 1 Thymus PMG

Interstitial Cystitis (IC) is a syndrome in which the lining of the bladder is constantly irritated, causing urgency to urinate (sometimes immediately after urinating), pain or discomfort that worsens as the bladder fills or is improved after emptying the bladder, pain when urinating, pelvic pain or pressure, and urinary frequency (8 to 50 times per day and 8 to 10 times per night). It occurs in both men and women, but it’s 5 times more common in women. 35,36 It often takes 5 to 7 years of suffering with symptoms before a proper diagnosis is made. IC is thought to be a chronic inflammation of the bladder, possibly due to a disorder in the inside wall of the bladder. Pain can range from mild burning or discomfort to severe debilitating pain in the bladder, lower abdomen, perineum, pelvis, vagina, low back, and thighs. 37 Menstruation and sexual intercourse aggravate symptoms in as many as 75% of women with IC. There are often flare-ups and remissions. Onset typically occurs in youth or middle age. The innermost portion of the bladder wall (glycosaminoglycan [GAG] layer or mucus membrane) is damaged. Various causes have been speculated—from being autoimmune or genetic to being an allergy or part of fibromyalgia—making it a complex condition to treat. 38 Although there are a number of theories, there is “imperfect evidence supporting each major theory.” Some theories seem to fit some people but not others. 39,40 Ulcerations of the bladder occur in 20% of patients but not in 80% of them. 41 In many sufferers mast cells infiltrate the bladder wall, but no one knows why. Mast cells are large tissue cells essential for inflammatory reactions mediated by IgE. High levels of histamine and methylhistamine are found in the urine of IC sufferers as compared to controls, suggesting that there is a reaction to something resulting in inflammation. This could be due to an allergic or sensitivity reaction or a reaction to toxins. 42 Other inflammatory mediators, such as interleukin-6, have also been found in the urine. 43 The majority of people with IC have sterile urine, so any role for microbes remains “uncertain.” 41 Some suggest renaming the syndrome “irritable bladder syndrome” as it’s similar in some respects to “irritable bowel syndrome.” 44 It has also been suggested that IC is a combination of issues involving the immune system, sensitivities or intolerances, psychological aspects, and others. Whatever the cause, the irritation is in the bladder wall. IC is common in people who have irritable bowel syndrome, spastic colon, abdominal cramping, hysterectomy, rheumatoid arthritis, fibromyalgia, hypothyroidism, chronic fatigue, vulvodynia, premenstrual syndrome, endometriosis, Sjogren’s syndrome, hay fever, asthma, and intolerances to foods and medications. 45,46

Some research indicates that there may be an acidic, heat-stable protein that is found only in people with IC. It may prevent the bladder’s epithelial lining from repairing itself, resulting in epithelial thinning and wounding. Up to 95% of more than 200 patients with IC had this protein activity in their urine compared with fewer than 10% of the control subjects. Urine from IC patients also contains lower levels of one type of growth factor and higher levels of other growth factors compared with urine from people who do not have IC. 41 Other research indicates that substances such as urea and potassium penetrate into deeper layers of the bladder wall in people with IC. 40 The bladder lining or wall may be so damaged or disrupted that caustic or toxic substances in the urine, normally prevented from entering deeper layers of the bladder wall, are able to penetrate into the connective tissue and muscle. There they may trigger nerve endings and mast cells, resulting in pain, inflammation and bladder spasms. 45 Also, there may be a difference in the composition, quality, or rate of turnover of the mucus. A study found less type-IV collagen in the basement membrane of the bladder epithelium. 46 A clinical trial directly applied a naturally occurring GAG (like that in the bladder wall) which resulted in reduced inflammation and symptoms. 47 There is a significant amount of evidence that the bladder lining has abnormal cells, causing the bladder surface to be “leaky” owing to the loss of the normal barrier function. This has prompted a likening

4 of IC to ‘leaky gut’ (increased intestinal permeability). 38 Since the bladder surface is more permeable than it should be, nerves in the wall can also become inflamed and more sensitive to metabolites of foods, beverages, some supplements, and toxins in the urine. Some people can have IC as a result of one mechanism more than another, or as a result of multiple mechanisms.

There is no reliable test to detect it. A thorough health history and physical examination may provide needed clues. Urinalysis may be performed to rule out cystitis (UTI) because it can have similar symptoms. There is no single ‘magic bullet’ for treatment either. Medical treatment often includes pain relievers, antidepressants, antihistamines, immunosuppressives, glycosaminoglycan layer substitutes, transcutaneous electrical nerve stimulation, surgical procedures to block off bladder nerve supply or to enlarge the bladder or to bypass the bladder and urethra and create a continent pouch. Antibiotics do not relieve symptoms. Therapeutic options, both conventional and alternative, are as varied as are theories for the cause of IC. The most commonly used and helpful treatment by both conventional and alternative practitioners is dietary changes. Patients often report that certain foods increase their symptoms. Responses to various foods are hugely variable and there is no consistent diet that works for all IC patients. An elimination diet would be best followed by reintroduction of one food at a time. Items that increase symptoms may be intolerances or simply irritants.

Alternative or complementary therapies can include:  Quitting smoking (which is important for anyone with bladder problems). 35  Relaxation techniques and stress management to help improve symptoms. Stress doesn’t necessarily cause IC but can make its symptoms worse. Anxiety can be a component of the problem. 35  Acupuncture helps 40-60% of people with chronic pelvic pain. 48,49  Myofascial release, a type of physical therapy focused on trigger points that develop in muscles due to chronic pain or overuse, is used to treat pelvic floor dysfunction, which can exist concurrently with IC. 49  Identifying possible underlying health issues such as a heavy toxic load, nutritional deficiencies, a sluggish immune system, endocrine imbalances (such as hypothyroidism, estrogen dominance, etc.). A detoxification program may be needed as a first step. 39,46  Drinking plenty of clean water and herbal teas such as corn silk, parsley leaves, and/or dandelion leaves to help keep the bladder flushed out and to lower the acidity of the urine. 49  Using herbs that support or modulate inflammation such as goldenrod (which may also aid spasm), goldenseal, turmeric, feverfew, astragalus, ashwaganda, and schisandra. Horsetail is mildly diuretic and primarily strengthening. Urinary tonics include mullein root, pipsissewa, and shepherd’s purse. Sedative and antispasmodic herbs may reduce pain while other therapies work on repairing the bladder lining; these include wild yam, black cohosh, valerian, kava, skullcap and lobelia. Urinary demulcents soothe the bladder wall and include licorice root, corn silk, marshmallow root, slippery elm, oat seed, plantain leaf, and mullein leaf. Saw palmetto berry relaxes smooth muscle in the bladder neck and helps reduce tissue enlargement. Chamomile appears to soothe cystitis and is relaxing. Chinese herbal formulas are being used to treat IC; most commonly used are gardenia, licorice, dianthus, poria, rhubarb, rehmannia, cornus, water plantain, ginseng, and plantain. 48,50,51  Food-concentrate supplements can be very helpful, first to coat and soothe the urinary tract lining (slippery elm, marshmallow root, oats, etc.) and then support repair. Sources of vitamin C complex (which includes bioflavonoids and quercitin), vitamins A and E complexes, carotenes, essential fatty acids, alkaline-producing minerals such as potassium, and amino acids important to urinary tissues can be supportive. Methyl donors include onion and garlic; these and other foods also serve as stabilizers for mast cells. Studies have found that people with IC have decreased nitric oxide (NO) synthase activity in their urine, so increasing synthesis of NO will nutritional aids may yield improvements. Beets (in fresh juice, grated on salads, or in supplement form) help increase the production of nitric oxide (NO) and its precursor nitric oxide synthase (NOS). NO promotes relaxation of urinary tract smooth muscle and may play a role in the immunological responses associated with IC. 48,51,52  Diet has a big impact. Food sensitivities or intolerances can make IC worse. Specific intolerances will vary; not all foods and beverages have the same effects on individuals. Many people with IC notice a dramatic and immediate reduction in symptoms with dietary modifications alone. There is concern that people may try to eliminate more foods than necessary and reduce nutrient intake. So, after eliminating all the foods suggested below and experiencing improvement in symptoms for three weeks or so, one 5

item at a time can be tried to ascertain if there is a problem with it. If not, it can be added back into the diet. Both diet and supplements need some experimentation and patience since some remedies work well for most people and some only work for a few people. With more healing and repair, eventually more foods may be tolerated. Avoidance of foods to which there is an intolerance and the use of supplements to support the urinary lining should be undertaken for at least 6 months, possibly longer. Here are the foods and beverages to avoid based on the most common responses:  Milk/dairy products: aged cheeses, sour cream, yogurt (cottage, ricotta & cream cheese may be okay).  Vegetables: Fava beans, lima beans, lentils, onions, garlic, tomatoes, soybeans and their products (including tofu). Chives, green onions and home-grown ripe tomatoes may be tolerated.  Fruits: Apples, apricots, avocados, bananas, cantaloupes, citrus, cranberries, grapes, guava, nectarines, peaches, pineapples, plums, pomegranates, prunes, raisins, rhubarb, strawberries, juices made from these fruits. Melons other than cantaloupes seem fine as do other berries, pears, mango.  Grains and starches: Rye and sourdough breads.  Meats and fish: Aged, canned, cured, processed or smoked meats and fish; pickled herring, anchovies, caviar, chicken livers, corned beef, meats that contain nitrates or nitrites.  Nuts: Most nuts except almonds, cashews, peanuts, and pine nuts.  Beverages: Alcoholic beverages (including beer and wine), carbonated drinks like soda, coffee, regular tea, fruit juices (especially citrus or cranberry). Some herbal teas may be good.  Seasonings: Mayonnaise, ketchup, mustard, salsa, spicy foods, chilies, soy sauce, miso, other soy- based condiments, salad dressings, vinegar (including balsamic and flavored vinegars). Homemade mayonnaise that does not include lemon juice, vinegar or prepared mustard can be tried.  Preservatives and additives: Benzol alcohol, citric acid, monosodium glutamate (MSG), artificial sweeteners (like aspartame and saccharine), chemical preservatives, artificial colors and flavors.  Miscellaneous: Tobacco, caffeine, chocolate, recreational drugs, cold and allergy drugs containing ephedrine or pseudoephedrine, diet pills, isolated or synthetic vitamins (especially ascorbic acid), over- processed and refined ‘junk’ foods (including refined sugars, refined flours, altered fats). 40,45,50,53

The following supplements can be considered for a person with interstitial cystitis: Just Before Two Meals: After Two Meals: With spasms, can add, 1 Renatrophin PMG—chew 1 Collinsonia Root 3 or 4 times per day, 1 Myotrophin PMG—chew (for 6 months only) 1 Pro-Synbiotic 1 Valerian Complex OR 1 Echinacea-C—chew 1 Cod Liver Oil 1 Wild Yam Complex 1 Organically-Bound Minerals—chew 1 Wheat Germ Oil 1 Betafood—chew

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