Interstitial Cystitis Natural Treatment Program

Interstitial cystitis (IC) is a health condition that involves a variety of factors (i.e, it is multifactorial) it may be caused either by multiple genetic or environmental factors, or by a combination of them. It is a significant problem for women, as about 90% of IC patients are female.¹ The onset normally occurs in middle age.

Symptoms of IC are pelvic and/or perineal pain urinary urgency an increase in pain caused by holding urine nocturia (excessive urination at night) and a continual urge to urinate. The pain can range from a mild discomfort or burning to severe pain in the bladder, lower abdomen, perineum, pelvis, vagina, low back and thighs. Sexual intercourse and menstruation may contribute to these symptoms in up to 75% of women. There can be a spontaneous remission in the condition, followed by flare-ups.

IC is common in patients with irritable bowel syndrome, spastic colon, abdominal cramping, hysterectomy, rheumatoid arthritis, fibromyalgia, hay fever, asthma, and allergies to foods and medications. Because IC is a multifactorial syndrome, a broad approach that addresses the many suspected causes brings the greatest chance for success.

IC may be considered an autoimmune disease, and is usually accompanied by inflammation and infection. One of the theories about IC is that the bladders in IC patients have abnormally permeable epithelial tissues, and there are low levels of glycosaminoglycans (GAG) in their bladders and urine, in which case supplements that increase the levels of glycoproteins in the bladder may be helpful. N-Acetyl Glucosamine (NAG) has been found to be an important supplement in the successful treatment of IC however, the addition of MSM or SAM-e may also be helpful, as the methyl donation of sulfur has both an anti-inflammatory and pain relieving effect on the bladder mucosa.

Botanical agents that are methyl group donors include beets, onion and garlic. However, since onion has been found to be implicated as a causative agent, I recommend including regular consumption of beets and fresh garlic. Beets, which are also high in nitrates and boost nitric oxide levels (see below) can be added to salads or juiced (with a vegetable juicer). Combining beets with other greens, carrot juice, and celery makes a wonderful highly-alkalizing drink that is ideal in the morning before breakfast. Blend garlic with healthful oils (with other spices, including Mrs. Dash) for delicious salad dressings, but leave out the lemon juice or vinegar.

While many of the reports are anecdotal, the use of aloe vera as a concentrated extract in capsule form has been effective at reducing the IC pain and symptoms for a high percentage of users, so I am also including this inexpensive supplement in this program. Freeze-dried or concentrated aloe is preferred over aloe vera juices because most of those juices contain citric acid or lemon juice as a preservative, and both should be avoided by IC sufferers. In Canada, NOW Foods has an excellent low cost aloe vera concentrate in soft gel capsule form.

Since it has also been noted that IC patients have low nitric oxide (NO) levels, L-Arginine has been recommended to increase NO synthesis. In one study, supplemental L-Arginine improved symptoms in 10 of 10 patients.³ Other studies have found equally impressive results from L-Arginine supplementation.⁴ Based on more recent research on the nitric oxide boosting benefits of L-Citrulline, I now recommend choosing L-Citrulline, and not L-Arginine, as research has found that, for many, L-Arginine's conversion into NO was relatively poor compared to that of L-Citrulline.

It is also highly recommended to increase the body's alkalinity by increasing one's intake of alkaline foods (i.e., vegetables) and decreasing the consumption of sugars, starches, processed foods and yeast-containing foods, as high levels of acids seem to aggravate IC. And because many with IC have been prescribed antibiotics, it is also essential to use a broad spectrum probiotic to repopulate the intestinal tract with beneficial bacteria, which can also provide benefits to the bladder. A number of recommended probiotic supplements are listed below. Adding fermented foods is also highly recommended. Many health-seekers are fermenting their own vegetables (cabbage into sauerkraut, etc.), and one of the most important areas of research today is the link between the microbiome (the bacterial health, or microbiota of the gastrointestinal system) and every aspect of health, including mental health. Health starts in the gut, so this is a critical element to healing any issue, but especially IC.

To combat inflammation, higher levels of marine and borage-seed-sourced essential fatty acids are recommended, along with anti-inflammatory herbs that include curcumin and Boswellia (there will be more detail on those, below). Other botanicals that may be helpful due to their anti-inflammatory effects include licorice, feverfew and ginger. Similarly, botanicals with demulcent (i.e., soothing to the mucosa) properties include licorice, slippery elm, marshmallow, oat seed, comfrey and corn silk. As licorice is naturally high in glycyrrhizin, which can be contraindicated for those with hypertension, choose a licorice that is low in glycyrrhizin, such as the DGL (deglycyrrhizinated licorice) chewable tablets from Enzymatic Therapy. Aloe vera is recommended due to its soothing and healing properties that work synergistically with the other supplements recommended.

Dietary changes and identification of foods that aggravate IC symptoms are important parts of a successful long term treatment plan. Foods that are often implicated include coffee, chocolate, carbonated soft drinks, citrus fruits, tomatoes and alcoholic beverages. Acid and potassium levels in foods have also been implicated in the phases of IC, so monitor whether foods high in acids or potassium aggravate symptoms.

To strengthen the immune system, I recommend taking buffered vitamin C that includes threonic acid and alpha lipoic acid, which helps regenerate vitamin C, E, and glutathione in the body, resulting in sustained blood levels of these important nutrients. Vitamin E as Gamma E with mixed tocopherols and tocotrienols is recommended over alpha tocopherol. I also recommend regular consumption of Aviva Rice Bran Solubles, high in tocotrienols and plant sterols.

Some important supplements in this program are Astaxanthin N-Acetyl Cysteine (a precursor to one of the most powerful antioxidants, glutathione) and quercetin, which has anti-inflammatory benefits that are synergistic with marine-based omega-3 essential fatty acids (EPA and DHA) from fish, as well as the anti-inflammatory omega-6, GLA, from borage seed oil.

DIETARY CHANGES

Foods to Avoid:

Alcohol, apples, Aspartame, avocados, bananas, cantaloupe, carbonated drinks, cheese, chicken livers, chilies/spicy foods, chocolate, citrus fruits, coffee, corned beef, cranberries, grapefruit, grapes. Guava, lemons, lentils, lima beans, limes, mayonnaise, nuts [**], onions, oranges, peaches, pickled herring, pineapple, plums, prunes, raisins, rye bread, saccharine, sour cream, soy sauce, strawberries, tea, tomatoes, vinegar, yogurt.

** Almonds, peanuts (only valencia), walnuts, sesame seeds, sunflower seeds, pumpkin seeds, sprouted flax seeds, hemp seeds, pistachio nuts, pine nuts are recommended, but strive for organic, if possible.

 

Recommended Supplements: (bid=take twice each day tid=three times a day)

ConcenTrace Mineral Drops - provides 250 mg ionic magnesium	40 drops per day, gradually by adding 3-4 drops to everything you eat or drink each day.
Aloe Vera Capsules	1-2 capsules, tid
N-acetyl glucosamine (NAG)	500 mg, tid
L-Citrulline	500 mg, tid
Maritime Pine Bark Extract (Pycnogenol is a trademarked version)	1 - 50 mg capsule, tid
Bioflavonoids	1,000 mg, bid
Vitamin C (buffered w/Alpha Lipoic Acid)	1,000 mg – 3,000 mg, tid (to bowel tolerance). I recommend Protocol ProtoSorb C which includes Threonic Acid and Alpha Lipoic acid, which helps to regenerate Vitamin C, Vitamin E and glutathione in the body.
Corn Silk	2 capsules, tid (important component in program)
Kava Kava	1 capsule 500/550 mg capsule, tid
Marshmallow Root	1-2 capsules, tid, or drink 3-4 cups of tea per day
DGL (deglycyrrhizinated licorice)	1-2 tablets, chewed slowly before or after meals
Astaxanthin	4-6 mg, bid
Panachia	Nature's richest source of plant based omega-3 and fibre, and high in antioxidants - 4 tablespoons per day (stir two tablespoons in a glass of water for 2 minutes and drink, bid).
Quercetin (w/bromelain, rutin and bioflavonoids)	800 mg, bid or 600 mg, tid
NAC – N-Acetyl Cysteine	600 mg, tid (choose time-release if you can find it)
Super Green Food Powdered Drink	As directed, tid. Mix with two tablespoons of Rice Bran Solubles.
Probiotic Supplement	Dr. Ohhira's Probiotics 12 Plus capsules or Olie Naturals New Beginnings
Vitamin/Mineral Supplement	With each meal, tid (see recommendations below)
Omega-3 Essential Fatty Acids	3-5 grams per day EPA/DHA (see recommendations below)
GLA from Borage Oil, 240 mg per capsule, 720 mg per day in 3 capsules	1 capsule, tid
Curcumin (BCM95) with Boswellia	1 capsule, tid (Curamin with DLPA)
Genestra HMF Cystgen	1 Sachet, bid, for two days, for up to six days
O'Donnell Formulas Flora Balance	Powder or capsules, 1 tid (take an hour before or after the probiotic).
Celliant Fibre Mattress Topper	Celliant fibre is proven to increase oxygen levels in the body during sleep, and is synergistic with the supplements in this program.

These recommendations may seem complex however, the synergy of these nutritional supplements should improve general overall health and immunity for everyone. As IC may be only one of many health concerns, this program should result in a significant overall health improvement.

The natural healing process can take time, but the long-term benefits will be long lasting, as there should be no reappearance of IC symptoms once the body has healed. The alkalizing super-green-food drink, together with added Rice Bran Solubles, probiotic, ConcenTrace mineral drops, multi vitamin, essential fatty acids, curcumin, Boswellia and vitamin C, provide foundational nutrients for improved health, and are recommended even for those without immediate health concerns who simply would like to improve their health and wellness, increase their energy levels, and strengthen their immune system.

Along with dietary changes, the addition of NAG, L-Citrulline, bioflavonoids, corn silk, quercetin and NAC have been shown in studies to assist the body in healing.³ Earlier studies have used L-Arginine, but I have seen better results when using L-Citrulline, the precursor to L-Arginine in the body, in place of L-Arginine, and recent research has confirmed that many people cannot properly metabolize L-Arginine, especially if they are over 40. As noted, the reason L-Citrulline (along with synergistic supplements including pine bark extract) is recommended is that higher levels of nitric oxide result in greatly improved circulation, which speed the healing process.

Other products and foods that help boost NO (nitric oxide) levels include Neo 40 Daily tablets (two per day, dissolved in the mouth) by Neogenis Labs quercetin maritime pine bark extract (or Pycnogenol) and beets, beet juice and leafy greens, including collard greens and kale. Our bodies convert the high nitrate levels in these foods into nitrites and then into nitric oxide, which is a powerful vasodilator. Vasodilation (from NO) causes the smooth muscles within blood vessel walls to relax, widening and enlarging blood vessels, which improves blood flow.

The nitrate to nitrite conversion is dependent on good digestion: the NO conversion starts in the mouth and continues in the stomach. The use of antiseptic mouthwashes can inhibit this process, (since they kill the bacteria in the mouth which convert the food nitrates into nitrites), as can proton pump inhibitors (e.g., Nexium Prilosec, Zantac), the acid-blocking drugs often prescribed to treat acid reflux (which lower stomach acid and bacteria levels in the stomach and small intestine).

Much like L-Citrulline, quercetin, an important supplement in this program, adds additional synergistic benefits for the endothelial cells that help control blood pressure and flow. By boosting the body's production of nitric oxide, it can help to relax blood vessels and arteries (through vasodilation), and to promote an improvement in blood flow.^9-11

Maritime Pine Bark Extract works synergistically with L-Citrulline and quercetin to boost nitric oxide levels, which provides a significant overall boost in circulation, and speeds all healing processes in the body. A trademarked version of Pine Bark Extract, Pycnogenol^®, provides the same benefits. One published study found that the combination of L-Arginine with Pycnogenol was far superior in improving symptoms of erectile dysfunction (ED) than L-Arginine alone.¹² I believe one of the primary reasons this program is so successful is due to the vasodilation improvements caused by the combination of the recommended nutritional products. Substituting L-Citrulline should provide even better results.

The research supporting the many health benefits of quercetin are compelling and extend far beyond treating IC. Studies suggest that, in addition to the cardiovascular and circulatory benefits mentioned above, quercetin may help reduce the onset of dementia by slowing neuro-degeneration, and may have benefits in helping to control blood sugar, while also offering protection against cancer, arthritis and bone loss. New Roots Herbal has a fine quercetin product, Quercetin Bioflavonoid Complex, which combines quercetin with rutin, bromelain and bioflavonoids. Bioflavonoids help strengthen capillaries, with the potential to reduce bleeding and strengthen blood vessels while making them less prone to damage due to fragility.

If a bladder infection accompanies IC, I recommend the addition of D-Mannose or Pure-Le Natural Goodbye UTIs (a superior formula that includes a probiotic and a prebiotic). One teaspoon dissolved in a glass of water every four hours is recommended over a three day period.

If a yeast infection accompanies IC, I recommend Flora Balance by O'Donnell Formulas, combined with Metagenics' UltraFlora Women's Probiotic (taken internally) and New Roots Herbal's Femina Flora (a vaginal suppository). If you suspect you have candida, I recommend implementing the Aviva Candida Control Program. Metagenics' UltraFlora Women's has two bacteria strains proven to maintain healthy vaginal microflora. Femina Flora includes an applicator and 10 capsules with a variety of bacteria strains that are effective in helping to eliminate yeast infections one capsule is inserted deep in the vagina each night at bedtime. Flora Balance is available in either capsules or powder, and is a specific strain (BOD) that kills the candida yeast.

Below is additional supporting information on the eight main foundational components of the Aviva IC Program outlined above. Those following it normally see some improvements within three months, and some have seen a 75% improvement within six months. After six months, a reduction in the levels of the specific nutrients can be made, but many are so pleased with the results that they are hesitant to change the treatment protocol.

1. Alkalizing Supplements, Super Green Food and Mineral Whey:
   
   
   • Super Green Food Powder: Consuming an alkalizing super-green-food drink made from vegetables, micro algae, mushroom extracts, herbs and grass-juice concentrates a minimum of twice each day to a maximum of four times a day. Since it is difficult to eat normal salads (as vinegar dressings will often exacerbate IC), drinking a super-green-food drink will provide the body with the antioxidants, vitamins and minerals that would otherwise require many salads to achieve. You can take many of the recommended supplements, including the aloe vera capsules, with the super-green-food drink. The alkalizing effect of the super-green-food powder (and the elimination of acid-forming food and drink including cow's milk and sugar, as well as refined and processed foods) is vital to the healing and successful treatment of IC. If you are consuming salads, make dressings without vinegars or citrus juices. It's surprising how delicious a salad can be simply with quality healthful oils, including extra virgin single estate olive (freeze pressed is best), Camelina, pumpkin seed, macadamia, and avocado, especially when you blend natural spices and garlic into the oil. Recommended super-green-food products include Barlean's Greens, and Genuine Health's Fermented Greens+ Whole Body. You can boost the immune system benefits of all green foods by adding to each glass two tablespoons of Aviva's Rice Bran Solubles - the richest natural source of plant sterols. Aviva Rice Bran Solubles is also high in tocotrienols: powerful vitamin E isomers with many health benefits.
     
     
   • Mt. Capra Mineral Whey: Also called Mineral Matrix by St. Francis Herb Farm, this is a wonderful product derived from goat's whey that makes a delicious hot drink that can be used to replace coffee or tea. It is very high in minerals that work synergistically with the super green foods to increase alkalinity at the cellular level. Many also find a cup of hot Mineral Whey to be ideal in helping induce relaxation and sleep before bedtime. It's even more enjoyable when Bambu (below) is added.
     
     
   • Bambu is a caffeine-free drink that many find to be the perfect coffee substitute when they are trying to reduce or avoid caffeine, or the high acidity levels that naturally occur with normally prepared coffee. Available either as an instant powder or as a ground product to be used in coffee makers, Bambu is made from acorns, figs, chicory, malted barley, and wheat. When combined with Mt. Capra Mineral Whey it makes an even more delicious coffee substitute.
     
     
2. Boosting mineral levels, including magnesium, by using ionic liquid supplements.
   
   
   • ConcenTrace Mineral Drops are recommended, which gradually boost magnesium levels. Add three drops to every 8 ounce glass of water (4 drops for a 12 ounce glass, etc.). Put three or four drops in everything you eat or drink, to equal a total of 40 drops per day. You can also put 10-20 drops in a 64 ounce water container and drink this throughout the day. You can use this water for making coffee or tea, or add 2-4 drops in each glass of tea. If you drink coffee, choose a low-acid method of brewing (Hourglass, or Toddy), which lowers the acidity by about 70%.
     
     
3. Supplementing the diet with a quality multi vitamin/mineral formula that is high in calcium and magnesium, to be taken with each meal.
   
   
   • Do not choose a one a day vitamin, since water soluble nutrients (B vitamins, C, and many antioxidants) are excreted within three to four hours of consumption. If you take a one a day vitamin mineral supplement in the morning, by noon the water soluble vitamins (vitamin C, all the B-vitamins) will no longer be available to assist as catalysts and cofactors for the production of many of the important enzymes, biochemicals and hormones that require these nutrients.
     
     
   • Recommended supplements include Ultra Preventive X and AOR Ortho-Core.
     
     
4. Omega-3 (EPA and DHA) and Omega-6 as GLA:
   
   
   • Omega-3 and omega-6 are known for their anti-inflammatory benefits. The right daily balance includes 3 grams of omega-3 (EPA and DHA in a 2-1 ratio), and 720 mg GLA (the healthy omega-6) from 3 borage seed oil capsules. The ratio of omega-3 to omega-6 is critical. Regular consumption of omega-3 and omega-6 as GLA provides a wide range of additional benefits, including healthy joints and eyes, as well as improved cardiovascular and cognitive health. Another benefit that many experience with regular consumption of omega-3 and omega-6 (as GLA) is a significant reduction in skin problems, including eczema and psoriasis.
     
     
   • Recommended brands of omega-3 include Nordic Naturals, Carlson Laboratories, and Aviva's own High Potency Omega-3 Ester (990 mg of EPA/DHA per capsule). For those that prefer liquid fish oils, I recommend products from Nordic Naturals, Carlson Laboratories and Sea-Licious Omega-3 Fish Oil, a delicious high quality liquid omega-3 supplement that has no fishy taste. Read the label closely when choosing an omega-3 product. Many will indicate 1000 mg (the amount of oil in the capsule) on the label, but this indicates the total amount of oil in the capsule, not the level of EPA and DHA. The actual amount of EPA and DHA in the capsule can be as high as 990 mg (as with Aviva Omega-3 Ester) or as low as 180 mg If there is only 180 mg of omega-3 in a 1000 mg capsule, there are 820 milligrams of other oils that are not omega-3. Take a minimum of three 990-1000 milligram capsules of EPA/DHA.
     
     
   • Omega-6 in the form of linoleic acid (LA) is the predominant form of omega-6 in the diet, as it is the form of omega-6 found in most seed oils and grains. High levels of LA are associated with inflammation. Only GLA, an anti-inflammatory form of omega-6, is recommended. A 1000 mg borage seed oil capsule contains 240 mg of GLA. Take three 1000 mg borage seed oil capsules per day to provide a total of 720 mg of GLA per day. You can take them all at once in the morning, or one with each meal. The Borage Oil can be taken at the same time as the omega-3. Recommended brands of borage seed oil are NOW and New Roots Herbal both are quality products. There will be 240 mg of GLA in each capsule.
     
     
5. A quality probiotic supplement, taken either before or with each meal, depending on the supplement chosen.
   
   
   • Initially, using HMF Cystgen (by Seroyal/Genestra) for two days as directed will populate the GI tract and bladder with beneficial bacteria while specific urine alkalizers help to alleviate pain. Following the two day treatment with Cystgen, use O'Donnell Formulas' Flora Balance and Metagenics' UltraFlora Women's formula.
   • Probiotics naturally inhabit the colon and vagina. Research has shown that the presence of beneficial bacteria is associated with a reduced risk of urinary tract infections (UTIs), IC, and bacterial vaginosis. Higher levels of beneficial bacteria in the vagina may inhibit the colonization of unwanted pathogenic bacteria.
     
     
   • Beneficial lactic bacteria also strengthen the immune system, aid digestion, and produce a wide variety of vitamins in the intestine. The L. rhamnosus GR-1^® and L. reuteri RC-14^® strains that are included in Metagenics UltraFlora Women's product are backed by more than 20 years of scientific research.
     
     
   • Several studies have reported on the significance of friendly bacteria in UTIs (Asahara et al. 2001 Reid 2000, Reid & Brice 2006 Strus et al. 2002). Different strains of Lactobacillus introduced orally and vaginally resulted in a reduced risk of UTIs and improvement of normal vaginal bacteria. Lactobacillus strains taken from healthy vaginal flora were antagonistic against bacteria known to cause urinary tract and vaginal infections.
     
     
6. Boosting Nitric Oxide, increasing antioxidant levels, and building collagen through the addition of Vitamin C, quercetin, pine bark extract, L-Citrulline, Astaxanthin, and N-Acetyl Cysteine.
   
   
7. Adding selected herbs to the diet, including:
   
   
   • Curcumin - Curcumin may be the most powerful of all herbs, with benefits for a wide variety of health conditions. Recent research has focused on the use of curcumin for both treatment and prevention of various cancers, as well as for cognitive and anti-inflammatory (Cox-2 inhibiting) benefits. The most bioavailable forms of curcumin include Meriva™, BCM-95, and Curcumin Longvida. These new formulations increase free curcumin substantially over previous formulas. I like MyoMotion and Terry Naturally's Curamin, as they use a combination of Boswellia and the highly bioavailable BCM-95 form of curcumin.
   • Boswellia - a powerful anti-inflammatory herb which complements curcumin beautifully.
   • Marshmallow Root - Ideally consumed three times a day as a tea, marshmallow has a long history of use for urinary and bladder issues. It soothes the bladder wall and helps heal the epithelium, resulting in benefits to the urinary tract. Marshmallow is also alkalizing, which makes it an ideal tea to complement this program.
   • Aloe Vera - Choose freeze dried or concentrate in capsule form, as liquids contain either citric acid or lemon juice, which should be avoided.
   • DGL - Deglycyrrhizinated Licorice.
     
     
8. Sleeping on a Celliant fibre mattress protector. Celliant fibre, which is now used in clothing and in an exciting new mattress protector from Fabrictech, incorporates into the fibre special minerals which are thermo-reactive - converting body heat into infrared energy, which is then reflected back into the body to help reduce fatigue and speed healing and recovery through vasodilation. By sleeping on a bed with a Celliant fibre mattress protector, you will improve circulation and naturally increase oxygen levels in the body. Celliant fibre has been proven to enhance cell vitality while regulating body temperature, keeping you cool in the summer and warm in the winter (wool mattress coverings have a similar effect however, combining both is best).
   
   Infrared light is another medically proven vasodilator. Medical professionals have used infrared light to speed healing and to treat many health conditions, including hypertension (high blood pressure), congestive heart failure, and rheumatoid arthritis. Other benefits include helping to reduce pain and improving athletic performance. Using an infrared sauna also provides vasodilation benefits, but not everyone can afford the high cost of a quality infrared sauna.

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Health Disclaimer. Copyright ©2006-2019. Originally published 2006, last major revision 2015. Nathan Zassman is a trained nutrition practitioner and the owner of Aviva Natural Health Solutions.

References

(1) Hanno P, Levin R, Monson F, et al. Diagnosis of interstitial cystitis. J Urol 1990143:275-81.

(2) Gillespie L. You don't have to live with cystitis. (New York: Avon Books, 1986:244).

(3) Smith S, Wheeler M, Foster H, Weiss H. Improvement in interstitial cystitis symptom scores during treatment with oral L-Arginine. J Urol 1997158:703.

(4) Korting G, Smith S, Wheeler M, et al. A randomized double-blind trial of oral L-Arginine for treatment of interstitial cystitis. J Urology 1999:161:558-65.

(5) Asahara T, Nomoto K, Watanuki M, Yokokura T. Antimicrobial activity of intraurethrally administered probiotic Lactobacillus casei in a murine model of Escherichia coli urinary tract infection. Antimicrob Agents Chemother 2001 Jun:45(6):1751-60.

(6) Reid G. Probiotic Therapy and Functional Foods for Prevention of Urinary Tract Infections: State of the Art and Science. Curr Infect Dis Rep. 2000 Dec:2(6):518-22.

(7) Reid G, Bruce AW. Probiotics to prevent urinary tract infections: the rationale and evidence. World J Urol. 2006 Feb:24(1):28-32.

(8) Strus M, Malinowska M, Heczko PB. In vitro antagonistic effect of Lactobacillus on organisms associated with bacterial vaginosis. J Reprod Med 2002 Jan:47(1):41-6.

(9) Chen CK, Pace-Asciak CR. Vasorelaxing activity of resveratrol and quercetin in isolated rat aorta. Gen Pharmacol. 1996:27:363-6.

(10) Nakayama H, Tsuge N, Sawada H, Higashi Y. Chronic intake of onion extract containing quercetin improved postprandial endothelial dysfunction in healthy men. J Am Coll Nutr. 2013:32(3):160-4.

(11) Durante M, Sgaragli G, Biasutto L, Mattarei A, Fusi F. Quercetin mitochondriotropic derivatives antagonize nitrate tolerance and endothelial dysfunction of isolated rat aorta rings. Planta Med. 2013 Apr:79(6):465-7.

(12) Stanislavov R, Nikolova V. Treatment of erectile dysfunction with pycnogenol and L-arginine. J Sex Marital Ther. 2003 May-Jun:29(3):207-13.