Saturday, November 12, 2011

Adding red to your diet

We are always happy receiving nice e-mails from users. Here is a recent letter:


Dear Aurametrix,

I would like to share with you some interesting results that really surprised me, even though they're a little embarrassing. 

I've been using Aurametrix now about 2 months but mostly on days when I experience a symptom (2 entries for diarrhea).  So about 20 entries in all, including food, a few feeling good plus these symptoms:

Diarrhea, experienced 1 bout around 2:30 PM PDT on September 18, 2011 

Diarrhea, experienced 1 bout around 3:30 PM PDT on October 30, 2011


I did an analysis on the second day: Diarrhea relative to Feeling Good, 12 hours 
These are the results copied from the tool:


Based on your Aura entries, the following may be contributing to "Diarrhea" in a 12 hour timeframe:
  • Lycopene (when consumed more than 5.9 micrograms, up to 2650.6)
  • Orange or Yellow fruits and veggies (when consumed more than 0.1 foods, up to 1.0)
I looked up lycopene and it's a chemical in orange-colored fruits. It so happens that I ate mango one day and a raw papaya on the other day I experienced the symptoms. I think I will avoid these fruits in the future (I haven't had any since I learned about it from Aurametrix)

You can post this if you want since I think it's worthwhile to let other people know that the tool really works and I don't have symptoms.
Regards,
Aurametrix User :)

Lycopene is a carotenoid, a pigment that gives fruits and vegetables a red color. It is found in some red, pink, orange and yellow fruits and vegetables such as tomatoes (especially skins), watermelons, grapefruits, apricots, papayas, and guavas.

Lycopene is an antioxidant, but in the human body it converts into lycopenoids with the help of carotenoid monooxygenase (CMO) enzymes. Lycopene metabolism depends on the person. It is more efficient in those with more active CMOs, higher testosteron and those not restricting dietary intake.

A number of studies have suggested that a higher intake of lycopene-containing foods decreases the risk of heart disease, prostate cancer, other cancers and infections, even cataracts and asthma. Lycopene is thought to prevent male infertility, osteoporosis, varicose veins and eye disease. Lycopene may also reduce or prevent the side effects of chemotherapy.

What are the potential side effects? In one Mayo Clinic study (Jatoi et al, 2007), the most common side effect for patients who took 15,000 micrograms of lycopene twice per day was diarrhea (41% of patients), followed by nausea (26%), abdominal distension (17%), and flatulence (4%).


The same effects were also observed by IBS sufferers - like this case of massive diarrhea from fresh tomato on a sandwich or this bad gut reaction to tomato sauce. Mangoes and Papayas are usually considered safe for IBS, yet occasional incidents are posted on the web.

So, should you limit your Lycopene intake if Aurametrix indicates it may cause your diarrhea? Take a note about it and keep analyzing your diet. Analyses that start from "Aura entries" examine food combinations and will tell you if there is something that negates the effect. Perhaps there was a day when you ate it and felt OK. You might not remember it, but Aurametrix will.


REFERENCES

Jatoi A, Burch P, Hillman D, Vanyo JM, Dakhil S, Nikcevich D, Rowland K, Morton R, Flynn PJ, Young C, Tan W, & North Central Cancer Treatment Group (2007). A tomato-based, lycopene-containing intervention for androgen-independent prostate cancer: results of a Phase II study from the North Central Cancer Treatment Group. Urology, 69 (2), 289-94 PMID: 17320666.

Kelkel M, Schumacher M, Dicato M, Diederich M. (2011) Antioxidant and anti-proliferative properties of lycopene. Free Radic Res. 2011 Aug;45(8):925-40. Epub 2011 May 26.

Brian L. Lindshield, Kirstie Canene-Adams, John W. Erdman Jr (2007) Lycopenoids: Are lycopene metabolites bioactive? Archives of Biochemistry and Biophysics. Volume 458, Issue 2, Pages 136-140.

Sunday, August 14, 2011

Hold the Starch?


Starch is that stuff that stiffens your shirts. It's also what most people eat for fuel. Wheat, rice, corn, oats, potatoes are all very starchy foods. Many popular diet plans call starch a second-rate food that should be avoided at all costs. No-starch and low starch diets are favored by irritable bowel communities, while former Weight Watchers, Jenny Craig and Atkins enthusiasts love the new Carb Lovers Diet praising starch. Yet, there may be something good about starch even for those with sensitive stomachs. 


Starch is a mixture of long and intermingled molecules digested with different rates and outcomes. Our bodies' response to eating starch depends on its amount and types along with our nature [1] and nurture, including intestinal microbes eating the leftovers [2].


Resistant Starch (RS), also called Functional Fiber, is a type of starch that may have beneficial physiological effects. It is further classified into four or five classes,  like RS2 in potatoes or RS3 (maltodextrin on food labels) formed when starchy foods are cooked and cooled. Resistant starch is not digested in the small intestine of healthy individuals. It is an effective prebiotic as it feeds and stimulates specific bacteria in the gut [3]. Bacteria consuming resistant starch raise levels of short-chain fatty acids (SCFA) and derivatives that can act as a source of energy [2,4] and provide other benefits like protection from inflammatory conditions of the bowel. 


Over 200 nutritional studies showed  that resistant starch increases satiety, reduces food consumption and can prevent weight regain, acting almost like exercise. It also lowered insulin levels and reduced the deposition of fat.

How much resistant starch do we need to eat?

Adults in most developed countries consume between 3-7 grams of resistant starch per day. The Carb lovers diet recommends 10-15 grams. According to an earlier Australian study [5], 20 grams per day may be even more beneficial. However, optimal levels of resistant starch in diet are very individual, depending on body weight, metabolism, microbial makeup and dietary preferences. Flatulence and belching are among potential side effects.

Resistant starch is like other types of fiber and prebiotics – everybody has their own individual threshold and every extra gram leads to production of excessive gas [6].
Fructooligosaccharides (FOS) and inulin, prebiotics selectively stimulating bacteria in the colon, usually lead to mild flatulence starting from about 10 grams per day. Isolated individuals experience discomfort even at 5 grams. 14-15 grams per day usually mark the threshold for significant increase in flatulence, stomach growling and cramping. Resistant starch may have slightly higher sensitivity thresholds [6].



Source
Total starch,  per 100 g
  Resistant starch, per 100 g
Lentils
53.3
25.4
Red kidney beans
42.6
24.6
Black-eyed peas
53.9
17.7
Potato chips
29.5
4.8
Long-grained rice, parboiled
25
3.7
Spaghetti, cooked for 9 mins
22
2.9
Mashed potatoes
8.5
2.4
Boiled potatoes
15
2
White bread
46.7
1.9
Rye crisps
67.4
1.4
Puffed wheat cereal
67
1.2
Medium-grained rice, boiled
25
0.6
Spaghetti, cooked for 12 mins
22
0.9
Oatmeal (Oat porridge)
9
0.3


Understanding what amounts are right for you takes careful analysis and evaluation  Don’t forget about the digestible starch that accompanies indigestible starch. Ideally, our enzymes can efficiently break down the digestible starch into glucose, but the process is so lengthy (5-7 hours) that overload could result in more starch leaking through pores in the small intestine before it has a chance to be digested. This leads to endotoxins and an excess of methane and carbon dioxide, in addition to other metabolic end products, in your system.  

So remember:  there are different types of starch and they usually come packaged with other food components for which you might have separate sensitivities. In other words, your mileage may vary.


REFERENCES


[1] Perry GH, Dominy NJ, Claw KG, Lee AS, Fiegler H, Redon R, Werner J, Villanea FA, Mountain JL, Misra R, Carter NP, Lee C, Stone AC.   Diet and the evolution of human amylase copy number variation. Nat Genet. 2007 Oct;39(10):1256-60. Epub 2007 Sep 9.


[2] Bird AR, Conlon MA, Christophersen CT, & Topping DL (2010). Resistant starch, large bowel fermentation and a broader perspective of prebiotics and probiotics. Beneficial microbes, 1 (4), 423-31 PMID: 21831780


[3] Gray, G. Dietary fibre – from definitions to public health messages (pages 159–161). Article first published online: 13 Aug 2008 | DOI: 10.1111/j.1467-3010.2008.00702

[4] Donohoe, DR, Garge, N, Zhang, X, Sun, W, O'Connell, TM, Bunger, MK, Bultman, SJ. (2011). The Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian Colon. Cell Metabolism 13 (5): 517–26

[5] Baghurst PA, Baghurst KI, Record SJ, Dietary fibre, non-starch polysaccharides and resistant starch – a review. Food Australia, 1996 Vol 48, No. 3:S1-S35.

[6] Brighenti F, Pellegrini N, Casiraghi MC, Testolin G (1995) In vitro studies to predict physiological effects of dietary fibre. European Journal of Clinical Nutrition 49, Suppl. 3, S81±S88

[7] Elmståhl, L.H. Resistant starch content in a selection of starchy foods on the Swedish market. European journal of clinical nutrition: 2002 Jun;56(6):500-5.

Monday, May 30, 2011

Tryptophan in food: Will it make you happy, sleepy or smelly?

And the answer is ... either or all of the above. And this is not a complete list of all that can happen. In some rare conditions, for example, tryptophan could also make your pee purple.


Tryptophan supplements were used as a popular sleeping aid until negative press in 1989. The FDA banned dietary tryptophan supplements from the market, just days before the arrival of Prozac rising as the new promise for chemical happiness. Further investigation showed that ill effects of tryptophan were actually due to a contaminant in the supplement not the amino acid itself.
Today you can find tryptophan at many supplement retailers. You can also get it from food - from chocolate or red meat, for example. What does it really do in our bodies?

Tryptophan is a complex aromatic amino acid  - one of eight "essential" amino acids that have to be taken with food as they cannot be created by the human body. Tryptophan metabolism is complex - KEGG pathway shows the multitude of reactions it participates in.
One of tryptophan metabolites - Kynurenic acid - is involved in the regulatory function of the gastrointestinal system and the modulation of the inflammatory response. Another metabolite is neurotransmitter Serotonin which has a calming and sleeping-inducing effect on the brain.
L-Tryptophan administration (2 g) as a single dose before a meal has been found to decrease subjective hunger ratings, food intake, and alertness in men (Hrboticky et al., 1985), but not women (Leiter et al., 1987).  Babies  were also found to get sleepier (20 mg supplementation, Yogman and Zeisel, 1983, 1985). Tryptophan can be used by the body to create 5-hydroxytryptophan (also known as 5-HTP and oxitriptan). 5-HTP is sold as a dietary supplement as an antidepressant and sleep aid. It is marketed under many different trade names such as Cincofarm, Levothym, Oxyfan and Triptum.  Studies showed that 5-HTP provides benefits with regard to depression, blood pressure and regular sleep patterns. So even though that fact that the Thanksgiving turkey is responsible for sleepiness is an urban legend, tryptophan could definitely contribute to calmness and happiness.

Yet, according to a study by British researchers, irritable bowel syndrome sufferers have an increase in gastrointestinal symptoms after ingestion of a large dose of tryptophan, in addition to having fewer symptoms of anxiety and depression. One of the reasons: tryptophan metabolism mostly happening along the kynurenine and not 5-HT pathway. Increased tryptophan catabolism was recently shown to be associated with depression, reduced motivation and pessimism in the elderly. According to earlier studies (like the referenced 1998 articles by Austrian scientists), people with fructose malabsorption have abnormal tryptophan metabolism too, leaving them with less available tryptophan, and it seems to be responsible for mental depression (Ledochowski et al., 1998).   Overdose of tryptophan  in healthy adults (5 g in a double-blind, placebo-controlled study) induced  severe nausea and headache and increased drowsiness soon after ingestion (Greenwood et al., 1975). 
What happens to tryptophan abnormally accumulated in intestines? Here come more bad news - it is utilized by intestinal bacteria (e.g. Lactobacillus) and converted into indole and skatole - metabolites responsible for strong fecal smell. The rate of production of these smelly compounds depends on the acidity  - it is greatest at pH 6.5 and less at pH 5.0 and 8.0. Food-food interaction could lessen or enhance the "smelly"effects. The suppression of tryptophan degradation by propolis, for example,  could contribute to beneficial health properties. Preliminary results were also reported for cocoa extracts, Fructooligosacharides (FOS) and resistant starch, but more studies are needed.

So, how much tryptophan do you really need?  Half a gram, 2 grams, even more? It depends on your metabolism, your life style and your diet. It may be a good idea to watch your wellbeing along with tryptophan intake, to find your own optimal daily value.
This post was chosen as an Editor's Selection for ResearchBlogging.org



REFERENCES

Capuron L, Schroecksnadel S, Féart C, Aubert A, Higueret D, Barberger-Gateau P, Layé S, & Fuchs D (2011). Chronic Low-Grade Inflammation in Elderly Persons Is Associated with Altered Tryptophan and Tyrosine Metabolism: Role in Neuropsychiatric Symptoms. Biological psychiatry PMID: 21277567

Christmas DM; Badawy AAB; Hince D; Davies SJC; Probert C; Creed T; Smithson J; Afzal M; et al. (Oct 2010). Increased serum free tryptophan in patients with diarrhea-predominant irritable bowel syndrome. NUTR RES. 30:678-688. DOI.

Hood SD; Hince DA; Davies SJC; Argyropoulos S; Robinson H; Potokar J; Nutt DJ. (Feb 2010). Effects of acute tryptophan depletion in serotonin reuptake inhibitor-remitted patients with generalized anxiety disorder. PSYCHOPHARMACOLOGY. 208:223-232. DOI.

Shufflebotham J; Hood S; Hendry J; Hince DA; Morris K; Nutt D; Probert C; Potokar J. (Nov 2006). Acute tryptophan depletion alters gastrointestinal and anxiety symptoms in irritable bowel syndrome. Am J Gastroenterol. 101:2582-2587. DOI.

Ledochowski M, Widner B, Murr C, Sperner-Unterweger B, Fuchs D. Fructose malabsorption is associated with decreased plasma tryptophan. Scand J Gastroenterol. 2001 Apr;36(4):367-71.

Ledochowski M, Sperner-Unterweger B, Widner B, Fuchs D. Fructose malabsorption is associated with early signs of mental depression. Eur J Med Res. 1998 Jun 17;3(6):295-8.

Xu ZR, Hu CH, Wang MQ. Effects of fructooligosaccharide on conversion of L-tryptophan to skatole and indole by mixed populations of pig fecal bacteria. J Gen Appl Microbiol. 2002 Apr;48(2):83-90.

Jones HE, Johnson RE, Bigelow GE, Silverman K, Mudric T, Strain EC. Safety and efficacy of L-tryptophan and behavioral incentives for treatment of cocaine dependence: a randomized clinical trial. Am J Addict. 2004 Oct-Dec;13(5):421-37. 

Jensen MT, Cox RP, Jensen BB. 3- Methylindole (skatole) and indole production by mixed population of pig fecal bacteria.  Appl Environ Microbiol. 1995 Aug;61(8):3180-4.

Celenza JL. Metabolism of tyrosine and tryptophan - new genes for old pathways. Curr Opin Plant Biol. 2001 Jun;4(3):234-40.

Monday, May 9, 2011

On seasonal allergies and IBS






Irritable Bowel Syndrome is nothing to sneeze at. Especially during the sneezing season. 
As a matter of fact, you are more prone to have irritable bowel if you have a seasonal allergy. The likelihood of IBS is 3 times higher in patients reporting atopic symptoms (2.67 times higher in patients with seasonal allergic rhinitis and 3. 85 times higher in patients with allergic eczema, according to Tobin and his colleagues who administered questionnaires to 125 patients).  So some of that abdominal pain may be part of  allergic disease. Almost any other symptom of IBS may owe to it, too. See for example this case involving leaky gut and diarrhea or this case of bloating and constipation.
It is May and grass pollen is adding to flowering trees in most of the US.  Europe is experiencing high birch pollen counts with grasses ready to pop up. The Mediterranean region is dominated by the pollination of grasses and olive trees. Allergy season is over in Japan, Australia and South Africa but new pollen sources will be soon waking up. 
Seasonal allergies are common. It is estimated that 15-20% of Americans suffer from seasonal and perennial allergies. Numbers of sufferers have been increasing over the years. 
The best way to control allergies is to avoid the triggers - stay indoors, wash hands and take showers after coming in from outdoors. Of course, there are also drugs. But relief from allergies could come in more natural ways. For example, from probiotics.
A recent study showed that Lactobacillus paracasei, commonly found in our orifices (oral and rectal mucosa to be more precise) could help with grass allergies. This is not news -  earlier research showed it was effective against diarrhea in infants and helped some patients with chronic fatigue syndrome and seasonal allergies. 
The research was sponsored by Nestle, one of several manufacturers already adding L. paracasei to their products. Their results,  based on a randomized, double-blind, placebo-controlled study, show that the ability of the nose to combat allergies significantly improves (NCT01150253).    Where are these probiotics found? Lactobacillus bacteria are involved in dairy fermentation and are present in fermented milk products and cheeses. Irish Cheddar, hand-made Spanish cheeses, Ricotta,  Italian hard cheeses and Mozzarella harbor many different strains of lactobacilli. Many of these products, however, are not tolerated well by the IBS population about half of which is lactose intolerant. 
The good news is that probiotics are not only in dairy products. Lactobacillus paracasei LMGP22043 found in artichokes was recently shown to be carried into the human gut and challenge the bad guys there (E.coli and Clostridium). And even though European food safety authority believes that LMGP22043 does not relieve gastrointestinal discomfort, there were studies showing that artichokes do help those with alternating IBS. So enjoy your vegetables and lets do more research!

Source

REFERENCES
Valerio F, de Candia S, Lonigro SL, Russo F, Riezzo G, Orlando A, De Bellis P, Sisto A, & Lavermicocca P (2011). Role of the probiotic strain Lactobacillus paracasei LMGP22043 carried by artichokes in influencing faecal bacteria and biochemical parameters in human subjects. Journal of applied microbiology PMID: 21447019

Wassenberg J, Nutten S, Audran R, Barbier N, Aubert V, Moulin J, Mercenier A, & Spertini F (2011). Effect of Lactobacillus paracasei ST11 on a nasal provocation test with grass pollen in allergic rhinitis. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 41 (4), 565-73 PMID: 21395878


Ann Allergy Asthma Immunol. 2008 Jan;100(1):49-53.


Sarker SA, Sultana S, Fuchs GJ, Alam NH, Azim T, Brüssow H, Hammarström L. Lactobacillus paracasei strain ST11 has no effect on rotavirus but ameliorates the outcome of nonrotavirus diarrhea in children from Bangladesh.  Pediatrics. 2005 Aug;116(2):e221-8. 

Wednesday, April 13, 2011

Finding the Right 'Them': Internet Support Groups for IBS

There is no cure for IBS and no definite causal links between bacteria, genes, lifestyles and health effects. Yet most people eventually learn how to manage their conditions and improve their health. The Internet has emerged as a key source of information for over 65 per cent of sufferers, with much of the knowledge coming from social media and ads.

Researchers are actively looking into the ways internet support groups help sufferers. Most studies find support groups are among the most successful approaches to managing chronic conditions and rare diseases. In fact, the more the members of these groups share common IBS symptoms, the better the outcomes.

According to other  studies, however, over 60% of IBS sufferers would be better off if they "ignored the ‘wacky’ advice flooding the Internet. An example: someone who tried unsuccessfully to relieve cramps and help constipation using a mixture of vinegar, ginger and egg. Interestingly, neither of those who commented on the article thought that the Internet was the problem: physicians could also provide insufficiently personalized advice. 

"There are no quick fixes, just common sense," comments another observer. After all, it takes time and effort to find the right "them" who are just like "us" in hopes of getting the right advice.


Here is a list of support groups for Irritable Bowel Syndrome:

IBSgroup.org: A Community for Irritable Bowel Syndrome and Digestive Health Sufferers
  • Members: over 41,000
  • Website  launched in May 1995 (charter founded in 1987)
Alternative Medicine Forum - Yahoo group that welcomes "all who search for healing, including those with: ... Irritable Bowel, Leaky Gut..."
    • Members: over 9,800
    • Founded: Oct 23, 2001
    Body Odor Support  - forum for sufferers of Irritable Bowel Syndrome, leaky gut, TMAU and undiagnosed conditions increasing body odor (update: moved to proboards)
    • Internet group was originally founded in 2000, bodyodorsupport website launched in January 2009, it was moved to proboards in summer 2011
    Eating for IBS - Yahoo group
    • Members: over 8,500
    • Founded: Jul 19, 2001
    • Members: over 1,300
    • Founded: Dec 16, 2006
    There are dozens more yahoo groups devoted to IBS, but they are either less active, small or over-spammed so are not listed here.

    Local support groups are usually not very popular among IBS sufferers - people are less eager to travel for in-person meetings. Yet a few groups exist:

    helpforIBS - forums for local IBS support groups 
    • Largest group in Sacramento, California; followed by Berkshire, UK, Texas and Toronto, Canada
    • Founded: Dec 16, 2006
      http://ibs.meetup.com/


      Check also these message boards:

      IBS support Q&A Community supported by Aurametrix
      BS forum at about.com
      HelpforIBS message board
      IBS community at HealingWell.com
      IBS group at Dailystrength.org
      IBS Blog forum
      Candida and IBS forum
      Curezone IBS forum
      WebMD IBS community
      IBS Group at SupportGroups
      Not active since 2010 IBS forum
      Colon cleansing and IBS forum
      IBS discussions at HealthMessageBoards
      I have IBS Chat Board, ExperienceProject
      IBS Tales - IBS personal stories 





      References

      Ramadas A, Quek KF, Chan CK, Oldenburg B. Web-based interventions for the management of type 2 diabetes mellitus: A systematic review of recent evidence. Int J Med Inform. 2011 Apr 8.


      Madan G, Stadler ME, Uhrich K, Reilly C, Drake AF. Adolescents with tracheostomies-Communications in cyberspace.  Int J Pediatr Otorhinolaryngol. 2011 Mar 14.

      Springer A, Reck CA, Huber C, Horcher E. Online hypospadias support group data analysis. J Pediatr Surg. 2011 Mar;46(3):520-4.

      Andersson G, Ljótsson B, Weise C. Internet-delivered treatment to promote health. Curr Opin Psychiatry. 2011 Mar;24(2):168-72.

      Wednesday, April 6, 2011

      Quality of Life in Irritable Bowel Syndrome

      It's not news that IBS is tough. The unpredictability of symptoms, misunderstanding by peers, fear,  misconceptions, desperation, all contribute to discrimination of sufferers and significant impairment of quality of life. In fact, IBS sufferers are affected by greater physiological and physical disturbances than patients of inflammatory bowel disease, proving that wellbeing is not directly associated with observable morbidity.

      The most common psychological problems of IBS are anxiety, depression, panic, and post-traumatic stress. According to an Australian study (Mikocka-Walu et al, 2008), anxiety is a greater problem than depression, while a recent Korean study (Hyun Sun Cho et al., 2011) shows the same prevalence for anxiety and depression (observed in 38.6% and 38.6% of IBS patients, and in 24.2% and 16.5% of healthy subjects, respectively). Indeed, different cultural environments enhance or decrease problems associated with IBS - Greeks, for example, take it harder than the Swiss (Faresjö et al., 2006). Differences in IBS prevalence could also be the result of different environments, creating a reluctance to talk about digestive issues. In countries such as United States and UK more people may be suffering in silence.

      The questionnaire below was developed by Kaiser Permanente (Longstreth et al., 2005) to capture the impact of irritable bowel syndrome and its treatment on patients’ lives.











      References

      Longstreth GF, Bolus R, Naliboff B, Chang L, Kulich KR, Carlsson J, Mayer EA, Naesdal J, Wiklund IK. Impact of irritable bowel syndrome on patients’ lives: development and psychometric documentation of a disease-specific measure for use in clinical trials European Journal of Gastroenterology & Hepatology 2005, 17:411–420

      Groll D, Vanner SJ, Depew WT, DaCosta LR, Simon JB, Groll A, Roblin N, Paterson WG. The IBS-36: a new quality of life measure for irritable bowel syndrome. Am J Gastroenterol. 2002 Apr;97(4):962-71.

      Faresjö A, Anastasiou F, Lionis C, Johansson S, Wallander MA, Faresjö T. Health-related quality of life of irritable bowel syndrome patients in different cultural settings. Health Qual Life Outcomes. 2006 Mar 27;4:21.

      Mikocka-Walus AA, Turnbull DA, Andrews JM, Moulding NT, Wilson IG, Harley HA, Hetzel DJ, Holtmann GJ. Psychological problems in gastroenterology outpatients: A South Australian experience. Psychological co-morbidity in IBD, IBS and hepatitis C. Clin Pract Epidemiol Ment Health. 2008 May 23;4:15.

      Cho HS, Park JM, Lim CH, Cho YK, Lee IS, Kim SW, Choi MG, Chung IS, Chung YK.
      Anxiety, Depression and Quality of Life in patients with irritable bowel syndrome  Gut Liver. 2011 Mar;5(1):29-36.