Integrative medicine in gastrointestinal disease: evaluating the evidence.
Mullin GE, Pickett-Blakely O, Clarke JO.

The Johns Hopkins Hospital, Division of Gastroenterology, Carnegie Building-Room 464, 600 North Wolfe Street, Baltimore, MD 21287, USA. gmullin1@jhmi.edu

Abstract
Current Western therapies for many gastrointestinal diseases are suboptimal and potentially toxic. The majority of patients with digestive diseases are turning to complementary and alternative medicine for symptom relief and improved quality of life, due to dissatisfaction with conventional medical therapies. There is emerging evidence that many of these complementary and alternative medicine modalities are highly effective in modulating the immune system, disrupting the proinflammatory cascade and restoring digestive health while improving patients’ quality of life. We present evidence to support the potential utility of complementary and alternative medicine modalities for irritable bowel syndrome and inflammatory bowel disease. For each condition, we detail the proposed mechanisms of action and explore the current data for the prevention and/or treatment of disease.

Data from 6275 children who were selected at random in the 2004 National Health and Nutrition Examination Survey (NHANES) showed vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] level <15 ng/mL) in 9% and insufficiency (15–29 ng/mL) in 61%, with considerably higher rates in non-Latino black teens. Data from NHANES also showed that 25(OH)D levels were related inversely to systolic blood pressure and plasma glucose in teens (JW Pediatr Adolesc Med Nov 4 2009).
In another study, researchers found that half of 1300 randomly selected older adults (age range, 65–88) had 25(OH)D levels <20 ng/mL (JW Gen Med Apr 23 2009). The results of this study, and one other study of 1300 men older than 65 (JW Gen Med Aug 13 2009), showed adverse effects on bone metabolism (as reflected by bone-mineral density, bone turnover markers, and serum parathyroid hormone levels) when 25(OH)D levels dropped lower than 20 ng/mL.

In a population-based study, investigators compared vitamin D levels recorded in the NHANES database for 1988–1994 and for 2001–2004; they found that levels of 25(OH)D are decreasing. The prevalence of a serum level 30 ng/mL dropped from 45% to 23%, a trend that was present in both sexes, across all ethnic groups, and across all age groups (JW Gen Med Apr 21 2009). A meta-analysis of eight randomized trials that involved 2426 older patients showed that higher doses of daily vitamin D supplements (700–1000 IU) lowered risk for falling by 19%, presumably because of better muscle strength (JW Gen Med Nov 3 2009). Previous research had suggested that high-dose supplementation also prevents fractures (JW Gen Med Jun 3 2005).

Major issues remain unresolved. A 25(OH)D level <20 ng/mL clearly is associated with adverse effects on bone. However, the protective effect of vitamin D on other diseases seems to be linear: Increasing levels are associated with a decreasing rate of morbidity (at least up to serum levels of around 70 ng/mL). So the definition of vitamin D “deficiency” remains unclear. Also unanswered is the question of whether doctors should obtain blood levels of 25(OH)D routinely and adjust supplemental doses to achieve a target blood level — and what should that level be? A very large multi-year randomized trial has been designed to evaluate the possible effects of supplementation on many diseases; recruitment will begin in January 2010. Past observational studies that suggested other vitamin supplements might improve health often have not been confirmed by randomized trials.
— Anthony L. Komaroff, MD

Published in Journal Watch General Medicine December 31, 2009

Zinc status in infantile wheezing.

Tahan F, Karakukcu C.

Department of Pediatric Allergy, Erciyes University School of Medicine, Kayseri, Turkey. tahanfulya@yahoo.com

The increase in prevalence of asthma is strongly dependent on environmental factors, including diet. Significant decreases in the intake of dietary zinc may be an important contributing factor to the increasing incidence of wheezing and asthma, but there have been no studies evaluating zinc levels in wheezy infants. Our objective was to investigate the zinc status of wheezy infants. Wheezy infants (n = 34) and healthy children (n = 14) were included in the study. Total IgE and eosinophil counts were obtained, and skin testing was done with a battery of 25 antigens with appropriate positive and negative controls. Levels of zinc were determined in hair, using a Polarized Zeeman Atomic Absorption Spectrophotometer (Hitachi Z-800). No significant difference was observed in peripheral blood eosinophil counts and total IgE levels among groups (P > 0.05). Hair zinc levels were significantly lower in wheezy infants (P < 0.001). In conclusion, hair zinc levels were lower in wheezy infants than in healthy controls, suggesting that zinc deficiency may influence the risk of wheezing in early childhood.

Department of Pediatrics [V.P.W.], Department of Microbiology [R.L.M.], Department of Medicine [R.L.M.], David Geffen School of Medicine at UCLA Los Angeles, CA 90095.

Over the past twenty years, a resurgence in vitamin D deficiency and nutritional rickets has been reported throughout the world, including the United States. Inadequate serum vitamin D concentrations have also been associated with complications from other health problems, including tuberculosis, cancer (prostate, breast and colon), multiple sclerosis and diabetes. These findings support the concept of vitamin D possessing important pleiotropic actions outside of calcium homeostasis and bone metabolism. In children, an association between nutritional rickets with respiratory compromise has long been recognized. Recent epidemiological studies clearly demonstrate the link between vitamin D deficiency and the increased incidence of respiratory infections. Further research has also elucidated the contribution of vitamin D in the host defense response to infection. However, the mechanism(s) by which vitamin D levels contribute to pediatric infections and immune function has yet to be determined. This knowledge is particularly relevant and timely, because infants and children appear more susceptible to viral rather than bacterial infections in the face of vitamin D deficiency. The connection between vitamin D, infections and immune function in the pediatric population indicates a possible role for vitamin D supplementation in potential interventions and adjuvant therapies.

Nursing and Midwifery Research Unit, School of Nursing and Midwifery, Queen’s University, Belfast BT9 5BN, UK.

Maternal vitamin D insufficiency is associated with childhood rickets and longer-term problems including schizophrenia and type 1 diabetes. Whilst maternal vitamin D insufficiency is common in mothers with highly pigmented skin, little is known about vitamin D status of Caucasian pregnant women. The aim was to investigate vitamin D status in healthy Caucasian pregnant women and a group of age-matched non-pregnant controls living at 54-55 degrees N. In a longitudinal study, plasma 25-hydroxyvitamin D (25(OH)D) was assessed in ninety-nine pregnant women at 12, 20 and 35 weeks of gestation, and in thirty-eight non-pregnant women sampled concurrently. Plasma 25(OH)D concentrations were lower in pregnant women compared to non-pregnant women (P < 0.0001). Of the pregnant women, 35, 44 and 16 % were classified as vitamin D deficient (25(OH)D < 25 nmol/l), and 96, 96 and 75 % were classified as vitamin D insufficient (25(OH)D < 50 nmol/l) at 12, 20 and 35 weeks gestation, respectively. Vitamin D status was higher in pregnant women who reported taking multivitamin supplements at 12 (P < 0.0001), 20 (P = 0.001) and 35 (P = 0.001) weeks gestation than in non-supplement users. Vitamin D insufficiency is evident in pregnant women living at 54-55 degrees N. Women reporting use of vitamin D-containing supplements had higher vitamin D status, however, vitamin D insufficiency was still evident even in the face of supplement use. Given the potential consequences of hypovitaminosis D on health outcomes, vitamin D supplementation, perhaps at higher doses than currently available, is needed to improve maternal vitamin D nutriture.

EMNet Coordinating Center, Massachusetts General Hospital, Boston, MA 02114, USA.

Over the past decade, interest has grown in the role of vitamin D in many nonskeletal medical conditions, including respiratory infection. Emerging evidence indicates that vitamin D-mediated innate immunity, particularly through enhanced expression of the human cathelicidin antimicrobial peptide (hCAP-18), is important in host defenses against respiratory tract pathogens. Observational studies suggest that vitamin D deficiency increases risk of respiratory infections. This increased risk may contribute to incident wheezing illness in children and adults and cause asthma exacerbations. Although unproven, the increased risk of specific respiratory infections in susceptible hosts may contribute to some cases of incident asthma. Vitamin D also modulates regulatory T-cell function and interleukin-10 production, which may increase the therapeutic response to glucocorticoids in steroid-resistant asthma. Future laboratory, epidemiologic, and randomized interventional studies are needed to better understand vitamin D’s effects on respiratory infection and asthma.

Colston KW.

Division of Cellular and Molecular Medicine, St George’s University of London, Cranmer Terrace, London SW17 0RE, UK. kcolston@sghms.ac.uk

In addition to its important role in the maintenance of the skeleton, there is mounting evidence that vitamin D has effects on other body systems, and that adequate supplies of vitamin D are likely to be required for optimal health. Vitamin D is obtained both from dietary sources and from cutaneous synthesis with exposure to sunlight. Some epidemiological studies have indicated that vitamin D deficiency and decreased exposure to solar UVB radiation increase the risk of some cancers, including breast cancer. The active metabolite of vitamin D, 1,25-dihydroxy-vitamin D(3), is synthesized primarily in the kidney, and has been shown in laboratory studies to have potent anti-proliferative effects on breast cancer cells. Normal and neoplastic breast tissues contain the vitamin D receptor, and gene ablation studies have implicated the receptor in normal breast development. Several polymorphisms have been identified in the vitamin D receptor gene, and these have been associated with risk of breast cancer in some studies. Local synthesis of 1,25-dihydroxyvitamin D(3) in breast tissue may contribute to maintenance of normal cell function, which could be impaired in vitamin D deficiency.

Ishihara J, Inoue M, Iwasaki M, Sasazuki S, Tsugane S.

Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.

BACKGROUND: Calcium and vitamin D have a potential protective effect against colorectal cancer. OBJECTIVE: We investigated the association of dietary intake of calcium and vitamin D with the risk of colorectal cancer in a large prospective cohort study of middle-aged Japanese men and women. DESIGN: A total of 74 639 subjects (35 194 men and 39 445 women) who participated in the Japan Public Health Center-based Prospective Study were followed from 1995-1999 to the end of 2004, during which time 761 cases of colorectal cancer (464 men, 297 women) were newly identified. Dietary intake of nutrients was calculated with the use of a 138-item self-administered food-frequency questionnaire. RESULTS: After adjusting for potential confounding factors, the multivariate hazard ratio in the highest quintile of dietary calcium intake compared with the lowest was 0.71 (95% CI: 0.52, 0.98) among men. The association appeared to decrease considerably among subjects in the second quintile without a clear further dose-response relation (P for trend: 0.09). No association was seen among women. No statistically significant association with dietary vitamin D intake was seen in either men or women, although men in the highest dietary intake group of both nutrients had a lower risk than did men in the lowest group. CONCLUSIONS: These findings indicate a potential decrease in the risk of colorectal cancer with higher dietary intake of calcium among middle-aged Japanese men, who have a relatively low dietary intake of calcium. Although vitamin D and colorectal cancer risk were not associated, potential effect modification between calcium and vitamin D on the risk of colorectal cancer was indicated.

Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a common, debilitating, multi-factorial, functional gastrointestinal disorder where a definitive aetiology has not been established and no uniformly successful treatment exists. The condition is very prevalent in developed countries with IBS symptoms experienced by 8-22% of the population. (1)
 

IBS is characterised by a combination of symptoms and signs, such as abdominal pain, constipation (IBS-C), diarrhoea (IBS-D) — or alternating between both (IBS-A) — a noted change in both the frequency and consistency of stools, rectal mucus due to hyper-secretion of colonic mucus, dyspeptic symptoms including anorexia, flatulence, gastro-oesophageal reflux (GOR) and nausea, and an emotional component where anxiety and/or depression are often noted. Abdominal pain is often relieved following defecation. . Originally, diagnosis for IBS was made based on the Rome I Criteria. This previous criteria specified that there should be at least 3 months of abdominal pain, either continuous or recurrent, that is relieved by defecation &/or is associated with either a change in the frequency or consistency of the stool. Conversely, the Rome II Criteria differs from that of the Rome I in that it specifies that the abdominal pain should be present either continuously, or recurring for a period of 12 weeks or >. Both the Rome I & Rome II Criteria are consistent in their description of what constitutes accompanying symptoms, i.e., relief of abdominal pain following defecation, &/or associated changes in both the frequency & consistency of the stool, but the Rome II Criteria is more specific in stipulating that at least 2 of these accompanying symptoms must be noted, along with abdominal pain. Although the Rome I Criteria was also quite detailed in specifying that an individual had to have two or more associated symptoms of IBS, e.g., altered stool frequency of more than 3 per day or < 3 per week; abdominal distension; bloating; passage of mucus, etc, > 25% of the time, the newer Rome II Criteria has helped in simplifying the diagnosis of IBS. Where patients are <45 years of age, & they meet three or more of the Rome II diagnostic criteria (without ominous symptoms), a confident diagnosis can be provided without the need for invasive testing.

Rome III

Recently, there has been a further change, and that is the new Rome III criteria.

According to this latest criteria, IBS is defined as recurrent abdominal pain or discomfort for at least 3 days per month during the previous 3 months associated with two or more of the following symptoms: improvement with defecation, onset associated with a change in the frequency of stool and/or onset associated with a change in form or appearance of stool (2). Defined simply, symptoms are now recommended to originate 6 months prior to diagnosis and be currently active (i.e., meet criteria) for 3 months. This time frame is less restrictive when compared to Rome II (12 weeks of symptoms over 12 months) and is easier to understand and apply in research and clinical practice. (3)
 

Gas, diet and IBS

The daily production of gas in the human gastro-intestinal tract (GIT) is 500-1500ml, and the volume found at any given time is 200ml. Five major gases are responsible for the development of flatus, i.e. carbon dioxide, hydrogen, hydrogen sulphide, methane, and oxygen. Oxygen found in the GIT is the result of swallowed air during the course of eating and drinking (aerophagia), or it may be due to hyperventilation in cases of anxiety. Greater amounts would be expected in subjects who eat too quickly, chew gum, or smoke, as not all is absorbed or expelled following belching.The human large intestine is host to at least 400 different bacterial species, and examples include carbohydrate-fermenting bacteria, methane-generating bacteria (methanogens), and pectinolytic bacteria. These bacteria are responsible for the production of carbon dioxide (the main gaseous product), hydrogen, hydrogen sulphide, and methane. Flatus is the by product of fermentable substrates (carbohydrates and proteins). Examples of these fermentable substrates include: beans, cabbage, Brussel sprouts, broccoli, and whole grains (which contain raffinose; and fruit, onions and wheat (which contain fructose). These non-absorbable carbohydrates, together with ingested sugars such as fructose found in fruits, dietary starches (that escapes small intestinal absorption), e.g. potatoes, corn, wheat; and dietary fibre, such as that found in oat bran, beans, and peas, are all capable of producing gas. This is the result of these foods being metabolised by the colonic flora, followed by bacterial fermentation.

A number of different treatment options are cited within the literature for IBS; however, dietary modifications are not viewed as a priority in many cases. Sulphur-containing foods such as beans, broccoli, Brussels sprouts, cabbage, cauliflower, garlic and onions have been identified as being extremely flatulogenic.

 
(4) Evidence relating to the exclusion of sulphur-containing foods is limited and, in many cases, dismisses exclusion diets as being of no use, limited use, or not proven to be effective. (5, 6) Nevertheless, other studies acknowledge that some foods may play a role in producing gas in the IBS patient. (7, 8-14)

The sulphur-containing amino acids cysteine, cystine, methionine and taurine are the main sources of dietary sulphur. Other sources are derived from glucosinolates found in Brassica vegetables (broccoli, Brussels sprouts, cabbage, cauliflower and turnip).

 
(15) In garlic and onions, the organic sulphur compounds are found in the form of diallyl thiosulfinates (allicin). Other dietary sources of sulphur are derived from meat or food additives used as preservatives (e.g. sulphur dioxide and sodium metabisulphite). Magee et al (16) found a significant dose-related increase in faecal sulphide concentrations associated with the intake of meat.
Some oligosaccharides, such as raffinose and stacchiose, appear to be the most important sources of gas from bean digestion, as these compounds cannot be degraded by intestinal mucosal enzymes. (17, 18) It might be expected that, following fermentation, these complex carbohydrates contribute to abdominal distension and bloating in IBS patients. Again, these patients might only demonstrate a greater sensitivity to due to their reduced gas handling ability as a result of altered motility. Information within the literature is limited as to the gas-producing ability of sulphur-containing foods and oligosaccharides, and addressing this knowledge gap may be important step in the treatment of IBS.

References

1. Spiller RC, et al. Irritable bowel or irritable mind? British Medical Journal 1994; 309(6969):1646

2. Hotoleanu C, et al. genetic determination of irritable bowel syndrome. World Journal of Gastroenterology 2008: 14(43): pp 6636-6640.

3. Drossman DA, Dumitrascu DL. Rome III: New standard for functional gastrointestinal disorders. Journal of Gastrointestinal Liver Disease 2006:15(3): pp 237-241

4. Dapoigny M, et al. Role of alimentation in irritable bowel syndrome. Digestion Basel 2003;67(4):225.

5. Hauschildt E. Exclusion diets have limited use in irritable bowel syndrome. J Hum Nut Dietet 2001;14:231–41.

6. Farthing MJG. Fortnightly review: Irritable bowel, irritable body, or irritable brain? BMJ 1995;310:171–5.

7. Dapoigny M, et al. Role of alimentation in irritable bowel syndrome. Digestion Basel 2003;67(4):225.

8. King TS, et al. Abnormal colonic fermentation in irritable bowel syndrome. Lancet 1998;352(9135):1187.

9. Spiller RC, et al. Irritable bowel or irritable mind? BMJ 1994;309(6969):1646.

10. Jones J, et al. British Society of Gastroenterology guidelines for the management of the irritable bowel syndrome: Gut 2000;47(suppl II):S1–19.

11. Simren M, et al. Food-related gastrointestinal symptoms in the irritable bowel syndrome: Digestion Basel 2001;63(2):108–15.

12. Biali S. Beating the bloat: dietary changes can improve irritable bowel syndrome, but psychologic and mind-body factors also play a strong factor. Medical Post Toronto 2003;
http://www.medicalpost.com/mpcontent/article.jsp?content=20030922_102242_3436

13. Spanier JA, et al. A systematic review of alternative therapies in the irritable bowel syndrome. Arch Intern Med 2003;163(3):265–74.

14. Hodges D. Calm irritable bowel by cutting fructose, fat: studies confirm significant benefits of modified diets. Medical Post. Toronto 2003;39(40):21.

15. Magee EA, et al. Contribution of dietary protein to sulfide production in the large intestine: an in vitro and a controlled study in humans. Am J Clin Nutr 2000;72(6):

1488-94.

16. Magee EA, et al. Contribution of dietary protein to sulfide production in the large intestine: an in vitro and a controlled study in humans. Am J Clin Nutr 2000;72(6):

1488-94.

17. Dapoigny M, et al. Role of alimentation in irritable bowel syndrome. Digestion Basel 2003;67(4):225.

18. Ahmed AJ. Intestinal gas: Not entirely a laughing matter. Total Health 1999;

21(3):50–1.

Have we become a society reliant on a quick fix?