Scandinavian Journal of Gastroenterology ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20 Assessment of the Therapeutic Value of an Elemental Diet in Chronic Inflammatory Bowel Disease Christen Axelsson & Stig Jarnum To cite this article: Christen Axelsson & Stig Jarnum (1977) Assessment of the Therapeutic Value of an Elemental Diet in Chronic Inflammatory Bowel Disease, Scandinavian Journal of Gastroenterology, 12:1, 89-96, DOI: 10.1080/00365521.1977.12031117 To link to this article: https://doi.org/10.1080/00365521.1977.12031117 Published online: 29 Oct 2018. Submit your article to this journal Article views: 1 Citing articles: 5 View citing articles Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=igas20 Assessn1ent of the Therapeutic Value of an Elemental Diet in Chronic lnflamn1atory Bowel Disease CHRISTEN AXELSSON & STIG JARNUM Medical Dept. P, Division of Gastroenterology, Rigshospitalet, Copenhagen, Denmark Axelsson, C. & Jarnum, S. Assessment of the therapeutic value of an elemental diet in chronic inflammatory bowel disease. Scan d. J. Gastroent, 1977, 12, 89-95 Thirty-four patients with chronic inflammatory bowel disease, 23 with ulcerative colitis. and II with Crohn's disease, were treated with elemental diet. Thirty-one patients had been on high dose prednisone therapy one to four weeks prior to the diet with no or insufficient response. Fifteen patients (44%) went into remission when elemental diet was introduced as the only change of treatment. Furthermore six patients (18%) went into remission when the dietary treatment was supplemented with high dose prednisone treatment (2 cases) or an increase of prednisone dose (4 cases). Remission occurred in 16 of 21 patients with disease of moderate activity, but in only 5 of 13 cases with severe disease. Remission rate was higher in patients with a limited extent of the lesion, but 8 patients with extensive colitis responded to treatment. There was no significant change of haemoglobin, serum iron, transferrin, albumin, orosomucoid, or renal excretion of creatinine. However, significant decreases were observed of sedimentation rate, renal urea excretion, faecal volume and daily number of bowel movements. Colectomy was performed in 8 patients whose condition remained unchanged or aggravated during treatment. Follow-up studies of non-operated patients who went into remission showed that 6 of 13 patients with ulcerative colitis were perfectly well 7-28 months after the study, 3 patients suffered a mild recurrence after 4-24 months, and 4 patients were colectomized 5-10 months later due to severe attack. Of 8 patients with Crohn's disease 4 remained unoperated and free of symptoms 22-35 months after the study. Key-words: Chronic inflammatory bowel disease; elemental diet Stig Jarnum. M. D., Medical Dept. P, Division of Gastroenterology, Rigshospitalet, 2100 Copenhagen 0, Denmark Administration of an elemental diet in chronic inflammatory bowel disease aims at a reduction of the intraluminal bowel content to a minimum. In this way bowel movements are slowed down. the inflamed organ is kept at rest, and potential pathogenic and antigenic components in the lumen decrease. Preliminary reports suggest that elemental diet may be useful in severe ulcerative colitis and Crohn 's disease (l, 6, 8). The present report is a study of the thera- pcutic value of elemental diet in 34 patients with moderate and severe chronic inflammatory bowel disease. CASE MATERIAL Twenty-three patients with ulcerative colitis and II patients with Crohn's disease were treated with elemental diet in the period June 1972 - February 1976. Pertinent clinical and pathoanatomical data are listed in Table I. 90 Christen Axe/sson & Stig Jarnum Table I. Clinical and pathoanatomical findings in 34 patients with chronic inflammatory bowel disease Ulceralive colitis Extension of lesion Sex Activity Total no. (Age years) F M Distal* 14 21-78 (mean 42) 16-75 (mean 53) 5 9 3 5 6 Moderate Severe 9 Extensive Distal half** colitis••• 4 6 5 2 I Crohn's disease Extent of lesion Sex Activity Moderate Severe Total no. Age (years) F M 7 4 18-46 (mean 28) 29-75 (mean 53) 4 3 3 I Term. il.+ small Term. il. Terminal segment +>half 'Panileum of colon of colon colitis' 2 3 2 2 2 Fistulas, internal or intestinocutaneous 3 2 *Distal: rectum and sigmoideum. **Distal half of colon: descendens+sigmoideum+rectum+/-part of transversum. •••Pancolitis or > half of colon. Seleclion of palienls In ulceralive coli lis elemental diet was initiated as the only treatment (no previous steroid therapy) in three cases with distal inflammation (i.e. rectum and the sigmoid), in six cases with insufficient remission after prednisone therapy (i.e. prednisone 10-60 mg per day for 1-4 weeks), and in 14 cases with no remission after high dose prednisone (i.e. 60-160 mg per day for l-4 weeks) as a last alternative to surgical treatment. In Crvhn's disease the diet was initiated in four cases with insufficient remission after prednisone therapy for 2-4 weeks, in two cases with no remission after prednisone therapy 60 mg per day for two weeks as a last alternative to surgical treatment, and in five cases as an attempt to close fistulas. Most of the patients in both groups had longstanding disease of several years' duration with intermittent activity. Several patients joined the study because they refused colectomy. Complicating disease. I~ the ulcerative colitis group one patient had non-tropical sprue since 1962, and one patient had diabetes requiring treatment with insulin. One patient had ankylosing spondylitis, and one patient had StevenJohnson's syndrome just before the treatment with elemental diet. Among the patients with Crohn's disease one patient had juvenile cirrhosis in 1969 treated with extracorporeal irradiation and prednisone, and one patient had ankylosing spondylitis. METHODS The elemental diet was Vivasorb1l! (Pfrimmer & Co., Erlangcn, West Germany), composed of aminoacids, very little fat, electrolytes, vitamins, trace elements and as the major energy source glucose. The diet was gradually built up over a week as reported elsewhere (3). The diet was given orally except in three cases, who could not manage to take sufficient doses perorally, and in whom a thin nasogastric tube was used. The patients received 1800-2400 calories per day with 3300 calories as a maximum. The Elemental Diet in Bowel Disease 91 Table II. The course of ulcerative colitis during treatment with elemental diet No. of patients in whom prednisone No. of patients was started or dose on constant Result Result or decreasing increased during una!- remis- Colee- treatment with una!- remis- ColeeTotal prednisone dose• aggrav. tered sion to my elemental diet•• aggrav. tered sion to my Activity no. Moderate 14 9 Severe 9 5 3 2 6 2 3 5 4 2 23 14 5 8 3 9 2 Total 2 4 1 2*** 5 3 •One patient with moderate ulcerative colitis received no prednisone treatment at any time. He went into remission on elemental diet. The remaining 13 patients all had prednisone from one to four weeks before elemental diet. • •Prednisone was started in three patients with moderate activity and in one patient with severe activity after one or two weeks of unsuccessful dietary treatment. In the remaining 5 patients prednisone had been given from one to four weeks before elemental diet. The dose was usually increased after one week of unsuccessful dietary treatment. ••*Ileostomy and decompressing colostomies were made in a patient with perforation of the colon. duration of the dietary treatment was decided from the clinical course when a complete diet had been maintained for one week. It lasted from II to 55 days, on an average 26 days. Routine laboratory tests were done at regu1ar intervals, usually biweekly. They included: haemoglobin, serum protein, albumin, iron, transferrin, orosomucoid, and creatinine. In 13 cases of ulcerative colitis and in three cases of Crohn's disease serum urea was determined at regular intervals. In eight cases of ulcerative colitis and in three cases of Crohn's disease daily renal excretion of urea and creatinine was measured. Body weight, pulse rate, temperature, faecal volume, and number of bowel movements were measured daily, and the faecal content of pus and blood was registered. Statistical analysis. For all calculations the Wilcoxon rank sum test for paired data was used. RESULTS The results are presented in two ways, as a clinical and as a laboratory evaluation. Clinical evaluation For the clinical evaluation three marks are used: aggravated, unaltered, and remission. Ulcerative colitis (Table II) Aggravated. Three patients. The clinical state deteriorated in two patients on elemental diet and even after addition of high dose prednisone in one of them. Colectomy was performed in both. After II days on elemental diet the third patient suddenly developed a toxic dilatation of the colon. Unaltered. The disease activity was unaltered in seven patients. Four patients were colectomized. Surgical treatment was intended in an additional patient with moderate disease activity, but he refused operation. Two patients were discharged on prednisone and azathioprine. Remission. Thirteen patients went into remission. In eight patients the remission occurred during treatment with elemental diet on unaltered or decreasing prednisone dose except in one patient who had no prednisone at all. In five patients the clinical state was unaltered or remission insufficient, but remission set in after intensified prednisone treatment (on an average 40-160 mg per day for 8-10 days), and in one patient after addition of azathioprine 200 mg per day. Grahn's disease (Table III) In none of .the eleven patients with Crohn's 92 Christen Axelsson & Stig Jarnum Table III. The course of Crohn's disease during treatment with elemental diet Prednisone started or No. of dose increased patients on during unchanged or elemental Closure Closure decreasing diet: Result Result of Coleeof Colee- No. of Total prednisone Activity no. dose• agg. unalt. remis. fistula to my patients agg. unalt. remis. fistula to my Moderate Severe Total 7 4 6 3 II 9 s 2 2 I of 2 0 of 2 7 I of 4 2 *One patient with severe disease activity and internal (ileorectal) fistula had no prednisone at all. He went into clinical remission. His fistula did not close. A diverting ileostomy was ultimately made. disease was aggravation of the clinical condition seen during treatment with elemental diet. In two patients with severe disease activity the clinical state was unaltered and both were colectomized. Two patients with severe disease activity and fistulas went into clinical remission. However, their fistulas did not close. Five patients with moderate disease activity went into remission during treatment with elemental diet and prednisone in constant or decreasing dose. Four of them were treated with elemental diet after insufficient remission on prednisone, one of the four as a last alternative to surgical treatment. One patient with moderate disease activity went into remission after addition of high dose prednisone treatment (80 mg per day), and his fistula closed. The fistulas closed in one patient (intestinovesical fistula), and nearly completely in another patient {intestino-cutaneous fistula), but in three patients operative closure was necessary. In two of them the clinical state improved significantly during the elemental diet, which made possible 'a froid' operation. The topographic extension of the lesion was related to the response to treatment in so far as· five of six patients with distal ulcerative colitis went into remison~ whereas only four of ten patients with extensive ulcerative colitis (affecting more than half of the colon) went into remission (Table IV). However, the differ- ence was not statistically significant (p > 0.05, Fisher's exact probability test). In contrast, in Crohn's disease four of six patients with lesions comprising more than half of the colon responded to treatment. There was no significant alteration in the pulse rate or body temperature during administration of the diet. On an average, the 34 patients lost 0.5 kg body weight during the 'building up' period of the diet. During the Table IV. Topographic extension of chronic inflammatory bowel disease in 34 patients treated with elemental diet or elemental diet+ high dose prednisone Patients who went into remission: Ulcerative colitis: Distal colitis: Distal half of colon: Extensive colitis: 4 4 Crohn's disease: Terminal ileum (T.I.): T.l.+ < 15 em colon: T.l.+>halfofcolon:. 2 2 4 13 S 8 Patients who did not respond to treatment: Ulcerative colitis: Distal colitis: 1 Distal half of colon: 3 Extensive colitis: 6 Crohn's disease: T.l.+<l5 em colon: Pancolitis: 10 3 1 2 Elemental Diet in Bowel Disease Table V. Laboratory results. Significant changes during treatment with elemental diet. (Wilcoxon's rank sum test for paired data) Before elemental diet (mean) Parameter After elemental diet (mean) Sedimenta17 mm/h rion rate 29 mm/h Serum 3.7 mmol/1 5.0 mmol/1 urea Urea ex225 mmol/24 h 136 mmol/24 h cretion Faecal 255 g/day volume 353 gjday Stool 3/day frequency 5/day p <0.05 <0.01 <0.01 <0.01 <0.05 rest of the regime two patients developed hypoalbuminaemic oedema and gained three and five kg in weight. The remaining 32 patients lost 1.5 kg on an average. Laboratory results There were no significant changes of haemoglobin, serum iron, transferrin, albumin, or orosomucoid. Nor were there significant changes of the renal excretion of creatinine taken as an average excretion of three days before and in the final period of the diet (p > 0.05). There was a significant decrease of the sedimentation rate (p < 0.05), and a highly significant fall of serum urea as well as renal excretion of urea (p < 0.0!) (Table V). In one patient we did not succeed in making a quantitative collection of the stools. In the remaning 33 patients there was a 28 per cent reduction of the daily faecal volume from, on an average, 353 g to 255 g, which is a significant reduction (p < 0.01). Also, in the same 33 patients there was a significant reduction of bowel movements from, on an average, 5 to 3 per day (p < 0.05). There were no significant changes of the faecal content of pus and blood. Complications. After 11 days on elemental diet one patient with severe ulcerative colitis developed a toxic dilatation and perforation 93 of the colon. The patient was operated on as an emergency, and an ileostomy and several diverting colostomies were made. Four weeks after the operation the patient developed fungal sepsis and died. One patient had diabetes. Her insulin dose had to be readjusted during the elemental diet. On one occasion she suffered hypoglycaemic coma. One patient developed an allergic exanthema, which, after the treatment, could be reproduced by the 'raspberry' -bag of the diet. It was probably due to the flavour or colour substance added. In three patients a 'steroid' diabetes was seen, but there were no complications when the patients were placed on the glucose-based elemental diet. Follow-up studies Ulcerative colitis. Thirteen patients went into remission. Six of them have been without relapse for seven months (one case), 11 months (one case), 16 months (two cases), 21 months (one case), and 28 months (one case). Three patients have developed a mild new aLtack 4, 17, and 24 months after the dietary regimen. Four patients had a major attack 5, 6, 7, and 10 months after the diet. Three of them were colectomized. The fourth patient was again treated with elemental diet. There was an insufficient remission, and proctocolectomy was performed 4 months later. In the group with unaltered activity after elemental diet three patients were not operated on. One of them refused colectomy. After four months with moderate disease activity, spontaneous remission suddenly occurred. Both he and the remaining two patients who subsequently improved on treatment with prea· nisone and azathioprine have been well for 5-24 months after the conclusion of treatment with elemental diet. Crohn"s diseme. Of the six patients with moderate activity who went into remission, one patient had a new major attack 16 months later and was colectomized, and one whose fistula almost closed was well for 9 months 94 Christen Axelsson & Stig Jarnum until anastomosal stenosis with recurring fistula required reresection. The remaining four patients are still in remission 22, 31, 34, and 35 months after the diet. DISCUSSION The present day requirement that a new therapeutic principle has to prove its value in a double-blind controlled trial was impossible to carry through in the present study of patients with chronic inflammatory bowel disease of moderate or severe disease activity. It would imply a placebo for elemental diet made up of water and electrolytes with additives of flavouring and colouring substances to blind doctor and patient. It means deprivation of the patient of energy, aminoacids, and vitamins, which is obviously unethical. A controlled study in which one half of the patients continue on an unaltered therapy after a selected period of prednisone therapy and the other half on prednisone therapy + elemental diet was also considered unethical, since most of the patients (27 of 34) had been on prednisone therapy for one to four weeks without or with only partial therapeutic success before the institution of elemental diet. The fact that all patients who went into remission did so during the same phase of treatment is, in our opinion, strong evidence that the successful management, at least in most cases, was caused by the treatment and not by spontaneous remission. So, it appears that treatment with elemental diet can induce remission in moderate and severe chronic inflammatory bowel disease as the only therapeutic agent (one case) or in combination with prednisone. Furthermore, many (nine) patients had been on prednisone therapy for up to several weeks, when they were transferred to this hospital. Sixteen patients or almost half the total case material complied with our indications for colectomy when they were placed on elemental diet as a last alternative to surgical treatment. Nine of them could be discharged without operation because of remission within a week or two. Altogether 15 of 34 patients (eight with ulcerative colitis and 7 with Crohn's disease) or 44 per cent went into remission when elemental diet was introduced as the only · change of treatment. Furthermore, five patients with ulcerative colitis and one with Crohn's disease who did not respond to elemental diet within a week went into remission when prednisone therapy was added (two cases) or intensified (four cases). A contributory effect of the diet in these six patients is probable, but undocumented. As one would expect, the remission rate depended on disease activity. Remission occurred in 16 of 21 patients with disease of moderate activity, but in only 5 of 13 cases with severe disease (Tables II and III). The topographic extent of the lesion influenced the therapeutic result (Table IV), in so far as a higher remission rate was found in patients with a limited extent of the lesion. However, eight patients with extensive colitis responded to treatment, which indicates that extensive lesions does not per se make a trial with dietary treatment futile. Although diarrhoea and sedimentation rate decreased significantly during treatment with elemental diet (Table V), a number of abnormal laboratory values failed to approach the normal range, for instance serum orosomucoid, which has proved to be a rather accurate indicator of disease activity (4). We also failed to show any change of plasma protein exudation or a reduction of intestinal flora (unpublished observations). Thus, the resolution of the disease appears to be a slowly ongoing process. It has been stressed (2, 5) that maintenance of a satisfactory nutritional state is a prerequisite for a successful outcome of treatment with elemental diet. In the present study, this goal was accomplished as judged from weight curves. However, nitrogen supply was low, from 4.7 to 6.9 g per day, and renal urea excretion was also low (on an average 136 mmol equal to 3.8 g nitrogen per day), and two patients had hypoalbuminaemic oedema during the study. Formula diets with higher nitrogen content than the diet used in the present study Elemental Diet in Bowel Disease are available (9), but they are much more expensive, and it remains to be proven that the extra cost increases the success rate of the treatment. An alternative therapy to elemental diet would be complete oral fasting and total parenteral nutrition (6, 7). A comparison between these two types of treatment might very well be made as a controlled trial. It was not carried out in the present study. However, the hazards of prolonged parenteral nutrition, i.e. thrombosis of central veins and septicaemia from the central catheter, are evaded, when elemental diet is applied. ACKNOWLEDGEMENT The work was supported by grants from Christian d. X's Fond and P. Carl Petersens Fond. Received 10 June 1976 Accepted 17 August 1976 95 REFERENCES I. Berg, G., Wagner, H. & Weber, L. Dtsch. Med. Wschr. 1972, 97, 826-829 2. Goode, A., Hawkins, T., Fcggetter, J. G. W. & Johnston, I. D. A. Lancet 1976, 1, 122-125 3. Jarnum, S. pp. 139-151 in Jonxis, J. H. P., Wisser, H. K. A. & Troelstra, J. A. (eds.) Therapeutic Aspects of Nutrition. Groningcn, 1973 4. Jensen, K. B., Jarnum, S., Koudal, G. & Kristensen, M. Scand. J. Gastroent. 1976, 11, 177-185 5. Rocchio, M. A., Cha, C-J. M., Haas, K. F. & Randall, H. T. Amer. J. Surg. 1974, 127, 469475 6. Stephens, R. V. & Randall, H. T. Ann. Surg. 1969, 170, 642-667 7. Truelove, S. C. & Jewell, D. P. Lancet 1974, 1, 1057-1070 8. Voitk, A. 1., Echave, V., Feller, J. H., Brown, R. A. & Gurd, F. N. Arch. Surg. 1973, 107, 329-333 9. Young, E. A., Meulcr, N., Russell, P. & Weser, E. Gastroenterology 1975, 69, 1338-1345 International Study Group on Gastric Cancer The Group was established in 1974 during the World Congress of Gastroenterology in Mexico in order to elucidate and standardize the different aspects useful for gastric cancer control and as a connecting forum for the various research workers in the field. Aims of the group are: To point out, in the different fields connected to gastric cancer control, the results obtained in various countries and to stress further research where promising data have been obtained, implementing cooperative research projects. To elaborate detailed protocols on possible etiological factors, diagnostic procedures, stage classification, therapeutic approaches, etc. for predisposing conditions and gastric cancer, which research workers of different countries may agree on and relay for a subsequent comparison of results. To disseminate information to the medical community about recent advances concerning diagnostic and therapeutic methods. The first Meeting of the Group took place in Siofok (Hungary) 20-22 June 1976. A report of the meeting wiH be published. Five sub-groups were established: l. Statistics and epidemiology, with special emphasis on risk conditions related to gastric cancer. Rapporteur: 0. Gregor (CSSR). 2. Natural history, including pathological classification of gastric cancer and predisposing conditions. Rapporteur: Si-Chun Ming (USA). 3. Diagnostic procedures. Present available methods that could be used for screening. Rapporteur: E. Seifert {F.R.G.). 1 4. Therapeutic protocols depending on disease stage. Rapporteur: S. Eckhardt (Hungary). 5. Follow-up schedules for risk conditions .. Rapporteur: K. Varis (Finland). Executive-Secretary of the Group: Massimo Crespi, M.D. Regina Elena Institute for Cancer Research Viale Regina Elena, 291 00161 ROME, Italy